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Antibiotics Pre-Appendectomy Don’t Lower Perforation Risk, But Reduce Infections
, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).
While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.
There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.
The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).
While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.
There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.
The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new study.
While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.
The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.
The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”
The findings were published online in JAMA Surgery on May 14, 2025.
Trial Design
PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.
All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.
The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.
No Difference in Appendiceal Perforation
Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.
Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.
The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).
The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.
“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.
Lower Infection Rates With Antibiotics
Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.
Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).
While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.
There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.
“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.
The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.
“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.
The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Gut Microbiome Changes in Chronic Pain — Test and Treat?
A new study adds to what has been emerging in the literature — namely that — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.
“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.
Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.
A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.
The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.
Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.
Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.
Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.
“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.
Causal Role?
“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.
However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”
Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.
Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.
The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.
SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.
This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.
Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.
The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.
Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.
Test and Treat: Are We There Yet?
The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.
At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.
“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.
He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.
“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.
One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.
“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.
Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.
“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.
Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
A new study adds to what has been emerging in the literature — namely that — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.
“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.
Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.
A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.
The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.
Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.
Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.
Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.
“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.
Causal Role?
“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.
However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”
Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.
Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.
The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.
SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.
This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.
Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.
The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.
Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.
Test and Treat: Are We There Yet?
The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.
At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.
“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.
He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.
“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.
One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.
“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.
Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.
“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.
Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
A new study adds to what has been emerging in the literature — namely that — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.
“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.
Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.
A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.
The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.
Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.
Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.
Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.
“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.
Causal Role?
“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.
However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”
Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.
Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.
The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.
SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.
This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.
Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.
The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.
Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.
Test and Treat: Are We There Yet?
The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.
At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.
“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.
He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.
“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.
One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.
“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.
Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.
“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.
Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
Journal Highlights: January-April 2025
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Landmark 20-Year Study Reshapes Understanding of PTSD
A large 20-year study — the longest and most detailed of its kind — shows that posttraumatic stress disorder (PTSD) symptoms can endure for decades, challenging conventional timelines for recovery and offering new insights to guide future treatment.
Researchers analyzed data from the World Trade Center Health Program (WTCHP), which is administered by the US CDC’s National Institute for Occupational Safety and Health (NIOSH), and found symptoms of PTSD persisted for as long as two decades in 10% of first responders involved in the World Trade Center disaster of September 2001.
Participation in the WTCHP is voluntary, but those who enroll receive free assessments, monitoring, and treatment, including psychiatric and behavioral healthcare. It is the longest and most detailed analysis of PTSD and includes 81,298 observations from 12,822 WTC responders.
Participants entered the WTCHP at different timepoints and were assessed annually. Not every enrollee was assessed every year, but the sheer number of participants and observations “just provides much greater density of data over that 20-year course than any previous study,” lead author Frank D. Mann, PhD, told this news organization.
The study was published online on May 27 in Nature Mental Health.
Filling the PTSD Knowledge Gap
Most PTSD research has focused on the short term, with limited insight into how symptoms evolve over the long haul. Without long-term data, it’s been difficult to understand whether PTSD resolves, persists, or worsens — hindering efforts to guide treatment and support. This study aimed to fill that gap by tracking symptom patterns over two decades.
Responders were assessed regularly using the PTSD Checklist for a Specific Stressor, a standardized tool that measures symptom severity on an 85-point scale. On average, each participant completed 6.3 assessments over the course of the study.
A score of ≥ 44 was considered indicative of clinically elevated PTSD symptoms. Between 2002 and 2022, the crude prevalence of elevated symptoms ranged from 8% to 15%. At the same time, 16% to 34% of responders each year reported little to no symptoms, scoring at or near the minimum on the scale.
The researchers found that symptom trajectories varied widely. Nearly as many participants experienced worsening symptoms as those who improved. As a result, the overall population average remained relatively flat over the 20-year period.
Among responders who met the threshold for PTSD, the median time to symptom improvement was 8.9 years — and by year 20, about 76% had shown improvement.
New Insights
Mann, a senior research scientist at Stony Brook University Renaissance School of Medicine, Stony Brook, New York, said the study not only reinforced existing knowledge about PTSD in responders but also uncovered new insights.
Most notably, it showed that PTSD symptoms tended to peak around a decade after 9/11 — significantly later than delayed-onset patterns reported in previous trauma studies.
He also noted a surprising outcome — the top 10% of responders who experienced worsening symptoms over the long term accounted for the majority of mental health costs. These individuals, Mann said, represent a critical gap in care, with current interventions proving largely ineffective for them.
Mann suggested that ongoing trauma exposure — especially for responders still in high-risk jobs — and potential genetic susceptibility may contribute to late-emerging or persistent symptoms.
“These individuals are an urgent priority for health systems, as available resources have not been effective for them,” the study authors wrote.
Mann and his colleagues also found that occupation offered the strongest protection against developing PTSD. Police officers and firefighters benefit from training designed to help them cope with trauma, and repeated exposure may build a degree of resilience.
In contrast, responders without such training — like construction workers — faced a 50% to 55% higher risk of developing PTSD symptoms. Mann emphasized that occupational status was a more powerful predictor of PTSD risk than the severity of the traumatic exposures themselves.
A Valuable Contribution
Commenting on the research for this news organization, Sandra Lowe, MD, medical director of the Mount Sinai WTCMH program, noted that while the study largely confirms what has been known about responders — such as the significant variability in symptom trajectories over time — it still makes a valuable contribution.
“Extending observations for up to 20 years is rare in any study, especially in a cohort this large,” said Lowe, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York City, who was not involved in the study.
Also commenting, James West, MD, chair of the American Psychiatric Association’s Committee on the Psychiatric Dimensions of Disaster, described the finding that 10% of responders continued to experience symptoms two decades after exposure as “sobering.”
However, he emphasized that it aligns with observations in the disaster recovery community, where the psychological impact “goes way beyond what most people see as the immediate aftermath and recovery.” West stressed the urgent need to develop effective treatments that enable those affected to live fuller, less impaired lives.
“We still need to be finding the effective treatments that can help these people live fuller lives without impairment from their trauma symptoms,” said West.
Lowe pointed out that the symptom peak around 10 years post-exposure is often linked to external factors. Some responders who had been managing symptoms might lose resilience due to major life changes such as retirement.
“One of the things that was able to keep them engaged is now lost,” she said. “They begin to spend more time reflecting on recollections, and symptoms can worsen.”
West agreed, adding that retirement or job loss often leads to symptom increases because it removes a primary coping mechanism. Both Lowe and Mann also highlighted that 9/11 memorial events can trigger new symptoms or exacerbate existing ones.
Lowe noted that responders with stronger coping skills tended to fare better over time. Effective coping strategies include maintaining regular schedules — especially for eating and sleeping — leading a structured life, and employing stress management techniques like meditation, yoga, or enjoyable hobbies. Social connection and being part of a community are also critical for resilience. She added that clinicians should always inquire about trauma history.
Lowe, West, and Mann all pointed out that PTSD is often accompanied by physical health issues, particularly cardiovascular problems, which tend to be worse in those with the disorder.
Responders with stronger coping skills tended to do better over time, said Lowe. Coping skills that can help make a difference include having a regular schedule, especially for eating and sleeping; having a structured life; and stress management tools, such as meditation or yoga or an enjoyable hobby. Social connection — being part of a community — is also critical, Lowe said.
Clinicians should always inquire about trauma, she said. Lowe, West, and Mann all noted that people with PTSD often have physical illness and that cardiovascular outcomes in particular are worse for those individuals.
WTCHP Future Uncertain
However, despite advances in understanding PTSD and the importance of ongoing care, the future of the program supporting World Trade Center responders remains uncertain.
Some 140,000 people are now enrolled in the WTCHP, which was established as a federal program in 2010. Congress has generally reauthorized the program whenever its funding came up for renewal.
However, earlier this year, the Trump administration dismissed two thirds of the NIOSH workforce, including John Howard, MD, the administrator of the WTCHP.
In response, members of Congress and advocates for 9/11 survivors urged the US Department of Health and Human Services (HHS) to reinstate Howard and the affected employees. Howard is listed as back on the job has since returned to his position, and HHS reportedly reinstated hundreds of NIOSH workers in May.
An HHS spokesperson told this news organization that the WTCHP continues to provide services and is actively “accepting, reviewing, and processing new enrollment applications and certification requests.”
Meanwhile, the Trump administration’s fiscal year 2026 budget proposal seeks to reduce CDC funding by $3.5 billion — approximately 40% — with a shift in focus toward infectious diseases. It remains unclear how the WTCHP will be affected by this new direction.
Mann said he is not involved in the program’s funding details but added, “Presumably, as long as some funding continues to keep the program alive, we will continue monitoring responders and providing free treatment until the very last World Trade Center responder passes.”
The study was partially funded through National Institutes of Health and CDC grants, the SUNY Research Foundation, and the CDC’s World Trade Center Health Program. Mann, Lowe, and West reported having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large 20-year study — the longest and most detailed of its kind — shows that posttraumatic stress disorder (PTSD) symptoms can endure for decades, challenging conventional timelines for recovery and offering new insights to guide future treatment.
Researchers analyzed data from the World Trade Center Health Program (WTCHP), which is administered by the US CDC’s National Institute for Occupational Safety and Health (NIOSH), and found symptoms of PTSD persisted for as long as two decades in 10% of first responders involved in the World Trade Center disaster of September 2001.
Participation in the WTCHP is voluntary, but those who enroll receive free assessments, monitoring, and treatment, including psychiatric and behavioral healthcare. It is the longest and most detailed analysis of PTSD and includes 81,298 observations from 12,822 WTC responders.
Participants entered the WTCHP at different timepoints and were assessed annually. Not every enrollee was assessed every year, but the sheer number of participants and observations “just provides much greater density of data over that 20-year course than any previous study,” lead author Frank D. Mann, PhD, told this news organization.
The study was published online on May 27 in Nature Mental Health.
Filling the PTSD Knowledge Gap
Most PTSD research has focused on the short term, with limited insight into how symptoms evolve over the long haul. Without long-term data, it’s been difficult to understand whether PTSD resolves, persists, or worsens — hindering efforts to guide treatment and support. This study aimed to fill that gap by tracking symptom patterns over two decades.
Responders were assessed regularly using the PTSD Checklist for a Specific Stressor, a standardized tool that measures symptom severity on an 85-point scale. On average, each participant completed 6.3 assessments over the course of the study.
A score of ≥ 44 was considered indicative of clinically elevated PTSD symptoms. Between 2002 and 2022, the crude prevalence of elevated symptoms ranged from 8% to 15%. At the same time, 16% to 34% of responders each year reported little to no symptoms, scoring at or near the minimum on the scale.
The researchers found that symptom trajectories varied widely. Nearly as many participants experienced worsening symptoms as those who improved. As a result, the overall population average remained relatively flat over the 20-year period.
Among responders who met the threshold for PTSD, the median time to symptom improvement was 8.9 years — and by year 20, about 76% had shown improvement.
New Insights
Mann, a senior research scientist at Stony Brook University Renaissance School of Medicine, Stony Brook, New York, said the study not only reinforced existing knowledge about PTSD in responders but also uncovered new insights.
Most notably, it showed that PTSD symptoms tended to peak around a decade after 9/11 — significantly later than delayed-onset patterns reported in previous trauma studies.
He also noted a surprising outcome — the top 10% of responders who experienced worsening symptoms over the long term accounted for the majority of mental health costs. These individuals, Mann said, represent a critical gap in care, with current interventions proving largely ineffective for them.
Mann suggested that ongoing trauma exposure — especially for responders still in high-risk jobs — and potential genetic susceptibility may contribute to late-emerging or persistent symptoms.
“These individuals are an urgent priority for health systems, as available resources have not been effective for them,” the study authors wrote.
Mann and his colleagues also found that occupation offered the strongest protection against developing PTSD. Police officers and firefighters benefit from training designed to help them cope with trauma, and repeated exposure may build a degree of resilience.
In contrast, responders without such training — like construction workers — faced a 50% to 55% higher risk of developing PTSD symptoms. Mann emphasized that occupational status was a more powerful predictor of PTSD risk than the severity of the traumatic exposures themselves.
A Valuable Contribution
Commenting on the research for this news organization, Sandra Lowe, MD, medical director of the Mount Sinai WTCMH program, noted that while the study largely confirms what has been known about responders — such as the significant variability in symptom trajectories over time — it still makes a valuable contribution.
“Extending observations for up to 20 years is rare in any study, especially in a cohort this large,” said Lowe, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York City, who was not involved in the study.
Also commenting, James West, MD, chair of the American Psychiatric Association’s Committee on the Psychiatric Dimensions of Disaster, described the finding that 10% of responders continued to experience symptoms two decades after exposure as “sobering.”
However, he emphasized that it aligns with observations in the disaster recovery community, where the psychological impact “goes way beyond what most people see as the immediate aftermath and recovery.” West stressed the urgent need to develop effective treatments that enable those affected to live fuller, less impaired lives.
“We still need to be finding the effective treatments that can help these people live fuller lives without impairment from their trauma symptoms,” said West.
Lowe pointed out that the symptom peak around 10 years post-exposure is often linked to external factors. Some responders who had been managing symptoms might lose resilience due to major life changes such as retirement.
“One of the things that was able to keep them engaged is now lost,” she said. “They begin to spend more time reflecting on recollections, and symptoms can worsen.”
West agreed, adding that retirement or job loss often leads to symptom increases because it removes a primary coping mechanism. Both Lowe and Mann also highlighted that 9/11 memorial events can trigger new symptoms or exacerbate existing ones.
Lowe noted that responders with stronger coping skills tended to fare better over time. Effective coping strategies include maintaining regular schedules — especially for eating and sleeping — leading a structured life, and employing stress management techniques like meditation, yoga, or enjoyable hobbies. Social connection and being part of a community are also critical for resilience. She added that clinicians should always inquire about trauma history.
Lowe, West, and Mann all pointed out that PTSD is often accompanied by physical health issues, particularly cardiovascular problems, which tend to be worse in those with the disorder.
Responders with stronger coping skills tended to do better over time, said Lowe. Coping skills that can help make a difference include having a regular schedule, especially for eating and sleeping; having a structured life; and stress management tools, such as meditation or yoga or an enjoyable hobby. Social connection — being part of a community — is also critical, Lowe said.
Clinicians should always inquire about trauma, she said. Lowe, West, and Mann all noted that people with PTSD often have physical illness and that cardiovascular outcomes in particular are worse for those individuals.
WTCHP Future Uncertain
However, despite advances in understanding PTSD and the importance of ongoing care, the future of the program supporting World Trade Center responders remains uncertain.
Some 140,000 people are now enrolled in the WTCHP, which was established as a federal program in 2010. Congress has generally reauthorized the program whenever its funding came up for renewal.
However, earlier this year, the Trump administration dismissed two thirds of the NIOSH workforce, including John Howard, MD, the administrator of the WTCHP.
In response, members of Congress and advocates for 9/11 survivors urged the US Department of Health and Human Services (HHS) to reinstate Howard and the affected employees. Howard is listed as back on the job has since returned to his position, and HHS reportedly reinstated hundreds of NIOSH workers in May.
An HHS spokesperson told this news organization that the WTCHP continues to provide services and is actively “accepting, reviewing, and processing new enrollment applications and certification requests.”
Meanwhile, the Trump administration’s fiscal year 2026 budget proposal seeks to reduce CDC funding by $3.5 billion — approximately 40% — with a shift in focus toward infectious diseases. It remains unclear how the WTCHP will be affected by this new direction.
Mann said he is not involved in the program’s funding details but added, “Presumably, as long as some funding continues to keep the program alive, we will continue monitoring responders and providing free treatment until the very last World Trade Center responder passes.”
The study was partially funded through National Institutes of Health and CDC grants, the SUNY Research Foundation, and the CDC’s World Trade Center Health Program. Mann, Lowe, and West reported having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large 20-year study — the longest and most detailed of its kind — shows that posttraumatic stress disorder (PTSD) symptoms can endure for decades, challenging conventional timelines for recovery and offering new insights to guide future treatment.
Researchers analyzed data from the World Trade Center Health Program (WTCHP), which is administered by the US CDC’s National Institute for Occupational Safety and Health (NIOSH), and found symptoms of PTSD persisted for as long as two decades in 10% of first responders involved in the World Trade Center disaster of September 2001.
Participation in the WTCHP is voluntary, but those who enroll receive free assessments, monitoring, and treatment, including psychiatric and behavioral healthcare. It is the longest and most detailed analysis of PTSD and includes 81,298 observations from 12,822 WTC responders.
Participants entered the WTCHP at different timepoints and were assessed annually. Not every enrollee was assessed every year, but the sheer number of participants and observations “just provides much greater density of data over that 20-year course than any previous study,” lead author Frank D. Mann, PhD, told this news organization.
The study was published online on May 27 in Nature Mental Health.
Filling the PTSD Knowledge Gap
Most PTSD research has focused on the short term, with limited insight into how symptoms evolve over the long haul. Without long-term data, it’s been difficult to understand whether PTSD resolves, persists, or worsens — hindering efforts to guide treatment and support. This study aimed to fill that gap by tracking symptom patterns over two decades.
Responders were assessed regularly using the PTSD Checklist for a Specific Stressor, a standardized tool that measures symptom severity on an 85-point scale. On average, each participant completed 6.3 assessments over the course of the study.
A score of ≥ 44 was considered indicative of clinically elevated PTSD symptoms. Between 2002 and 2022, the crude prevalence of elevated symptoms ranged from 8% to 15%. At the same time, 16% to 34% of responders each year reported little to no symptoms, scoring at or near the minimum on the scale.
The researchers found that symptom trajectories varied widely. Nearly as many participants experienced worsening symptoms as those who improved. As a result, the overall population average remained relatively flat over the 20-year period.
Among responders who met the threshold for PTSD, the median time to symptom improvement was 8.9 years — and by year 20, about 76% had shown improvement.
New Insights
Mann, a senior research scientist at Stony Brook University Renaissance School of Medicine, Stony Brook, New York, said the study not only reinforced existing knowledge about PTSD in responders but also uncovered new insights.
Most notably, it showed that PTSD symptoms tended to peak around a decade after 9/11 — significantly later than delayed-onset patterns reported in previous trauma studies.
He also noted a surprising outcome — the top 10% of responders who experienced worsening symptoms over the long term accounted for the majority of mental health costs. These individuals, Mann said, represent a critical gap in care, with current interventions proving largely ineffective for them.
Mann suggested that ongoing trauma exposure — especially for responders still in high-risk jobs — and potential genetic susceptibility may contribute to late-emerging or persistent symptoms.
“These individuals are an urgent priority for health systems, as available resources have not been effective for them,” the study authors wrote.
Mann and his colleagues also found that occupation offered the strongest protection against developing PTSD. Police officers and firefighters benefit from training designed to help them cope with trauma, and repeated exposure may build a degree of resilience.
In contrast, responders without such training — like construction workers — faced a 50% to 55% higher risk of developing PTSD symptoms. Mann emphasized that occupational status was a more powerful predictor of PTSD risk than the severity of the traumatic exposures themselves.
A Valuable Contribution
Commenting on the research for this news organization, Sandra Lowe, MD, medical director of the Mount Sinai WTCMH program, noted that while the study largely confirms what has been known about responders — such as the significant variability in symptom trajectories over time — it still makes a valuable contribution.
“Extending observations for up to 20 years is rare in any study, especially in a cohort this large,” said Lowe, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York City, who was not involved in the study.
Also commenting, James West, MD, chair of the American Psychiatric Association’s Committee on the Psychiatric Dimensions of Disaster, described the finding that 10% of responders continued to experience symptoms two decades after exposure as “sobering.”
However, he emphasized that it aligns with observations in the disaster recovery community, where the psychological impact “goes way beyond what most people see as the immediate aftermath and recovery.” West stressed the urgent need to develop effective treatments that enable those affected to live fuller, less impaired lives.
“We still need to be finding the effective treatments that can help these people live fuller lives without impairment from their trauma symptoms,” said West.
Lowe pointed out that the symptom peak around 10 years post-exposure is often linked to external factors. Some responders who had been managing symptoms might lose resilience due to major life changes such as retirement.
“One of the things that was able to keep them engaged is now lost,” she said. “They begin to spend more time reflecting on recollections, and symptoms can worsen.”
West agreed, adding that retirement or job loss often leads to symptom increases because it removes a primary coping mechanism. Both Lowe and Mann also highlighted that 9/11 memorial events can trigger new symptoms or exacerbate existing ones.
Lowe noted that responders with stronger coping skills tended to fare better over time. Effective coping strategies include maintaining regular schedules — especially for eating and sleeping — leading a structured life, and employing stress management techniques like meditation, yoga, or enjoyable hobbies. Social connection and being part of a community are also critical for resilience. She added that clinicians should always inquire about trauma history.
Lowe, West, and Mann all pointed out that PTSD is often accompanied by physical health issues, particularly cardiovascular problems, which tend to be worse in those with the disorder.
Responders with stronger coping skills tended to do better over time, said Lowe. Coping skills that can help make a difference include having a regular schedule, especially for eating and sleeping; having a structured life; and stress management tools, such as meditation or yoga or an enjoyable hobby. Social connection — being part of a community — is also critical, Lowe said.
Clinicians should always inquire about trauma, she said. Lowe, West, and Mann all noted that people with PTSD often have physical illness and that cardiovascular outcomes in particular are worse for those individuals.
WTCHP Future Uncertain
However, despite advances in understanding PTSD and the importance of ongoing care, the future of the program supporting World Trade Center responders remains uncertain.
Some 140,000 people are now enrolled in the WTCHP, which was established as a federal program in 2010. Congress has generally reauthorized the program whenever its funding came up for renewal.
However, earlier this year, the Trump administration dismissed two thirds of the NIOSH workforce, including John Howard, MD, the administrator of the WTCHP.
In response, members of Congress and advocates for 9/11 survivors urged the US Department of Health and Human Services (HHS) to reinstate Howard and the affected employees. Howard is listed as back on the job has since returned to his position, and HHS reportedly reinstated hundreds of NIOSH workers in May.
An HHS spokesperson told this news organization that the WTCHP continues to provide services and is actively “accepting, reviewing, and processing new enrollment applications and certification requests.”
Meanwhile, the Trump administration’s fiscal year 2026 budget proposal seeks to reduce CDC funding by $3.5 billion — approximately 40% — with a shift in focus toward infectious diseases. It remains unclear how the WTCHP will be affected by this new direction.
Mann said he is not involved in the program’s funding details but added, “Presumably, as long as some funding continues to keep the program alive, we will continue monitoring responders and providing free treatment until the very last World Trade Center responder passes.”
The study was partially funded through National Institutes of Health and CDC grants, the SUNY Research Foundation, and the CDC’s World Trade Center Health Program. Mann, Lowe, and West reported having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MENTAL HEALTH
Posttraumatic Stress Disorder May Increase Morbidity Risk in Veterans With HIV
TOPLINE:
Posttraumatic stress disorder (PTSD) among veterans living with HIV significantly increased the risk for AIDS and multiple comorbidities, particularly arthritis, cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and multimorbidity — with the greatest impact seen in the first decade after diagnosis.
METHODOLOGY:
- Researchers conducted a prospective cohort study to assess whether PTSD is associated with increased risk for adverse clinical outcomes in veterans with HIV who received care at the Department of Veterans Affairs.
- They included 3206 veterans (97.4% men; median age at HIV diagnosis, 31.7 years; 42.1% with PTSD) who were deployed in Iraq and Afghanistan while serving in the military and initiated antiretroviral therapy before December 31, 2020.
- Participants were followed-up until December 2022, with censoring at death, the last health care visit, or study termination. The association between PTSD with morbidity and mortality, considering the number of deployments and levels of combat exposure were determined.
TAKEAWAY:
- PTSD significantly increased the overall risks for AIDS by 11% (adjusted hazard ratio [aHR], 1.11), CKD by 21% (aHR, 1.21), COPD by 46% (aHR, 1.46), multimorbidity by 49% (aHR, 1.49), CVD by 57% (aHR, 1.57), and arthritis by two folds (aHR, 1.95; P <.05 for all).
- Among veterans with a single deployment, those with PTSD had 92%, 87%, 80%, 53%, 44%, 32%, and 27% higher risks for asthma, CVD, arthritis, multimorbidity, COPD, liver disease, and AIDS, respectively, than those without PTSD.
- Veterans with PTSD and combat exposure had a lower risk for AIDS but higher risks for multimorbidity, asthma, CVD, and arthritis than those never diagnosed with PTSD and unexposed to combat.
- The associations of PTSD with mortality and morbidity appeared most pronounced in the first decade post-diagnosis, followed by a gradual decline in association strength; however, risks remained elevated.
IN PRACTICE:
“It is recommended that providers who work with VWH [veterans with HIV] consider adopting a trauma-informed model of HIV care and that providers screen veterans for PTSD, so that their unique trauma history can help guide medical decisions and treatment,” the authors wrote.
SOURCE:
This study was led by Kartavya J. Vyas, PhD, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta. It was published online in AIDS .
LIMITATIONS:
The data could not capture each individual’s true index trauma or the severity of their PTSD. Additionally, the study was limited by considerable loss to follow-up, potential uncontrolled confounding related to homelessness, and a lack of generalizability to veterans with HIV who were not receiving antiretroviral therapy.
DISCLOSURES:
The study did not receive any specific funding. Two authors reported receiving federal research support — one from the Emory Center for AIDS Research and the National Institute of Allergy and Infectious Diseases, and the other from the National Institutes of Health and the CDC — in addition to investigator-initiated grants and consulting fees from various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Posttraumatic stress disorder (PTSD) among veterans living with HIV significantly increased the risk for AIDS and multiple comorbidities, particularly arthritis, cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and multimorbidity — with the greatest impact seen in the first decade after diagnosis.
METHODOLOGY:
- Researchers conducted a prospective cohort study to assess whether PTSD is associated with increased risk for adverse clinical outcomes in veterans with HIV who received care at the Department of Veterans Affairs.
- They included 3206 veterans (97.4% men; median age at HIV diagnosis, 31.7 years; 42.1% with PTSD) who were deployed in Iraq and Afghanistan while serving in the military and initiated antiretroviral therapy before December 31, 2020.
- Participants were followed-up until December 2022, with censoring at death, the last health care visit, or study termination. The association between PTSD with morbidity and mortality, considering the number of deployments and levels of combat exposure were determined.
TAKEAWAY:
- PTSD significantly increased the overall risks for AIDS by 11% (adjusted hazard ratio [aHR], 1.11), CKD by 21% (aHR, 1.21), COPD by 46% (aHR, 1.46), multimorbidity by 49% (aHR, 1.49), CVD by 57% (aHR, 1.57), and arthritis by two folds (aHR, 1.95; P <.05 for all).
- Among veterans with a single deployment, those with PTSD had 92%, 87%, 80%, 53%, 44%, 32%, and 27% higher risks for asthma, CVD, arthritis, multimorbidity, COPD, liver disease, and AIDS, respectively, than those without PTSD.
- Veterans with PTSD and combat exposure had a lower risk for AIDS but higher risks for multimorbidity, asthma, CVD, and arthritis than those never diagnosed with PTSD and unexposed to combat.
- The associations of PTSD with mortality and morbidity appeared most pronounced in the first decade post-diagnosis, followed by a gradual decline in association strength; however, risks remained elevated.
IN PRACTICE:
“It is recommended that providers who work with VWH [veterans with HIV] consider adopting a trauma-informed model of HIV care and that providers screen veterans for PTSD, so that their unique trauma history can help guide medical decisions and treatment,” the authors wrote.
SOURCE:
This study was led by Kartavya J. Vyas, PhD, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta. It was published online in AIDS .
LIMITATIONS:
The data could not capture each individual’s true index trauma or the severity of their PTSD. Additionally, the study was limited by considerable loss to follow-up, potential uncontrolled confounding related to homelessness, and a lack of generalizability to veterans with HIV who were not receiving antiretroviral therapy.
DISCLOSURES:
The study did not receive any specific funding. Two authors reported receiving federal research support — one from the Emory Center for AIDS Research and the National Institute of Allergy and Infectious Diseases, and the other from the National Institutes of Health and the CDC — in addition to investigator-initiated grants and consulting fees from various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Posttraumatic stress disorder (PTSD) among veterans living with HIV significantly increased the risk for AIDS and multiple comorbidities, particularly arthritis, cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and multimorbidity — with the greatest impact seen in the first decade after diagnosis.
METHODOLOGY:
- Researchers conducted a prospective cohort study to assess whether PTSD is associated with increased risk for adverse clinical outcomes in veterans with HIV who received care at the Department of Veterans Affairs.
- They included 3206 veterans (97.4% men; median age at HIV diagnosis, 31.7 years; 42.1% with PTSD) who were deployed in Iraq and Afghanistan while serving in the military and initiated antiretroviral therapy before December 31, 2020.
- Participants were followed-up until December 2022, with censoring at death, the last health care visit, or study termination. The association between PTSD with morbidity and mortality, considering the number of deployments and levels of combat exposure were determined.
TAKEAWAY:
- PTSD significantly increased the overall risks for AIDS by 11% (adjusted hazard ratio [aHR], 1.11), CKD by 21% (aHR, 1.21), COPD by 46% (aHR, 1.46), multimorbidity by 49% (aHR, 1.49), CVD by 57% (aHR, 1.57), and arthritis by two folds (aHR, 1.95; P <.05 for all).
- Among veterans with a single deployment, those with PTSD had 92%, 87%, 80%, 53%, 44%, 32%, and 27% higher risks for asthma, CVD, arthritis, multimorbidity, COPD, liver disease, and AIDS, respectively, than those without PTSD.
- Veterans with PTSD and combat exposure had a lower risk for AIDS but higher risks for multimorbidity, asthma, CVD, and arthritis than those never diagnosed with PTSD and unexposed to combat.
- The associations of PTSD with mortality and morbidity appeared most pronounced in the first decade post-diagnosis, followed by a gradual decline in association strength; however, risks remained elevated.
IN PRACTICE:
“It is recommended that providers who work with VWH [veterans with HIV] consider adopting a trauma-informed model of HIV care and that providers screen veterans for PTSD, so that their unique trauma history can help guide medical decisions and treatment,” the authors wrote.
SOURCE:
This study was led by Kartavya J. Vyas, PhD, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta. It was published online in AIDS .
LIMITATIONS:
The data could not capture each individual’s true index trauma or the severity of their PTSD. Additionally, the study was limited by considerable loss to follow-up, potential uncontrolled confounding related to homelessness, and a lack of generalizability to veterans with HIV who were not receiving antiretroviral therapy.
DISCLOSURES:
The study did not receive any specific funding. Two authors reported receiving federal research support — one from the Emory Center for AIDS Research and the National Institute of Allergy and Infectious Diseases, and the other from the National Institutes of Health and the CDC — in addition to investigator-initiated grants and consulting fees from various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Can Patients Really Say No to Life-Saving Cancer Care?
Mrs G.O. is an 80-year-old retired teacher who was widowed a decade ago. With no close relatives, she lives alone, accompanied by only two cats and a dog that she has rescued. “I am alone,” she told Gustavo Kusminsky, MD, consultant in Hematology and Hematopoietic Transplant Service at Austral University Hospital and lecturer in medicine at the Hospital Universitario Austral, Buenos Aires, Argentina. She said this calmly while refusing treatment for life-threatening multiple myeloma. “Doctor, I would rather not,” she added — her words lingering in the quiet consulting room. That moment is now the focus of a recent article in the journal Medicina.
In the article, Kusminsky described how he made an effort to clarify to the patient that she needed cancer treatment. He explained that the treatment was mostly oral, required no initial hospitalization, and that consultations could be spaced out. However, Mrs G.O. maintained her position.
“The patient had no signs of depression, and her argument was logical. Mrs G.O. was already receiving several medications for high blood pressure, was on anticoagulation therapy for atrial fibrillation, and managed dyslipidemia with fenofibrate. But she preferred not to receive treatment for her multiple myeloma.” Kusminsky noted.
“Doctor, I have lived my life. I am old. I am already taking too many medications. I do not have a family, and it would be very difficult to deal with the side effects and be dependent on the hospital. As long as I can take care of myself, I do not want any more treatment, at least not for now. We will talk in a few months if I am still here,” she told him before leaving.
The article mentioned that responses such as Mrs G.O. spark perplexity in modern medicine to the extent that clinicians initiate protocols to rule out depression or other psychological factors when a patient rejects treatments that could prolong their life. On the contrary, no such checks are made when patients agree to treatment, because acceptance is deemed “normal.”
Because of collective assumptions and the war metaphors often used in oncology, Mrs G.O. risked being labeled a “deserter from the battalion” of patients with cancer.
In truth, her decision invites reflection on the doctor-patient relationship, respect for autonomy, and the benefits of modern cancer care offered today, Kusminsky said.
This provides an opportunity to consider the patient’s perspective rather than a purely medical perspective.
Jennifer Hincapié Sánchez, PhD, professor in the Faculty of Medicine at the National Autonomous University of Mexico (UNAM). She is the director of the UNAM University Bioethics Program and coordinates its Institutional Ethics and Bioethics Program for the Faculty of Medicine in Mexico. Although not involved in the article, she regards it as vital. “It’s crucial to remind medical staff that their role is to promote patients’ well-being and that this is related to the life plan that patients have set for themselves, even though this vision is sometimes not aligned with biomedical progress,” she said.
Patient Autonomy
Science-guided medicine aims to prolong life, improve quality, and relieve suffering. However, acceptance or refusal of treatment remains a personal choice for anyone with cancer.
Some evidence showed that patients who decline treatment do not always experience rapid decline. Many can live acceptable, even fulfilling, lives on their own for varying periods, even though they know that there is a possibility of shorter survival. Valuing fewer side effects and better quality of life. This suggested that quality of life is subjective and cannot be measured solely by biomedical standards but also by the meaning each person finds in their existence, even in the face of serious illness.
“There is a myth that quality of life is only valid when defined by objective success. Our task is to explain that it is subjective, and life can be meaningful despite limitations.” Kusminsky said.
Mrs G.O. knew her prognosis and treatment options but chose not to pursue treatment, which, while medically advisable, did not align with her values or vision of life.
Hincapié Sánchez stated that the priority is always to honor the patient’s choice. Clinicians must ensure that the patient has all necessary information that is always appropriate to their sociocultural context before making the decision.
“If the decision persists despite being informed and aware of the effects of the patient’s choice, all we can do is provide support, manage the pain, and seek the patient’s comfort,” she emphasized.
Medical Omnipotence
Physicians should not view the refusal of treatment as an abandonment of the fundamental principles of the profession. Rather, it means respecting patient priorities and recognizing medicine as a dialogue between science and humanity, not as an exercise of control.
However, many clinicians struggle with such decisions because they conflict with their impulse to act and a sense of medical omnipotence. Hincapié Sánchez attributed these difficulties to medical training.
“We are taught to preserve life at all costs. If treatment even slightly prolongs life, many doctors continue to recommend it. The question becomes: Is it valid to extend life when its quality is in doubt?” she asked.
“Medicine is more than a science; it is an art. It is the most human in the sciences and the most scientific in the humanities. Let us not lose sight of the human element that allows us to see the patient as a person, not just a disease to be treated,” Hincapié Sánchez urges.
Kusminsky describes a common therapeutic obstinacy — doctors’ reluctance to stop “doing something,” to avoid “throwing in the towel,” or to uphold “hope is the last thing to be lost.”
“But physicians are growing more aware of these situations, and change is slowly coming,” he said. However, he added: “Of course, there is the issue of the perceived omnipotence of doctors — their words descending with authority to ‘prescribe’ treatment, issue ‘medical orders,’ or dictate ‘pharmacological’ therapy.
For the specialist, such terminology reflects a view of the doctor-patient relationship not as a mutual, two-way exchange, but as a vertical, paternalistic dynamic.
He suggested looking at ancient Greece for perspective. “Hippocrates, or rather the Hippocratic school, taught that the doctor-patient encounter is inherently one of compassion. We must approach this in that way. Reflecting on that bond, improving communication, humanizing relationships, and, above all, being available to listen are key,” Kusminsky said.
Another intersection that has long fascinated Kusminsky is between literature and medicine. This interest led him to explore the field of narrative medicine, serve on the board of directors of the Argentine Society of Narrative Medicine (SAMEN), and join the roster of speakers at the upcoming second SAMEN Conference in Buenos Aires on July 10 and 11, 2025.
“Narrative medicine uses storytelling tools to absorb, process, acknowledge, and empathize with patients’ illness narratives, aiming to restore humanism to practice,” he explained.
According to Kusminsky, the circumstances under which Mrs G.O. expressed her wish not to begin treatment immediately reminded him of a text by Melville’s famous “I would prefer not to” from Bartleby, the Scrivener.
This reflection inspired him to publish an article cited at its beginning. At the same time, it reinforced his belief that what patients say can itself be a form of narrative that extends beyond the confines of clinical history.
Mrs G.O. chose not to pursue treatment for multiple myeloma. However, she returned to Kusminsky’s office approximately 2 months ago. She felt well, and her disease slowly progressed; however, she still had no clinical signs or symptoms.
Kusminsky and Hincapié Sánchez have declared no relevant financial conflicts of interest.
This story was translated from Medscape’s Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Mrs G.O. is an 80-year-old retired teacher who was widowed a decade ago. With no close relatives, she lives alone, accompanied by only two cats and a dog that she has rescued. “I am alone,” she told Gustavo Kusminsky, MD, consultant in Hematology and Hematopoietic Transplant Service at Austral University Hospital and lecturer in medicine at the Hospital Universitario Austral, Buenos Aires, Argentina. She said this calmly while refusing treatment for life-threatening multiple myeloma. “Doctor, I would rather not,” she added — her words lingering in the quiet consulting room. That moment is now the focus of a recent article in the journal Medicina.
In the article, Kusminsky described how he made an effort to clarify to the patient that she needed cancer treatment. He explained that the treatment was mostly oral, required no initial hospitalization, and that consultations could be spaced out. However, Mrs G.O. maintained her position.
“The patient had no signs of depression, and her argument was logical. Mrs G.O. was already receiving several medications for high blood pressure, was on anticoagulation therapy for atrial fibrillation, and managed dyslipidemia with fenofibrate. But she preferred not to receive treatment for her multiple myeloma.” Kusminsky noted.
“Doctor, I have lived my life. I am old. I am already taking too many medications. I do not have a family, and it would be very difficult to deal with the side effects and be dependent on the hospital. As long as I can take care of myself, I do not want any more treatment, at least not for now. We will talk in a few months if I am still here,” she told him before leaving.
The article mentioned that responses such as Mrs G.O. spark perplexity in modern medicine to the extent that clinicians initiate protocols to rule out depression or other psychological factors when a patient rejects treatments that could prolong their life. On the contrary, no such checks are made when patients agree to treatment, because acceptance is deemed “normal.”
Because of collective assumptions and the war metaphors often used in oncology, Mrs G.O. risked being labeled a “deserter from the battalion” of patients with cancer.
In truth, her decision invites reflection on the doctor-patient relationship, respect for autonomy, and the benefits of modern cancer care offered today, Kusminsky said.
This provides an opportunity to consider the patient’s perspective rather than a purely medical perspective.
Jennifer Hincapié Sánchez, PhD, professor in the Faculty of Medicine at the National Autonomous University of Mexico (UNAM). She is the director of the UNAM University Bioethics Program and coordinates its Institutional Ethics and Bioethics Program for the Faculty of Medicine in Mexico. Although not involved in the article, she regards it as vital. “It’s crucial to remind medical staff that their role is to promote patients’ well-being and that this is related to the life plan that patients have set for themselves, even though this vision is sometimes not aligned with biomedical progress,” she said.
Patient Autonomy
Science-guided medicine aims to prolong life, improve quality, and relieve suffering. However, acceptance or refusal of treatment remains a personal choice for anyone with cancer.
Some evidence showed that patients who decline treatment do not always experience rapid decline. Many can live acceptable, even fulfilling, lives on their own for varying periods, even though they know that there is a possibility of shorter survival. Valuing fewer side effects and better quality of life. This suggested that quality of life is subjective and cannot be measured solely by biomedical standards but also by the meaning each person finds in their existence, even in the face of serious illness.
“There is a myth that quality of life is only valid when defined by objective success. Our task is to explain that it is subjective, and life can be meaningful despite limitations.” Kusminsky said.
Mrs G.O. knew her prognosis and treatment options but chose not to pursue treatment, which, while medically advisable, did not align with her values or vision of life.
Hincapié Sánchez stated that the priority is always to honor the patient’s choice. Clinicians must ensure that the patient has all necessary information that is always appropriate to their sociocultural context before making the decision.
“If the decision persists despite being informed and aware of the effects of the patient’s choice, all we can do is provide support, manage the pain, and seek the patient’s comfort,” she emphasized.
Medical Omnipotence
Physicians should not view the refusal of treatment as an abandonment of the fundamental principles of the profession. Rather, it means respecting patient priorities and recognizing medicine as a dialogue between science and humanity, not as an exercise of control.
However, many clinicians struggle with such decisions because they conflict with their impulse to act and a sense of medical omnipotence. Hincapié Sánchez attributed these difficulties to medical training.
“We are taught to preserve life at all costs. If treatment even slightly prolongs life, many doctors continue to recommend it. The question becomes: Is it valid to extend life when its quality is in doubt?” she asked.
“Medicine is more than a science; it is an art. It is the most human in the sciences and the most scientific in the humanities. Let us not lose sight of the human element that allows us to see the patient as a person, not just a disease to be treated,” Hincapié Sánchez urges.
Kusminsky describes a common therapeutic obstinacy — doctors’ reluctance to stop “doing something,” to avoid “throwing in the towel,” or to uphold “hope is the last thing to be lost.”
“But physicians are growing more aware of these situations, and change is slowly coming,” he said. However, he added: “Of course, there is the issue of the perceived omnipotence of doctors — their words descending with authority to ‘prescribe’ treatment, issue ‘medical orders,’ or dictate ‘pharmacological’ therapy.
For the specialist, such terminology reflects a view of the doctor-patient relationship not as a mutual, two-way exchange, but as a vertical, paternalistic dynamic.
He suggested looking at ancient Greece for perspective. “Hippocrates, or rather the Hippocratic school, taught that the doctor-patient encounter is inherently one of compassion. We must approach this in that way. Reflecting on that bond, improving communication, humanizing relationships, and, above all, being available to listen are key,” Kusminsky said.
Another intersection that has long fascinated Kusminsky is between literature and medicine. This interest led him to explore the field of narrative medicine, serve on the board of directors of the Argentine Society of Narrative Medicine (SAMEN), and join the roster of speakers at the upcoming second SAMEN Conference in Buenos Aires on July 10 and 11, 2025.
“Narrative medicine uses storytelling tools to absorb, process, acknowledge, and empathize with patients’ illness narratives, aiming to restore humanism to practice,” he explained.
According to Kusminsky, the circumstances under which Mrs G.O. expressed her wish not to begin treatment immediately reminded him of a text by Melville’s famous “I would prefer not to” from Bartleby, the Scrivener.
This reflection inspired him to publish an article cited at its beginning. At the same time, it reinforced his belief that what patients say can itself be a form of narrative that extends beyond the confines of clinical history.
Mrs G.O. chose not to pursue treatment for multiple myeloma. However, she returned to Kusminsky’s office approximately 2 months ago. She felt well, and her disease slowly progressed; however, she still had no clinical signs or symptoms.
Kusminsky and Hincapié Sánchez have declared no relevant financial conflicts of interest.
This story was translated from Medscape’s Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Mrs G.O. is an 80-year-old retired teacher who was widowed a decade ago. With no close relatives, she lives alone, accompanied by only two cats and a dog that she has rescued. “I am alone,” she told Gustavo Kusminsky, MD, consultant in Hematology and Hematopoietic Transplant Service at Austral University Hospital and lecturer in medicine at the Hospital Universitario Austral, Buenos Aires, Argentina. She said this calmly while refusing treatment for life-threatening multiple myeloma. “Doctor, I would rather not,” she added — her words lingering in the quiet consulting room. That moment is now the focus of a recent article in the journal Medicina.
In the article, Kusminsky described how he made an effort to clarify to the patient that she needed cancer treatment. He explained that the treatment was mostly oral, required no initial hospitalization, and that consultations could be spaced out. However, Mrs G.O. maintained her position.
“The patient had no signs of depression, and her argument was logical. Mrs G.O. was already receiving several medications for high blood pressure, was on anticoagulation therapy for atrial fibrillation, and managed dyslipidemia with fenofibrate. But she preferred not to receive treatment for her multiple myeloma.” Kusminsky noted.
“Doctor, I have lived my life. I am old. I am already taking too many medications. I do not have a family, and it would be very difficult to deal with the side effects and be dependent on the hospital. As long as I can take care of myself, I do not want any more treatment, at least not for now. We will talk in a few months if I am still here,” she told him before leaving.
The article mentioned that responses such as Mrs G.O. spark perplexity in modern medicine to the extent that clinicians initiate protocols to rule out depression or other psychological factors when a patient rejects treatments that could prolong their life. On the contrary, no such checks are made when patients agree to treatment, because acceptance is deemed “normal.”
Because of collective assumptions and the war metaphors often used in oncology, Mrs G.O. risked being labeled a “deserter from the battalion” of patients with cancer.
In truth, her decision invites reflection on the doctor-patient relationship, respect for autonomy, and the benefits of modern cancer care offered today, Kusminsky said.
This provides an opportunity to consider the patient’s perspective rather than a purely medical perspective.
Jennifer Hincapié Sánchez, PhD, professor in the Faculty of Medicine at the National Autonomous University of Mexico (UNAM). She is the director of the UNAM University Bioethics Program and coordinates its Institutional Ethics and Bioethics Program for the Faculty of Medicine in Mexico. Although not involved in the article, she regards it as vital. “It’s crucial to remind medical staff that their role is to promote patients’ well-being and that this is related to the life plan that patients have set for themselves, even though this vision is sometimes not aligned with biomedical progress,” she said.
Patient Autonomy
Science-guided medicine aims to prolong life, improve quality, and relieve suffering. However, acceptance or refusal of treatment remains a personal choice for anyone with cancer.
Some evidence showed that patients who decline treatment do not always experience rapid decline. Many can live acceptable, even fulfilling, lives on their own for varying periods, even though they know that there is a possibility of shorter survival. Valuing fewer side effects and better quality of life. This suggested that quality of life is subjective and cannot be measured solely by biomedical standards but also by the meaning each person finds in their existence, even in the face of serious illness.
“There is a myth that quality of life is only valid when defined by objective success. Our task is to explain that it is subjective, and life can be meaningful despite limitations.” Kusminsky said.
Mrs G.O. knew her prognosis and treatment options but chose not to pursue treatment, which, while medically advisable, did not align with her values or vision of life.
Hincapié Sánchez stated that the priority is always to honor the patient’s choice. Clinicians must ensure that the patient has all necessary information that is always appropriate to their sociocultural context before making the decision.
“If the decision persists despite being informed and aware of the effects of the patient’s choice, all we can do is provide support, manage the pain, and seek the patient’s comfort,” she emphasized.
Medical Omnipotence
Physicians should not view the refusal of treatment as an abandonment of the fundamental principles of the profession. Rather, it means respecting patient priorities and recognizing medicine as a dialogue between science and humanity, not as an exercise of control.
However, many clinicians struggle with such decisions because they conflict with their impulse to act and a sense of medical omnipotence. Hincapié Sánchez attributed these difficulties to medical training.
“We are taught to preserve life at all costs. If treatment even slightly prolongs life, many doctors continue to recommend it. The question becomes: Is it valid to extend life when its quality is in doubt?” she asked.
“Medicine is more than a science; it is an art. It is the most human in the sciences and the most scientific in the humanities. Let us not lose sight of the human element that allows us to see the patient as a person, not just a disease to be treated,” Hincapié Sánchez urges.
Kusminsky describes a common therapeutic obstinacy — doctors’ reluctance to stop “doing something,” to avoid “throwing in the towel,” or to uphold “hope is the last thing to be lost.”
“But physicians are growing more aware of these situations, and change is slowly coming,” he said. However, he added: “Of course, there is the issue of the perceived omnipotence of doctors — their words descending with authority to ‘prescribe’ treatment, issue ‘medical orders,’ or dictate ‘pharmacological’ therapy.
For the specialist, such terminology reflects a view of the doctor-patient relationship not as a mutual, two-way exchange, but as a vertical, paternalistic dynamic.
He suggested looking at ancient Greece for perspective. “Hippocrates, or rather the Hippocratic school, taught that the doctor-patient encounter is inherently one of compassion. We must approach this in that way. Reflecting on that bond, improving communication, humanizing relationships, and, above all, being available to listen are key,” Kusminsky said.
Another intersection that has long fascinated Kusminsky is between literature and medicine. This interest led him to explore the field of narrative medicine, serve on the board of directors of the Argentine Society of Narrative Medicine (SAMEN), and join the roster of speakers at the upcoming second SAMEN Conference in Buenos Aires on July 10 and 11, 2025.
“Narrative medicine uses storytelling tools to absorb, process, acknowledge, and empathize with patients’ illness narratives, aiming to restore humanism to practice,” he explained.
According to Kusminsky, the circumstances under which Mrs G.O. expressed her wish not to begin treatment immediately reminded him of a text by Melville’s famous “I would prefer not to” from Bartleby, the Scrivener.
This reflection inspired him to publish an article cited at its beginning. At the same time, it reinforced his belief that what patients say can itself be a form of narrative that extends beyond the confines of clinical history.
Mrs G.O. chose not to pursue treatment for multiple myeloma. However, she returned to Kusminsky’s office approximately 2 months ago. She felt well, and her disease slowly progressed; however, she still had no clinical signs or symptoms.
Kusminsky and Hincapié Sánchez have declared no relevant financial conflicts of interest.
This story was translated from Medscape’s Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
2026 VA Budget Bill Narrowly Passed by House Appropriations Committee
2026 VA Budget Bill Narrowly Passed by House Appropriations Committee
The US House Appropriations Committee approved a $453 billion budget to fund the US Department of Veterans (VA), military construction, and other programs in 2026 by a 36-27 vote. The bill includes $34 billion proposed for community care programs, an increase of > 50% from 2025 community care funding levels.
The discretionary funding would also send $2.5 billion to the VA electronic health records modernization program. Mandatory spending includes $53 billion for the Toxic Exposures Fund, which supports benefits and health care costs associated with the PACT Act.
Although VA budget bills are typically bipartisan in nature, this bill passed by a much narrower margin than is typical. Rep. Debbie Wasserman Schultz (D-FL), ranking member of the Military Construction, Veterans Affairs and Related Agencies Appropriations Subcommittee, said the bill “diverts far too many resources away from the vital, VA-based care that veterans consistently tell us they want, and it pushes them into pricier, subpar corporate hospitals.”
Committee Democrats offered dozens of amendments. All amendments were rejected except for a modification that would block staff reductions at the Veterans Crisis Line and other VA suicide prevention programs.
The bill now moves to the full House of Representatives for consideration. House leaders have not yet announced when that vote will take place; the House is in recess the week of June 16, 2025.
The committee also released the Fiscal Year 2026 Military Construction, Veterans Affairs, and Related Agencies Bill, which would spend > $83 million, a 22% increase over the 2025.
The US House Appropriations Committee approved a $453 billion budget to fund the US Department of Veterans (VA), military construction, and other programs in 2026 by a 36-27 vote. The bill includes $34 billion proposed for community care programs, an increase of > 50% from 2025 community care funding levels.
The discretionary funding would also send $2.5 billion to the VA electronic health records modernization program. Mandatory spending includes $53 billion for the Toxic Exposures Fund, which supports benefits and health care costs associated with the PACT Act.
Although VA budget bills are typically bipartisan in nature, this bill passed by a much narrower margin than is typical. Rep. Debbie Wasserman Schultz (D-FL), ranking member of the Military Construction, Veterans Affairs and Related Agencies Appropriations Subcommittee, said the bill “diverts far too many resources away from the vital, VA-based care that veterans consistently tell us they want, and it pushes them into pricier, subpar corporate hospitals.”
Committee Democrats offered dozens of amendments. All amendments were rejected except for a modification that would block staff reductions at the Veterans Crisis Line and other VA suicide prevention programs.
The bill now moves to the full House of Representatives for consideration. House leaders have not yet announced when that vote will take place; the House is in recess the week of June 16, 2025.
The committee also released the Fiscal Year 2026 Military Construction, Veterans Affairs, and Related Agencies Bill, which would spend > $83 million, a 22% increase over the 2025.
The US House Appropriations Committee approved a $453 billion budget to fund the US Department of Veterans (VA), military construction, and other programs in 2026 by a 36-27 vote. The bill includes $34 billion proposed for community care programs, an increase of > 50% from 2025 community care funding levels.
The discretionary funding would also send $2.5 billion to the VA electronic health records modernization program. Mandatory spending includes $53 billion for the Toxic Exposures Fund, which supports benefits and health care costs associated with the PACT Act.
Although VA budget bills are typically bipartisan in nature, this bill passed by a much narrower margin than is typical. Rep. Debbie Wasserman Schultz (D-FL), ranking member of the Military Construction, Veterans Affairs and Related Agencies Appropriations Subcommittee, said the bill “diverts far too many resources away from the vital, VA-based care that veterans consistently tell us they want, and it pushes them into pricier, subpar corporate hospitals.”
Committee Democrats offered dozens of amendments. All amendments were rejected except for a modification that would block staff reductions at the Veterans Crisis Line and other VA suicide prevention programs.
The bill now moves to the full House of Representatives for consideration. House leaders have not yet announced when that vote will take place; the House is in recess the week of June 16, 2025.
The committee also released the Fiscal Year 2026 Military Construction, Veterans Affairs, and Related Agencies Bill, which would spend > $83 million, a 22% increase over the 2025.
2026 VA Budget Bill Narrowly Passed by House Appropriations Committee
2026 VA Budget Bill Narrowly Passed by House Appropriations Committee
Hepatic Encephalopathy: Improve Diagnosis, Management, and Care
.1 HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).
The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:
- More than 2 million Americans had alcohol-associated cirrhosis as of 2017.2
- Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.3
- The economic burden is staggering – from $1 billion4 in 2003 to over $7 billion5 in hospital costs for cirrhosis-related admissions today.
These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.
Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.6, 7
Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.
To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:
- The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
- Assessment guidelines and best practices for HE diagnosis and management.
- How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.
Take the course today: https://tinyurl.com/3muwhmj5
Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.
References
1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview
2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.
3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.
4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.
5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.
6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.
7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.
.1 HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).
The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:
- More than 2 million Americans had alcohol-associated cirrhosis as of 2017.2
- Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.3
- The economic burden is staggering – from $1 billion4 in 2003 to over $7 billion5 in hospital costs for cirrhosis-related admissions today.
These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.
Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.6, 7
Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.
To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:
- The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
- Assessment guidelines and best practices for HE diagnosis and management.
- How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.
Take the course today: https://tinyurl.com/3muwhmj5
Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.
References
1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview
2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.
3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.
4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.
5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.
6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.
7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.
.1 HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).
The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:
- More than 2 million Americans had alcohol-associated cirrhosis as of 2017.2
- Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.3
- The economic burden is staggering – from $1 billion4 in 2003 to over $7 billion5 in hospital costs for cirrhosis-related admissions today.
These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.
Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.6, 7
Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.
To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:
- The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
- Assessment guidelines and best practices for HE diagnosis and management.
- How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.
Take the course today: https://tinyurl.com/3muwhmj5
Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.
References
1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview
2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.
3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.
4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.
5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.
6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.
7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.
Video Capsule Endoscopy Aids Targeted Treatment in Quiescent Crohn’s
A treat-to target (T2T) strategy based on video capsule endoscopy (VCE) identified Crohn’s disease (CD) patients in clinical remission but with small bowel inflammation, resulting in fewer clinical flares versus a treat-by-symptoms standard approach.
“A VCE-guided treat-to-target strategy for patients with CD in remission confers superior clinical outcomes compared with continued standard care,” investigators led by Shomron Ben-Horin, MD, director of gastroenterology at Sheba Medical Center in Ramat-Gan, Israel.
Published in Gastroenterology, the CURE-CD (Comprehensive Individualized Proactive Therapy of Crohn’s Disease), a prospective, temporally blinded, randomized controled trial, looked at 60 adult patients with quiescent CD involving the small bowel (either L1 or L3 iof the terminal ileum and upper colon).
The researchers defined quiescent disease as corticosteroid-free clinical remission with a Crohn’s Disease Activity Index (CDAI) of <50 for the past 3 months on a stable regimen.
Patients ingested a VCE at baseline and those with a Lewis inflammatory score (LS) of ≥350 were designated high risk (n = 40) and randomized to either T2T optimization (n = 20) or continuing standard care (n = 20).
T2T was optimized with repeat VCE results every 6 months. Patients with LS <350 (“low risk”) continued standard care. The primary outcome was the rate of disease exacerbation, demonstrated by a CDAI increase of >70 points and a score >150, or hospitalization/surgery, in high-risk standard care vs T2T groups at 24 months.
Treatment intensification in the high-risk group allocated to a proactive strategy comprised biologic dose escalation (n = 11 of 20), starting a biologic (n = 8 of 20), or swapping biologics (n = 1 of 20).
The primary outcome, clinical flare by 24 months, occurred in 5 of 20 (25%) of high-risk treat-to-target patients vs 14 of 20 (70%) of the high-risk standard-care group (odds ratio [OR], .14; 95% confidence interval [CI], .04–.57, P = .006).
Mucosal healing was significantly more common in the T2T group when determined by a cutoff LS < 350 (OR, 4.5, 95% CI, 1.7–17.4, nominal P value = .03), but not by the combined scores of total LS < 450 and highest-segment LS < 350.
Among all patients continuing standard care (n = 40), baseline LS was numerically higher among relapsers vs nonrelapsers (450, 225–900 vs 225, 135–600, respectively, P = .07).
As to safety, of 221 VCEs ingested, there was a single (.4%) temporary retention, which spontaneously resolved.
“VCE monitoring of CD was approved into government reimbursement in Israel last year, and I know several European countries are also considering the inclusion of this new indication for VCE in their payer reimbursement,” Ben-Horin told GI & Hepatology News. “Uptake in Israel is still baby-stepping. In our center it’s much more common to monitor T2T for small bowel patients, but this approach is still not widely applied.”
The authors cautioned that since the focus was the small bowel, the findings are not necessarily generalizable to patients with Crohn’s colitis.
The study was supported by the Leona M. & Harry B. Helmsley Charitable Trust, Medtronic (USA), AbbVie (Israel), and Takeda. The funders did not intervene in the design or interpretation of the study.
Ben-Horin reported advisory, consulting fees, research support, and/or stocks/options from several pharmaceutical firms. Several coauthors disclosed similar relations with private-sector companies.
As treat-to-target (T2T) strategies continue to redefine inflammatory bowel disease (IBD) care, this randomized controlled trial by Ben-Horin et al. highlights the value of proactive video capsule endoscopy (VCE) monitoring in patients with quiescent small bowel Crohn’s disease (CD).
The study demonstrated that scheduled VCE every six months, used to guide treatment adjustments, significantly reduced clinical flares over 24 months compared to symptom-based standard care. While differences in mucosal healing between groups were less pronounced, the results underscore that monitoring objective inflammation, even in asymptomatic patients, can improve clinical outcomes.
In clinical practice, symptom-driven management remains common, often due to limited access to endoscopy or patient hesitancy toward invasive procedures. VCE offers a non-invasive, well-tolerated alternative that may improve patient adherence to disease monitoring, particularly in small bowel CD. This approach addresses a significant gap in care, as nearly half of IBD patients do not undergo objective disease assessment within a year of starting biologics.
Clinicians should consider integrating VCE into individualized T2T strategies, especially in settings where endoscopic access is constrained. Furthermore, adjunctive non-invasive tools such as intestinal ultrasound (IUS) with biomarkers could further support a non-invasive, patient-centered monitoring approach. As the definition of remission evolves toward more ambitious targets like transmural healing, the integration of cross-sectional imaging modalities such as IUS into routine monitoring protocols may become essential. Aligning monitoring techniques with evolving therapeutic targets and patient preferences will be key to optimizing long-term disease control in CD.
Mariangela Allocca, MD, PhD, is head of the IBD Center at IRCCS Hospital San Raffaele, and professor of gastroenterology at Vita-Salute San Raffaele University, both in Milan, Italy. Silvio Danese, MD, PhD, is professor of gastroenterology at Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan. Both authors report consulting and/or speaking fees from multiple drug and device companies.
As treat-to-target (T2T) strategies continue to redefine inflammatory bowel disease (IBD) care, this randomized controlled trial by Ben-Horin et al. highlights the value of proactive video capsule endoscopy (VCE) monitoring in patients with quiescent small bowel Crohn’s disease (CD).
The study demonstrated that scheduled VCE every six months, used to guide treatment adjustments, significantly reduced clinical flares over 24 months compared to symptom-based standard care. While differences in mucosal healing between groups were less pronounced, the results underscore that monitoring objective inflammation, even in asymptomatic patients, can improve clinical outcomes.
In clinical practice, symptom-driven management remains common, often due to limited access to endoscopy or patient hesitancy toward invasive procedures. VCE offers a non-invasive, well-tolerated alternative that may improve patient adherence to disease monitoring, particularly in small bowel CD. This approach addresses a significant gap in care, as nearly half of IBD patients do not undergo objective disease assessment within a year of starting biologics.
Clinicians should consider integrating VCE into individualized T2T strategies, especially in settings where endoscopic access is constrained. Furthermore, adjunctive non-invasive tools such as intestinal ultrasound (IUS) with biomarkers could further support a non-invasive, patient-centered monitoring approach. As the definition of remission evolves toward more ambitious targets like transmural healing, the integration of cross-sectional imaging modalities such as IUS into routine monitoring protocols may become essential. Aligning monitoring techniques with evolving therapeutic targets and patient preferences will be key to optimizing long-term disease control in CD.
Mariangela Allocca, MD, PhD, is head of the IBD Center at IRCCS Hospital San Raffaele, and professor of gastroenterology at Vita-Salute San Raffaele University, both in Milan, Italy. Silvio Danese, MD, PhD, is professor of gastroenterology at Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan. Both authors report consulting and/or speaking fees from multiple drug and device companies.
As treat-to-target (T2T) strategies continue to redefine inflammatory bowel disease (IBD) care, this randomized controlled trial by Ben-Horin et al. highlights the value of proactive video capsule endoscopy (VCE) monitoring in patients with quiescent small bowel Crohn’s disease (CD).
The study demonstrated that scheduled VCE every six months, used to guide treatment adjustments, significantly reduced clinical flares over 24 months compared to symptom-based standard care. While differences in mucosal healing between groups were less pronounced, the results underscore that monitoring objective inflammation, even in asymptomatic patients, can improve clinical outcomes.
In clinical practice, symptom-driven management remains common, often due to limited access to endoscopy or patient hesitancy toward invasive procedures. VCE offers a non-invasive, well-tolerated alternative that may improve patient adherence to disease monitoring, particularly in small bowel CD. This approach addresses a significant gap in care, as nearly half of IBD patients do not undergo objective disease assessment within a year of starting biologics.
Clinicians should consider integrating VCE into individualized T2T strategies, especially in settings where endoscopic access is constrained. Furthermore, adjunctive non-invasive tools such as intestinal ultrasound (IUS) with biomarkers could further support a non-invasive, patient-centered monitoring approach. As the definition of remission evolves toward more ambitious targets like transmural healing, the integration of cross-sectional imaging modalities such as IUS into routine monitoring protocols may become essential. Aligning monitoring techniques with evolving therapeutic targets and patient preferences will be key to optimizing long-term disease control in CD.
Mariangela Allocca, MD, PhD, is head of the IBD Center at IRCCS Hospital San Raffaele, and professor of gastroenterology at Vita-Salute San Raffaele University, both in Milan, Italy. Silvio Danese, MD, PhD, is professor of gastroenterology at Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan. Both authors report consulting and/or speaking fees from multiple drug and device companies.
A treat-to target (T2T) strategy based on video capsule endoscopy (VCE) identified Crohn’s disease (CD) patients in clinical remission but with small bowel inflammation, resulting in fewer clinical flares versus a treat-by-symptoms standard approach.
“A VCE-guided treat-to-target strategy for patients with CD in remission confers superior clinical outcomes compared with continued standard care,” investigators led by Shomron Ben-Horin, MD, director of gastroenterology at Sheba Medical Center in Ramat-Gan, Israel.
Published in Gastroenterology, the CURE-CD (Comprehensive Individualized Proactive Therapy of Crohn’s Disease), a prospective, temporally blinded, randomized controled trial, looked at 60 adult patients with quiescent CD involving the small bowel (either L1 or L3 iof the terminal ileum and upper colon).
The researchers defined quiescent disease as corticosteroid-free clinical remission with a Crohn’s Disease Activity Index (CDAI) of <50 for the past 3 months on a stable regimen.
Patients ingested a VCE at baseline and those with a Lewis inflammatory score (LS) of ≥350 were designated high risk (n = 40) and randomized to either T2T optimization (n = 20) or continuing standard care (n = 20).
T2T was optimized with repeat VCE results every 6 months. Patients with LS <350 (“low risk”) continued standard care. The primary outcome was the rate of disease exacerbation, demonstrated by a CDAI increase of >70 points and a score >150, or hospitalization/surgery, in high-risk standard care vs T2T groups at 24 months.
Treatment intensification in the high-risk group allocated to a proactive strategy comprised biologic dose escalation (n = 11 of 20), starting a biologic (n = 8 of 20), or swapping biologics (n = 1 of 20).
The primary outcome, clinical flare by 24 months, occurred in 5 of 20 (25%) of high-risk treat-to-target patients vs 14 of 20 (70%) of the high-risk standard-care group (odds ratio [OR], .14; 95% confidence interval [CI], .04–.57, P = .006).
Mucosal healing was significantly more common in the T2T group when determined by a cutoff LS < 350 (OR, 4.5, 95% CI, 1.7–17.4, nominal P value = .03), but not by the combined scores of total LS < 450 and highest-segment LS < 350.
Among all patients continuing standard care (n = 40), baseline LS was numerically higher among relapsers vs nonrelapsers (450, 225–900 vs 225, 135–600, respectively, P = .07).
As to safety, of 221 VCEs ingested, there was a single (.4%) temporary retention, which spontaneously resolved.
“VCE monitoring of CD was approved into government reimbursement in Israel last year, and I know several European countries are also considering the inclusion of this new indication for VCE in their payer reimbursement,” Ben-Horin told GI & Hepatology News. “Uptake in Israel is still baby-stepping. In our center it’s much more common to monitor T2T for small bowel patients, but this approach is still not widely applied.”
The authors cautioned that since the focus was the small bowel, the findings are not necessarily generalizable to patients with Crohn’s colitis.
The study was supported by the Leona M. & Harry B. Helmsley Charitable Trust, Medtronic (USA), AbbVie (Israel), and Takeda. The funders did not intervene in the design or interpretation of the study.
Ben-Horin reported advisory, consulting fees, research support, and/or stocks/options from several pharmaceutical firms. Several coauthors disclosed similar relations with private-sector companies.
A treat-to target (T2T) strategy based on video capsule endoscopy (VCE) identified Crohn’s disease (CD) patients in clinical remission but with small bowel inflammation, resulting in fewer clinical flares versus a treat-by-symptoms standard approach.
“A VCE-guided treat-to-target strategy for patients with CD in remission confers superior clinical outcomes compared with continued standard care,” investigators led by Shomron Ben-Horin, MD, director of gastroenterology at Sheba Medical Center in Ramat-Gan, Israel.
Published in Gastroenterology, the CURE-CD (Comprehensive Individualized Proactive Therapy of Crohn’s Disease), a prospective, temporally blinded, randomized controled trial, looked at 60 adult patients with quiescent CD involving the small bowel (either L1 or L3 iof the terminal ileum and upper colon).
The researchers defined quiescent disease as corticosteroid-free clinical remission with a Crohn’s Disease Activity Index (CDAI) of <50 for the past 3 months on a stable regimen.
Patients ingested a VCE at baseline and those with a Lewis inflammatory score (LS) of ≥350 were designated high risk (n = 40) and randomized to either T2T optimization (n = 20) or continuing standard care (n = 20).
T2T was optimized with repeat VCE results every 6 months. Patients with LS <350 (“low risk”) continued standard care. The primary outcome was the rate of disease exacerbation, demonstrated by a CDAI increase of >70 points and a score >150, or hospitalization/surgery, in high-risk standard care vs T2T groups at 24 months.
Treatment intensification in the high-risk group allocated to a proactive strategy comprised biologic dose escalation (n = 11 of 20), starting a biologic (n = 8 of 20), or swapping biologics (n = 1 of 20).
The primary outcome, clinical flare by 24 months, occurred in 5 of 20 (25%) of high-risk treat-to-target patients vs 14 of 20 (70%) of the high-risk standard-care group (odds ratio [OR], .14; 95% confidence interval [CI], .04–.57, P = .006).
Mucosal healing was significantly more common in the T2T group when determined by a cutoff LS < 350 (OR, 4.5, 95% CI, 1.7–17.4, nominal P value = .03), but not by the combined scores of total LS < 450 and highest-segment LS < 350.
Among all patients continuing standard care (n = 40), baseline LS was numerically higher among relapsers vs nonrelapsers (450, 225–900 vs 225, 135–600, respectively, P = .07).
As to safety, of 221 VCEs ingested, there was a single (.4%) temporary retention, which spontaneously resolved.
“VCE monitoring of CD was approved into government reimbursement in Israel last year, and I know several European countries are also considering the inclusion of this new indication for VCE in their payer reimbursement,” Ben-Horin told GI & Hepatology News. “Uptake in Israel is still baby-stepping. In our center it’s much more common to monitor T2T for small bowel patients, but this approach is still not widely applied.”
The authors cautioned that since the focus was the small bowel, the findings are not necessarily generalizable to patients with Crohn’s colitis.
The study was supported by the Leona M. & Harry B. Helmsley Charitable Trust, Medtronic (USA), AbbVie (Israel), and Takeda. The funders did not intervene in the design or interpretation of the study.
Ben-Horin reported advisory, consulting fees, research support, and/or stocks/options from several pharmaceutical firms. Several coauthors disclosed similar relations with private-sector companies.
FROM GASTROENTEROLOGY
MASH Driving Global Epidemic of Primary Liver Cancer
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY