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Real-World HDV Study Characterizes Responses to Bulevirtide
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
FROM GASTRO HEP ADVANCES
Computer-Aided Colonoscopy Falls Short in Real-World Practice
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Liquid Biopsy for Colorectal Cancer Appears Promising But Still Lacks Robust Efficacy
, according to two new modeling studies and an expert consensus commentary.
Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.
“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.
The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.
The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.
Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
Comparing CRC Screening Methods
In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.
Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).
However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.
In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.
Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.
Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.
Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.
“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
Additional Considerations
The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.
However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.
In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.
Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.
“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.
Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.
, according to two new modeling studies and an expert consensus commentary.
Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.
“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.
The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.
The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.
Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
Comparing CRC Screening Methods
In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.
Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).
However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.
In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.
Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.
Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.
Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.
“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
Additional Considerations
The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.
However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.
In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.
Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.
“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.
Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.
, according to two new modeling studies and an expert consensus commentary.
Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.
“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.
The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.
The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.
Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
Comparing CRC Screening Methods
In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.
Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).
However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.
In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.
Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.
Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.
Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.
“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
Additional Considerations
The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.
However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.
In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.
Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.
“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.
Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.
IBS Placebo Responses Predicted By Patient Beliefs, Relationship with Provider
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
Global Rates of H. Pylori, Gastric Cancer, Dropping Together
, according to investigators.
These findings suggest that decreasing H. pylori prevalence does indeed reduce rates of gastric cancer, although large-scale clinical trials are needed to solidify confidence in this apparent relationship, reported lead author Yi Chun Chen, PhD, of National Taiwan University, Taipei, and colleagues.
“Eradication of H. pylori infection heals chronic active gastritis and peptic ulcer disease and reduces the risk of peptic ulcer bleeding in aspirin users and the risk of gastric cancer in infected individuals,” the investigators wrote in Gastroenterology. “However, whether reduction of the prevalence of H. pylori is associated with a reduction of the incidence of gastric cancer at the population level remains uncertain.”
According to several previous meta-analyses, the global rate of H. pylori infection has been in a downtrend, but Dr. Chen and colleagues pointed out several limitations of these publications, including scarcity of recent data, insufficiently representative data, inconsistent diagnostic methods, and lack of adjustment for socioeconomic status.
“We therefore conducted this comprehensive systematic review and meta-analysis, including healthy individuals recruited in hospital-based studies, to provide an updated global prevalence and the secular trend of H. pylori infection,” the investigators wrote, noting that they leveraged meta-regression analysis to “identify factors affecting heterogeneity of the prevalence,” and concurrently evaluated the corresponding global incidence of gastric cancer.
Their dataset, which included 1,748 articles from 111 countries, suggested that the global rate of H. pylori is indeed in a downtrend.
From a crude global prevalence of 52.6% prior to 1990, the rate of H. pylori decreased to 43.9% among adults in 2015-2022, but was “still as high as” 35.1% among children and adolescents in the same 2015-2022 period. Multivariate regression analysis showed that prevalence decreased significantly, by 15.9%, among adults, but not in children and adolescents.
“The significant reduction of H. pylori prevalence in adults can be explained by the improvement of socioeconomic status, cleaner water supply, better sanitation and hygiene status, and widening of indication for eradication therapy,” Dr. Chen and colleagues wrote. “The higher prevalence in adults than in children/adolescents is explained by the cohort effect because most H. pylori infection is acquired in childhood.”
Global incidence of gastric cancer among both male and female individuals declined approximately in parallel with decreasing prevalence of H. pylori. Rates of gastric cancer decreased most in high-incidence countries such as Brazil, Japan, and China.
“These studies collectively provide evidence for the causal association of H. pylori infection and gastric cancer and that elimination of this bacterium can prevent the development of gastric cancer,” the investigators wrote.
Still, more work is needed.
“Future prospective studies should be conducted to confirm whether public health interventions or mass screening and eradication of H. pylori infection to reduce its prevalence may reduce the incidence of gastric cancer at population level,” Dr. Chen and colleagues concluded. “Besides, it is also important to consider the potential adverse consequences of H. pylori eradication, such as emergence of antibiotic resistance. The benefit-to-harm ratio and cost-effectiveness should also be taken into account.”
The study was funded by the National Taiwan University Hospital, the Taiwan Ministry of Science and Technology, the Taiwan Ministry of Health and Welfare, and others. The investigators disclosed no conflicts of interest.
Chen et al.’s study establishes a connection between the global decline in H. pylori infection rates and the decrease in gastric cancer cases, analyzing data from 1,748 articles across 111 countries. It highlights a significant drop in adult H. pylori prevalence from 52.6% before 1990 to 43.9% between 2015 and 2022, crediting improvements in socioeconomic conditions, water quality, and sanitation, along with targeted eradication efforts. This emphasizes the critical role of public health measures in reducing H. pylori infections and, consequently, gastric cancer risks, showcasing the success of eradication campaigns and widespread screening.
Nevertheless, the research advises caution regarding the widespread elimination of H. pylori due to the risk of antibiotic resistance. It advocates for a measured evaluation of the pros and cons, as well as the cost-effectiveness of such interventions. The authors call for additional large-scale clinical trials to verify these results and improve public health tactics.
The findings indicate that precise public health actions can greatly influence disease prevention, underlining the necessity of well-informed policies backed by ongoing clinical research and trials. Such an informed approach is essential to confirm that the advantages of eradication surpass the potential dangers, particularly considering the growing concern over antibiotic resistance. This study lays the groundwork for effective gastric cancer prevention strategies and emphasizes the ongoing need for research to shape sound public health policies and actions.
Li-Ju Chen, PhD, is a postdoctoral researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, Heidelberg, Germany. She declared no conflicts of interest in regard to this review.
Chen et al.’s study establishes a connection between the global decline in H. pylori infection rates and the decrease in gastric cancer cases, analyzing data from 1,748 articles across 111 countries. It highlights a significant drop in adult H. pylori prevalence from 52.6% before 1990 to 43.9% between 2015 and 2022, crediting improvements in socioeconomic conditions, water quality, and sanitation, along with targeted eradication efforts. This emphasizes the critical role of public health measures in reducing H. pylori infections and, consequently, gastric cancer risks, showcasing the success of eradication campaigns and widespread screening.
Nevertheless, the research advises caution regarding the widespread elimination of H. pylori due to the risk of antibiotic resistance. It advocates for a measured evaluation of the pros and cons, as well as the cost-effectiveness of such interventions. The authors call for additional large-scale clinical trials to verify these results and improve public health tactics.
The findings indicate that precise public health actions can greatly influence disease prevention, underlining the necessity of well-informed policies backed by ongoing clinical research and trials. Such an informed approach is essential to confirm that the advantages of eradication surpass the potential dangers, particularly considering the growing concern over antibiotic resistance. This study lays the groundwork for effective gastric cancer prevention strategies and emphasizes the ongoing need for research to shape sound public health policies and actions.
Li-Ju Chen, PhD, is a postdoctoral researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, Heidelberg, Germany. She declared no conflicts of interest in regard to this review.
Chen et al.’s study establishes a connection between the global decline in H. pylori infection rates and the decrease in gastric cancer cases, analyzing data from 1,748 articles across 111 countries. It highlights a significant drop in adult H. pylori prevalence from 52.6% before 1990 to 43.9% between 2015 and 2022, crediting improvements in socioeconomic conditions, water quality, and sanitation, along with targeted eradication efforts. This emphasizes the critical role of public health measures in reducing H. pylori infections and, consequently, gastric cancer risks, showcasing the success of eradication campaigns and widespread screening.
Nevertheless, the research advises caution regarding the widespread elimination of H. pylori due to the risk of antibiotic resistance. It advocates for a measured evaluation of the pros and cons, as well as the cost-effectiveness of such interventions. The authors call for additional large-scale clinical trials to verify these results and improve public health tactics.
The findings indicate that precise public health actions can greatly influence disease prevention, underlining the necessity of well-informed policies backed by ongoing clinical research and trials. Such an informed approach is essential to confirm that the advantages of eradication surpass the potential dangers, particularly considering the growing concern over antibiotic resistance. This study lays the groundwork for effective gastric cancer prevention strategies and emphasizes the ongoing need for research to shape sound public health policies and actions.
Li-Ju Chen, PhD, is a postdoctoral researcher in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center, Heidelberg, Germany. She declared no conflicts of interest in regard to this review.
, according to investigators.
These findings suggest that decreasing H. pylori prevalence does indeed reduce rates of gastric cancer, although large-scale clinical trials are needed to solidify confidence in this apparent relationship, reported lead author Yi Chun Chen, PhD, of National Taiwan University, Taipei, and colleagues.
“Eradication of H. pylori infection heals chronic active gastritis and peptic ulcer disease and reduces the risk of peptic ulcer bleeding in aspirin users and the risk of gastric cancer in infected individuals,” the investigators wrote in Gastroenterology. “However, whether reduction of the prevalence of H. pylori is associated with a reduction of the incidence of gastric cancer at the population level remains uncertain.”
According to several previous meta-analyses, the global rate of H. pylori infection has been in a downtrend, but Dr. Chen and colleagues pointed out several limitations of these publications, including scarcity of recent data, insufficiently representative data, inconsistent diagnostic methods, and lack of adjustment for socioeconomic status.
“We therefore conducted this comprehensive systematic review and meta-analysis, including healthy individuals recruited in hospital-based studies, to provide an updated global prevalence and the secular trend of H. pylori infection,” the investigators wrote, noting that they leveraged meta-regression analysis to “identify factors affecting heterogeneity of the prevalence,” and concurrently evaluated the corresponding global incidence of gastric cancer.
Their dataset, which included 1,748 articles from 111 countries, suggested that the global rate of H. pylori is indeed in a downtrend.
From a crude global prevalence of 52.6% prior to 1990, the rate of H. pylori decreased to 43.9% among adults in 2015-2022, but was “still as high as” 35.1% among children and adolescents in the same 2015-2022 period. Multivariate regression analysis showed that prevalence decreased significantly, by 15.9%, among adults, but not in children and adolescents.
“The significant reduction of H. pylori prevalence in adults can be explained by the improvement of socioeconomic status, cleaner water supply, better sanitation and hygiene status, and widening of indication for eradication therapy,” Dr. Chen and colleagues wrote. “The higher prevalence in adults than in children/adolescents is explained by the cohort effect because most H. pylori infection is acquired in childhood.”
Global incidence of gastric cancer among both male and female individuals declined approximately in parallel with decreasing prevalence of H. pylori. Rates of gastric cancer decreased most in high-incidence countries such as Brazil, Japan, and China.
“These studies collectively provide evidence for the causal association of H. pylori infection and gastric cancer and that elimination of this bacterium can prevent the development of gastric cancer,” the investigators wrote.
Still, more work is needed.
“Future prospective studies should be conducted to confirm whether public health interventions or mass screening and eradication of H. pylori infection to reduce its prevalence may reduce the incidence of gastric cancer at population level,” Dr. Chen and colleagues concluded. “Besides, it is also important to consider the potential adverse consequences of H. pylori eradication, such as emergence of antibiotic resistance. The benefit-to-harm ratio and cost-effectiveness should also be taken into account.”
The study was funded by the National Taiwan University Hospital, the Taiwan Ministry of Science and Technology, the Taiwan Ministry of Health and Welfare, and others. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that decreasing H. pylori prevalence does indeed reduce rates of gastric cancer, although large-scale clinical trials are needed to solidify confidence in this apparent relationship, reported lead author Yi Chun Chen, PhD, of National Taiwan University, Taipei, and colleagues.
“Eradication of H. pylori infection heals chronic active gastritis and peptic ulcer disease and reduces the risk of peptic ulcer bleeding in aspirin users and the risk of gastric cancer in infected individuals,” the investigators wrote in Gastroenterology. “However, whether reduction of the prevalence of H. pylori is associated with a reduction of the incidence of gastric cancer at the population level remains uncertain.”
According to several previous meta-analyses, the global rate of H. pylori infection has been in a downtrend, but Dr. Chen and colleagues pointed out several limitations of these publications, including scarcity of recent data, insufficiently representative data, inconsistent diagnostic methods, and lack of adjustment for socioeconomic status.
“We therefore conducted this comprehensive systematic review and meta-analysis, including healthy individuals recruited in hospital-based studies, to provide an updated global prevalence and the secular trend of H. pylori infection,” the investigators wrote, noting that they leveraged meta-regression analysis to “identify factors affecting heterogeneity of the prevalence,” and concurrently evaluated the corresponding global incidence of gastric cancer.
Their dataset, which included 1,748 articles from 111 countries, suggested that the global rate of H. pylori is indeed in a downtrend.
From a crude global prevalence of 52.6% prior to 1990, the rate of H. pylori decreased to 43.9% among adults in 2015-2022, but was “still as high as” 35.1% among children and adolescents in the same 2015-2022 period. Multivariate regression analysis showed that prevalence decreased significantly, by 15.9%, among adults, but not in children and adolescents.
“The significant reduction of H. pylori prevalence in adults can be explained by the improvement of socioeconomic status, cleaner water supply, better sanitation and hygiene status, and widening of indication for eradication therapy,” Dr. Chen and colleagues wrote. “The higher prevalence in adults than in children/adolescents is explained by the cohort effect because most H. pylori infection is acquired in childhood.”
Global incidence of gastric cancer among both male and female individuals declined approximately in parallel with decreasing prevalence of H. pylori. Rates of gastric cancer decreased most in high-incidence countries such as Brazil, Japan, and China.
“These studies collectively provide evidence for the causal association of H. pylori infection and gastric cancer and that elimination of this bacterium can prevent the development of gastric cancer,” the investigators wrote.
Still, more work is needed.
“Future prospective studies should be conducted to confirm whether public health interventions or mass screening and eradication of H. pylori infection to reduce its prevalence may reduce the incidence of gastric cancer at population level,” Dr. Chen and colleagues concluded. “Besides, it is also important to consider the potential adverse consequences of H. pylori eradication, such as emergence of antibiotic resistance. The benefit-to-harm ratio and cost-effectiveness should also be taken into account.”
The study was funded by the National Taiwan University Hospital, the Taiwan Ministry of Science and Technology, the Taiwan Ministry of Health and Welfare, and others. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Study Characterizes Pathologic B-Cell Maturation in Crohn’s Disease
, according to investigators.
These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.
“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”
Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.
To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.
First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.
The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.
Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.
Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.
Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.
Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.
BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.
“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”
The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
, according to investigators.
These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.
“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”
Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.
To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.
First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.
The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.
Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.
Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.
Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.
Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.
BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.
“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”
The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.
“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”
Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.
To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.
First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.
The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.
Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.
Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.
Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.
Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.
BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.
“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”
The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
AGA Supports Fecal Microbiota Therapies for CDI but Not IBD or IBS
Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.
The AGA’s recommendations were published in Gastroenterology.
“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”
“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.
Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
Recommendations
The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:
- In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
- In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
- In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
- Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
- For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
- In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
- In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.
“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.
This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.
None of the panel members had any conflicts of interest to report.
Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.
The AGA’s recommendations were published in Gastroenterology.
“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”
“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.
Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
Recommendations
The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:
- In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
- In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
- In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
- Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
- For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
- In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
- In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.
“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.
This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.
None of the panel members had any conflicts of interest to report.
Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.
The AGA’s recommendations were published in Gastroenterology.
“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”
“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.
Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
Recommendations
The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:
- In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
- In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
- In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
- Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
- For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
- In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
- In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.
“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.
This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.
None of the panel members had any conflicts of interest to report.
FROM GASTROENTEROLOGY
Global Meta-Analysis: 1 in 12 Adults May Have Fecal Incontinence
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
The Paradox of Achalasia Symptoms
In contrast to most diseases, as achalasia progresses, the symptoms improve. Specifically, reduction of symptoms of dysphagia lulls the gastroenterologist into thinking their patients are doing well.
This improvement in dysphagia is likely due to two mechanisms. The first is that as the esophagus dilates, there is a greater capacity for food accumulation before sensation occurs. Whether this is completely a volume issue or whether there is a contribution from increased esophageal body distensibility is unclear. Similarly, as achalasia results from inflammation and destruction of the motor neurons of the myenteric plexus, sensory neurons are also damaged. As a result, the patient’s ability to sense food retention lessens. To some degree, this explains the phenomenon of patients presenting with megaesophagus; after years of initially diminishing or stable symptoms managed with patient accommodation, patients present with end-stage disease manifested by a food-impacted esophagus, nocturnal aspiration, and weight loss.
This aspect of the natural history of achalasia has led esophagologists to follow patients with achalasia after treatment at regular intervals with objective examinations such as timed esophagography to mitigate against this worsening yet symptomatically stable course.
Dr. Katzka is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York. He receives research support from Medtronic and is an associate editor for GI & Hepatology News. Previously published in Gastro Hep Advances. 2024 Jan 19. doi: 10.1016/j.gastha.2024.01.006.
In contrast to most diseases, as achalasia progresses, the symptoms improve. Specifically, reduction of symptoms of dysphagia lulls the gastroenterologist into thinking their patients are doing well.
This improvement in dysphagia is likely due to two mechanisms. The first is that as the esophagus dilates, there is a greater capacity for food accumulation before sensation occurs. Whether this is completely a volume issue or whether there is a contribution from increased esophageal body distensibility is unclear. Similarly, as achalasia results from inflammation and destruction of the motor neurons of the myenteric plexus, sensory neurons are also damaged. As a result, the patient’s ability to sense food retention lessens. To some degree, this explains the phenomenon of patients presenting with megaesophagus; after years of initially diminishing or stable symptoms managed with patient accommodation, patients present with end-stage disease manifested by a food-impacted esophagus, nocturnal aspiration, and weight loss.
This aspect of the natural history of achalasia has led esophagologists to follow patients with achalasia after treatment at regular intervals with objective examinations such as timed esophagography to mitigate against this worsening yet symptomatically stable course.
Dr. Katzka is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York. He receives research support from Medtronic and is an associate editor for GI & Hepatology News. Previously published in Gastro Hep Advances. 2024 Jan 19. doi: 10.1016/j.gastha.2024.01.006.
In contrast to most diseases, as achalasia progresses, the symptoms improve. Specifically, reduction of symptoms of dysphagia lulls the gastroenterologist into thinking their patients are doing well.
This improvement in dysphagia is likely due to two mechanisms. The first is that as the esophagus dilates, there is a greater capacity for food accumulation before sensation occurs. Whether this is completely a volume issue or whether there is a contribution from increased esophageal body distensibility is unclear. Similarly, as achalasia results from inflammation and destruction of the motor neurons of the myenteric plexus, sensory neurons are also damaged. As a result, the patient’s ability to sense food retention lessens. To some degree, this explains the phenomenon of patients presenting with megaesophagus; after years of initially diminishing or stable symptoms managed with patient accommodation, patients present with end-stage disease manifested by a food-impacted esophagus, nocturnal aspiration, and weight loss.
This aspect of the natural history of achalasia has led esophagologists to follow patients with achalasia after treatment at regular intervals with objective examinations such as timed esophagography to mitigate against this worsening yet symptomatically stable course.
Dr. Katzka is based in the Division of Digestive and Liver Diseases, Columbia University Medical Center, New York. He receives research support from Medtronic and is an associate editor for GI & Hepatology News. Previously published in Gastro Hep Advances. 2024 Jan 19. doi: 10.1016/j.gastha.2024.01.006.
AGA Guides Usage of GLP-1 Receptor Agonists Before Endoscopy
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY