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according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES