GI and Hepatology News

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log₁₀ IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log₁₀ IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log₁₀ IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log₁₀ IU/mL or > 8 log₁₀ IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log₁₀ IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log₁₀ IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log₁₀ IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log₁₀ IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log₁₀ IU/mL or > 8 log₁₀ IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log₁₀ IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log₁₀ IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log₁₀ IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log₁₀ IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log₁₀ IU/mL or > 8 log₁₀ IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log₁₀ IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Hispanic adults in the US experience significantly higher risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH), compared with non-Hispanic adults, according to a new systematic review and meta-analysis.

These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.

Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH. 

“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”

The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic. 

Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).

The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.

“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote. 

Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations. 

The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities. 

Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.

Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.

“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.

Hispanic adults in the US experience significantly higher risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH), compared with non-Hispanic adults, according to a new systematic review and meta-analysis.

These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.

Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH. 

“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”

The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic. 

Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).

The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.

“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote. 

Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations. 

The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities. 

Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.

Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.

“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.

Hispanic adults in the US experience significantly higher risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH), compared with non-Hispanic adults, according to a new systematic review and meta-analysis.

These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.

Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH. 

“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”

The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic. 

Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).

The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.

“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote. 

Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations. 

The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities. 

Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.

Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.

“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.

Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs.

“P-CABs are a newer medication class now available in the US, associated with more rapid, potent, and prolonged gastric acid inhibition than PPI formulations,” said lead author Amit Patel, MD, a gastroenterologist at the Duke University School of Medicine and Durham Veterans Affairs Medical Center, Durham, North Carolina.

 

“P-CABs have potentially significant clinical benefits in the management of Helicobacter pylori infection and GERD, particularly more severe erosive esophagitis,” he said. “Emerging data are affording additional insights into the clinical benefits of P-CABs in settings such as on-demand therapy for reflux-associated symptoms, bleeding gastroduodenal ulcers, and endoscopic eradication therapy for Barrett’s esophagus.”

The update was published in Gastroenterology .

 

P-CAB Developments

For most patients, PPIs and histamine-2 receptor antagonists remain the primary way to inhibit gastric acid secretion for common upper gastrointestinal conditions, the authors wrote. However, P-CABs such as vonoprazan and tegoprazan may provide relief when PPIs have limitations.

Unlike PPIs, P-CABs are considered acid-stable, don’t require premeal dosing, aren’t prodrugs, and don’t require conversion to an active form to provide pharmacologic effects. They tend to have longer half-lives and more rapid onset. Serum gastrin levels typically remain higher with P-CABs.

In terms of safety, randomized trial data indicate that P-CABs are generally well tolerated and have short-term and medium-term safety similar to PPIs. Due to potent acid suppression, enteric infection risks remain higher, though long-term safety data is needed, the authors wrote.

Overall, P-CABs appear to be equally as potent or more potent than PPIs, though more potent acid inhibition isn’t necessarily associated with better outcomes, the authors wrote. For most foregut acid-related disorders — such as heartburn and prevention of nonsteroidal anti-inflammatory drug–associated ulcers — P-CABs can help when patients fail PPI therapy.

In general, though, nonclinical factors related to cost, barriers to obtaining medication, and limited long-term safety data may outweigh the advantages of P-CABs, especially if clinical superiority isn’t yet known, the authors wrote. 

For GERD, clinicians generally shouldn’t use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. However, P-CABs should be used for those with documented acid-related reflux who fail therapy with twice-daily PPIs. They may also be appropriate for on-demand heartburn therapy, although more evidence is needed.

For erosive esophagitis, P-CABs generally shouldn’t be used for milder cases but can be considered for patients with more severe cases that haven’t responded to PPIs, including refractory esophagitis.

For H pylori, P-CABs should be used in place of PPIs for eradication regimens, including among patients with clarithromycin-resistant strains. In contrast with most of the other indications in the update, the short-term duration of H pylori treatment reduced the authors’ concerns about P-CAB costs and safety.

For peptic ulcer disease, P-CABs generally shouldn’t be used as first-line treatment or prophylaxis. However, the rapid onset and potent acid inhibition could be useful for patients with bleeding gastroduodenal ulcers and high-risk stigmata.

“Emerging data will allow refinements in the populations and clinical settings for which P-CABs at various doses may be considered and advised — and may reveal more clinical scenarios in which they can provide meaningful benefit,” Patel said. “Further investigations, including additional populations and novel indicators, as well as evaluating long-term safety data and cost-effectiveness, are warranted, as P-CABs are incorporated more broadly into clinical practice worldwide.”
 
The authors received no specific funding for this update. Patel reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs.

“P-CABs are a newer medication class now available in the US, associated with more rapid, potent, and prolonged gastric acid inhibition than PPI formulations,” said lead author Amit Patel, MD, a gastroenterologist at the Duke University School of Medicine and Durham Veterans Affairs Medical Center, Durham, North Carolina.

 

“P-CABs have potentially significant clinical benefits in the management of Helicobacter pylori infection and GERD, particularly more severe erosive esophagitis,” he said. “Emerging data are affording additional insights into the clinical benefits of P-CABs in settings such as on-demand therapy for reflux-associated symptoms, bleeding gastroduodenal ulcers, and endoscopic eradication therapy for Barrett’s esophagus.”

The update was published in Gastroenterology .

 

P-CAB Developments

For most patients, PPIs and histamine-2 receptor antagonists remain the primary way to inhibit gastric acid secretion for common upper gastrointestinal conditions, the authors wrote. However, P-CABs such as vonoprazan and tegoprazan may provide relief when PPIs have limitations.

Unlike PPIs, P-CABs are considered acid-stable, don’t require premeal dosing, aren’t prodrugs, and don’t require conversion to an active form to provide pharmacologic effects. They tend to have longer half-lives and more rapid onset. Serum gastrin levels typically remain higher with P-CABs.

In terms of safety, randomized trial data indicate that P-CABs are generally well tolerated and have short-term and medium-term safety similar to PPIs. Due to potent acid suppression, enteric infection risks remain higher, though long-term safety data is needed, the authors wrote.

Overall, P-CABs appear to be equally as potent or more potent than PPIs, though more potent acid inhibition isn’t necessarily associated with better outcomes, the authors wrote. For most foregut acid-related disorders — such as heartburn and prevention of nonsteroidal anti-inflammatory drug–associated ulcers — P-CABs can help when patients fail PPI therapy.

In general, though, nonclinical factors related to cost, barriers to obtaining medication, and limited long-term safety data may outweigh the advantages of P-CABs, especially if clinical superiority isn’t yet known, the authors wrote. 

For GERD, clinicians generally shouldn’t use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. However, P-CABs should be used for those with documented acid-related reflux who fail therapy with twice-daily PPIs. They may also be appropriate for on-demand heartburn therapy, although more evidence is needed.

For erosive esophagitis, P-CABs generally shouldn’t be used for milder cases but can be considered for patients with more severe cases that haven’t responded to PPIs, including refractory esophagitis.

For H pylori, P-CABs should be used in place of PPIs for eradication regimens, including among patients with clarithromycin-resistant strains. In contrast with most of the other indications in the update, the short-term duration of H pylori treatment reduced the authors’ concerns about P-CAB costs and safety.

For peptic ulcer disease, P-CABs generally shouldn’t be used as first-line treatment or prophylaxis. However, the rapid onset and potent acid inhibition could be useful for patients with bleeding gastroduodenal ulcers and high-risk stigmata.

“Emerging data will allow refinements in the populations and clinical settings for which P-CABs at various doses may be considered and advised — and may reveal more clinical scenarios in which they can provide meaningful benefit,” Patel said. “Further investigations, including additional populations and novel indicators, as well as evaluating long-term safety data and cost-effectiveness, are warranted, as P-CABs are incorporated more broadly into clinical practice worldwide.”
 
The authors received no specific funding for this update. Patel reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs.

“P-CABs are a newer medication class now available in the US, associated with more rapid, potent, and prolonged gastric acid inhibition than PPI formulations,” said lead author Amit Patel, MD, a gastroenterologist at the Duke University School of Medicine and Durham Veterans Affairs Medical Center, Durham, North Carolina.

 

“P-CABs have potentially significant clinical benefits in the management of Helicobacter pylori infection and GERD, particularly more severe erosive esophagitis,” he said. “Emerging data are affording additional insights into the clinical benefits of P-CABs in settings such as on-demand therapy for reflux-associated symptoms, bleeding gastroduodenal ulcers, and endoscopic eradication therapy for Barrett’s esophagus.”

The update was published in Gastroenterology .

 

P-CAB Developments

For most patients, PPIs and histamine-2 receptor antagonists remain the primary way to inhibit gastric acid secretion for common upper gastrointestinal conditions, the authors wrote. However, P-CABs such as vonoprazan and tegoprazan may provide relief when PPIs have limitations.

Unlike PPIs, P-CABs are considered acid-stable, don’t require premeal dosing, aren’t prodrugs, and don’t require conversion to an active form to provide pharmacologic effects. They tend to have longer half-lives and more rapid onset. Serum gastrin levels typically remain higher with P-CABs.

In terms of safety, randomized trial data indicate that P-CABs are generally well tolerated and have short-term and medium-term safety similar to PPIs. Due to potent acid suppression, enteric infection risks remain higher, though long-term safety data is needed, the authors wrote.

Overall, P-CABs appear to be equally as potent or more potent than PPIs, though more potent acid inhibition isn’t necessarily associated with better outcomes, the authors wrote. For most foregut acid-related disorders — such as heartburn and prevention of nonsteroidal anti-inflammatory drug–associated ulcers — P-CABs can help when patients fail PPI therapy.

In general, though, nonclinical factors related to cost, barriers to obtaining medication, and limited long-term safety data may outweigh the advantages of P-CABs, especially if clinical superiority isn’t yet known, the authors wrote. 

For GERD, clinicians generally shouldn’t use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. However, P-CABs should be used for those with documented acid-related reflux who fail therapy with twice-daily PPIs. They may also be appropriate for on-demand heartburn therapy, although more evidence is needed.

For erosive esophagitis, P-CABs generally shouldn’t be used for milder cases but can be considered for patients with more severe cases that haven’t responded to PPIs, including refractory esophagitis.

For H pylori, P-CABs should be used in place of PPIs for eradication regimens, including among patients with clarithromycin-resistant strains. In contrast with most of the other indications in the update, the short-term duration of H pylori treatment reduced the authors’ concerns about P-CAB costs and safety.

For peptic ulcer disease, P-CABs generally shouldn’t be used as first-line treatment or prophylaxis. However, the rapid onset and potent acid inhibition could be useful for patients with bleeding gastroduodenal ulcers and high-risk stigmata.

“Emerging data will allow refinements in the populations and clinical settings for which P-CABs at various doses may be considered and advised — and may reveal more clinical scenarios in which they can provide meaningful benefit,” Patel said. “Further investigations, including additional populations and novel indicators, as well as evaluating long-term safety data and cost-effectiveness, are warranted, as P-CABs are incorporated more broadly into clinical practice worldwide.”
 
The authors received no specific funding for this update. Patel reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) predicts long-term outcomes among pediatric patients with biliary atresia, according to investigators.

These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.

 

“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”

To this end, VCTE has been gaining increasing support in the pediatric setting.

“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”

The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.

The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.

LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).

Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.

LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm³ per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.

Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.

“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) predicts long-term outcomes among pediatric patients with biliary atresia, according to investigators.

These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.

 

“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”

To this end, VCTE has been gaining increasing support in the pediatric setting.

“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”

The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.

The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.

LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).

Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.

LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm³ per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.

Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.

“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) predicts long-term outcomes among pediatric patients with biliary atresia, according to investigators.

These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.

 

“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”

To this end, VCTE has been gaining increasing support in the pediatric setting.

“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”

The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.

The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.

LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).

Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.

LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm³ per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.

Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.

“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.

Lipophilic statins are associated with reduced risk of developing hepatocellular carcinoma (HCC) among patients with hepatic fibrosis and cirrhosis, 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.

Lipophilic statins are associated with reduced risk of developing hepatocellular carcinoma (HCC) among patients with hepatic fibrosis and cirrhosis, 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.

Lipophilic statins are associated with reduced risk of developing hepatocellular carcinoma (HCC) among patients with hepatic fibrosis and cirrhosis, 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.

Research creates successful practices. Patients benefit from GI research daily in practices. Scientists are working hard to develop new treatments and therapies, and to discover cures to advance the field and better patient care. But they can’t do this without research funding.

AGA Legacy Society members have answered this call for support. They recognize the value that research has had in their profession, both in academic medicine and in private practice, and are showing their appreciation by giving back.

“I donated to the AGA Research Foundation to ensure the vitality of our specialty, and to fund the research of future generations of gastroenterologists,” said Michael Camilleri, MD, AGAF, of Mayo Clinic, Rochester, Minn., and an AGA Legacy Society member who currently serves as AGA Research Foundation Chair. “Funding from organizations like the AGA Research Foundation is crucial for young scientists and gastroenterologists to launch their careers. At the start of my career, I received two AGA research awards. As a grateful recipient of such funding, I felt it was my turn to support the mission of the organization that I regard as my academic home away from home institution.”

AGA Legacy Society members see the promise the future holds and are committed to furthering research in gastroenterology and hepatology through their generous donations. 

AGA members who make gifts at the AGA Legacy Society level any time before Digestive Disease Week® (DDW) 2025 will receive an invitation to the AGA Research Foundation Benefactor’s Event in San Diego, California. Interested in learning more about the AGA Legacy Society membership? Contact [email protected] or visit https://foundation.gastro.org/our-donors/aga-legacy-society/ for more information about the AGA Legacy Society.







 

Research creates successful practices. Patients benefit from GI research daily in practices. Scientists are working hard to develop new treatments and therapies, and to discover cures to advance the field and better patient care. But they can’t do this without research funding.

AGA Legacy Society members have answered this call for support. They recognize the value that research has had in their profession, both in academic medicine and in private practice, and are showing their appreciation by giving back.

“I donated to the AGA Research Foundation to ensure the vitality of our specialty, and to fund the research of future generations of gastroenterologists,” said Michael Camilleri, MD, AGAF, of Mayo Clinic, Rochester, Minn., and an AGA Legacy Society member who currently serves as AGA Research Foundation Chair. “Funding from organizations like the AGA Research Foundation is crucial for young scientists and gastroenterologists to launch their careers. At the start of my career, I received two AGA research awards. As a grateful recipient of such funding, I felt it was my turn to support the mission of the organization that I regard as my academic home away from home institution.”

AGA Legacy Society members see the promise the future holds and are committed to furthering research in gastroenterology and hepatology through their generous donations. 

AGA members who make gifts at the AGA Legacy Society level any time before Digestive Disease Week® (DDW) 2025 will receive an invitation to the AGA Research Foundation Benefactor’s Event in San Diego, California. Interested in learning more about the AGA Legacy Society membership? Contact [email protected] or visit https://foundation.gastro.org/our-donors/aga-legacy-society/ for more information about the AGA Legacy Society.







 

Research creates successful practices. Patients benefit from GI research daily in practices. Scientists are working hard to develop new treatments and therapies, and to discover cures to advance the field and better patient care. But they can’t do this without research funding.

AGA Legacy Society members have answered this call for support. They recognize the value that research has had in their profession, both in academic medicine and in private practice, and are showing their appreciation by giving back.

“I donated to the AGA Research Foundation to ensure the vitality of our specialty, and to fund the research of future generations of gastroenterologists,” said Michael Camilleri, MD, AGAF, of Mayo Clinic, Rochester, Minn., and an AGA Legacy Society member who currently serves as AGA Research Foundation Chair. “Funding from organizations like the AGA Research Foundation is crucial for young scientists and gastroenterologists to launch their careers. At the start of my career, I received two AGA research awards. As a grateful recipient of such funding, I felt it was my turn to support the mission of the organization that I regard as my academic home away from home institution.”

AGA Legacy Society members see the promise the future holds and are committed to furthering research in gastroenterology and hepatology through their generous donations. 

AGA members who make gifts at the AGA Legacy Society level any time before Digestive Disease Week® (DDW) 2025 will receive an invitation to the AGA Research Foundation Benefactor’s Event in San Diego, California. Interested in learning more about the AGA Legacy Society membership? Contact [email protected] or visit https://foundation.gastro.org/our-donors/aga-legacy-society/ for more information about the AGA Legacy Society.







 

Dear colleagues,

Gastroesophageal reflux disease (GERD) is a common reason for referral to gastroenterology. It affects a broad cross-section of our population and is often managed through a combination of lifestyle modifications and proton pump inhibitors (PPIs). However, in the era of PPIs, we must ask: Are lifestyle changes still necessary? And were they ever truly effective?

While PPIs are highly effective, concerns about their potential side effects frequently make headlines. Moreover, the financial burden of lifelong PPI use is a growing consideration. In this issue of Perspectives, Dr. Brijesh B. Patel and Dr. Juan D. Gomez Cifuentes explore these questions. Dr. Gomez Cifuentes highlights the benefits of lifestyle changes and identifies which strategies have proved most effective in his practice. Dr. Patel examines the ubiquitous use of PPIs and the challenges of sustaining adherence to lifestyle modifications. We hope these discussions will spark new ideas for managing GERD in your own practice. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Do Lifestyle Changes Still Apply in the Treatment of GERD?

BY JUAN D. GOMEZ CIFUENTES, MD

Lifestyle changes are an essential part of managing gastroesophageal reflux disease (GERD). Increasingly, patients are asking about non-medication approaches to control their symptoms. These lifestyle modifications can be categorized into four main areas: 1) Weight loss, the cornerstone intervention, with significant symptom improvement observed after losing as little as 1.7 BMI points. 2) Dietary modifications, which includes both the traditional avoidance of trigger foods and the newer focus on a diet low in simple carbohydrates. 3) Bedtime adjustments, strategies that include elevating the head of the bed, sleeping on the left side, using anti-reflux pillows, and avoiding late-night meals. 4) Tobacco cessation, a key measure for reducing GERD symptoms and promoting overall health. I routinely discuss these changes with my patients, as they not only help manage GERD but also foster healthy habits and have a positive impact beyond the gastrointestinal tract.

Weight loss is the most impactful lifestyle intervention for GERD. Research shows a clear linear improvement in symptoms with weight reduction. Traditionally, losing 10% of body weight is a widely accepted goal, extrapolated from other obesity-associated conditions. A reduction in 3.5 points of BMI led to significant symptom improvement in landmark studies but also a modest reduction of 1.7 BMI points has been shown to provide symptom relief.¹ Abdominal circumference is another key metric used to track progress, as central obesity rather than BMI alone is strongly linked with GERD. Goals are typically set at less than 40 inches for men and 35 inches for women. Patients using GLP-1 agonists should be informed that these medications may temporarily worsen GERD symptoms due to delayed gastric emptying, however in the long-term these symptoms are expected to improve once significant weight loss is achieved.

Food triggers vary among individuals, with common culprits including fatty meals, spicy foods, chocolate, tomato sauce, citrus fruits, and carbonated beverages. Patients tend to overemphasize diet elimination based on triggers and engage in strict diets. Patients are frequently afraid of these foods causing direct damage to the esophageal mucosa but the hypothesis is that these triggers worsen GERD by increasing transient relaxations of the lower esophageal sphincter. The evidence behind this and diet elimination based on triggers has always been weak. In my practice, I encourage patients to follow a diet low in simple carbohydrates. Simple carbohydrates are present in highly processed food, the average western diet contains ~140 g/day. In a trial, a diet low in simple sugars (monosaccharides and disaccharides < 62 g/day) without reducing total daily calories, objectively improved total acid exposure time in pH study.²

Thanks to gravity, nocturnal GERD symptoms are the culprit of many restless nights in these patients. I recommend avoiding food 3 hours before lying down. Since the stomach empties approximately 90% of its contents after 4 hours, waiting longer is not recommended and may result in hunger, making it harder to fall asleep. Sleeping on the left side, which takes advantage of the gastric anatomy, has proved to objectively decrease nocturnal acid exposure time, though some patients may find it challenging to maintain this position all night.³

Elevating the head of the bed is another effective intervention, but it must involve raising the upper body from the waist. Patients should avoid stacking ordinary pillows as this will only elevate the neck and place the body in an unnatural position for sleeping. The most effective strategies are putting blocks/bricks under the feet of the bed, using a bed wedge between the mattress and the box spring or using an adjustable bed frame. There are two types of pillows that have been shown to improve nocturnal GERD symptoms. The classic wedge pillows and the more expensive Medcline reflux relief system®. The Medcline pillow has a dual mechanism that elevates the upper body but also keeps the body on the left side position.⁴

Tobacco cessation is strongly recommended. Tobacco worsens GERD symptoms by reducing the lower esophageal sphincter pressure and decreasing saliva production which is one of the key components of the normal esophageal acid barrier. Moreover, it is a known risk factor for esophageal cancer. Alcohol has a variety of negative health impacts and decreasing alcohol intake is advised; however, the link between alcohol and GERD symptoms is less robust, especially in patients with low occasional consumption.

In summary, lifestyle modifications play a pivotal role in managing GERD symptoms, offering patients effective, non-pharmacologic strategies to complement medical treatments. Weight loss remains the cornerstone, with even modest reductions in BMI showing significant symptom relief. Dietary adjustments, particularly adopting a low-simple-carbohydrate diet, provide an evidence-based approach. Various bedtime interventions are available to improve nocturnal GERD symptoms. Finally, tobacco cessation is essential, not only for GERD symptom relief but also for overall health. By integrating these lifestyle changes into their routine, patients can improve GERD symptoms while building healthy habits.

Dr. Gomez Cifuentes is vice-chair in the section of gastroenterology at Presbyterian Healthcare Services, Albuquerque, New Mexico. He declares no conflicts of interest.

References

1. Ness-Jensen E et al. Lifestyle Intervention in Gastroesophageal Reflux Disease. Clin Gastroenterol Hepatol. 2016 Feb;14(2):175-82.e1-3. doi: 10.1016/j.cgh.2015.04.176.

2. Gu C et al. The Effects of Modifying Amount and Type of Dietary Carbohydrate on Esophageal Acid Exposure Time and Esophageal Reflux Symptoms: A Randomized Controlled Trial. Am J Gastroenterol. 2022 Oct 1;117(10):1655-1667. doi: 10.14309/ajg.0000000000001889.

3. Schuitenmaker JM et al. Associations Between Sleep Position and Nocturnal Gastroesophageal Reflux: A Study Using Concurrent Monitoring of Sleep Position and Esophageal pH and Impedance. Am J Gastroenterol. 2022 Feb 1;117(2):346-351. doi: 10.14309/ajg.0000000000001588.

4. Person E et al. A Novel Sleep Positioning Device Reduces Gastroesophageal Reflux: A Randomized Controlled Trial. J Clin Gastroenterol. 2015 Sep;49(8):655-9. doi: 10.1097/MCG.0000000000000359.

Medical Therapy Is the Cornerstone of Effective GERD Treatment

BY BRIJESH B. PATEL, MD

Today, I saw Mr. S in the office for gastroesophageal reflux disease (GERD). He has been on a trial of proton pump inhibitors (PPIs) and has implemented several lifestyle modifications to manage his reflux. He shared his frustrations, saying, “Doctor, I’ve tried changing my diet, sleeping in a recliner, and adjusting the timing of my meals. I’m practically not enjoying food anymore, and these lifestyle changes have affected my quality of life. Despite all this, I still wake up in the middle of the night with a ‘horrible taste’ in my mouth, and it’s ruining my sleep.”

Later that day, during a discussion with my trainees, one posed an important question: “What about lifestyle measures in the treatment of GERD?” This is a common query in both clinical and academic settings. GERD, with a prevalence estimated at ~20%, is often underreported as many patients begin self-medicating with over-the-counter acid suppressive therapies before seeking medical care. For gastroenterologists, PPIs, histamine-2 receptor antagonists (H2RAs), and now potassium-competitive acid blockers (PCABs) form the cornerstone of GERD management.

When I lecture medical students, residents, and fellows about GERD, I emphasize a standard approach: initiating an 8- to 12-week trial of PPIs followed by reassessment. I also stress the importance of combining medical therapy with lifestyle measures. However, the question remains: How adherent are our patients to these lifestyle changes? Similarly, how effectively are trainees integrating the value of lifestyle modifications into their practice? As an academic gastroenterologist, I can teach the theory, but is it being translated into real-world patient care?

The advent of PPIs has been a game changer for managing GERD symptoms and preventing disease progression. PPIs are the backbone of treatment in both gastroenterology and primary care, and they have profoundly improved patients’ quality of life. Most of my patients who present with GERD — whether due to uncontrolled reflux or acid exposure — have already been on a trial of PPIs before seeing me. My role often involves optimizing their timing of PPI administration, addressing incorrect usage, and reinforcing the importance of adherence. In some cases, I incorporate H2RAs as adjunctive therapy for patients who fail to respond adequately to PPIs, particularly when objective disease activity is confirmed through pH studies. These studies also highlight how challenging it is for many patients to maintain a refluxogenic-free lifestyle.

Lifestyle modifications should supplement and support GERD management. Regardless of medical specialty, lifestyle measures should be the first line of treatment. However, adherence and effectiveness vary widely. In reality, achieving sustained weight loss, meal timing adjustments, and dietary modifications (e.g., eliminating trigger foods like red wine, chocolate, coffee, and tomato-based sauces) is a significant challenge for patients. While these measures can reduce the need for PPIs in some cases, they are rarely sufficient as standalone treatments. Until lifestyle modifications are consistently and sustainably incorporated into daily routines, acid-suppressive therapy will remain the mainstay of GERD management.

Turning to newer therapies, PCABs are now FDA-approved for treating GERD. Early efficacy data suggest that PCABs are non-inferior to PPIs, with promising results in managing LA Class C and D esophagitis and maintaining symptom-free days. However, like PPIs, PCABs are associated with potential adverse effects, including C. difficile colitis, impacts on bone health, renal impairment, and mineral deficiencies. While these risks must be carefully discussed with patients, the benefits of medical therapy far outweigh the risks, especially for those with erosive esophagitis, Barrett’s esophagus, or a high-risk profile for esophageal cancer. In such cases, medical therapies provide superior disease control compared to lifestyle measures, supported by both subjective and objective data.

Managing GERD requires a multipronged approach. Relying solely on lifestyle measures rarely provides complete benefit, as restrictive dietary regimens are difficult to sustain long term. Like many, I can maintain a restrictive diet temporarily but find it unsustainable over time. Conversely, adherence to daily or twice-daily medications tends to be much higher than compliance with multi-level lifestyle changes (e.g., restrictive diets, weight loss, and trigger-food avoidance).

Our therapeutic arsenal for GERD continues to expand, enabling more effective management of patients with uncontrolled acid reflux. While I will continue to counsel patients and educate trainees on the value of lifestyle modifications, I emphasize the importance of adherence to timely medical therapy — whether with PPIs, H2RAs, or PCABs — as the cornerstone of effective GERD treatment.

Dr. Patel is associate program director in the division of digestive diseases & nutrition, at USF Health, Tampa, Fla. He declares no conflicts of interest.

Dear colleagues,

Gastroesophageal reflux disease (GERD) is a common reason for referral to gastroenterology. It affects a broad cross-section of our population and is often managed through a combination of lifestyle modifications and proton pump inhibitors (PPIs). However, in the era of PPIs, we must ask: Are lifestyle changes still necessary? And were they ever truly effective?

While PPIs are highly effective, concerns about their potential side effects frequently make headlines. Moreover, the financial burden of lifelong PPI use is a growing consideration. In this issue of Perspectives, Dr. Brijesh B. Patel and Dr. Juan D. Gomez Cifuentes explore these questions. Dr. Gomez Cifuentes highlights the benefits of lifestyle changes and identifies which strategies have proved most effective in his practice. Dr. Patel examines the ubiquitous use of PPIs and the challenges of sustaining adherence to lifestyle modifications. We hope these discussions will spark new ideas for managing GERD in your own practice. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Do Lifestyle Changes Still Apply in the Treatment of GERD?

BY JUAN D. GOMEZ CIFUENTES, MD

Lifestyle changes are an essential part of managing gastroesophageal reflux disease (GERD). Increasingly, patients are asking about non-medication approaches to control their symptoms. These lifestyle modifications can be categorized into four main areas: 1) Weight loss, the cornerstone intervention, with significant symptom improvement observed after losing as little as 1.7 BMI points. 2) Dietary modifications, which includes both the traditional avoidance of trigger foods and the newer focus on a diet low in simple carbohydrates. 3) Bedtime adjustments, strategies that include elevating the head of the bed, sleeping on the left side, using anti-reflux pillows, and avoiding late-night meals. 4) Tobacco cessation, a key measure for reducing GERD symptoms and promoting overall health. I routinely discuss these changes with my patients, as they not only help manage GERD but also foster healthy habits and have a positive impact beyond the gastrointestinal tract.

Weight loss is the most impactful lifestyle intervention for GERD. Research shows a clear linear improvement in symptoms with weight reduction. Traditionally, losing 10% of body weight is a widely accepted goal, extrapolated from other obesity-associated conditions. A reduction in 3.5 points of BMI led to significant symptom improvement in landmark studies but also a modest reduction of 1.7 BMI points has been shown to provide symptom relief.¹ Abdominal circumference is another key metric used to track progress, as central obesity rather than BMI alone is strongly linked with GERD. Goals are typically set at less than 40 inches for men and 35 inches for women. Patients using GLP-1 agonists should be informed that these medications may temporarily worsen GERD symptoms due to delayed gastric emptying, however in the long-term these symptoms are expected to improve once significant weight loss is achieved.

Food triggers vary among individuals, with common culprits including fatty meals, spicy foods, chocolate, tomato sauce, citrus fruits, and carbonated beverages. Patients tend to overemphasize diet elimination based on triggers and engage in strict diets. Patients are frequently afraid of these foods causing direct damage to the esophageal mucosa but the hypothesis is that these triggers worsen GERD by increasing transient relaxations of the lower esophageal sphincter. The evidence behind this and diet elimination based on triggers has always been weak. In my practice, I encourage patients to follow a diet low in simple carbohydrates. Simple carbohydrates are present in highly processed food, the average western diet contains ~140 g/day. In a trial, a diet low in simple sugars (monosaccharides and disaccharides < 62 g/day) without reducing total daily calories, objectively improved total acid exposure time in pH study.²

Thanks to gravity, nocturnal GERD symptoms are the culprit of many restless nights in these patients. I recommend avoiding food 3 hours before lying down. Since the stomach empties approximately 90% of its contents after 4 hours, waiting longer is not recommended and may result in hunger, making it harder to fall asleep. Sleeping on the left side, which takes advantage of the gastric anatomy, has proved to objectively decrease nocturnal acid exposure time, though some patients may find it challenging to maintain this position all night.³

Elevating the head of the bed is another effective intervention, but it must involve raising the upper body from the waist. Patients should avoid stacking ordinary pillows as this will only elevate the neck and place the body in an unnatural position for sleeping. The most effective strategies are putting blocks/bricks under the feet of the bed, using a bed wedge between the mattress and the box spring or using an adjustable bed frame. There are two types of pillows that have been shown to improve nocturnal GERD symptoms. The classic wedge pillows and the more expensive Medcline reflux relief system®. The Medcline pillow has a dual mechanism that elevates the upper body but also keeps the body on the left side position.⁴

Tobacco cessation is strongly recommended. Tobacco worsens GERD symptoms by reducing the lower esophageal sphincter pressure and decreasing saliva production which is one of the key components of the normal esophageal acid barrier. Moreover, it is a known risk factor for esophageal cancer. Alcohol has a variety of negative health impacts and decreasing alcohol intake is advised; however, the link between alcohol and GERD symptoms is less robust, especially in patients with low occasional consumption.

In summary, lifestyle modifications play a pivotal role in managing GERD symptoms, offering patients effective, non-pharmacologic strategies to complement medical treatments. Weight loss remains the cornerstone, with even modest reductions in BMI showing significant symptom relief. Dietary adjustments, particularly adopting a low-simple-carbohydrate diet, provide an evidence-based approach. Various bedtime interventions are available to improve nocturnal GERD symptoms. Finally, tobacco cessation is essential, not only for GERD symptom relief but also for overall health. By integrating these lifestyle changes into their routine, patients can improve GERD symptoms while building healthy habits.

Dr. Gomez Cifuentes is vice-chair in the section of gastroenterology at Presbyterian Healthcare Services, Albuquerque, New Mexico. He declares no conflicts of interest.

References

1. Ness-Jensen E et al. Lifestyle Intervention in Gastroesophageal Reflux Disease. Clin Gastroenterol Hepatol. 2016 Feb;14(2):175-82.e1-3. doi: 10.1016/j.cgh.2015.04.176.

2. Gu C et al. The Effects of Modifying Amount and Type of Dietary Carbohydrate on Esophageal Acid Exposure Time and Esophageal Reflux Symptoms: A Randomized Controlled Trial. Am J Gastroenterol. 2022 Oct 1;117(10):1655-1667. doi: 10.14309/ajg.0000000000001889.

3. Schuitenmaker JM et al. Associations Between Sleep Position and Nocturnal Gastroesophageal Reflux: A Study Using Concurrent Monitoring of Sleep Position and Esophageal pH and Impedance. Am J Gastroenterol. 2022 Feb 1;117(2):346-351. doi: 10.14309/ajg.0000000000001588.

4. Person E et al. A Novel Sleep Positioning Device Reduces Gastroesophageal Reflux: A Randomized Controlled Trial. J Clin Gastroenterol. 2015 Sep;49(8):655-9. doi: 10.1097/MCG.0000000000000359.

Medical Therapy Is the Cornerstone of Effective GERD Treatment

BY BRIJESH B. PATEL, MD

Today, I saw Mr. S in the office for gastroesophageal reflux disease (GERD). He has been on a trial of proton pump inhibitors (PPIs) and has implemented several lifestyle modifications to manage his reflux. He shared his frustrations, saying, “Doctor, I’ve tried changing my diet, sleeping in a recliner, and adjusting the timing of my meals. I’m practically not enjoying food anymore, and these lifestyle changes have affected my quality of life. Despite all this, I still wake up in the middle of the night with a ‘horrible taste’ in my mouth, and it’s ruining my sleep.”

Later that day, during a discussion with my trainees, one posed an important question: “What about lifestyle measures in the treatment of GERD?” This is a common query in both clinical and academic settings. GERD, with a prevalence estimated at ~20%, is often underreported as many patients begin self-medicating with over-the-counter acid suppressive therapies before seeking medical care. For gastroenterologists, PPIs, histamine-2 receptor antagonists (H2RAs), and now potassium-competitive acid blockers (PCABs) form the cornerstone of GERD management.

When I lecture medical students, residents, and fellows about GERD, I emphasize a standard approach: initiating an 8- to 12-week trial of PPIs followed by reassessment. I also stress the importance of combining medical therapy with lifestyle measures. However, the question remains: How adherent are our patients to these lifestyle changes? Similarly, how effectively are trainees integrating the value of lifestyle modifications into their practice? As an academic gastroenterologist, I can teach the theory, but is it being translated into real-world patient care?

The advent of PPIs has been a game changer for managing GERD symptoms and preventing disease progression. PPIs are the backbone of treatment in both gastroenterology and primary care, and they have profoundly improved patients’ quality of life. Most of my patients who present with GERD — whether due to uncontrolled reflux or acid exposure — have already been on a trial of PPIs before seeing me. My role often involves optimizing their timing of PPI administration, addressing incorrect usage, and reinforcing the importance of adherence. In some cases, I incorporate H2RAs as adjunctive therapy for patients who fail to respond adequately to PPIs, particularly when objective disease activity is confirmed through pH studies. These studies also highlight how challenging it is for many patients to maintain a refluxogenic-free lifestyle.

Lifestyle modifications should supplement and support GERD management. Regardless of medical specialty, lifestyle measures should be the first line of treatment. However, adherence and effectiveness vary widely. In reality, achieving sustained weight loss, meal timing adjustments, and dietary modifications (e.g., eliminating trigger foods like red wine, chocolate, coffee, and tomato-based sauces) is a significant challenge for patients. While these measures can reduce the need for PPIs in some cases, they are rarely sufficient as standalone treatments. Until lifestyle modifications are consistently and sustainably incorporated into daily routines, acid-suppressive therapy will remain the mainstay of GERD management.

Turning to newer therapies, PCABs are now FDA-approved for treating GERD. Early efficacy data suggest that PCABs are non-inferior to PPIs, with promising results in managing LA Class C and D esophagitis and maintaining symptom-free days. However, like PPIs, PCABs are associated with potential adverse effects, including C. difficile colitis, impacts on bone health, renal impairment, and mineral deficiencies. While these risks must be carefully discussed with patients, the benefits of medical therapy far outweigh the risks, especially for those with erosive esophagitis, Barrett’s esophagus, or a high-risk profile for esophageal cancer. In such cases, medical therapies provide superior disease control compared to lifestyle measures, supported by both subjective and objective data.

Managing GERD requires a multipronged approach. Relying solely on lifestyle measures rarely provides complete benefit, as restrictive dietary regimens are difficult to sustain long term. Like many, I can maintain a restrictive diet temporarily but find it unsustainable over time. Conversely, adherence to daily or twice-daily medications tends to be much higher than compliance with multi-level lifestyle changes (e.g., restrictive diets, weight loss, and trigger-food avoidance).

Our therapeutic arsenal for GERD continues to expand, enabling more effective management of patients with uncontrolled acid reflux. While I will continue to counsel patients and educate trainees on the value of lifestyle modifications, I emphasize the importance of adherence to timely medical therapy — whether with PPIs, H2RAs, or PCABs — as the cornerstone of effective GERD treatment.

Dr. Patel is associate program director in the division of digestive diseases & nutrition, at USF Health, Tampa, Fla. He declares no conflicts of interest.

Dear colleagues,

Gastroesophageal reflux disease (GERD) is a common reason for referral to gastroenterology. It affects a broad cross-section of our population and is often managed through a combination of lifestyle modifications and proton pump inhibitors (PPIs). However, in the era of PPIs, we must ask: Are lifestyle changes still necessary? And were they ever truly effective?

While PPIs are highly effective, concerns about their potential side effects frequently make headlines. Moreover, the financial burden of lifelong PPI use is a growing consideration. In this issue of Perspectives, Dr. Brijesh B. Patel and Dr. Juan D. Gomez Cifuentes explore these questions. Dr. Gomez Cifuentes highlights the benefits of lifestyle changes and identifies which strategies have proved most effective in his practice. Dr. Patel examines the ubiquitous use of PPIs and the challenges of sustaining adherence to lifestyle modifications. We hope these discussions will spark new ideas for managing GERD in your own practice. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Do Lifestyle Changes Still Apply in the Treatment of GERD?

BY JUAN D. GOMEZ CIFUENTES, MD

Lifestyle changes are an essential part of managing gastroesophageal reflux disease (GERD). Increasingly, patients are asking about non-medication approaches to control their symptoms. These lifestyle modifications can be categorized into four main areas: 1) Weight loss, the cornerstone intervention, with significant symptom improvement observed after losing as little as 1.7 BMI points. 2) Dietary modifications, which includes both the traditional avoidance of trigger foods and the newer focus on a diet low in simple carbohydrates. 3) Bedtime adjustments, strategies that include elevating the head of the bed, sleeping on the left side, using anti-reflux pillows, and avoiding late-night meals. 4) Tobacco cessation, a key measure for reducing GERD symptoms and promoting overall health. I routinely discuss these changes with my patients, as they not only help manage GERD but also foster healthy habits and have a positive impact beyond the gastrointestinal tract.

Weight loss is the most impactful lifestyle intervention for GERD. Research shows a clear linear improvement in symptoms with weight reduction. Traditionally, losing 10% of body weight is a widely accepted goal, extrapolated from other obesity-associated conditions. A reduction in 3.5 points of BMI led to significant symptom improvement in landmark studies but also a modest reduction of 1.7 BMI points has been shown to provide symptom relief.¹ Abdominal circumference is another key metric used to track progress, as central obesity rather than BMI alone is strongly linked with GERD. Goals are typically set at less than 40 inches for men and 35 inches for women. Patients using GLP-1 agonists should be informed that these medications may temporarily worsen GERD symptoms due to delayed gastric emptying, however in the long-term these symptoms are expected to improve once significant weight loss is achieved.

Food triggers vary among individuals, with common culprits including fatty meals, spicy foods, chocolate, tomato sauce, citrus fruits, and carbonated beverages. Patients tend to overemphasize diet elimination based on triggers and engage in strict diets. Patients are frequently afraid of these foods causing direct damage to the esophageal mucosa but the hypothesis is that these triggers worsen GERD by increasing transient relaxations of the lower esophageal sphincter. The evidence behind this and diet elimination based on triggers has always been weak. In my practice, I encourage patients to follow a diet low in simple carbohydrates. Simple carbohydrates are present in highly processed food, the average western diet contains ~140 g/day. In a trial, a diet low in simple sugars (monosaccharides and disaccharides < 62 g/day) without reducing total daily calories, objectively improved total acid exposure time in pH study.²

Thanks to gravity, nocturnal GERD symptoms are the culprit of many restless nights in these patients. I recommend avoiding food 3 hours before lying down. Since the stomach empties approximately 90% of its contents after 4 hours, waiting longer is not recommended and may result in hunger, making it harder to fall asleep. Sleeping on the left side, which takes advantage of the gastric anatomy, has proved to objectively decrease nocturnal acid exposure time, though some patients may find it challenging to maintain this position all night.³

Elevating the head of the bed is another effective intervention, but it must involve raising the upper body from the waist. Patients should avoid stacking ordinary pillows as this will only elevate the neck and place the body in an unnatural position for sleeping. The most effective strategies are putting blocks/bricks under the feet of the bed, using a bed wedge between the mattress and the box spring or using an adjustable bed frame. There are two types of pillows that have been shown to improve nocturnal GERD symptoms. The classic wedge pillows and the more expensive Medcline reflux relief system®. The Medcline pillow has a dual mechanism that elevates the upper body but also keeps the body on the left side position.⁴

Tobacco cessation is strongly recommended. Tobacco worsens GERD symptoms by reducing the lower esophageal sphincter pressure and decreasing saliva production which is one of the key components of the normal esophageal acid barrier. Moreover, it is a known risk factor for esophageal cancer. Alcohol has a variety of negative health impacts and decreasing alcohol intake is advised; however, the link between alcohol and GERD symptoms is less robust, especially in patients with low occasional consumption.

In summary, lifestyle modifications play a pivotal role in managing GERD symptoms, offering patients effective, non-pharmacologic strategies to complement medical treatments. Weight loss remains the cornerstone, with even modest reductions in BMI showing significant symptom relief. Dietary adjustments, particularly adopting a low-simple-carbohydrate diet, provide an evidence-based approach. Various bedtime interventions are available to improve nocturnal GERD symptoms. Finally, tobacco cessation is essential, not only for GERD symptom relief but also for overall health. By integrating these lifestyle changes into their routine, patients can improve GERD symptoms while building healthy habits.

Dr. Gomez Cifuentes is vice-chair in the section of gastroenterology at Presbyterian Healthcare Services, Albuquerque, New Mexico. He declares no conflicts of interest.

References

1. Ness-Jensen E et al. Lifestyle Intervention in Gastroesophageal Reflux Disease. Clin Gastroenterol Hepatol. 2016 Feb;14(2):175-82.e1-3. doi: 10.1016/j.cgh.2015.04.176.

2. Gu C et al. The Effects of Modifying Amount and Type of Dietary Carbohydrate on Esophageal Acid Exposure Time and Esophageal Reflux Symptoms: A Randomized Controlled Trial. Am J Gastroenterol. 2022 Oct 1;117(10):1655-1667. doi: 10.14309/ajg.0000000000001889.

3. Schuitenmaker JM et al. Associations Between Sleep Position and Nocturnal Gastroesophageal Reflux: A Study Using Concurrent Monitoring of Sleep Position and Esophageal pH and Impedance. Am J Gastroenterol. 2022 Feb 1;117(2):346-351. doi: 10.14309/ajg.0000000000001588.

4. Person E et al. A Novel Sleep Positioning Device Reduces Gastroesophageal Reflux: A Randomized Controlled Trial. J Clin Gastroenterol. 2015 Sep;49(8):655-9. doi: 10.1097/MCG.0000000000000359.

Medical Therapy Is the Cornerstone of Effective GERD Treatment

BY BRIJESH B. PATEL, MD

Today, I saw Mr. S in the office for gastroesophageal reflux disease (GERD). He has been on a trial of proton pump inhibitors (PPIs) and has implemented several lifestyle modifications to manage his reflux. He shared his frustrations, saying, “Doctor, I’ve tried changing my diet, sleeping in a recliner, and adjusting the timing of my meals. I’m practically not enjoying food anymore, and these lifestyle changes have affected my quality of life. Despite all this, I still wake up in the middle of the night with a ‘horrible taste’ in my mouth, and it’s ruining my sleep.”

Later that day, during a discussion with my trainees, one posed an important question: “What about lifestyle measures in the treatment of GERD?” This is a common query in both clinical and academic settings. GERD, with a prevalence estimated at ~20%, is often underreported as many patients begin self-medicating with over-the-counter acid suppressive therapies before seeking medical care. For gastroenterologists, PPIs, histamine-2 receptor antagonists (H2RAs), and now potassium-competitive acid blockers (PCABs) form the cornerstone of GERD management.

When I lecture medical students, residents, and fellows about GERD, I emphasize a standard approach: initiating an 8- to 12-week trial of PPIs followed by reassessment. I also stress the importance of combining medical therapy with lifestyle measures. However, the question remains: How adherent are our patients to these lifestyle changes? Similarly, how effectively are trainees integrating the value of lifestyle modifications into their practice? As an academic gastroenterologist, I can teach the theory, but is it being translated into real-world patient care?

The advent of PPIs has been a game changer for managing GERD symptoms and preventing disease progression. PPIs are the backbone of treatment in both gastroenterology and primary care, and they have profoundly improved patients’ quality of life. Most of my patients who present with GERD — whether due to uncontrolled reflux or acid exposure — have already been on a trial of PPIs before seeing me. My role often involves optimizing their timing of PPI administration, addressing incorrect usage, and reinforcing the importance of adherence. In some cases, I incorporate H2RAs as adjunctive therapy for patients who fail to respond adequately to PPIs, particularly when objective disease activity is confirmed through pH studies. These studies also highlight how challenging it is for many patients to maintain a refluxogenic-free lifestyle.

Lifestyle modifications should supplement and support GERD management. Regardless of medical specialty, lifestyle measures should be the first line of treatment. However, adherence and effectiveness vary widely. In reality, achieving sustained weight loss, meal timing adjustments, and dietary modifications (e.g., eliminating trigger foods like red wine, chocolate, coffee, and tomato-based sauces) is a significant challenge for patients. While these measures can reduce the need for PPIs in some cases, they are rarely sufficient as standalone treatments. Until lifestyle modifications are consistently and sustainably incorporated into daily routines, acid-suppressive therapy will remain the mainstay of GERD management.

Turning to newer therapies, PCABs are now FDA-approved for treating GERD. Early efficacy data suggest that PCABs are non-inferior to PPIs, with promising results in managing LA Class C and D esophagitis and maintaining symptom-free days. However, like PPIs, PCABs are associated with potential adverse effects, including C. difficile colitis, impacts on bone health, renal impairment, and mineral deficiencies. While these risks must be carefully discussed with patients, the benefits of medical therapy far outweigh the risks, especially for those with erosive esophagitis, Barrett’s esophagus, or a high-risk profile for esophageal cancer. In such cases, medical therapies provide superior disease control compared to lifestyle measures, supported by both subjective and objective data.

Managing GERD requires a multipronged approach. Relying solely on lifestyle measures rarely provides complete benefit, as restrictive dietary regimens are difficult to sustain long term. Like many, I can maintain a restrictive diet temporarily but find it unsustainable over time. Conversely, adherence to daily or twice-daily medications tends to be much higher than compliance with multi-level lifestyle changes (e.g., restrictive diets, weight loss, and trigger-food avoidance).

Our therapeutic arsenal for GERD continues to expand, enabling more effective management of patients with uncontrolled acid reflux. While I will continue to counsel patients and educate trainees on the value of lifestyle modifications, I emphasize the importance of adherence to timely medical therapy — whether with PPIs, H2RAs, or PCABs — as the cornerstone of effective GERD treatment.

Dr. Patel is associate program director in the division of digestive diseases & nutrition, at USF Health, Tampa, Fla. He declares no conflicts of interest.