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Random Biopsy Improves IBD Dysplasia Detection, With Caveats
according to a recent review and meta-analysis.
Random biopsies collected in studies after 2011 provided limited additional yield, suggesting that high-definition equipment alone may be sufficient to achieve a high detection rate, lead author Li Gao, MD, of Air Force Medical University, Xi’an, China, and colleagues reported. In contrast, patients with primary sclerosing cholangitis (PSC) consistently benefited from random biopsy, offering clearer support for use in this subgroup.
“Random biopsy has been proposed as a strategy that may detect dysplastic lesions that cannot be identified endoscopically, thus minimizing the occurrence of missed colitis-associated dysplasia during colonoscopy,” the investigators wrote in Clinical Gastroenterology and Hepatology. However, the role of random biopsies in colonoscopic surveillance for patients with IBD remains a topic of ongoing debate.”
The SCENIC guidelines remain inconclusive on the role of random biopsy in IBD surveillance, the investigators noted, while other guidelines recommend random biopsy with high-definition white light endoscopy, but not chromoendoscopy.
The present meta-analysis aimed to characterize the impact of random biopsy on dysplasia detection. The investigators aggregated prospective and retrospective studies published in English through September 2023, all of which compared random biopsy with other surveillance techniques and reported the proportion of dysplasia detected exclusively through random biopsy.
“To the best of our knowledge, this systematic review and meta-analysis was the first comprehensive summary of the additional yield of random biopsy during colorectal cancer surveillance in patients with IBD,” Dr. Gao and colleagues noted.
The final dataset comprised 37 studies with 9,051 patients undergoing colorectal cancer surveillance for IBD. Patients had diverse baseline characteristics, including different proportions of ulcerative colitis and Crohn’s disease, as well as varying prevalence of PSC, a known risk factor for colorectal neoplasia.
The pooled additional yield of random biopsy was 10.34% in per-patient analysis and 16.20% in per-lesion analysis, meaning that approximately 1 in 10 patients and 1 in 6 lesions were detected exclusively through random biopsy. Despite these benefits, detection rates were relatively low: 1.31% per patient and 2.82% per lesion.
Subgroup analyses showed a decline in random biopsy additional yield over time. Studies conducted before 2011 reported an additional yield of 14.43% in per-patient analysis, compared to just 0.42% in studies conducted after 2011. This decline coincided with the widespread adoption of high-definition endoscopy.
PSC status strongly influenced detection rates throughout the study period. In patients without PSC (0%-10% PSC prevalence), the additional yield of random biopsy was 4.83% in per-patient analysis and 11.23% in per-lesion analysis. In studies where all patients had PSC, the additional yield increased dramatically to 56.05% and 45.22%, respectively.
“These findings highlight the incremental benefits of random biopsy and provide valuable insights into the management of endoscopic surveillance in patients with IBD,” the investigators wrote. “Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating random biopsy in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.”This study was supported by the National Key R&D Program of China, the Key Research and Development Program of Shaanxi Province, and the Nanchang High-Level Scientific and Technological Innovation Talents “Double Hundred Plan” project. The investigators disclosed no conflicts of interest.
Patients with inflammatory bowel diseases (IBD) with colonic involvement are at two- to threefold increased risk of colorectal cancer (CRC), compared with the general population. The development and progression of dysplasia in these patients with IBD does not follow the typical adenoma-carcinoma sequence; rather, patients with IBD at increased risk of colorectal cancer may have field cancerization changes. Historically, these mucosal changes have been difficult to visualize endoscopically, at least with standard definition endoscopes. As a result, systematic, four-quadrant, random biopsies — 8 in each segment of the colon, totaling to 32 biopsies — are recommended for dysplasia detection. The practice has been adopted and accepted widely. Over time, there have been significant advancements in the management of IBD, with improved colonoscopic resolution, adjunct surveillance techniques, focus on quality of colonoscopic exams and evolution of treatments and treatment targets, and these have resulted in a reduction in the risk of CRC in patients with IBD. The value of random biopsies for dysplasia surveillance in patients with colonic IBD has been questioned.
In this context, the systematic review and meta-analysis from Gao and colleagues provides critical insights into the yield of random biopsies for dysplasia surveillance in patients with IBD. Through a detailed analysis of 37 studies published between 2003 to 2023, with 9051 patients who underwent dysplasia surveillance with random biopsies, they ascertained the incremental yield of random biopsies. Overall, 1.3% of patients who underwent random biopsies were detected to have dysplasia. Of these, 1 in 10 patients were detected to have dysplasia only on random biopsies. On per-lesion analysis, one in six dysplastic lesions were only detected on random biopsies. Interestingly, this yield of random biopsies varied markedly depending on the era, as a surrogate for quality of colonoscopies. In studies that fully enrolled and published before 2011 (majority of patients recruited in the 1990s to early 2000s), the per-patient incremental yield of random biopsies was 14%; this dropped precipitously to 0.4% in studies published after 2011 (majority of patients recruited in late 2000s to 2010s). The incremental yield of random biopsies remained markedly high in studies with a high proportion of patients with primary sclerosing cholangitis (PSC), a condition consistently associated with a four- to sixfold higher risk of CRC in patients with IBD.
These findings lend support to the notion that improvements in endoscopy equipment with wide adoption of high-definition white-light colonoscopes and an emphasis on quality of endoscopic examination may be leading to better endoscopic detection of previously “invisible” dysplastic lesions, leading to a markedly lower incremental yield of random biopsies in the current era. This questions the utility of routinely collecting 32 random biopsies during a surveillance exam for a patient with IBD at increased risk of CRC (as long as a thorough high-quality exam is being performed), though there may be subpopulations such as patients with PSC where there may be benefit. Large ongoing trials comparing the yield of targeted biopsies vs random and targeted biopsies in patients with IBD undergoing dysplasia surveillance with high-definition colonoscopes will help to definitively address this question.
Siddharth Singh, MD, MS, is associate professor of medicine and director of the UCSD IBD Center in the division of gastroenterology, University of California, San Diego. He declares no conflicts of interest relative to this article.
Patients with inflammatory bowel diseases (IBD) with colonic involvement are at two- to threefold increased risk of colorectal cancer (CRC), compared with the general population. The development and progression of dysplasia in these patients with IBD does not follow the typical adenoma-carcinoma sequence; rather, patients with IBD at increased risk of colorectal cancer may have field cancerization changes. Historically, these mucosal changes have been difficult to visualize endoscopically, at least with standard definition endoscopes. As a result, systematic, four-quadrant, random biopsies — 8 in each segment of the colon, totaling to 32 biopsies — are recommended for dysplasia detection. The practice has been adopted and accepted widely. Over time, there have been significant advancements in the management of IBD, with improved colonoscopic resolution, adjunct surveillance techniques, focus on quality of colonoscopic exams and evolution of treatments and treatment targets, and these have resulted in a reduction in the risk of CRC in patients with IBD. The value of random biopsies for dysplasia surveillance in patients with colonic IBD has been questioned.
In this context, the systematic review and meta-analysis from Gao and colleagues provides critical insights into the yield of random biopsies for dysplasia surveillance in patients with IBD. Through a detailed analysis of 37 studies published between 2003 to 2023, with 9051 patients who underwent dysplasia surveillance with random biopsies, they ascertained the incremental yield of random biopsies. Overall, 1.3% of patients who underwent random biopsies were detected to have dysplasia. Of these, 1 in 10 patients were detected to have dysplasia only on random biopsies. On per-lesion analysis, one in six dysplastic lesions were only detected on random biopsies. Interestingly, this yield of random biopsies varied markedly depending on the era, as a surrogate for quality of colonoscopies. In studies that fully enrolled and published before 2011 (majority of patients recruited in the 1990s to early 2000s), the per-patient incremental yield of random biopsies was 14%; this dropped precipitously to 0.4% in studies published after 2011 (majority of patients recruited in late 2000s to 2010s). The incremental yield of random biopsies remained markedly high in studies with a high proportion of patients with primary sclerosing cholangitis (PSC), a condition consistently associated with a four- to sixfold higher risk of CRC in patients with IBD.
These findings lend support to the notion that improvements in endoscopy equipment with wide adoption of high-definition white-light colonoscopes and an emphasis on quality of endoscopic examination may be leading to better endoscopic detection of previously “invisible” dysplastic lesions, leading to a markedly lower incremental yield of random biopsies in the current era. This questions the utility of routinely collecting 32 random biopsies during a surveillance exam for a patient with IBD at increased risk of CRC (as long as a thorough high-quality exam is being performed), though there may be subpopulations such as patients with PSC where there may be benefit. Large ongoing trials comparing the yield of targeted biopsies vs random and targeted biopsies in patients with IBD undergoing dysplasia surveillance with high-definition colonoscopes will help to definitively address this question.
Siddharth Singh, MD, MS, is associate professor of medicine and director of the UCSD IBD Center in the division of gastroenterology, University of California, San Diego. He declares no conflicts of interest relative to this article.
Patients with inflammatory bowel diseases (IBD) with colonic involvement are at two- to threefold increased risk of colorectal cancer (CRC), compared with the general population. The development and progression of dysplasia in these patients with IBD does not follow the typical adenoma-carcinoma sequence; rather, patients with IBD at increased risk of colorectal cancer may have field cancerization changes. Historically, these mucosal changes have been difficult to visualize endoscopically, at least with standard definition endoscopes. As a result, systematic, four-quadrant, random biopsies — 8 in each segment of the colon, totaling to 32 biopsies — are recommended for dysplasia detection. The practice has been adopted and accepted widely. Over time, there have been significant advancements in the management of IBD, with improved colonoscopic resolution, adjunct surveillance techniques, focus on quality of colonoscopic exams and evolution of treatments and treatment targets, and these have resulted in a reduction in the risk of CRC in patients with IBD. The value of random biopsies for dysplasia surveillance in patients with colonic IBD has been questioned.
In this context, the systematic review and meta-analysis from Gao and colleagues provides critical insights into the yield of random biopsies for dysplasia surveillance in patients with IBD. Through a detailed analysis of 37 studies published between 2003 to 2023, with 9051 patients who underwent dysplasia surveillance with random biopsies, they ascertained the incremental yield of random biopsies. Overall, 1.3% of patients who underwent random biopsies were detected to have dysplasia. Of these, 1 in 10 patients were detected to have dysplasia only on random biopsies. On per-lesion analysis, one in six dysplastic lesions were only detected on random biopsies. Interestingly, this yield of random biopsies varied markedly depending on the era, as a surrogate for quality of colonoscopies. In studies that fully enrolled and published before 2011 (majority of patients recruited in the 1990s to early 2000s), the per-patient incremental yield of random biopsies was 14%; this dropped precipitously to 0.4% in studies published after 2011 (majority of patients recruited in late 2000s to 2010s). The incremental yield of random biopsies remained markedly high in studies with a high proportion of patients with primary sclerosing cholangitis (PSC), a condition consistently associated with a four- to sixfold higher risk of CRC in patients with IBD.
These findings lend support to the notion that improvements in endoscopy equipment with wide adoption of high-definition white-light colonoscopes and an emphasis on quality of endoscopic examination may be leading to better endoscopic detection of previously “invisible” dysplastic lesions, leading to a markedly lower incremental yield of random biopsies in the current era. This questions the utility of routinely collecting 32 random biopsies during a surveillance exam for a patient with IBD at increased risk of CRC (as long as a thorough high-quality exam is being performed), though there may be subpopulations such as patients with PSC where there may be benefit. Large ongoing trials comparing the yield of targeted biopsies vs random and targeted biopsies in patients with IBD undergoing dysplasia surveillance with high-definition colonoscopes will help to definitively address this question.
Siddharth Singh, MD, MS, is associate professor of medicine and director of the UCSD IBD Center in the division of gastroenterology, University of California, San Diego. He declares no conflicts of interest relative to this article.
according to a recent review and meta-analysis.
Random biopsies collected in studies after 2011 provided limited additional yield, suggesting that high-definition equipment alone may be sufficient to achieve a high detection rate, lead author Li Gao, MD, of Air Force Medical University, Xi’an, China, and colleagues reported. In contrast, patients with primary sclerosing cholangitis (PSC) consistently benefited from random biopsy, offering clearer support for use in this subgroup.
“Random biopsy has been proposed as a strategy that may detect dysplastic lesions that cannot be identified endoscopically, thus minimizing the occurrence of missed colitis-associated dysplasia during colonoscopy,” the investigators wrote in Clinical Gastroenterology and Hepatology. However, the role of random biopsies in colonoscopic surveillance for patients with IBD remains a topic of ongoing debate.”
The SCENIC guidelines remain inconclusive on the role of random biopsy in IBD surveillance, the investigators noted, while other guidelines recommend random biopsy with high-definition white light endoscopy, but not chromoendoscopy.
The present meta-analysis aimed to characterize the impact of random biopsy on dysplasia detection. The investigators aggregated prospective and retrospective studies published in English through September 2023, all of which compared random biopsy with other surveillance techniques and reported the proportion of dysplasia detected exclusively through random biopsy.
“To the best of our knowledge, this systematic review and meta-analysis was the first comprehensive summary of the additional yield of random biopsy during colorectal cancer surveillance in patients with IBD,” Dr. Gao and colleagues noted.
The final dataset comprised 37 studies with 9,051 patients undergoing colorectal cancer surveillance for IBD. Patients had diverse baseline characteristics, including different proportions of ulcerative colitis and Crohn’s disease, as well as varying prevalence of PSC, a known risk factor for colorectal neoplasia.
The pooled additional yield of random biopsy was 10.34% in per-patient analysis and 16.20% in per-lesion analysis, meaning that approximately 1 in 10 patients and 1 in 6 lesions were detected exclusively through random biopsy. Despite these benefits, detection rates were relatively low: 1.31% per patient and 2.82% per lesion.
Subgroup analyses showed a decline in random biopsy additional yield over time. Studies conducted before 2011 reported an additional yield of 14.43% in per-patient analysis, compared to just 0.42% in studies conducted after 2011. This decline coincided with the widespread adoption of high-definition endoscopy.
PSC status strongly influenced detection rates throughout the study period. In patients without PSC (0%-10% PSC prevalence), the additional yield of random biopsy was 4.83% in per-patient analysis and 11.23% in per-lesion analysis. In studies where all patients had PSC, the additional yield increased dramatically to 56.05% and 45.22%, respectively.
“These findings highlight the incremental benefits of random biopsy and provide valuable insights into the management of endoscopic surveillance in patients with IBD,” the investigators wrote. “Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating random biopsy in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.”This study was supported by the National Key R&D Program of China, the Key Research and Development Program of Shaanxi Province, and the Nanchang High-Level Scientific and Technological Innovation Talents “Double Hundred Plan” project. The investigators disclosed no conflicts of interest.
according to a recent review and meta-analysis.
Random biopsies collected in studies after 2011 provided limited additional yield, suggesting that high-definition equipment alone may be sufficient to achieve a high detection rate, lead author Li Gao, MD, of Air Force Medical University, Xi’an, China, and colleagues reported. In contrast, patients with primary sclerosing cholangitis (PSC) consistently benefited from random biopsy, offering clearer support for use in this subgroup.
“Random biopsy has been proposed as a strategy that may detect dysplastic lesions that cannot be identified endoscopically, thus minimizing the occurrence of missed colitis-associated dysplasia during colonoscopy,” the investigators wrote in Clinical Gastroenterology and Hepatology. However, the role of random biopsies in colonoscopic surveillance for patients with IBD remains a topic of ongoing debate.”
The SCENIC guidelines remain inconclusive on the role of random biopsy in IBD surveillance, the investigators noted, while other guidelines recommend random biopsy with high-definition white light endoscopy, but not chromoendoscopy.
The present meta-analysis aimed to characterize the impact of random biopsy on dysplasia detection. The investigators aggregated prospective and retrospective studies published in English through September 2023, all of which compared random biopsy with other surveillance techniques and reported the proportion of dysplasia detected exclusively through random biopsy.
“To the best of our knowledge, this systematic review and meta-analysis was the first comprehensive summary of the additional yield of random biopsy during colorectal cancer surveillance in patients with IBD,” Dr. Gao and colleagues noted.
The final dataset comprised 37 studies with 9,051 patients undergoing colorectal cancer surveillance for IBD. Patients had diverse baseline characteristics, including different proportions of ulcerative colitis and Crohn’s disease, as well as varying prevalence of PSC, a known risk factor for colorectal neoplasia.
The pooled additional yield of random biopsy was 10.34% in per-patient analysis and 16.20% in per-lesion analysis, meaning that approximately 1 in 10 patients and 1 in 6 lesions were detected exclusively through random biopsy. Despite these benefits, detection rates were relatively low: 1.31% per patient and 2.82% per lesion.
Subgroup analyses showed a decline in random biopsy additional yield over time. Studies conducted before 2011 reported an additional yield of 14.43% in per-patient analysis, compared to just 0.42% in studies conducted after 2011. This decline coincided with the widespread adoption of high-definition endoscopy.
PSC status strongly influenced detection rates throughout the study period. In patients without PSC (0%-10% PSC prevalence), the additional yield of random biopsy was 4.83% in per-patient analysis and 11.23% in per-lesion analysis. In studies where all patients had PSC, the additional yield increased dramatically to 56.05% and 45.22%, respectively.
“These findings highlight the incremental benefits of random biopsy and provide valuable insights into the management of endoscopic surveillance in patients with IBD,” the investigators wrote. “Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating random biopsy in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.”This study was supported by the National Key R&D Program of China, the Key Research and Development Program of Shaanxi Province, and the Nanchang High-Level Scientific and Technological Innovation Talents “Double Hundred Plan” project. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Hispanic Patients Face Disparities in MASLD
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.
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.
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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Liver Stiffness Measurement Predicts Long-Term Outcomes In Pediatric 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.
Grading liver stiffness using elastography is a widely utilized tool in adult populations, and its application is expanding in pediatric hepatology clinics. Clinicians incorporate liver stiffness measurements (LSM) alongside clinical findings and biochemical markers to noninvasively assess the degree of hepatic fibrosis and cirrhosis. Molleston and colleagues leveraged the robust data from the National Institute of Diabetes and Digestive and Kidney Diseases–supported network ChiLDReN and found that LSM in children with biliary atresia (BA) correlate with the progression to complications associated with portal hypertension and liver transplantation. While these findings are not unexpected, this compelling investigation accomplishes the important function of validating the utility of elastography in this cohort.
Prognosticating the timeline of complications stemming from biliary atresia is a central tenet of pediatric hepatology. Helping families understand what the future may hold for their child is critical in fostering long-term relationships between clinicians and caregivers. Furthermore, establishing clear expectations regarding follow-up care and monitoring is beneficial for both providers and patients. Of particular importance is minimizing the need for invasive procedures, such as liver biopsy, which, while relatively safe, remains burdensome and is rarely used to assess fibrosis in BA.
Pediatric hepatologists already consider multiple factors — including age at hepatoportoenterostomy, subsequent clearance of cholestasis, exam findings such as splenomegaly, and platelet count — to predict the clinical course of infants with BA. The addition of a data-driven approach to interpreting liver stiffness measurements represents a valuable new tool in this expanding repertoire, offering an encouraging prospect for both providers and families navigating the complexities of pediatric liver disease.
Aaron Bennett, MD, is a fellow in the Division of Gastroenterology, Hepatology and Nutrition at Children’s Hospital of Philadelphia in Pennsylvania. Elizabeth B. Rand, MD, is the medical director of the Liver Transplant Program, director of the Gastroenterology Fellowship Program, and director of the Advanced Transplant Hepatology Program at Children’s Hospital of Philadelphia.
Grading liver stiffness using elastography is a widely utilized tool in adult populations, and its application is expanding in pediatric hepatology clinics. Clinicians incorporate liver stiffness measurements (LSM) alongside clinical findings and biochemical markers to noninvasively assess the degree of hepatic fibrosis and cirrhosis. Molleston and colleagues leveraged the robust data from the National Institute of Diabetes and Digestive and Kidney Diseases–supported network ChiLDReN and found that LSM in children with biliary atresia (BA) correlate with the progression to complications associated with portal hypertension and liver transplantation. While these findings are not unexpected, this compelling investigation accomplishes the important function of validating the utility of elastography in this cohort.
Prognosticating the timeline of complications stemming from biliary atresia is a central tenet of pediatric hepatology. Helping families understand what the future may hold for their child is critical in fostering long-term relationships between clinicians and caregivers. Furthermore, establishing clear expectations regarding follow-up care and monitoring is beneficial for both providers and patients. Of particular importance is minimizing the need for invasive procedures, such as liver biopsy, which, while relatively safe, remains burdensome and is rarely used to assess fibrosis in BA.
Pediatric hepatologists already consider multiple factors — including age at hepatoportoenterostomy, subsequent clearance of cholestasis, exam findings such as splenomegaly, and platelet count — to predict the clinical course of infants with BA. The addition of a data-driven approach to interpreting liver stiffness measurements represents a valuable new tool in this expanding repertoire, offering an encouraging prospect for both providers and families navigating the complexities of pediatric liver disease.
Aaron Bennett, MD, is a fellow in the Division of Gastroenterology, Hepatology and Nutrition at Children’s Hospital of Philadelphia in Pennsylvania. Elizabeth B. Rand, MD, is the medical director of the Liver Transplant Program, director of the Gastroenterology Fellowship Program, and director of the Advanced Transplant Hepatology Program at Children’s Hospital of Philadelphia.
Grading liver stiffness using elastography is a widely utilized tool in adult populations, and its application is expanding in pediatric hepatology clinics. Clinicians incorporate liver stiffness measurements (LSM) alongside clinical findings and biochemical markers to noninvasively assess the degree of hepatic fibrosis and cirrhosis. Molleston and colleagues leveraged the robust data from the National Institute of Diabetes and Digestive and Kidney Diseases–supported network ChiLDReN and found that LSM in children with biliary atresia (BA) correlate with the progression to complications associated with portal hypertension and liver transplantation. While these findings are not unexpected, this compelling investigation accomplishes the important function of validating the utility of elastography in this cohort.
Prognosticating the timeline of complications stemming from biliary atresia is a central tenet of pediatric hepatology. Helping families understand what the future may hold for their child is critical in fostering long-term relationships between clinicians and caregivers. Furthermore, establishing clear expectations regarding follow-up care and monitoring is beneficial for both providers and patients. Of particular importance is minimizing the need for invasive procedures, such as liver biopsy, which, while relatively safe, remains burdensome and is rarely used to assess fibrosis in BA.
Pediatric hepatologists already consider multiple factors — including age at hepatoportoenterostomy, subsequent clearance of cholestasis, exam findings such as splenomegaly, and platelet count — to predict the clinical course of infants with BA. The addition of a data-driven approach to interpreting liver stiffness measurements represents a valuable new tool in this expanding repertoire, offering an encouraging prospect for both providers and families navigating the complexities of pediatric liver disease.
Aaron Bennett, MD, is a fellow in the Division of Gastroenterology, Hepatology and Nutrition at Children’s Hospital of Philadelphia in Pennsylvania. Elizabeth B. Rand, MD, is the medical director of the Liver Transplant Program, director of the Gastroenterology Fellowship Program, and director of the Advanced Transplant Hepatology Program at Children’s Hospital of Philadelphia.
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.
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.
FROM GASTROENTEROLOGY
Lipophilic Statins May Protect Against HCC In Select Liver Disease Patients
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
Digestive Disease Mortality Higher for US Indigenous Communities
which experience the highest death rates and ongoing increases, according to a recent study.
Policymakers, healthcare providers, and communities need to respond with targeted interventions and collaborative efforts that address these inequities and advance digestive health equity, lead author Wafa A. Aldhaleei, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues reported.
“Several studies have reported the epidemiological characteristics of certain digestive diseases such as pancreatitis, liver and biliary diseases, and inflammatory bowel disease,” the investigators wrote in Clinical Gastroenterology and Hepatology. “These studies provide insights into the US burden by sex and racial and ethnic disparities of various digestive diseases individually. However, little is known about racial disparities in the United States digestive diseases mortality burden.”
As part of the Global Burden of Disease Study, the investigators analyzed data from the Institute of Health Metrics and Evaluation Global Health Data Exchange, including age-standardized digestive disease mortality rates for five racial and ethnic groups (Black, White, American Indian and Alaska Native, Asian and Pacific Islander, and Latino) between 2000 and 2019, with further subgroups based on sex, state, and county. Joinpoint regression analysis was employed to determine overall temporal trends by demography.
Results showed striking mortality rate differences across racial and ethnic groups. In 2019, digestive disease mortality rates were highest among American Indian and Alaska Native individuals, reaching 86.2 per 100,000 — over twice the rate seen in White (35.5 per 100,000), Black (33.6 per 100,000), and Latino (33.6 per 100,000) populations, and more than five times higher than in Asian and Pacific Islander individuals (15.6 per 100,000). Over the study period, American Indian and Alaska Native individuals experienced a significant 0.87% average annual increase in mortality rates, while White individuals saw a smaller increase of 0.12% annually. In contrast, Latino, Black, and Asian and Pacific Islander individuals had declining average annual rates.
Geographic disparities in digestive disease mortality were significant, with West Virginia recording the highest state-level rate in 2019 at 44.8 deaths per 100,000, well above the national rate of 34.5 per 100,000. Certain regions with high concentrations of American Indian and Alaska Native populations, such as the Southwest Tribes service area (including Arizona and New Mexico) and the Plain Indians service area (spanning Montana, North Dakota, and South Dakota), reported mortality rates exceeding 70 per 100,000, more than double the national average. In Alaska, the American Indian and Alaska Native population’s mortality rate surged with annual increases of up to 3.53% during some periods.
Analyses also revealed some notable sex-based trends. Among American Indian and Alaska Native individuals, males experienced a mortality rate increase of 0.87% annually, reaching 93.5 per 100,000 by 2019, while females saw an even sharper rise at 1.11% per year, with a mortality rate of 79.6 per 100,000 in 2019. For White individuals, the average annual percentage increase was 0.12% for males, bringing their rate to 40.2 per 100,000, and 0.30% for females, with a rate of 31.0 per 100,000 in 2019.
“Our study reveals persistent racial, ethnic, and geographic disparities in digestive diseases mortality in the United States,” the investigators concluded. “Targeted interventions and further research are needed to address these disparities and promote digestive health equity. Collaboration among researchers, policymakers, healthcare providers, and communities is essential to achieve this goal.”This research was conducted as part of Global Burden of Disease, Injuries and Risk Factors Study, coordinated by the Institute of Health Metrics and Evaluation. The investigators disclosed no conflicts of interest.
which experience the highest death rates and ongoing increases, according to a recent study.
Policymakers, healthcare providers, and communities need to respond with targeted interventions and collaborative efforts that address these inequities and advance digestive health equity, lead author Wafa A. Aldhaleei, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues reported.
“Several studies have reported the epidemiological characteristics of certain digestive diseases such as pancreatitis, liver and biliary diseases, and inflammatory bowel disease,” the investigators wrote in Clinical Gastroenterology and Hepatology. “These studies provide insights into the US burden by sex and racial and ethnic disparities of various digestive diseases individually. However, little is known about racial disparities in the United States digestive diseases mortality burden.”
As part of the Global Burden of Disease Study, the investigators analyzed data from the Institute of Health Metrics and Evaluation Global Health Data Exchange, including age-standardized digestive disease mortality rates for five racial and ethnic groups (Black, White, American Indian and Alaska Native, Asian and Pacific Islander, and Latino) between 2000 and 2019, with further subgroups based on sex, state, and county. Joinpoint regression analysis was employed to determine overall temporal trends by demography.
Results showed striking mortality rate differences across racial and ethnic groups. In 2019, digestive disease mortality rates were highest among American Indian and Alaska Native individuals, reaching 86.2 per 100,000 — over twice the rate seen in White (35.5 per 100,000), Black (33.6 per 100,000), and Latino (33.6 per 100,000) populations, and more than five times higher than in Asian and Pacific Islander individuals (15.6 per 100,000). Over the study period, American Indian and Alaska Native individuals experienced a significant 0.87% average annual increase in mortality rates, while White individuals saw a smaller increase of 0.12% annually. In contrast, Latino, Black, and Asian and Pacific Islander individuals had declining average annual rates.
Geographic disparities in digestive disease mortality were significant, with West Virginia recording the highest state-level rate in 2019 at 44.8 deaths per 100,000, well above the national rate of 34.5 per 100,000. Certain regions with high concentrations of American Indian and Alaska Native populations, such as the Southwest Tribes service area (including Arizona and New Mexico) and the Plain Indians service area (spanning Montana, North Dakota, and South Dakota), reported mortality rates exceeding 70 per 100,000, more than double the national average. In Alaska, the American Indian and Alaska Native population’s mortality rate surged with annual increases of up to 3.53% during some periods.
Analyses also revealed some notable sex-based trends. Among American Indian and Alaska Native individuals, males experienced a mortality rate increase of 0.87% annually, reaching 93.5 per 100,000 by 2019, while females saw an even sharper rise at 1.11% per year, with a mortality rate of 79.6 per 100,000 in 2019. For White individuals, the average annual percentage increase was 0.12% for males, bringing their rate to 40.2 per 100,000, and 0.30% for females, with a rate of 31.0 per 100,000 in 2019.
“Our study reveals persistent racial, ethnic, and geographic disparities in digestive diseases mortality in the United States,” the investigators concluded. “Targeted interventions and further research are needed to address these disparities and promote digestive health equity. Collaboration among researchers, policymakers, healthcare providers, and communities is essential to achieve this goal.”This research was conducted as part of Global Burden of Disease, Injuries and Risk Factors Study, coordinated by the Institute of Health Metrics and Evaluation. The investigators disclosed no conflicts of interest.
which experience the highest death rates and ongoing increases, according to a recent study.
Policymakers, healthcare providers, and communities need to respond with targeted interventions and collaborative efforts that address these inequities and advance digestive health equity, lead author Wafa A. Aldhaleei, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues reported.
“Several studies have reported the epidemiological characteristics of certain digestive diseases such as pancreatitis, liver and biliary diseases, and inflammatory bowel disease,” the investigators wrote in Clinical Gastroenterology and Hepatology. “These studies provide insights into the US burden by sex and racial and ethnic disparities of various digestive diseases individually. However, little is known about racial disparities in the United States digestive diseases mortality burden.”
As part of the Global Burden of Disease Study, the investigators analyzed data from the Institute of Health Metrics and Evaluation Global Health Data Exchange, including age-standardized digestive disease mortality rates for five racial and ethnic groups (Black, White, American Indian and Alaska Native, Asian and Pacific Islander, and Latino) between 2000 and 2019, with further subgroups based on sex, state, and county. Joinpoint regression analysis was employed to determine overall temporal trends by demography.
Results showed striking mortality rate differences across racial and ethnic groups. In 2019, digestive disease mortality rates were highest among American Indian and Alaska Native individuals, reaching 86.2 per 100,000 — over twice the rate seen in White (35.5 per 100,000), Black (33.6 per 100,000), and Latino (33.6 per 100,000) populations, and more than five times higher than in Asian and Pacific Islander individuals (15.6 per 100,000). Over the study period, American Indian and Alaska Native individuals experienced a significant 0.87% average annual increase in mortality rates, while White individuals saw a smaller increase of 0.12% annually. In contrast, Latino, Black, and Asian and Pacific Islander individuals had declining average annual rates.
Geographic disparities in digestive disease mortality were significant, with West Virginia recording the highest state-level rate in 2019 at 44.8 deaths per 100,000, well above the national rate of 34.5 per 100,000. Certain regions with high concentrations of American Indian and Alaska Native populations, such as the Southwest Tribes service area (including Arizona and New Mexico) and the Plain Indians service area (spanning Montana, North Dakota, and South Dakota), reported mortality rates exceeding 70 per 100,000, more than double the national average. In Alaska, the American Indian and Alaska Native population’s mortality rate surged with annual increases of up to 3.53% during some periods.
Analyses also revealed some notable sex-based trends. Among American Indian and Alaska Native individuals, males experienced a mortality rate increase of 0.87% annually, reaching 93.5 per 100,000 by 2019, while females saw an even sharper rise at 1.11% per year, with a mortality rate of 79.6 per 100,000 in 2019. For White individuals, the average annual percentage increase was 0.12% for males, bringing their rate to 40.2 per 100,000, and 0.30% for females, with a rate of 31.0 per 100,000 in 2019.
“Our study reveals persistent racial, ethnic, and geographic disparities in digestive diseases mortality in the United States,” the investigators concluded. “Targeted interventions and further research are needed to address these disparities and promote digestive health equity. Collaboration among researchers, policymakers, healthcare providers, and communities is essential to achieve this goal.”This research was conducted as part of Global Burden of Disease, Injuries and Risk Factors Study, coordinated by the Institute of Health Metrics and Evaluation. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Human Milk Boosts Intestinal Growth, Immune Health of Fetal Organoids
These findings suggest an important role for human milk in supporting intestinal health, and may inform strategies for reducing the risk of necrotizing enterocolitis (NEC) in preterm infants, lead author Lauren Smith, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Compelling evidence has revealed that the largest risk factor for NEC apart from prematurity is formula feeding, while conversely, parental milk (PM) confers protection, with a 6- to 10-fold lower incidence of NEC among PM-fed infants compared to formula,” the investigators wrote in Gastro Hep Advances. “It is unknown whether this is due to the many known protective factors in PM or as a result of an injurious component present in formula or a combination of both.”
To learn more, the investigators studied organoids cultured in a three-dimensional matrix and exposed to one of four dietary conditions: PM, donor human milk (DHM), standard formula (SF), or extensively hydrolyzed formula (HF). Organoids were grown in growth media supplemented with these diets for 5 days, followed by differentiation media for an additional 5 days. Growth, differentiation, and immune-related factors were analyzed using advanced imaging, RNA sequencing, and cytokine profiling.
The results demonstrated that human milk–fed organoids significantly outperformed formula-fed organoids in several measures. By the fifth day of growth media exposure, organoids supplemented with PM or DHM were larger and exhibited higher rates of proliferation, as evidenced by Ki67 staining. Organoids exposed to SF were the smallest and had the lowest proliferation and highest levels of apoptosis, while HF-fed organoids showed intermediate growth performance.
During the differentiation phase, organoids exposed to human milk developed more complex structures, forming buds with greater length and diameter compared to formula-fed organoids. PM was particularly effective, though DHM also promoted substantial differentiation. RNA sequencing revealed that organoids cultured with human milk upregulated genes involved in fatty acid metabolism and Wnt signaling, which are critical for cellular energy production and epithelial proliferation. In contrast, formula-fed organoids exhibited downregulation of cell-cycle-promoting genes and showed an inflammatory gene signature.
Cytokine profiling further underscored the benefits of human milk. Organoids exposed to PM and DHM secreted higher levels of immune-regulating cytokines, such as thymic stromal lymphopoietin (TSLP) and macrophage colony-stimulating factor (M-CSF). In contrast, formula-fed organoids produced lower levels of these beneficial cytokines and higher levels of pro-inflammatory markers, including interleukin-18 (IL-18).
These findings suggest that human milk supports intestinal growth, differentiation, and immune regulation in ways that formula does not, and the investigators emphasized the importance of identifying specific bioactive factors in human milk.
“If the factors responsible for this effect can be identified, there could be significant clinical value in supplementing these components in DHM and formula to help prevent NEC and foster normal intestinal development in preterm infants,” they concluded.
Future research will aim to isolate and supplement key components of human milk to enhance the nutritional and protective value of donor milk and formula. In addition, the investigators noted the need to explore potential sex-based differences in intestinal development, as the current study used only male-derived samples.The research was supported by the Yale School of Medicine Medical Student Research Fellowship. The investigators disclosed no conflicts of interest.
These findings suggest an important role for human milk in supporting intestinal health, and may inform strategies for reducing the risk of necrotizing enterocolitis (NEC) in preterm infants, lead author Lauren Smith, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Compelling evidence has revealed that the largest risk factor for NEC apart from prematurity is formula feeding, while conversely, parental milk (PM) confers protection, with a 6- to 10-fold lower incidence of NEC among PM-fed infants compared to formula,” the investigators wrote in Gastro Hep Advances. “It is unknown whether this is due to the many known protective factors in PM or as a result of an injurious component present in formula or a combination of both.”
To learn more, the investigators studied organoids cultured in a three-dimensional matrix and exposed to one of four dietary conditions: PM, donor human milk (DHM), standard formula (SF), or extensively hydrolyzed formula (HF). Organoids were grown in growth media supplemented with these diets for 5 days, followed by differentiation media for an additional 5 days. Growth, differentiation, and immune-related factors were analyzed using advanced imaging, RNA sequencing, and cytokine profiling.
The results demonstrated that human milk–fed organoids significantly outperformed formula-fed organoids in several measures. By the fifth day of growth media exposure, organoids supplemented with PM or DHM were larger and exhibited higher rates of proliferation, as evidenced by Ki67 staining. Organoids exposed to SF were the smallest and had the lowest proliferation and highest levels of apoptosis, while HF-fed organoids showed intermediate growth performance.
During the differentiation phase, organoids exposed to human milk developed more complex structures, forming buds with greater length and diameter compared to formula-fed organoids. PM was particularly effective, though DHM also promoted substantial differentiation. RNA sequencing revealed that organoids cultured with human milk upregulated genes involved in fatty acid metabolism and Wnt signaling, which are critical for cellular energy production and epithelial proliferation. In contrast, formula-fed organoids exhibited downregulation of cell-cycle-promoting genes and showed an inflammatory gene signature.
Cytokine profiling further underscored the benefits of human milk. Organoids exposed to PM and DHM secreted higher levels of immune-regulating cytokines, such as thymic stromal lymphopoietin (TSLP) and macrophage colony-stimulating factor (M-CSF). In contrast, formula-fed organoids produced lower levels of these beneficial cytokines and higher levels of pro-inflammatory markers, including interleukin-18 (IL-18).
These findings suggest that human milk supports intestinal growth, differentiation, and immune regulation in ways that formula does not, and the investigators emphasized the importance of identifying specific bioactive factors in human milk.
“If the factors responsible for this effect can be identified, there could be significant clinical value in supplementing these components in DHM and formula to help prevent NEC and foster normal intestinal development in preterm infants,” they concluded.
Future research will aim to isolate and supplement key components of human milk to enhance the nutritional and protective value of donor milk and formula. In addition, the investigators noted the need to explore potential sex-based differences in intestinal development, as the current study used only male-derived samples.The research was supported by the Yale School of Medicine Medical Student Research Fellowship. The investigators disclosed no conflicts of interest.
These findings suggest an important role for human milk in supporting intestinal health, and may inform strategies for reducing the risk of necrotizing enterocolitis (NEC) in preterm infants, lead author Lauren Smith, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Compelling evidence has revealed that the largest risk factor for NEC apart from prematurity is formula feeding, while conversely, parental milk (PM) confers protection, with a 6- to 10-fold lower incidence of NEC among PM-fed infants compared to formula,” the investigators wrote in Gastro Hep Advances. “It is unknown whether this is due to the many known protective factors in PM or as a result of an injurious component present in formula or a combination of both.”
To learn more, the investigators studied organoids cultured in a three-dimensional matrix and exposed to one of four dietary conditions: PM, donor human milk (DHM), standard formula (SF), or extensively hydrolyzed formula (HF). Organoids were grown in growth media supplemented with these diets for 5 days, followed by differentiation media for an additional 5 days. Growth, differentiation, and immune-related factors were analyzed using advanced imaging, RNA sequencing, and cytokine profiling.
The results demonstrated that human milk–fed organoids significantly outperformed formula-fed organoids in several measures. By the fifth day of growth media exposure, organoids supplemented with PM or DHM were larger and exhibited higher rates of proliferation, as evidenced by Ki67 staining. Organoids exposed to SF were the smallest and had the lowest proliferation and highest levels of apoptosis, while HF-fed organoids showed intermediate growth performance.
During the differentiation phase, organoids exposed to human milk developed more complex structures, forming buds with greater length and diameter compared to formula-fed organoids. PM was particularly effective, though DHM also promoted substantial differentiation. RNA sequencing revealed that organoids cultured with human milk upregulated genes involved in fatty acid metabolism and Wnt signaling, which are critical for cellular energy production and epithelial proliferation. In contrast, formula-fed organoids exhibited downregulation of cell-cycle-promoting genes and showed an inflammatory gene signature.
Cytokine profiling further underscored the benefits of human milk. Organoids exposed to PM and DHM secreted higher levels of immune-regulating cytokines, such as thymic stromal lymphopoietin (TSLP) and macrophage colony-stimulating factor (M-CSF). In contrast, formula-fed organoids produced lower levels of these beneficial cytokines and higher levels of pro-inflammatory markers, including interleukin-18 (IL-18).
These findings suggest that human milk supports intestinal growth, differentiation, and immune regulation in ways that formula does not, and the investigators emphasized the importance of identifying specific bioactive factors in human milk.
“If the factors responsible for this effect can be identified, there could be significant clinical value in supplementing these components in DHM and formula to help prevent NEC and foster normal intestinal development in preterm infants,” they concluded.
Future research will aim to isolate and supplement key components of human milk to enhance the nutritional and protective value of donor milk and formula. In addition, the investigators noted the need to explore potential sex-based differences in intestinal development, as the current study used only male-derived samples.The research was supported by the Yale School of Medicine Medical Student Research Fellowship. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
Biomarkers Predict Villous Atrophy in Potential Celiac Disease Patients
according to investigators.
Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.
“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”
The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.
After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.
Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.
Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.
“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”
The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.
“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”
The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.
Patients with positive celiac serologies but normal villous architecture on biopsy are considered to have potential celiac disease (PCD). While the prevalence of PCD is not well-established, it is estimated to be around 1%. This study by Auricchio and colleagues investigates seven serum proteomic biomarkers that could help predict whether asymptomatic patients with PCD are at risk of developing villous atrophy (VA).
The study also identifies specific inflammatory proteins present in PCD patients who are likely to develop VA. These biomarkers provide valuable insights into the pathogenesis of celiac disease and the development of VA in genetically predisposed individuals.
As celiac disease is increasingly diagnosed without biopsies, serum proteomic biomarkers could be crucial in identifying patients who may benefit from starting a gluten-free diet (GFD) earlier, potentially preventing complications. According to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, children can be diagnosed with celiac disease if their tissue transglutaminase IgA level is 10 times the upper limit of normal, confirmed by a positive endomysial antibody test. However, this approach may lead to many patients committing to a lifelong GFD despite having only PCD, as biopsies may not have been performed. In this study, 60% of patients with PCD did not progress to VA, suggesting that biomarkers could help prevent unnecessary long-term GFD commitments.
Stephanie M. Moleski, MD, is the director of the Jefferson Celiac Center and associate professor in the division of gastroenterology at Thomas Jefferson University Hospital in Philadelphia. She reported no conflicts of interest.
Patients with positive celiac serologies but normal villous architecture on biopsy are considered to have potential celiac disease (PCD). While the prevalence of PCD is not well-established, it is estimated to be around 1%. This study by Auricchio and colleagues investigates seven serum proteomic biomarkers that could help predict whether asymptomatic patients with PCD are at risk of developing villous atrophy (VA).
The study also identifies specific inflammatory proteins present in PCD patients who are likely to develop VA. These biomarkers provide valuable insights into the pathogenesis of celiac disease and the development of VA in genetically predisposed individuals.
As celiac disease is increasingly diagnosed without biopsies, serum proteomic biomarkers could be crucial in identifying patients who may benefit from starting a gluten-free diet (GFD) earlier, potentially preventing complications. According to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, children can be diagnosed with celiac disease if their tissue transglutaminase IgA level is 10 times the upper limit of normal, confirmed by a positive endomysial antibody test. However, this approach may lead to many patients committing to a lifelong GFD despite having only PCD, as biopsies may not have been performed. In this study, 60% of patients with PCD did not progress to VA, suggesting that biomarkers could help prevent unnecessary long-term GFD commitments.
Stephanie M. Moleski, MD, is the director of the Jefferson Celiac Center and associate professor in the division of gastroenterology at Thomas Jefferson University Hospital in Philadelphia. She reported no conflicts of interest.
Patients with positive celiac serologies but normal villous architecture on biopsy are considered to have potential celiac disease (PCD). While the prevalence of PCD is not well-established, it is estimated to be around 1%. This study by Auricchio and colleagues investigates seven serum proteomic biomarkers that could help predict whether asymptomatic patients with PCD are at risk of developing villous atrophy (VA).
The study also identifies specific inflammatory proteins present in PCD patients who are likely to develop VA. These biomarkers provide valuable insights into the pathogenesis of celiac disease and the development of VA in genetically predisposed individuals.
As celiac disease is increasingly diagnosed without biopsies, serum proteomic biomarkers could be crucial in identifying patients who may benefit from starting a gluten-free diet (GFD) earlier, potentially preventing complications. According to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, children can be diagnosed with celiac disease if their tissue transglutaminase IgA level is 10 times the upper limit of normal, confirmed by a positive endomysial antibody test. However, this approach may lead to many patients committing to a lifelong GFD despite having only PCD, as biopsies may not have been performed. In this study, 60% of patients with PCD did not progress to VA, suggesting that biomarkers could help prevent unnecessary long-term GFD commitments.
Stephanie M. Moleski, MD, is the director of the Jefferson Celiac Center and associate professor in the division of gastroenterology at Thomas Jefferson University Hospital in Philadelphia. She reported no conflicts of interest.
according to investigators.
Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.
“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”
The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.
After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.
Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.
Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.
“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”
The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.
“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”
The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.
according to investigators.
Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.
“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”
The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.
After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.
Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.
Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.
“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”
The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.
“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”
The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
New UTI Guideline Offers Treatment Clarity, Reveals Gaps in Knowledge
New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.
While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.
“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”
The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.
This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.
“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.
Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.
“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.
The key guideline recommendations are briefly summarized below.
Preventive Strategies for UTI
The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.
Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.
For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.
“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”
Empirical Treatment Recommendations
According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.
Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.
For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.
Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.
Stewardship and Clinical Management
The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.
While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.
Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”
Special Considerations for Urologic Procedures
Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.
Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.
“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”
She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.
“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.
Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.
“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”
The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.
A version of this article first appeared on Medscape.com.
New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.
While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.
“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”
The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.
This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.
“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.
Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.
“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.
The key guideline recommendations are briefly summarized below.
Preventive Strategies for UTI
The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.
Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.
For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.
“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”
Empirical Treatment Recommendations
According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.
Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.
For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.
Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.
Stewardship and Clinical Management
The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.
While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.
Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”
Special Considerations for Urologic Procedures
Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.
Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.
“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”
She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.
“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.
Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.
“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”
The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.
A version of this article first appeared on Medscape.com.
New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.
While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.
“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”
The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.
This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.
“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.
Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.
“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.
The key guideline recommendations are briefly summarized below.
Preventive Strategies for UTI
The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.
Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.
For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.
“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”
Empirical Treatment Recommendations
According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.
Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.
For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.
Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.
Stewardship and Clinical Management
The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.
While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.
Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”
Special Considerations for Urologic Procedures
Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.
Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.
“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”
She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.
“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.
Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.
“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”
The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Common Crohn’s Immune Response to Gut Bacteria Suggests Therapeutic Target
Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.
These findings suggest that lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.
Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.
“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.
To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.
Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.
This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.
Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.
“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”
Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.
Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.
These findings suggest that lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.
Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.
“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.
To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.
Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.
This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.
Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.
“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”
Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.
Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.
These findings suggest that lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.
Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.
“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.
To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.
Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.
This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.
Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.
“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”
Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.
FROM GASTROENTEROLOGY
Liquid Fasting Mitigates Negative Pre-Surgery Impact of Semaglutide
These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.
“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.
The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.
The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.
Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).
This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.
However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.
“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”
Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.
“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”
After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.
Dr. Korlipara disclosed no conflicts of interest.
These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.
“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.
The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.
The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.
Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).
This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.
However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.
“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”
Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.
“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”
After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.
Dr. Korlipara disclosed no conflicts of interest.
These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.
“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.
The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.
The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.
Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).
This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.
However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.
“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”
Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.
“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”
After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.
Dr. Korlipara disclosed no conflicts of interest.
FROM TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY