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Colorectal Cancer Awareness Month is Here!
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Fecal Hemoglobin Levels From Negative FITs Signal CRC Risk
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
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
Suboptimal Diets Tied to Global Doubling of GI Cancer Cases
according to a recent study.
Writing in Gastroenterology, researchers led by Li Liu, PhD, of the department of epidemiology and biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported that excessive consumption of processed meats (the biggest culprit), insufficient fruit intake, and insufficient whole grain intake were the leading dietary risk factors. In addition, the number of diet-related cases doubled from 1990 to 2018.
“In regions with limited access to healthy foods, policy interventions like taxing unhealthy foods and subsidizing nutritious options may help shift dietary patterns and reduce cancer risk,” Liu said in an interview.
The study examined meta-analyses from 184 countries in seven regions for the period 1990-2018 looking at rates of six major GI cancers: colorectal, liver, esophageal, pancreatic, and gallbladder/biliary tract. Among these, the age-standardized incidence of liver, pancreatic, and colorectal increased significantly over the past 3 decades.
The research team used a comparative risk assessment model to estimate the impact of diet on GI cancer independent of energy intake and adiposity. Although the principal dietary risk factors varied across individual cancers, suboptimal intake of the three aforementioned components was responsible for 66.51% of all diet-attributable GI cancers in 2018. The global mean processed meat consumption was 17 g/d in 2018, falling to a low in South Asia of 3 g/d.
The investigators also found diet-linked cancer incidence positively correlated with the Sociodemographic Index (SDI), an integrated measure of national development, income, and fertility. Incidence varied across world regions, with the highest proportion of cases in Central and Eastern Europe, Central Asia, Latin America, the Caribbean, and in high-income countries. The findings support the development of targeted diet-related public health interventions in various regions and nations to reduce GI cancer incidence, the authors wrote.
Among the study’s specific findings:
- In 2018, 21.5% (95% uncertainty interval [UI], 19.1-24.5) of incident GI cancer cases globally were attributable to suboptimal diets, a relatively stable proportion since 1990 (22.4%; 95% UI, 19.7-25.6).
- Absolute diet-attributable cases doubled from 580,862 (95% UI, 510,658-664,076) in 1990 to 1,039,877 (95% UI, 923,482-1,187,244) in 2018.
- Excessive processed meat consumption (5.9%; 95% UI, 4.2%-7.9%), insufficient fruit intake (4.8%; 95% UI, 3.8%-5.9%), and insufficient whole grain intake (3.6%; 95% UI, 2.8%-5.1%) were the most significant dietary risk factors in 2018 — a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake.
Given the well-established link between diet and GI cancers, the incidence findings came as no surprise. “However, the dramatic doubling of diet-attributable cases over the past few decades was truly unexpected,” Liu said. “This increase can likely be attributed to global population growth and aging. While aging is an irreversible process, we can still reduce the growing burden of diet-related GI cancers by focusing on modifiable behaviors, particularly through targeted dietary interventions.”
A Modifiable Risk Factor
Commenting on the analysis but not involved in it, Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston, noted that his own group’s studies also support the association of diet with an increased risk for GI cancers, particularly colorectal cancers.
“Although much work needs to be done to clarify the precise mechanisms underlying this association, there are substantial data that diet may cause changes in the gut microbiome, which in turn promotes cancer,” Chan said in an interview. “Going forward, we are working to develop strategies in which diet is modified to mitigate the risk of cancer associated with suboptimal diets.”
In other study findings, Liu’s group observed that two regional groups, Central and Eastern Europe, Central Asia, Latin America, and the Caribbean, as well as high-income countries, bore the top three diet-attributable burdens worldwide in 2018, all driven mostly by an upward-trending excess of processed meat.
By regions, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in 1990 (31.6%; UI, 27.0%-37.4%) and 2018 (31.6%; UI, 27.3%-36.5%).
As for the impact of the SDI, the authors explained that diet-attributable GI cancer burden was higher among adults with higher education and living in urban areas than among those with lower education and rural residency. “Some dietary habits tended to be worse in higher-SDI countries, specifically, higher consumption of processed meats,” they wrote.
Although the proportional attributable GI incidence remains relatively stable, they added, the doubling of absolute cases from 1990 to 2018, along with the discrepancies between urbanicity and countries/regions, supports more targeted preventive measures.
And while the diet-GI cancer connection is clear, they agreed with Chan in that “the precise pathogenesis from suboptimal diets to these cancers remains unclear and requires further basic studies to clarify the mechanism.”
In the meantime, the findings “underscore the urgent need for proactive public health interventions. Diet, as a modifiable risk factor, still offers substantial potential for improvement,” Liu said.
This study was funded by the National Natural Science Foundation of China and the American Cancer Society. The authors and Chan disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
according to a recent study.
Writing in Gastroenterology, researchers led by Li Liu, PhD, of the department of epidemiology and biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported that excessive consumption of processed meats (the biggest culprit), insufficient fruit intake, and insufficient whole grain intake were the leading dietary risk factors. In addition, the number of diet-related cases doubled from 1990 to 2018.
“In regions with limited access to healthy foods, policy interventions like taxing unhealthy foods and subsidizing nutritious options may help shift dietary patterns and reduce cancer risk,” Liu said in an interview.
The study examined meta-analyses from 184 countries in seven regions for the period 1990-2018 looking at rates of six major GI cancers: colorectal, liver, esophageal, pancreatic, and gallbladder/biliary tract. Among these, the age-standardized incidence of liver, pancreatic, and colorectal increased significantly over the past 3 decades.
The research team used a comparative risk assessment model to estimate the impact of diet on GI cancer independent of energy intake and adiposity. Although the principal dietary risk factors varied across individual cancers, suboptimal intake of the three aforementioned components was responsible for 66.51% of all diet-attributable GI cancers in 2018. The global mean processed meat consumption was 17 g/d in 2018, falling to a low in South Asia of 3 g/d.
The investigators also found diet-linked cancer incidence positively correlated with the Sociodemographic Index (SDI), an integrated measure of national development, income, and fertility. Incidence varied across world regions, with the highest proportion of cases in Central and Eastern Europe, Central Asia, Latin America, the Caribbean, and in high-income countries. The findings support the development of targeted diet-related public health interventions in various regions and nations to reduce GI cancer incidence, the authors wrote.
Among the study’s specific findings:
- In 2018, 21.5% (95% uncertainty interval [UI], 19.1-24.5) of incident GI cancer cases globally were attributable to suboptimal diets, a relatively stable proportion since 1990 (22.4%; 95% UI, 19.7-25.6).
- Absolute diet-attributable cases doubled from 580,862 (95% UI, 510,658-664,076) in 1990 to 1,039,877 (95% UI, 923,482-1,187,244) in 2018.
- Excessive processed meat consumption (5.9%; 95% UI, 4.2%-7.9%), insufficient fruit intake (4.8%; 95% UI, 3.8%-5.9%), and insufficient whole grain intake (3.6%; 95% UI, 2.8%-5.1%) were the most significant dietary risk factors in 2018 — a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake.
Given the well-established link between diet and GI cancers, the incidence findings came as no surprise. “However, the dramatic doubling of diet-attributable cases over the past few decades was truly unexpected,” Liu said. “This increase can likely be attributed to global population growth and aging. While aging is an irreversible process, we can still reduce the growing burden of diet-related GI cancers by focusing on modifiable behaviors, particularly through targeted dietary interventions.”
A Modifiable Risk Factor
Commenting on the analysis but not involved in it, Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston, noted that his own group’s studies also support the association of diet with an increased risk for GI cancers, particularly colorectal cancers.
“Although much work needs to be done to clarify the precise mechanisms underlying this association, there are substantial data that diet may cause changes in the gut microbiome, which in turn promotes cancer,” Chan said in an interview. “Going forward, we are working to develop strategies in which diet is modified to mitigate the risk of cancer associated with suboptimal diets.”
In other study findings, Liu’s group observed that two regional groups, Central and Eastern Europe, Central Asia, Latin America, and the Caribbean, as well as high-income countries, bore the top three diet-attributable burdens worldwide in 2018, all driven mostly by an upward-trending excess of processed meat.
By regions, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in 1990 (31.6%; UI, 27.0%-37.4%) and 2018 (31.6%; UI, 27.3%-36.5%).
As for the impact of the SDI, the authors explained that diet-attributable GI cancer burden was higher among adults with higher education and living in urban areas than among those with lower education and rural residency. “Some dietary habits tended to be worse in higher-SDI countries, specifically, higher consumption of processed meats,” they wrote.
Although the proportional attributable GI incidence remains relatively stable, they added, the doubling of absolute cases from 1990 to 2018, along with the discrepancies between urbanicity and countries/regions, supports more targeted preventive measures.
And while the diet-GI cancer connection is clear, they agreed with Chan in that “the precise pathogenesis from suboptimal diets to these cancers remains unclear and requires further basic studies to clarify the mechanism.”
In the meantime, the findings “underscore the urgent need for proactive public health interventions. Diet, as a modifiable risk factor, still offers substantial potential for improvement,” Liu said.
This study was funded by the National Natural Science Foundation of China and the American Cancer Society. The authors and Chan disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
according to a recent study.
Writing in Gastroenterology, researchers led by Li Liu, PhD, of the department of epidemiology and biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported that excessive consumption of processed meats (the biggest culprit), insufficient fruit intake, and insufficient whole grain intake were the leading dietary risk factors. In addition, the number of diet-related cases doubled from 1990 to 2018.
“In regions with limited access to healthy foods, policy interventions like taxing unhealthy foods and subsidizing nutritious options may help shift dietary patterns and reduce cancer risk,” Liu said in an interview.
The study examined meta-analyses from 184 countries in seven regions for the period 1990-2018 looking at rates of six major GI cancers: colorectal, liver, esophageal, pancreatic, and gallbladder/biliary tract. Among these, the age-standardized incidence of liver, pancreatic, and colorectal increased significantly over the past 3 decades.
The research team used a comparative risk assessment model to estimate the impact of diet on GI cancer independent of energy intake and adiposity. Although the principal dietary risk factors varied across individual cancers, suboptimal intake of the three aforementioned components was responsible for 66.51% of all diet-attributable GI cancers in 2018. The global mean processed meat consumption was 17 g/d in 2018, falling to a low in South Asia of 3 g/d.
The investigators also found diet-linked cancer incidence positively correlated with the Sociodemographic Index (SDI), an integrated measure of national development, income, and fertility. Incidence varied across world regions, with the highest proportion of cases in Central and Eastern Europe, Central Asia, Latin America, the Caribbean, and in high-income countries. The findings support the development of targeted diet-related public health interventions in various regions and nations to reduce GI cancer incidence, the authors wrote.
Among the study’s specific findings:
- In 2018, 21.5% (95% uncertainty interval [UI], 19.1-24.5) of incident GI cancer cases globally were attributable to suboptimal diets, a relatively stable proportion since 1990 (22.4%; 95% UI, 19.7-25.6).
- Absolute diet-attributable cases doubled from 580,862 (95% UI, 510,658-664,076) in 1990 to 1,039,877 (95% UI, 923,482-1,187,244) in 2018.
- Excessive processed meat consumption (5.9%; 95% UI, 4.2%-7.9%), insufficient fruit intake (4.8%; 95% UI, 3.8%-5.9%), and insufficient whole grain intake (3.6%; 95% UI, 2.8%-5.1%) were the most significant dietary risk factors in 2018 — a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake.
Given the well-established link between diet and GI cancers, the incidence findings came as no surprise. “However, the dramatic doubling of diet-attributable cases over the past few decades was truly unexpected,” Liu said. “This increase can likely be attributed to global population growth and aging. While aging is an irreversible process, we can still reduce the growing burden of diet-related GI cancers by focusing on modifiable behaviors, particularly through targeted dietary interventions.”
A Modifiable Risk Factor
Commenting on the analysis but not involved in it, Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston, noted that his own group’s studies also support the association of diet with an increased risk for GI cancers, particularly colorectal cancers.
“Although much work needs to be done to clarify the precise mechanisms underlying this association, there are substantial data that diet may cause changes in the gut microbiome, which in turn promotes cancer,” Chan said in an interview. “Going forward, we are working to develop strategies in which diet is modified to mitigate the risk of cancer associated with suboptimal diets.”
In other study findings, Liu’s group observed that two regional groups, Central and Eastern Europe, Central Asia, Latin America, and the Caribbean, as well as high-income countries, bore the top three diet-attributable burdens worldwide in 2018, all driven mostly by an upward-trending excess of processed meat.
By regions, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in 1990 (31.6%; UI, 27.0%-37.4%) and 2018 (31.6%; UI, 27.3%-36.5%).
As for the impact of the SDI, the authors explained that diet-attributable GI cancer burden was higher among adults with higher education and living in urban areas than among those with lower education and rural residency. “Some dietary habits tended to be worse in higher-SDI countries, specifically, higher consumption of processed meats,” they wrote.
Although the proportional attributable GI incidence remains relatively stable, they added, the doubling of absolute cases from 1990 to 2018, along with the discrepancies between urbanicity and countries/regions, supports more targeted preventive measures.
And while the diet-GI cancer connection is clear, they agreed with Chan in that “the precise pathogenesis from suboptimal diets to these cancers remains unclear and requires further basic studies to clarify the mechanism.”
In the meantime, the findings “underscore the urgent need for proactive public health interventions. Diet, as a modifiable risk factor, still offers substantial potential for improvement,” Liu said.
This study was funded by the National Natural Science Foundation of China and the American Cancer Society. The authors and Chan disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Promising New Blood Test for Colorectal Cancer Screening
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Low-Dose Aspirin Cuts CRC Recurrence
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Quality, Not Type, of Diet Linked to Microbiome Health
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
FROM NATURE MICROBIOLOGY
Obesity Linked with Malignant Progression of Barrett’s Esophagus
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
New Model Estimates Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
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