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Large Language Models Cut Time, Cost of Guideline Development
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
FROM GASTROENTEROLOGY
New Guidelines for Pregnancy and IBD Aim to Quell Fears
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
, suggesting this approach will not harm the fetus.
The guidelines also recommend that all women with IBD receive preconception counseling and be followed as high-risk pregnancies.
“Management of chronic illness in pregnant women has always been defined by fear of harming the fetus,” said Uma Mahadevan, MD, AGAF, director of the Colitis and Crohn’s Disease Center at the University of California San Francisco and chair of the Global Consensus Consortium that developed the guidelines.
As a result, pregnant women are excluded from clinical trials of experimental therapies for IBD. And when a new therapy achieves regulatory approval, there are no human pregnancy safety data, only animal data. To fill this gap, the PIANO study, of which Mahadevan is principal investigator, looked at the safety of IBD medications in pregnancy and short- and long-term outcomes of the children.
“With our ongoing work in pregnancy in the patient with IBD, we realized that inflammation in the mother is the leading cause of poor outcome for the infant,” she told GI & Hepatology News.
“We also have a better understanding of placental transfer of biologic agents” and the lack of exposure to the fetus during the first trimester, “a key period of organogenesis,” she added.
Final recommendations were published simultaneously in six international journals, namely, Clinical Gastroenterology and Hepatology, American Journal of Gastroenterology, GUT, Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, and Alimentary Pharmacology and Therapeutics.
Surprising, Novel Findings
Limited provider knowledge led to varied practices in caring for women with IBD who become pregnant, according to the consensus authors. Practices are affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus.
“The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike,” the authors of the guidelines wrote.
Therefore, the Global Consensus Consortium — a group of 39 IBD experts, including teratologists and maternal fetal medicine specialists and seven patient advocates from six continents — convened to review and assess current data and come to an agreement on best practices. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used when sufficient published data were available, and the Research and Development process when expert opinion was needed to guide consistent practice.
“Some of the findings were expected, but others were novel,” said Mahadevan.
Recommendations that might surprise clinicians include GRADE statement 9, which suggests that pregnant women with IBD take low-dose aspirin by 12 to 16 weeks’ gestation to prevent preterm preeclampsia. “This is based on the ASPRE study, showing that women at risk of preeclampsia can lower their risk by taking low-dose aspirin,” with no risk for flare, Mahadevan said.
In addition, GRADE statements 17-20 recommend/suggest that women continue their biologic throughout pregnancy without stopping. “North America has always recommended continuing during the third trimester, while Europe only recently has come to this,” Mahadevan said. “However, there was always some looseness about stopping at week X, Y, or Z. Now, we do recommend continuing the dose on schedule with no holding.”
Continuing medications considered low risk for use during pregnancy, such as 5-amino salicylic acids, sulfasalazine, thiopurines, and all monoclonal antibodies during preconception, pregnancy, and lactation, was also recommended.
However, small-molecule drugs such as S1P receptor molecules and JAK inhibitors should be avoided for at least 1 month, and in some cases for 3 months prior to attempting conception, unless there is no alternative for the health of the mother. They should also be avoided during lactation.
Grade statement 33, which suggests that live rotavirus vaccine may be provided in children with in utero exposure to biologics, is also new, Mahadevan noted. “All prior recommendations were that no live vaccine should be given in the first 6 months or longer if infants were exposed to biologics in utero, but based on a prospective Canadian study, there is no harm when given to these infants.”
Another novel recommendation is that women with IBD on any monoclonal antibodies, including newer interleukin-23s, may breastfeed even though there are not clinical trial data at this point. The recommendation to continue them through pregnancy and lactation is based on placental physiology, as well as on the physiology of monoclonal antibody transfer in breast milk, according to the consortium.
Furthermore, the authors noted, there was no increase in infant infections at 4 months or 12 months if they were exposed to a biologic or thiopurine (or both) during pregnancy.
Overall, the consortium recommended that all pregnancies for women with IBD be considered as “high risk” for complications. This is due to the fact that many parts of the world, including the US, are “resource-limited,” Mahadevan explained. Since maternal fetal medicine specialists are not widely available, the consortium suggested all these patients be followed with increased monitoring and surveillance based on available resources.
In addition to the guidelines, patient videos in seven languages, a professional slide deck in English and Spanish, and a video on the global consensus are all available at https://pianostudy.org/.
This study was funded by The Leona B. and Harry H. Helmsley Charitable Trust.
Mahadevan reported being a consultant for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck, Pfizer, Protagonist, Roivant, and Takeda.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
GLP-1 Use After Bariatric Surgery on the Rise
, a large retrospective cohort study showed.
GLP-1 initiation was also more common among women, those who underwent sleeve gastrectomy, and those with lower postoperative weight loss as measured by BMI.
“Some patients do not lose as much weight as expected, or they regain weight after a few years. In such cases, GLP-1 therapies are emerging as an important option for weight management,” said principal investigator Hemalkumar Mehta, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health in Baltimore.
“We also noted many personal stories circulating on social media in which patients shared their experiences using GLP-1 after bariatric surgery,” he told GI & Hepatology News.
But when the researchers reviewed the scientific literature, they found no published evidence on GLP-1 use in this setting and little or no data on outcomes with the newer drugs such as semaglutide and tirzepatide. “This gap motivated us to conduct the current study,” said Mehta. The study was published in JAMA Surgery.
The researchers analyzed data from a national multicenter database of electronic health records of approximately 113 million US adults to characterize the use of and factors associated with GLP-1 initiation after bariatric surgery.
Among 112,858 individuals undergoing bariatric surgery during the study period, the mean age was 45.2 years, and 78.9% were women.
By self-report race, 1.1% were Asian, 22.1% were Black or African American, 64.2% were White individuals, and 12.6% reported belonging to other races (American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or unknown).
A total of 15,749 individuals (14%) initiated GLP-1s post-surgery, with 3391 (21.5%) beginning within 2 years of surgery and the remainder initiating during postsurgical years 3-4 (32.3%), 5-6 (25.2%), or later (21%).
Notably, the proportion of GLP-1 use increased more in the more recent cohort, from 1.7% in the January 2015-December 2019 cohort to 12.6% from June 2020 to May 2025.
Differences Between Users and Nonusers
Those who initiated GLP-1s differed significantly from those who did not: GLP-1 users vs nonusers were younger (mean age, 44.9 years vs 45.2 years), and use was more common among women vs men (15.1% vs 9.7%), among Black or African American vs White patients (15.8% vs 13.5%), and among those who underwent sleeve gastrectomy vs Roux-en-Y gastric bypass (14.9% vs 12.1%).
Looked at another way, women (adjusted hazard ratio [aHR], 1.61), those undergoing sleeve gastrectomy (aHR, 1.42), and those with type 2 diabetes (aHR, 1.34) were more likely to initiate GLP-1s than their counterparts.
The overall median presurgical BMI was 42. On analyzing obesity classification based on BMI, the researchers found that the chances of GLP-1 use were 1.73 times higher among class 1 obesity patients (BMI, 30.0-34.9), 2.19 times higher among class 2 obesity patients (BMI, 35.0-39.9), and 2.69 times higher among patients with class 3 obesity (BMI ≥ 40) than among overweight patients (BMI, 25.0-29.9).
The median post-surgery BMI for GLP-1 users at drug initiation was 36.7. Each one-unit increase in postsurgical BMI was associated with an 8% increase in the likelihood of GLP-1 initiation (aHR, 1.08).
“Importantly, our study did not specifically evaluate the effectiveness of GLP-1 therapy on weight loss after surgery,” Mehta noted. That issue and others, such as optimal timing for initiating GLP-1s, are currently under investigation.
In a related editorial, Kate Lauer, MD, of the University of Wisconsin-Madison and colleagues noted that the study had several limitations. It relied on data prior to the USFDA approvals of semaglutide and tirzepatide, the two most prescribed GLP-1s currently, potentially limiting its applicability to current practice.
Furthermore, the prescribing data did not capture dose, titration schedules, or adherence, which are “critical for understanding treatment efficacy,” they wrote. “Nonetheless, the findings highlight two important trends: (1) GLP-1s are being increasingly used as an adjunct after bariatric surgery, and (2) there is substantial variability in the timing of their initiation.”
‘Logical’ to Use GLP-1s Post Surgery
Commenting on the study findings for GI & Hepatology News, Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, who was not involved in the study, said, “I think it is perfectly logical to use GLP-1s in patients who have had bariatric surgery.”
In this study, weight loss in those who took GLP-1s was about 12% (from a median BMI of 42 pre-surgery to 36.7 when a GLP-1 was initiated), which is significantly less than average, Aronne noted. “The patients still had Class 2 obesity.”
“Obesity is the same as other metabolic diseases,” he added. “We have to use common sense and good medical judgment when treating patients. If surgery isn’t completely effective and weight loss is inadequate, I would recommend medications.”
Of note, his team has found that lower doses of GLP-1s are required in those who have had surgery than in those who have not. “My opinion is that patients who have undergone bariatric surgery seem to be more sensitive to the medications than the average patient, but this hasn’t been carefully studied.”
To prepare patients for the possible use of GLP1s post-surgery, he suggested telling those with very high BMI that “they may need medication in addition to the procedure in order to get the best result.”
Mehta added, “Ultimately, the decision to start GLP-1s after surgery is shared between patients and clinicians. Given the amount of media coverage on GLP-1 therapies, it is not surprising that more patients are initiating these discussions with their doctors.”
Mehta is supported by the US National Institute on Aging and reported receiving grants from the institute for this study; no other funding was reported. Lauer reported receiving grants from the US National Institutes of Health.
A version of this article first appeared on Medscape.com.
, a large retrospective cohort study showed.
GLP-1 initiation was also more common among women, those who underwent sleeve gastrectomy, and those with lower postoperative weight loss as measured by BMI.
“Some patients do not lose as much weight as expected, or they regain weight after a few years. In such cases, GLP-1 therapies are emerging as an important option for weight management,” said principal investigator Hemalkumar Mehta, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health in Baltimore.
“We also noted many personal stories circulating on social media in which patients shared their experiences using GLP-1 after bariatric surgery,” he told GI & Hepatology News.
But when the researchers reviewed the scientific literature, they found no published evidence on GLP-1 use in this setting and little or no data on outcomes with the newer drugs such as semaglutide and tirzepatide. “This gap motivated us to conduct the current study,” said Mehta. The study was published in JAMA Surgery.
The researchers analyzed data from a national multicenter database of electronic health records of approximately 113 million US adults to characterize the use of and factors associated with GLP-1 initiation after bariatric surgery.
Among 112,858 individuals undergoing bariatric surgery during the study period, the mean age was 45.2 years, and 78.9% were women.
By self-report race, 1.1% were Asian, 22.1% were Black or African American, 64.2% were White individuals, and 12.6% reported belonging to other races (American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or unknown).
A total of 15,749 individuals (14%) initiated GLP-1s post-surgery, with 3391 (21.5%) beginning within 2 years of surgery and the remainder initiating during postsurgical years 3-4 (32.3%), 5-6 (25.2%), or later (21%).
Notably, the proportion of GLP-1 use increased more in the more recent cohort, from 1.7% in the January 2015-December 2019 cohort to 12.6% from June 2020 to May 2025.
Differences Between Users and Nonusers
Those who initiated GLP-1s differed significantly from those who did not: GLP-1 users vs nonusers were younger (mean age, 44.9 years vs 45.2 years), and use was more common among women vs men (15.1% vs 9.7%), among Black or African American vs White patients (15.8% vs 13.5%), and among those who underwent sleeve gastrectomy vs Roux-en-Y gastric bypass (14.9% vs 12.1%).
Looked at another way, women (adjusted hazard ratio [aHR], 1.61), those undergoing sleeve gastrectomy (aHR, 1.42), and those with type 2 diabetes (aHR, 1.34) were more likely to initiate GLP-1s than their counterparts.
The overall median presurgical BMI was 42. On analyzing obesity classification based on BMI, the researchers found that the chances of GLP-1 use were 1.73 times higher among class 1 obesity patients (BMI, 30.0-34.9), 2.19 times higher among class 2 obesity patients (BMI, 35.0-39.9), and 2.69 times higher among patients with class 3 obesity (BMI ≥ 40) than among overweight patients (BMI, 25.0-29.9).
The median post-surgery BMI for GLP-1 users at drug initiation was 36.7. Each one-unit increase in postsurgical BMI was associated with an 8% increase in the likelihood of GLP-1 initiation (aHR, 1.08).
“Importantly, our study did not specifically evaluate the effectiveness of GLP-1 therapy on weight loss after surgery,” Mehta noted. That issue and others, such as optimal timing for initiating GLP-1s, are currently under investigation.
In a related editorial, Kate Lauer, MD, of the University of Wisconsin-Madison and colleagues noted that the study had several limitations. It relied on data prior to the USFDA approvals of semaglutide and tirzepatide, the two most prescribed GLP-1s currently, potentially limiting its applicability to current practice.
Furthermore, the prescribing data did not capture dose, titration schedules, or adherence, which are “critical for understanding treatment efficacy,” they wrote. “Nonetheless, the findings highlight two important trends: (1) GLP-1s are being increasingly used as an adjunct after bariatric surgery, and (2) there is substantial variability in the timing of their initiation.”
‘Logical’ to Use GLP-1s Post Surgery
Commenting on the study findings for GI & Hepatology News, Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, who was not involved in the study, said, “I think it is perfectly logical to use GLP-1s in patients who have had bariatric surgery.”
In this study, weight loss in those who took GLP-1s was about 12% (from a median BMI of 42 pre-surgery to 36.7 when a GLP-1 was initiated), which is significantly less than average, Aronne noted. “The patients still had Class 2 obesity.”
“Obesity is the same as other metabolic diseases,” he added. “We have to use common sense and good medical judgment when treating patients. If surgery isn’t completely effective and weight loss is inadequate, I would recommend medications.”
Of note, his team has found that lower doses of GLP-1s are required in those who have had surgery than in those who have not. “My opinion is that patients who have undergone bariatric surgery seem to be more sensitive to the medications than the average patient, but this hasn’t been carefully studied.”
To prepare patients for the possible use of GLP1s post-surgery, he suggested telling those with very high BMI that “they may need medication in addition to the procedure in order to get the best result.”
Mehta added, “Ultimately, the decision to start GLP-1s after surgery is shared between patients and clinicians. Given the amount of media coverage on GLP-1 therapies, it is not surprising that more patients are initiating these discussions with their doctors.”
Mehta is supported by the US National Institute on Aging and reported receiving grants from the institute for this study; no other funding was reported. Lauer reported receiving grants from the US National Institutes of Health.
A version of this article first appeared on Medscape.com.
, a large retrospective cohort study showed.
GLP-1 initiation was also more common among women, those who underwent sleeve gastrectomy, and those with lower postoperative weight loss as measured by BMI.
“Some patients do not lose as much weight as expected, or they regain weight after a few years. In such cases, GLP-1 therapies are emerging as an important option for weight management,” said principal investigator Hemalkumar Mehta, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health in Baltimore.
“We also noted many personal stories circulating on social media in which patients shared their experiences using GLP-1 after bariatric surgery,” he told GI & Hepatology News.
But when the researchers reviewed the scientific literature, they found no published evidence on GLP-1 use in this setting and little or no data on outcomes with the newer drugs such as semaglutide and tirzepatide. “This gap motivated us to conduct the current study,” said Mehta. The study was published in JAMA Surgery.
The researchers analyzed data from a national multicenter database of electronic health records of approximately 113 million US adults to characterize the use of and factors associated with GLP-1 initiation after bariatric surgery.
Among 112,858 individuals undergoing bariatric surgery during the study period, the mean age was 45.2 years, and 78.9% were women.
By self-report race, 1.1% were Asian, 22.1% were Black or African American, 64.2% were White individuals, and 12.6% reported belonging to other races (American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or unknown).
A total of 15,749 individuals (14%) initiated GLP-1s post-surgery, with 3391 (21.5%) beginning within 2 years of surgery and the remainder initiating during postsurgical years 3-4 (32.3%), 5-6 (25.2%), or later (21%).
Notably, the proportion of GLP-1 use increased more in the more recent cohort, from 1.7% in the January 2015-December 2019 cohort to 12.6% from June 2020 to May 2025.
Differences Between Users and Nonusers
Those who initiated GLP-1s differed significantly from those who did not: GLP-1 users vs nonusers were younger (mean age, 44.9 years vs 45.2 years), and use was more common among women vs men (15.1% vs 9.7%), among Black or African American vs White patients (15.8% vs 13.5%), and among those who underwent sleeve gastrectomy vs Roux-en-Y gastric bypass (14.9% vs 12.1%).
Looked at another way, women (adjusted hazard ratio [aHR], 1.61), those undergoing sleeve gastrectomy (aHR, 1.42), and those with type 2 diabetes (aHR, 1.34) were more likely to initiate GLP-1s than their counterparts.
The overall median presurgical BMI was 42. On analyzing obesity classification based on BMI, the researchers found that the chances of GLP-1 use were 1.73 times higher among class 1 obesity patients (BMI, 30.0-34.9), 2.19 times higher among class 2 obesity patients (BMI, 35.0-39.9), and 2.69 times higher among patients with class 3 obesity (BMI ≥ 40) than among overweight patients (BMI, 25.0-29.9).
The median post-surgery BMI for GLP-1 users at drug initiation was 36.7. Each one-unit increase in postsurgical BMI was associated with an 8% increase in the likelihood of GLP-1 initiation (aHR, 1.08).
“Importantly, our study did not specifically evaluate the effectiveness of GLP-1 therapy on weight loss after surgery,” Mehta noted. That issue and others, such as optimal timing for initiating GLP-1s, are currently under investigation.
In a related editorial, Kate Lauer, MD, of the University of Wisconsin-Madison and colleagues noted that the study had several limitations. It relied on data prior to the USFDA approvals of semaglutide and tirzepatide, the two most prescribed GLP-1s currently, potentially limiting its applicability to current practice.
Furthermore, the prescribing data did not capture dose, titration schedules, or adherence, which are “critical for understanding treatment efficacy,” they wrote. “Nonetheless, the findings highlight two important trends: (1) GLP-1s are being increasingly used as an adjunct after bariatric surgery, and (2) there is substantial variability in the timing of their initiation.”
‘Logical’ to Use GLP-1s Post Surgery
Commenting on the study findings for GI & Hepatology News, Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, who was not involved in the study, said, “I think it is perfectly logical to use GLP-1s in patients who have had bariatric surgery.”
In this study, weight loss in those who took GLP-1s was about 12% (from a median BMI of 42 pre-surgery to 36.7 when a GLP-1 was initiated), which is significantly less than average, Aronne noted. “The patients still had Class 2 obesity.”
“Obesity is the same as other metabolic diseases,” he added. “We have to use common sense and good medical judgment when treating patients. If surgery isn’t completely effective and weight loss is inadequate, I would recommend medications.”
Of note, his team has found that lower doses of GLP-1s are required in those who have had surgery than in those who have not. “My opinion is that patients who have undergone bariatric surgery seem to be more sensitive to the medications than the average patient, but this hasn’t been carefully studied.”
To prepare patients for the possible use of GLP1s post-surgery, he suggested telling those with very high BMI that “they may need medication in addition to the procedure in order to get the best result.”
Mehta added, “Ultimately, the decision to start GLP-1s after surgery is shared between patients and clinicians. Given the amount of media coverage on GLP-1 therapies, it is not surprising that more patients are initiating these discussions with their doctors.”
Mehta is supported by the US National Institute on Aging and reported receiving grants from the institute for this study; no other funding was reported. Lauer reported receiving grants from the US National Institutes of Health.
A version of this article first appeared on Medscape.com.
SGLT2 Inhibition Promising for Patients With Cirrhosis and on Diuretics
, a large cohort study of more than 10,000 patients found.
Reporting in JAMA Network Open, Dian J. Chiang, MD, MPH, a section head of Hepatology at the Cleveland Clinic in Cleveland looked at the impact of these antihyperglycemic agents, also known as gliflozins, used in diabetes and kidney disease to block the reabsorption of glucose in the kidneys and causing more glucose to be excreted in the urine.
“Patients with cirrhosis were previously not included in SGLT2 inhibition clinical trials, and there is no large real-world evidence on the safety and effectiveness of this class of medication in patients with cirrhosis. Therefore, we decided to conduct the study to assess its safety and effectiveness,” Chiang told GI & Hepatology News.
The study’s primary endpoint was a composite of serious hepatic events, defined as ascites, varices, hyponatremia, and all-cause mortality. Secondary outcomes included variceal bleeding, paracentesis, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, liver carcinoma, hypoglycemia, and all-cause hospitalizations.
The cohort consisted of 10,660 propensity-matched adult patients with cirrhosis from more than 120 healthcare organizations in the TriNetX database who were receiving furosemide and spironolactone from January 2013 to July 2021. Those also receiving SGLT2 inhibitors (n = 5330) were compared with a matched control group receiving diuretics only (n = 5330). The mean age of participants was 63.8 years, 57.8% were men, 66.3% were White individuals, and all were followed for 3 years.
The SGLT2 inhibitor group had a 32% lower incidence of serious liver events than the control group, for a hazard ratio (HR) of 0.68 (95% CI, 0.66-0.71; P < .001).
Secondary risk reductions in the intervention group were as follows:
- Hepatorenal syndrome: HR, 0.47 (95% CI, 0.40-0.56)
- Spontaneous bacterial peritonitis: HR, 0.55 (95% CI, 0.46-0.65)
- Paracentesis: HR, 0.54 (95% CI, 0.50-0.60)
- Variceal bleeding: HR, 0.79 (95% CI, 0.73-0.84)
- Hypoglycemia: HR, 0.75 (95% CI, 0.62-0.91)
- All-cause hospitalizations: HR, 0.67 (95% CI, 0.63-0.71)
The authors conjectured that SGLT2 inhibition might also benefit patients with other stages of liver disease. They pointed to a 2020 study in patients with diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and high baseline fibrosis that revealed a significant reduction in fibrosis after 12 months’ SGLT2 inhibition.
The study findings also align with those of another large propensity-matched cohort in which patients with type 2 diabetes and cirrhosis receiving metformin plus SGLT2 inhibition showed significantly lower 5-year mortality, decreased incidence of decompensated cirrhosis, and reduced hepatocellular carcinoma incidence compared with those taking metformin alone.
Prospective trials are needed to further evaluate safety and efficacy, however, the authors stressed. Future studies should specifically examine changes in sodium levels following SGLT2 inhibitor initiation, as well as the incidence of recurrent urinary tract infections and euglycemic diabetic ketoacidosis, given that these are known adverse effects of this drug class. Additionally, research comparing different types and dosing regimens would provide valuable insights into optimizing treatment.
Commenting on the analysis but not participating in it, Karn Wijarnpreecha, MD, MPH, a hepatologist at College of Medicine, The University of Arizona, Phoenix, said the study was interesting but did not show the adjusted HR for all-cause mortality separately from other serious liver events, “so we do not know if SGLT2 inhibitor group was associated with lower mortality.”
It would be premature to conclude that using SGLT2 inhibitors in patients with cirrhosis and ascites and on diuretics will decrease the need for liver transplant or significantly improve liver-related outcomes based on this study, Wijarnpreecha told GI & Hepatology News. “Moreover, we do not know the dose of diuretics or specific drugs and doses for SGLT2 inhibitors that were used in the study. Indications for using SGLT2 inhibitors are mainly from diabetes and heart failure, so this may not apply to those with cirrhosis without these two conditions as well.”
In addition, the etiology of cirrhosis in this database study is unknown. “Is it mainly from MASLD or alcohol or other conditions such as viral hepatitis or autoimmmunity? We need more thorough study to answer this question.” He also pointed out that the authors urged caution in using SGLT2 inhibitors in the context of hepatic encephalopathy (HE), which could be worsened with these agents. “This should be taken into consideration before starting medication in decompensated cirrhosis with HE,” Wijarnpreecha said.
In an accompanying commentary, Mohamed I. Elsaid, PhD, MPH, a biomedical informatics researcher and assistant professor at The Ohio State University in Columbus, Ohio, said that if confirmed, the findings could substantially improve cirrhosis care. “The signal is exciting but needs strong confirmation from large observational studies and prospective trials,” he wrote. “To turn promise into practice, the next wave of observational studies must embrace the target-trial emulation framework for bolstering firm causal conclusions and doubly robust learners that tease apart who benefits, who does not, and why.”
He added that head-to-head comparisons with the type 2 diabetes drugs known as incretin mimetics will clarify the best antihyperglycemic agents for different patient phenotypes. “With these advanced causal-inference approaches, repurposed type 2 diabetes therapies could shift cirrhosis management from reactive to proactive, improving quality of life and bending the mortality curve,” Elsaid wrote.
For Wijarnpreecha, important pending questions include the benefits of SGLT2 inhibition in cirrhosis without diabetes or heart failure “Can it be used to prevent cirrhosis in MASLD if we start at the early fibrosis stage in F0-F3?”
Chiang conceded that the study had limitations as it relied on 10th revision of the International Classification of Diseases codes to define outcomes, which may not have captured the complexity of cirrhotic complications. “And the retrospective design may have introduced confounding, selection, and information bias, which could have impacted the results,” he said. “Future prospective studies may help confirm our findings.”
No specific funding was reported for this study. The study authors and Wijarnpreecha had no relevant conflicts of interest to declare. Elsaid reported receiving research funding from Genentech and AstraZeneca outside of the submitted work.
A version of this article first appeared on Medscape.com.
, a large cohort study of more than 10,000 patients found.
Reporting in JAMA Network Open, Dian J. Chiang, MD, MPH, a section head of Hepatology at the Cleveland Clinic in Cleveland looked at the impact of these antihyperglycemic agents, also known as gliflozins, used in diabetes and kidney disease to block the reabsorption of glucose in the kidneys and causing more glucose to be excreted in the urine.
“Patients with cirrhosis were previously not included in SGLT2 inhibition clinical trials, and there is no large real-world evidence on the safety and effectiveness of this class of medication in patients with cirrhosis. Therefore, we decided to conduct the study to assess its safety and effectiveness,” Chiang told GI & Hepatology News.
The study’s primary endpoint was a composite of serious hepatic events, defined as ascites, varices, hyponatremia, and all-cause mortality. Secondary outcomes included variceal bleeding, paracentesis, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, liver carcinoma, hypoglycemia, and all-cause hospitalizations.
The cohort consisted of 10,660 propensity-matched adult patients with cirrhosis from more than 120 healthcare organizations in the TriNetX database who were receiving furosemide and spironolactone from January 2013 to July 2021. Those also receiving SGLT2 inhibitors (n = 5330) were compared with a matched control group receiving diuretics only (n = 5330). The mean age of participants was 63.8 years, 57.8% were men, 66.3% were White individuals, and all were followed for 3 years.
The SGLT2 inhibitor group had a 32% lower incidence of serious liver events than the control group, for a hazard ratio (HR) of 0.68 (95% CI, 0.66-0.71; P < .001).
Secondary risk reductions in the intervention group were as follows:
- Hepatorenal syndrome: HR, 0.47 (95% CI, 0.40-0.56)
- Spontaneous bacterial peritonitis: HR, 0.55 (95% CI, 0.46-0.65)
- Paracentesis: HR, 0.54 (95% CI, 0.50-0.60)
- Variceal bleeding: HR, 0.79 (95% CI, 0.73-0.84)
- Hypoglycemia: HR, 0.75 (95% CI, 0.62-0.91)
- All-cause hospitalizations: HR, 0.67 (95% CI, 0.63-0.71)
The authors conjectured that SGLT2 inhibition might also benefit patients with other stages of liver disease. They pointed to a 2020 study in patients with diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and high baseline fibrosis that revealed a significant reduction in fibrosis after 12 months’ SGLT2 inhibition.
The study findings also align with those of another large propensity-matched cohort in which patients with type 2 diabetes and cirrhosis receiving metformin plus SGLT2 inhibition showed significantly lower 5-year mortality, decreased incidence of decompensated cirrhosis, and reduced hepatocellular carcinoma incidence compared with those taking metformin alone.
Prospective trials are needed to further evaluate safety and efficacy, however, the authors stressed. Future studies should specifically examine changes in sodium levels following SGLT2 inhibitor initiation, as well as the incidence of recurrent urinary tract infections and euglycemic diabetic ketoacidosis, given that these are known adverse effects of this drug class. Additionally, research comparing different types and dosing regimens would provide valuable insights into optimizing treatment.
Commenting on the analysis but not participating in it, Karn Wijarnpreecha, MD, MPH, a hepatologist at College of Medicine, The University of Arizona, Phoenix, said the study was interesting but did not show the adjusted HR for all-cause mortality separately from other serious liver events, “so we do not know if SGLT2 inhibitor group was associated with lower mortality.”
It would be premature to conclude that using SGLT2 inhibitors in patients with cirrhosis and ascites and on diuretics will decrease the need for liver transplant or significantly improve liver-related outcomes based on this study, Wijarnpreecha told GI & Hepatology News. “Moreover, we do not know the dose of diuretics or specific drugs and doses for SGLT2 inhibitors that were used in the study. Indications for using SGLT2 inhibitors are mainly from diabetes and heart failure, so this may not apply to those with cirrhosis without these two conditions as well.”
In addition, the etiology of cirrhosis in this database study is unknown. “Is it mainly from MASLD or alcohol or other conditions such as viral hepatitis or autoimmmunity? We need more thorough study to answer this question.” He also pointed out that the authors urged caution in using SGLT2 inhibitors in the context of hepatic encephalopathy (HE), which could be worsened with these agents. “This should be taken into consideration before starting medication in decompensated cirrhosis with HE,” Wijarnpreecha said.
In an accompanying commentary, Mohamed I. Elsaid, PhD, MPH, a biomedical informatics researcher and assistant professor at The Ohio State University in Columbus, Ohio, said that if confirmed, the findings could substantially improve cirrhosis care. “The signal is exciting but needs strong confirmation from large observational studies and prospective trials,” he wrote. “To turn promise into practice, the next wave of observational studies must embrace the target-trial emulation framework for bolstering firm causal conclusions and doubly robust learners that tease apart who benefits, who does not, and why.”
He added that head-to-head comparisons with the type 2 diabetes drugs known as incretin mimetics will clarify the best antihyperglycemic agents for different patient phenotypes. “With these advanced causal-inference approaches, repurposed type 2 diabetes therapies could shift cirrhosis management from reactive to proactive, improving quality of life and bending the mortality curve,” Elsaid wrote.
For Wijarnpreecha, important pending questions include the benefits of SGLT2 inhibition in cirrhosis without diabetes or heart failure “Can it be used to prevent cirrhosis in MASLD if we start at the early fibrosis stage in F0-F3?”
Chiang conceded that the study had limitations as it relied on 10th revision of the International Classification of Diseases codes to define outcomes, which may not have captured the complexity of cirrhotic complications. “And the retrospective design may have introduced confounding, selection, and information bias, which could have impacted the results,” he said. “Future prospective studies may help confirm our findings.”
No specific funding was reported for this study. The study authors and Wijarnpreecha had no relevant conflicts of interest to declare. Elsaid reported receiving research funding from Genentech and AstraZeneca outside of the submitted work.
A version of this article first appeared on Medscape.com.
, a large cohort study of more than 10,000 patients found.
Reporting in JAMA Network Open, Dian J. Chiang, MD, MPH, a section head of Hepatology at the Cleveland Clinic in Cleveland looked at the impact of these antihyperglycemic agents, also known as gliflozins, used in diabetes and kidney disease to block the reabsorption of glucose in the kidneys and causing more glucose to be excreted in the urine.
“Patients with cirrhosis were previously not included in SGLT2 inhibition clinical trials, and there is no large real-world evidence on the safety and effectiveness of this class of medication in patients with cirrhosis. Therefore, we decided to conduct the study to assess its safety and effectiveness,” Chiang told GI & Hepatology News.
The study’s primary endpoint was a composite of serious hepatic events, defined as ascites, varices, hyponatremia, and all-cause mortality. Secondary outcomes included variceal bleeding, paracentesis, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, liver carcinoma, hypoglycemia, and all-cause hospitalizations.
The cohort consisted of 10,660 propensity-matched adult patients with cirrhosis from more than 120 healthcare organizations in the TriNetX database who were receiving furosemide and spironolactone from January 2013 to July 2021. Those also receiving SGLT2 inhibitors (n = 5330) were compared with a matched control group receiving diuretics only (n = 5330). The mean age of participants was 63.8 years, 57.8% were men, 66.3% were White individuals, and all were followed for 3 years.
The SGLT2 inhibitor group had a 32% lower incidence of serious liver events than the control group, for a hazard ratio (HR) of 0.68 (95% CI, 0.66-0.71; P < .001).
Secondary risk reductions in the intervention group were as follows:
- Hepatorenal syndrome: HR, 0.47 (95% CI, 0.40-0.56)
- Spontaneous bacterial peritonitis: HR, 0.55 (95% CI, 0.46-0.65)
- Paracentesis: HR, 0.54 (95% CI, 0.50-0.60)
- Variceal bleeding: HR, 0.79 (95% CI, 0.73-0.84)
- Hypoglycemia: HR, 0.75 (95% CI, 0.62-0.91)
- All-cause hospitalizations: HR, 0.67 (95% CI, 0.63-0.71)
The authors conjectured that SGLT2 inhibition might also benefit patients with other stages of liver disease. They pointed to a 2020 study in patients with diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and high baseline fibrosis that revealed a significant reduction in fibrosis after 12 months’ SGLT2 inhibition.
The study findings also align with those of another large propensity-matched cohort in which patients with type 2 diabetes and cirrhosis receiving metformin plus SGLT2 inhibition showed significantly lower 5-year mortality, decreased incidence of decompensated cirrhosis, and reduced hepatocellular carcinoma incidence compared with those taking metformin alone.
Prospective trials are needed to further evaluate safety and efficacy, however, the authors stressed. Future studies should specifically examine changes in sodium levels following SGLT2 inhibitor initiation, as well as the incidence of recurrent urinary tract infections and euglycemic diabetic ketoacidosis, given that these are known adverse effects of this drug class. Additionally, research comparing different types and dosing regimens would provide valuable insights into optimizing treatment.
Commenting on the analysis but not participating in it, Karn Wijarnpreecha, MD, MPH, a hepatologist at College of Medicine, The University of Arizona, Phoenix, said the study was interesting but did not show the adjusted HR for all-cause mortality separately from other serious liver events, “so we do not know if SGLT2 inhibitor group was associated with lower mortality.”
It would be premature to conclude that using SGLT2 inhibitors in patients with cirrhosis and ascites and on diuretics will decrease the need for liver transplant or significantly improve liver-related outcomes based on this study, Wijarnpreecha told GI & Hepatology News. “Moreover, we do not know the dose of diuretics or specific drugs and doses for SGLT2 inhibitors that were used in the study. Indications for using SGLT2 inhibitors are mainly from diabetes and heart failure, so this may not apply to those with cirrhosis without these two conditions as well.”
In addition, the etiology of cirrhosis in this database study is unknown. “Is it mainly from MASLD or alcohol or other conditions such as viral hepatitis or autoimmmunity? We need more thorough study to answer this question.” He also pointed out that the authors urged caution in using SGLT2 inhibitors in the context of hepatic encephalopathy (HE), which could be worsened with these agents. “This should be taken into consideration before starting medication in decompensated cirrhosis with HE,” Wijarnpreecha said.
In an accompanying commentary, Mohamed I. Elsaid, PhD, MPH, a biomedical informatics researcher and assistant professor at The Ohio State University in Columbus, Ohio, said that if confirmed, the findings could substantially improve cirrhosis care. “The signal is exciting but needs strong confirmation from large observational studies and prospective trials,” he wrote. “To turn promise into practice, the next wave of observational studies must embrace the target-trial emulation framework for bolstering firm causal conclusions and doubly robust learners that tease apart who benefits, who does not, and why.”
He added that head-to-head comparisons with the type 2 diabetes drugs known as incretin mimetics will clarify the best antihyperglycemic agents for different patient phenotypes. “With these advanced causal-inference approaches, repurposed type 2 diabetes therapies could shift cirrhosis management from reactive to proactive, improving quality of life and bending the mortality curve,” Elsaid wrote.
For Wijarnpreecha, important pending questions include the benefits of SGLT2 inhibition in cirrhosis without diabetes or heart failure “Can it be used to prevent cirrhosis in MASLD if we start at the early fibrosis stage in F0-F3?”
Chiang conceded that the study had limitations as it relied on 10th revision of the International Classification of Diseases codes to define outcomes, which may not have captured the complexity of cirrhotic complications. “And the retrospective design may have introduced confounding, selection, and information bias, which could have impacted the results,” he said. “Future prospective studies may help confirm our findings.”
No specific funding was reported for this study. The study authors and Wijarnpreecha had no relevant conflicts of interest to declare. Elsaid reported receiving research funding from Genentech and AstraZeneca outside of the submitted work.
A version of this article first appeared on Medscape.com.
Forceps Assistance Improves Outcomes in Difficult ERCP Cannulations
The results emerged from the small, single-center SOCCER trial of 152 patients recruited from March 2022 to October 2024 and are published in The American Journal of Gastroenterology.
Both groups had a slightly higher number of female participants, and the mean ages of the participants were 61.9 years in the forceps group and 68.3 years in the no forceps group.
First author Steven M. Hadley Jr, an MD candidate at Northwestern Feinberg School of Medicine in Chicago, and colleagues reported that forceps assistance in difficult cannulations yielded significantly higher success rates than no forceps assistance (100% vs 83.9%; P < .001).
The investigators noted that difficult cannulations during ERCP have a frequency of 42%. Cannulation failure is associated with increased morbidity — including longer hospitalization, increased ICU admissions, readmissions, and increased financial cost — as well as mortality rates of up to 10%.
SOCCER defined difficult cannulation as a papilla in or on the rim of a diverticulum, five or more attempts, attempts lasting 5 or more minutes, or two or more unintended pancreatic duct wire passages. Other features were redundant tissue overlaying the papilla or a type 2, 3, or 4 papilla.
The study found forceps assistance also had a nonstatistically significant lower rate of difficult cannulations than no forceps (57.1% vs 69.1%; P = .132). The rate of post-ERCP pancreatitis (PEP) was similarly low in both groups: 5.7% with forceps vs 3.7% without forceps (P = .705). The no forceps group had significantly more cannulation attempts after randomization than the forceps group (14 vs 8.3; P = .026).
Patients who crossed over to forceps assistance all had successful cannulations.
The technique has long been used to overcome cannulation difficulties, said Timothy B. Gardner, MD, MS, a gastroenterologist at the Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire, and a coauthor of the study. “It was particularly effective for cannulations with redundant tissue limiting access to the papilla,” Gardner told GI & Hepatology News. “We decided to design a randomized trial to determine the extent to which this technique worked. We believed our study would answer an important question that would hopefully lead to an improvement in endoscopy practice.”
While a few case reports and video demos had described the technique, no trials had assessed its effectiveness, Hadley added. “We found the technique to be effective based on our experience, but it was exciting to see that a rigorously designed randomized trial proved that it is indeed a very effective technique to facilitate cannulation.”
Hadley noted the technique does not increase PEP incidence, unlike the commonly used precut sphincterotomy and the double-wire method for difficult cannulations. “As a result, the forceps-assisted technique may be an effective first-line option and may reduce the need for additional, more invasive procedures including surgery and repeat ERCP to obtain the therapeutic intent of the original ERCP.”
The paper outlines the technique’s methodology, he added, “so we believe endoscopists who read the manuscript will be able to start implementing the technique into their practice.”
Commenting on the paper but not involved in it, Christopher J. DiMaio, MD, regional director of Endoscopy for Northwell Health Physician Partners Gastroenterology and a gastroenterologist in Greenlawn, New York, called it potentially helpful but aimed at a niche group of expert practitioners. “The technique appears safe and very effective, which is the number one concern, and I would definitely keep it in my back pocket,” he said. “I expect it will be used more commonly now because of this study.”
He added that although expert endoscopists are familiar with the approach, they use more time-tested and sometimes more aggressive maneuvers to cope with difficult cannulations. “But this is a simple technique using a device that should be available to most high-volume endoscopists.”
DiMaio also noted that he would have liked to see an actual decrease in PEP incidence in the intervention group.
Looking ahead, Hadley said it would be interesting to compare the effectiveness of the double-wire technique against forceps-assisted cannulation in a randomized context. “A study we’re already looking into is seeing whether physician experience with the technique impacts outcomes.”
This study was supported by the American College of Gastroenterology. The authors and DiMaio reported having no relevant competing interests.
A version of this article first appeared on Medscape.com.
The results emerged from the small, single-center SOCCER trial of 152 patients recruited from March 2022 to October 2024 and are published in The American Journal of Gastroenterology.
Both groups had a slightly higher number of female participants, and the mean ages of the participants were 61.9 years in the forceps group and 68.3 years in the no forceps group.
First author Steven M. Hadley Jr, an MD candidate at Northwestern Feinberg School of Medicine in Chicago, and colleagues reported that forceps assistance in difficult cannulations yielded significantly higher success rates than no forceps assistance (100% vs 83.9%; P < .001).
The investigators noted that difficult cannulations during ERCP have a frequency of 42%. Cannulation failure is associated with increased morbidity — including longer hospitalization, increased ICU admissions, readmissions, and increased financial cost — as well as mortality rates of up to 10%.
SOCCER defined difficult cannulation as a papilla in or on the rim of a diverticulum, five or more attempts, attempts lasting 5 or more minutes, or two or more unintended pancreatic duct wire passages. Other features were redundant tissue overlaying the papilla or a type 2, 3, or 4 papilla.
The study found forceps assistance also had a nonstatistically significant lower rate of difficult cannulations than no forceps (57.1% vs 69.1%; P = .132). The rate of post-ERCP pancreatitis (PEP) was similarly low in both groups: 5.7% with forceps vs 3.7% without forceps (P = .705). The no forceps group had significantly more cannulation attempts after randomization than the forceps group (14 vs 8.3; P = .026).
Patients who crossed over to forceps assistance all had successful cannulations.
The technique has long been used to overcome cannulation difficulties, said Timothy B. Gardner, MD, MS, a gastroenterologist at the Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire, and a coauthor of the study. “It was particularly effective for cannulations with redundant tissue limiting access to the papilla,” Gardner told GI & Hepatology News. “We decided to design a randomized trial to determine the extent to which this technique worked. We believed our study would answer an important question that would hopefully lead to an improvement in endoscopy practice.”
While a few case reports and video demos had described the technique, no trials had assessed its effectiveness, Hadley added. “We found the technique to be effective based on our experience, but it was exciting to see that a rigorously designed randomized trial proved that it is indeed a very effective technique to facilitate cannulation.”
Hadley noted the technique does not increase PEP incidence, unlike the commonly used precut sphincterotomy and the double-wire method for difficult cannulations. “As a result, the forceps-assisted technique may be an effective first-line option and may reduce the need for additional, more invasive procedures including surgery and repeat ERCP to obtain the therapeutic intent of the original ERCP.”
The paper outlines the technique’s methodology, he added, “so we believe endoscopists who read the manuscript will be able to start implementing the technique into their practice.”
Commenting on the paper but not involved in it, Christopher J. DiMaio, MD, regional director of Endoscopy for Northwell Health Physician Partners Gastroenterology and a gastroenterologist in Greenlawn, New York, called it potentially helpful but aimed at a niche group of expert practitioners. “The technique appears safe and very effective, which is the number one concern, and I would definitely keep it in my back pocket,” he said. “I expect it will be used more commonly now because of this study.”
He added that although expert endoscopists are familiar with the approach, they use more time-tested and sometimes more aggressive maneuvers to cope with difficult cannulations. “But this is a simple technique using a device that should be available to most high-volume endoscopists.”
DiMaio also noted that he would have liked to see an actual decrease in PEP incidence in the intervention group.
Looking ahead, Hadley said it would be interesting to compare the effectiveness of the double-wire technique against forceps-assisted cannulation in a randomized context. “A study we’re already looking into is seeing whether physician experience with the technique impacts outcomes.”
This study was supported by the American College of Gastroenterology. The authors and DiMaio reported having no relevant competing interests.
A version of this article first appeared on Medscape.com.
The results emerged from the small, single-center SOCCER trial of 152 patients recruited from March 2022 to October 2024 and are published in The American Journal of Gastroenterology.
Both groups had a slightly higher number of female participants, and the mean ages of the participants were 61.9 years in the forceps group and 68.3 years in the no forceps group.
First author Steven M. Hadley Jr, an MD candidate at Northwestern Feinberg School of Medicine in Chicago, and colleagues reported that forceps assistance in difficult cannulations yielded significantly higher success rates than no forceps assistance (100% vs 83.9%; P < .001).
The investigators noted that difficult cannulations during ERCP have a frequency of 42%. Cannulation failure is associated with increased morbidity — including longer hospitalization, increased ICU admissions, readmissions, and increased financial cost — as well as mortality rates of up to 10%.
SOCCER defined difficult cannulation as a papilla in or on the rim of a diverticulum, five or more attempts, attempts lasting 5 or more minutes, or two or more unintended pancreatic duct wire passages. Other features were redundant tissue overlaying the papilla or a type 2, 3, or 4 papilla.
The study found forceps assistance also had a nonstatistically significant lower rate of difficult cannulations than no forceps (57.1% vs 69.1%; P = .132). The rate of post-ERCP pancreatitis (PEP) was similarly low in both groups: 5.7% with forceps vs 3.7% without forceps (P = .705). The no forceps group had significantly more cannulation attempts after randomization than the forceps group (14 vs 8.3; P = .026).
Patients who crossed over to forceps assistance all had successful cannulations.
The technique has long been used to overcome cannulation difficulties, said Timothy B. Gardner, MD, MS, a gastroenterologist at the Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire, and a coauthor of the study. “It was particularly effective for cannulations with redundant tissue limiting access to the papilla,” Gardner told GI & Hepatology News. “We decided to design a randomized trial to determine the extent to which this technique worked. We believed our study would answer an important question that would hopefully lead to an improvement in endoscopy practice.”
While a few case reports and video demos had described the technique, no trials had assessed its effectiveness, Hadley added. “We found the technique to be effective based on our experience, but it was exciting to see that a rigorously designed randomized trial proved that it is indeed a very effective technique to facilitate cannulation.”
Hadley noted the technique does not increase PEP incidence, unlike the commonly used precut sphincterotomy and the double-wire method for difficult cannulations. “As a result, the forceps-assisted technique may be an effective first-line option and may reduce the need for additional, more invasive procedures including surgery and repeat ERCP to obtain the therapeutic intent of the original ERCP.”
The paper outlines the technique’s methodology, he added, “so we believe endoscopists who read the manuscript will be able to start implementing the technique into their practice.”
Commenting on the paper but not involved in it, Christopher J. DiMaio, MD, regional director of Endoscopy for Northwell Health Physician Partners Gastroenterology and a gastroenterologist in Greenlawn, New York, called it potentially helpful but aimed at a niche group of expert practitioners. “The technique appears safe and very effective, which is the number one concern, and I would definitely keep it in my back pocket,” he said. “I expect it will be used more commonly now because of this study.”
He added that although expert endoscopists are familiar with the approach, they use more time-tested and sometimes more aggressive maneuvers to cope with difficult cannulations. “But this is a simple technique using a device that should be available to most high-volume endoscopists.”
DiMaio also noted that he would have liked to see an actual decrease in PEP incidence in the intervention group.
Looking ahead, Hadley said it would be interesting to compare the effectiveness of the double-wire technique against forceps-assisted cannulation in a randomized context. “A study we’re already looking into is seeing whether physician experience with the technique impacts outcomes.”
This study was supported by the American College of Gastroenterology. The authors and DiMaio reported having no relevant competing interests.
A version of this article first appeared on Medscape.com.
GI Disorders Linked With Sleep Problems
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Intestinal Methanogen Overgrowth Fosters More Constipation, Less Diarrhea
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.
“The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies,” wrote investigators led by gastroenterologist Ali Rezaie, MD, MSc, medical director of the GI Motility Program at Cedars-Sinai Medical Center and director of biotechnology in the center’s Medically Associated Science and Technology (MAST) Program. Recognizing specific GI symptom profiles can improve diagnosis and treatment strategies, facilitating further clinical trials and targeted microbiome studies to optimize patient care.
Excessive luminal loads of methanogenic archaea – archaea being bacteria-like prokaryotes and one of the main three domains of the tree of life – have been implicated in the pathophysiology of various diseases, including constipation.
The Study
To elucidate the phenotypical presentation of IMO in patients, Rezaie’s group compared the prevalence and severity of gastrointestinal (GI) symptoms in individuals who had IMO with those who did not have IMO. IMO was based on excess levels of this gaseous GI byproduct in exhaled breath tests.
Searching electronic databases from inception to September 2023, the researchers identified 19 eligible studies from diverse geographical regions with 1293 IMO patients and 3208 controls. Eleven studies were performed in the United States; the other studies were conducted in France (n = 2), India (n = 2), New Zealand (n = 1), South Korea (n = 1), Italy (n = 1), and the United Kingdom (n = 1). Thirteen studies were of high quality, as defined by a Newcastle-Ottawa Assessment Scale score of 6.
Patients with IMO were found to exhibit a range of GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%).
In other findings:
- Patients with IMO had a significantly higher prevalence of constipation vs controls: 47% vs 38% (odds ratio [OR], 2.04, 95% confidence interval [CI], 1.48-2.83, P < .0001).
- They had a lower prevalence of diarrhea: 37% vs 52% (OR .58, 95% CI, .37-.90, P = .01); and nausea: 32% vs 45%; (OR, .75; 95% CI, .60-.94, P = .01).
- Patients with IMO had more severe constipation: standard mean deviation [SMD], .77 (95% CI, .11-1.43, P = .02) and a lower severity of diarrhea: SMD, –.71 (95% CI, –1.39 to –.03, P = .04). Significant heterogeneity of effect, however, was detected.
- Constipation was more prevalent in IMO diagnosed with the lactulose breath test and the glucose breath test and constipation was particularly prevalent in Europe and the United States.
Mechanism of Action
The findings on constipation and diarrhea corroborate methane’s slowing physiologic effects on motility, the authors noted. It has been consistently found to delay gut transit, both small bowel and colonic transit.
Mechanistically, methane reduces small intestinal peristaltic velocity while augmenting non-propagating contraction amplitude, suggesting that reduction of intestinal transit time is mediated through promotion of non-propulsive contractions.
“This study further consolidates methane’s causal role in constipation and paves the way to establish validated disease-specific patient-reported outcomes,” Rezaie and associates wrote, calling for longitudinal and mechanistic studies assessing the archaeome in order to advance understanding of IMO.
This study was funded in part by Nancy Stark and Stanley Lezman in support of the MAST Program’s Innovation Project at Cedars-Sinai.
Rezaie serves as a consultant/speaker for Bausch Health. Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech, in which Rezaie and coauthor Pimentel have equity. They also hold equity in Good LIFE. Pimentel consults for and has received grant support from Bausch Health.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Common Medications Do Not Raise Microscopic Colitis Risk in Seniors
“Sensitivity analyses suggest that previously reported associations and persistent association with SSRI [selective serotonin reuptake inhibitor] initiation may be due to surveillance bias,” wrote gastroenterologist Hamed Khalili, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues in Annals of Internal Medicine, advising clinicians to carefully balance the benefits of these medication classes against the very low likelihood of a causal relationship with MC.
While two smaller studies had challenged the belief that these medications can cause MC, Khalili told GI & Hepatology News, “the quality of the data that supported or refuted this hypothesis were low. Nevertheless, most in the field consider MC to be largely related to medications so we thought it was important to systematically answer this question.”
While most medications thought to trigger MC were found not to be causally linked, he added, “we did observe a marginal association with SSRIs but could not rule out the possibility that the association is related to residual bias.”
The authors noted that the incidence of MC in older persons is rising rapidly and is thought to account for more than 30% of chronic diarrhea cases in this group.
Despite weak evidence in the literature, the treatment guidelines of several societies, including the American Gastroenterological Association, recommend discontinuing potential pharmacologic triggers as first-line prevention or as an adjunct therapy, particularly in recurrent or refractory MC. But this approach may be ineffective in patients with established disease and could lead to inappropriate discontinuation of medication such as antihypertensives, the authors argued.
As to proposed mechanisms of action, said Khalili, “for PPIs [proton-pump inhibitors,] people thought it was related to changes in the gut microbiome. For NSAIDs [nonsteroidal anti-inflammatory drugs], people thought it could be related to changes in the gut barrier function. But overall, not a single mechanism would have explained all the prior associations that were observed.”
While medications such as PPIs and SSRIs can cause diarrhea in a small subset of users, Khalili added, “most patients generally catch these side effects very quickly and realize that stopping these medications will improve their diarrhea. This is very different than most patients we as gastroenterologists see with a new diagnosis of MC. Many of them may have been on these medications for a long time. We believe that stopping medications in these patients is unnecessary.”
Study Details
The investigators looked at eligible residents in Sweden age 65 years or older in the years 2006 to 2017 (n = 191,482 to 2,634,777). Participants had no history of inflammatory bowel disease and different cohorts were examined for various common medications from calcium channel blockers to statins.
With a primary outcome of biopsy-verified MC, dates of diagnosis were obtained from Sweden’s national histopathology cohort ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden). Among the findings:
- The 12- and 24-month cumulative incidences of MC were less than 0.05% under all treatment strategies.
- Estimated 12-month risk differences were close to null under angiotensin-converting enzyme vs calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker vs CCB initiation, NSAID initiation vs noninitiation, PPI inhibitor initiation vs noninitiation, and statin initiation vs noninitiation.
- The estimated 12-month risk difference was 0.04% (95% CI, 0.03%-0.05%) for SSRIs vs mirtazapine.
- Results were similar for 24-month risk differences. Several medications such as SSRIs were also associated with increased risk for undergoing colonoscopy with a normal colorectal mucosa biopsy result.
“We think it’s unlikely that stopping these medications will improve symptoms of MC,” Khalili said.
Commenting on the paper but not involved in it, Jordan E. Axelrad, MD, MPH, codirector of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City, said, “This study strengthens the argument that MC is an immune-mediated disease, not primarily driven by drug exposures. But future studies in diverse cohorts are required to validate these findings.” He said the study nevertheless provides reassurance that previously reported associations may have been overstated or confounded by factors such as reverse causation and increased healthcare utilization preceding the MC diagnosis.
In the meantime, Axelrad added, the findings “may reduce the inclination to promptly discontinue medications historically associated with MC in newly diagnosed cases. Also, these data help shift the clinical focus away from medication cessation alone and toward a needed and broader MC management strategy. US-based validation would likely highlight these changes in our patients.”
Despite concerns about the study’s unmeasured confounding because of differential healthcare utilization or surveillance, the modest association observed between SSRI and MC is supported by literature linking catecholamine and serotonin to gut innate immunity and microbiota, Khalili’s group wrote. “However, this finding may also be confounded by other factors including persisting surveillance and protopathic bias, especially since an association was also seen for risk for receipt of a colonoscopy with normal mucosa.”
Khalili believes the Swedish results are applicable even to the more diverse US population. He noted that lack of primary care data limited measurement of and adjustment for symptoms and medical diagnoses that increase risk. But according to Axelrad, MC is more prevalent in White, older patients, who are well-represented in Swedish cohorts but to a lesser extent in US populations. “Additionally, environmental factors and medication use patterns differ between Sweden and the US, particularly in regard to over-the-counter medication access.”
The findings have implications for future research in pharmacoepidemiologic studies of gastrointestinal-related outcomes. Since many routinely prescribed medications such as SSRIs were associated with an apparent increased risk for colonoscopies with normal colorectal biopsy results, future studies that examine gastrointestinal-specific adverse events should carefully consider potential surveillance bias.
In the meantime, Khalili stressed, it’s important to highlight that while some of these medications cause diarrhea in a small subset of patients, stopping medications in these patients is unnecessary.
This study was supported by the National Institutes of Health (NIH) and the Swedish Research Council. Khalili disclosed grants from the Crohn’s & Coiltis Foundation, the NIH and the Helmsley CharitableTrust, as well as stock ownership in Cylinder Health. One coauthor is employed by Massachusetts General Hospital. Axelrad had no relevant competing interests.
“Sensitivity analyses suggest that previously reported associations and persistent association with SSRI [selective serotonin reuptake inhibitor] initiation may be due to surveillance bias,” wrote gastroenterologist Hamed Khalili, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues in Annals of Internal Medicine, advising clinicians to carefully balance the benefits of these medication classes against the very low likelihood of a causal relationship with MC.
While two smaller studies had challenged the belief that these medications can cause MC, Khalili told GI & Hepatology News, “the quality of the data that supported or refuted this hypothesis were low. Nevertheless, most in the field consider MC to be largely related to medications so we thought it was important to systematically answer this question.”
While most medications thought to trigger MC were found not to be causally linked, he added, “we did observe a marginal association with SSRIs but could not rule out the possibility that the association is related to residual bias.”
The authors noted that the incidence of MC in older persons is rising rapidly and is thought to account for more than 30% of chronic diarrhea cases in this group.
Despite weak evidence in the literature, the treatment guidelines of several societies, including the American Gastroenterological Association, recommend discontinuing potential pharmacologic triggers as first-line prevention or as an adjunct therapy, particularly in recurrent or refractory MC. But this approach may be ineffective in patients with established disease and could lead to inappropriate discontinuation of medication such as antihypertensives, the authors argued.
As to proposed mechanisms of action, said Khalili, “for PPIs [proton-pump inhibitors,] people thought it was related to changes in the gut microbiome. For NSAIDs [nonsteroidal anti-inflammatory drugs], people thought it could be related to changes in the gut barrier function. But overall, not a single mechanism would have explained all the prior associations that were observed.”
While medications such as PPIs and SSRIs can cause diarrhea in a small subset of users, Khalili added, “most patients generally catch these side effects very quickly and realize that stopping these medications will improve their diarrhea. This is very different than most patients we as gastroenterologists see with a new diagnosis of MC. Many of them may have been on these medications for a long time. We believe that stopping medications in these patients is unnecessary.”
Study Details
The investigators looked at eligible residents in Sweden age 65 years or older in the years 2006 to 2017 (n = 191,482 to 2,634,777). Participants had no history of inflammatory bowel disease and different cohorts were examined for various common medications from calcium channel blockers to statins.
With a primary outcome of biopsy-verified MC, dates of diagnosis were obtained from Sweden’s national histopathology cohort ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden). Among the findings:
- The 12- and 24-month cumulative incidences of MC were less than 0.05% under all treatment strategies.
- Estimated 12-month risk differences were close to null under angiotensin-converting enzyme vs calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker vs CCB initiation, NSAID initiation vs noninitiation, PPI inhibitor initiation vs noninitiation, and statin initiation vs noninitiation.
- The estimated 12-month risk difference was 0.04% (95% CI, 0.03%-0.05%) for SSRIs vs mirtazapine.
- Results were similar for 24-month risk differences. Several medications such as SSRIs were also associated with increased risk for undergoing colonoscopy with a normal colorectal mucosa biopsy result.
“We think it’s unlikely that stopping these medications will improve symptoms of MC,” Khalili said.
Commenting on the paper but not involved in it, Jordan E. Axelrad, MD, MPH, codirector of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City, said, “This study strengthens the argument that MC is an immune-mediated disease, not primarily driven by drug exposures. But future studies in diverse cohorts are required to validate these findings.” He said the study nevertheless provides reassurance that previously reported associations may have been overstated or confounded by factors such as reverse causation and increased healthcare utilization preceding the MC diagnosis.
In the meantime, Axelrad added, the findings “may reduce the inclination to promptly discontinue medications historically associated with MC in newly diagnosed cases. Also, these data help shift the clinical focus away from medication cessation alone and toward a needed and broader MC management strategy. US-based validation would likely highlight these changes in our patients.”
Despite concerns about the study’s unmeasured confounding because of differential healthcare utilization or surveillance, the modest association observed between SSRI and MC is supported by literature linking catecholamine and serotonin to gut innate immunity and microbiota, Khalili’s group wrote. “However, this finding may also be confounded by other factors including persisting surveillance and protopathic bias, especially since an association was also seen for risk for receipt of a colonoscopy with normal mucosa.”
Khalili believes the Swedish results are applicable even to the more diverse US population. He noted that lack of primary care data limited measurement of and adjustment for symptoms and medical diagnoses that increase risk. But according to Axelrad, MC is more prevalent in White, older patients, who are well-represented in Swedish cohorts but to a lesser extent in US populations. “Additionally, environmental factors and medication use patterns differ between Sweden and the US, particularly in regard to over-the-counter medication access.”
The findings have implications for future research in pharmacoepidemiologic studies of gastrointestinal-related outcomes. Since many routinely prescribed medications such as SSRIs were associated with an apparent increased risk for colonoscopies with normal colorectal biopsy results, future studies that examine gastrointestinal-specific adverse events should carefully consider potential surveillance bias.
In the meantime, Khalili stressed, it’s important to highlight that while some of these medications cause diarrhea in a small subset of patients, stopping medications in these patients is unnecessary.
This study was supported by the National Institutes of Health (NIH) and the Swedish Research Council. Khalili disclosed grants from the Crohn’s & Coiltis Foundation, the NIH and the Helmsley CharitableTrust, as well as stock ownership in Cylinder Health. One coauthor is employed by Massachusetts General Hospital. Axelrad had no relevant competing interests.
“Sensitivity analyses suggest that previously reported associations and persistent association with SSRI [selective serotonin reuptake inhibitor] initiation may be due to surveillance bias,” wrote gastroenterologist Hamed Khalili, MD, MPH, of Massachusetts General Hospital, Boston, and colleagues in Annals of Internal Medicine, advising clinicians to carefully balance the benefits of these medication classes against the very low likelihood of a causal relationship with MC.
While two smaller studies had challenged the belief that these medications can cause MC, Khalili told GI & Hepatology News, “the quality of the data that supported or refuted this hypothesis were low. Nevertheless, most in the field consider MC to be largely related to medications so we thought it was important to systematically answer this question.”
While most medications thought to trigger MC were found not to be causally linked, he added, “we did observe a marginal association with SSRIs but could not rule out the possibility that the association is related to residual bias.”
The authors noted that the incidence of MC in older persons is rising rapidly and is thought to account for more than 30% of chronic diarrhea cases in this group.
Despite weak evidence in the literature, the treatment guidelines of several societies, including the American Gastroenterological Association, recommend discontinuing potential pharmacologic triggers as first-line prevention or as an adjunct therapy, particularly in recurrent or refractory MC. But this approach may be ineffective in patients with established disease and could lead to inappropriate discontinuation of medication such as antihypertensives, the authors argued.
As to proposed mechanisms of action, said Khalili, “for PPIs [proton-pump inhibitors,] people thought it was related to changes in the gut microbiome. For NSAIDs [nonsteroidal anti-inflammatory drugs], people thought it could be related to changes in the gut barrier function. But overall, not a single mechanism would have explained all the prior associations that were observed.”
While medications such as PPIs and SSRIs can cause diarrhea in a small subset of users, Khalili added, “most patients generally catch these side effects very quickly and realize that stopping these medications will improve their diarrhea. This is very different than most patients we as gastroenterologists see with a new diagnosis of MC. Many of them may have been on these medications for a long time. We believe that stopping medications in these patients is unnecessary.”
Study Details
The investigators looked at eligible residents in Sweden age 65 years or older in the years 2006 to 2017 (n = 191,482 to 2,634,777). Participants had no history of inflammatory bowel disease and different cohorts were examined for various common medications from calcium channel blockers to statins.
With a primary outcome of biopsy-verified MC, dates of diagnosis were obtained from Sweden’s national histopathology cohort ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden). Among the findings:
- The 12- and 24-month cumulative incidences of MC were less than 0.05% under all treatment strategies.
- Estimated 12-month risk differences were close to null under angiotensin-converting enzyme vs calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker vs CCB initiation, NSAID initiation vs noninitiation, PPI inhibitor initiation vs noninitiation, and statin initiation vs noninitiation.
- The estimated 12-month risk difference was 0.04% (95% CI, 0.03%-0.05%) for SSRIs vs mirtazapine.
- Results were similar for 24-month risk differences. Several medications such as SSRIs were also associated with increased risk for undergoing colonoscopy with a normal colorectal mucosa biopsy result.
“We think it’s unlikely that stopping these medications will improve symptoms of MC,” Khalili said.
Commenting on the paper but not involved in it, Jordan E. Axelrad, MD, MPH, codirector of the Inflammatory Bowel Disease Center at NYU Langone Health in New York City, said, “This study strengthens the argument that MC is an immune-mediated disease, not primarily driven by drug exposures. But future studies in diverse cohorts are required to validate these findings.” He said the study nevertheless provides reassurance that previously reported associations may have been overstated or confounded by factors such as reverse causation and increased healthcare utilization preceding the MC diagnosis.
In the meantime, Axelrad added, the findings “may reduce the inclination to promptly discontinue medications historically associated with MC in newly diagnosed cases. Also, these data help shift the clinical focus away from medication cessation alone and toward a needed and broader MC management strategy. US-based validation would likely highlight these changes in our patients.”
Despite concerns about the study’s unmeasured confounding because of differential healthcare utilization or surveillance, the modest association observed between SSRI and MC is supported by literature linking catecholamine and serotonin to gut innate immunity and microbiota, Khalili’s group wrote. “However, this finding may also be confounded by other factors including persisting surveillance and protopathic bias, especially since an association was also seen for risk for receipt of a colonoscopy with normal mucosa.”
Khalili believes the Swedish results are applicable even to the more diverse US population. He noted that lack of primary care data limited measurement of and adjustment for symptoms and medical diagnoses that increase risk. But according to Axelrad, MC is more prevalent in White, older patients, who are well-represented in Swedish cohorts but to a lesser extent in US populations. “Additionally, environmental factors and medication use patterns differ between Sweden and the US, particularly in regard to over-the-counter medication access.”
The findings have implications for future research in pharmacoepidemiologic studies of gastrointestinal-related outcomes. Since many routinely prescribed medications such as SSRIs were associated with an apparent increased risk for colonoscopies with normal colorectal biopsy results, future studies that examine gastrointestinal-specific adverse events should carefully consider potential surveillance bias.
In the meantime, Khalili stressed, it’s important to highlight that while some of these medications cause diarrhea in a small subset of patients, stopping medications in these patients is unnecessary.
This study was supported by the National Institutes of Health (NIH) and the Swedish Research Council. Khalili disclosed grants from the Crohn’s & Coiltis Foundation, the NIH and the Helmsley CharitableTrust, as well as stock ownership in Cylinder Health. One coauthor is employed by Massachusetts General Hospital. Axelrad had no relevant competing interests.
New Evidence Red Meat–Rich Diet Can Exacerbate IBD
Researchers from China observed that mice fed a red meat diet experienced more severe intestinal inflammation after colitis was experimentally induced compared to those on a control diet.
“These results highlight the necessity of dietary optimization, particularly the reduction of red meat consumption, as a preventive strategy against the development of IBD,” wrote Dan Tian, MD, PhD, with Capital Medical University, Beijing, China, and colleagues. The study was published online in Molecular Nutrition & Food Research.
Environmental Trigger
The exact causes of IBD remain unclear, but diet has long been considered a key environmental trigger. Western dietary patterns, which often feature high consumption of red and processed meats and low fiber, have been associated with higher IBD rates, especially ulcerative colitis.
Tian and colleagues tested the aggravating effects of three red meat diets on intestinal inflammation, gut microbiota composition, and susceptibility to colitis in mice.
They fed mice red meat diets prepared from pork, beef, and mutton for 2 weeks before inducing colitis using dextran sulfate sodium. They monitored the animals for changes in weight, colon length, tissue damage, and immune activity.
Histological analysis revealed that all three red meat diets aggravated colonic inflammation, with mutton producing the most pronounced effects.
RNA sequencing of colon tissue further showed that red meat intake activated pathways linked to inflammation. “Notably,” expression off proinflammatory cytokines, including interleukin (IL)-1 beta and IL-6, was significantly upregulated and expression of genes related to myeloid cell chemotaxis and activation was also increased, the researchers reported.
Flow cytometry confirmed that red meat diets promoted a surge in colonic myeloid immune cells, potentially driving inflammation. However, only minimal changes in T lymphocytes were observed, suggesting that red meat primarily drives innate immune rather than adaptive immune activation, they suggested.
While overall microbial diversity was not significantly altered, red meat-fed mice displayed marked dysbiosis.
Beneficial bacteria such as Streptococcus, Akkermansia, Faecalibacterium, and Lactococcus declined, while harmful groups including Clostridium and Mucispirillum increased. Each type of meat had distinct microbial effects, but all skewed the balance toward potentially harmful bacteria known to promote gut inflammation.
Overall, these results suggest that red meat diets exacerbate colitis by simultaneously promoting immune cell infiltration and disturbing microbial communities in the gut.
The fact that these effects occurred without significant change in weight, suggests that red meat consumption exerts proinflammatory effects through mechanisms other than weight gain.
“These results offer valuable insights into the relationship between dietary interventions and IBD, suggesting that a balanced diet, adequate nutrients, and moderated red meat consumption may help prevent the development of IBD,” the researchers concluded.
In support of their findings, a 2024 umbrella review that synthesized data from multiple cohort and observational studies, found strong associations between Western-style dietary patterns — including high processed/red meat, saturated fats, and additives — and both the incidence and progression of IBD.
The study had no commercial funding. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
Researchers from China observed that mice fed a red meat diet experienced more severe intestinal inflammation after colitis was experimentally induced compared to those on a control diet.
“These results highlight the necessity of dietary optimization, particularly the reduction of red meat consumption, as a preventive strategy against the development of IBD,” wrote Dan Tian, MD, PhD, with Capital Medical University, Beijing, China, and colleagues. The study was published online in Molecular Nutrition & Food Research.
Environmental Trigger
The exact causes of IBD remain unclear, but diet has long been considered a key environmental trigger. Western dietary patterns, which often feature high consumption of red and processed meats and low fiber, have been associated with higher IBD rates, especially ulcerative colitis.
Tian and colleagues tested the aggravating effects of three red meat diets on intestinal inflammation, gut microbiota composition, and susceptibility to colitis in mice.
They fed mice red meat diets prepared from pork, beef, and mutton for 2 weeks before inducing colitis using dextran sulfate sodium. They monitored the animals for changes in weight, colon length, tissue damage, and immune activity.
Histological analysis revealed that all three red meat diets aggravated colonic inflammation, with mutton producing the most pronounced effects.
RNA sequencing of colon tissue further showed that red meat intake activated pathways linked to inflammation. “Notably,” expression off proinflammatory cytokines, including interleukin (IL)-1 beta and IL-6, was significantly upregulated and expression of genes related to myeloid cell chemotaxis and activation was also increased, the researchers reported.
Flow cytometry confirmed that red meat diets promoted a surge in colonic myeloid immune cells, potentially driving inflammation. However, only minimal changes in T lymphocytes were observed, suggesting that red meat primarily drives innate immune rather than adaptive immune activation, they suggested.
While overall microbial diversity was not significantly altered, red meat-fed mice displayed marked dysbiosis.
Beneficial bacteria such as Streptococcus, Akkermansia, Faecalibacterium, and Lactococcus declined, while harmful groups including Clostridium and Mucispirillum increased. Each type of meat had distinct microbial effects, but all skewed the balance toward potentially harmful bacteria known to promote gut inflammation.
Overall, these results suggest that red meat diets exacerbate colitis by simultaneously promoting immune cell infiltration and disturbing microbial communities in the gut.
The fact that these effects occurred without significant change in weight, suggests that red meat consumption exerts proinflammatory effects through mechanisms other than weight gain.
“These results offer valuable insights into the relationship between dietary interventions and IBD, suggesting that a balanced diet, adequate nutrients, and moderated red meat consumption may help prevent the development of IBD,” the researchers concluded.
In support of their findings, a 2024 umbrella review that synthesized data from multiple cohort and observational studies, found strong associations between Western-style dietary patterns — including high processed/red meat, saturated fats, and additives — and both the incidence and progression of IBD.
The study had no commercial funding. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
Researchers from China observed that mice fed a red meat diet experienced more severe intestinal inflammation after colitis was experimentally induced compared to those on a control diet.
“These results highlight the necessity of dietary optimization, particularly the reduction of red meat consumption, as a preventive strategy against the development of IBD,” wrote Dan Tian, MD, PhD, with Capital Medical University, Beijing, China, and colleagues. The study was published online in Molecular Nutrition & Food Research.
Environmental Trigger
The exact causes of IBD remain unclear, but diet has long been considered a key environmental trigger. Western dietary patterns, which often feature high consumption of red and processed meats and low fiber, have been associated with higher IBD rates, especially ulcerative colitis.
Tian and colleagues tested the aggravating effects of three red meat diets on intestinal inflammation, gut microbiota composition, and susceptibility to colitis in mice.
They fed mice red meat diets prepared from pork, beef, and mutton for 2 weeks before inducing colitis using dextran sulfate sodium. They monitored the animals for changes in weight, colon length, tissue damage, and immune activity.
Histological analysis revealed that all three red meat diets aggravated colonic inflammation, with mutton producing the most pronounced effects.
RNA sequencing of colon tissue further showed that red meat intake activated pathways linked to inflammation. “Notably,” expression off proinflammatory cytokines, including interleukin (IL)-1 beta and IL-6, was significantly upregulated and expression of genes related to myeloid cell chemotaxis and activation was also increased, the researchers reported.
Flow cytometry confirmed that red meat diets promoted a surge in colonic myeloid immune cells, potentially driving inflammation. However, only minimal changes in T lymphocytes were observed, suggesting that red meat primarily drives innate immune rather than adaptive immune activation, they suggested.
While overall microbial diversity was not significantly altered, red meat-fed mice displayed marked dysbiosis.
Beneficial bacteria such as Streptococcus, Akkermansia, Faecalibacterium, and Lactococcus declined, while harmful groups including Clostridium and Mucispirillum increased. Each type of meat had distinct microbial effects, but all skewed the balance toward potentially harmful bacteria known to promote gut inflammation.
Overall, these results suggest that red meat diets exacerbate colitis by simultaneously promoting immune cell infiltration and disturbing microbial communities in the gut.
The fact that these effects occurred without significant change in weight, suggests that red meat consumption exerts proinflammatory effects through mechanisms other than weight gain.
“These results offer valuable insights into the relationship between dietary interventions and IBD, suggesting that a balanced diet, adequate nutrients, and moderated red meat consumption may help prevent the development of IBD,” the researchers concluded.
In support of their findings, a 2024 umbrella review that synthesized data from multiple cohort and observational studies, found strong associations between Western-style dietary patterns — including high processed/red meat, saturated fats, and additives — and both the incidence and progression of IBD.
The study had no commercial funding. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
Elevated Serologic Markers Insufficient to Diagnose Celiac Disease
, a large pediatric cohort study in North America found.
Because tTG-IgA assay performance varied widely across labs, diagnostic confirmation by a specialist is essential before gluten-targeted dietary changes are made, according to Denis Chang, MD, MS, of the Division of Gastroenterology and Nutrition at Boston Children’s Hospital in Boston, and colleagues reported in Pediatrics.
“Currently, small intestinal biopsy is the gold standard for diagnosing pediatric celiac disease, but recent European diagnostic criteria allow a nonbiopsy pathway for serologic diagnosis,” Chang told GI & Heaptology News. The European guidelines allow this pathway when a very high tTG-IgA is confirmed by a positive endomysial IgA antibody (EMA) in a second blood sample.
Those guidelines have not been adopted on this continent, however, so Chang’s group assessed the positive predictive value (PPV) of the North American tTG-IgA assay to identify histologic findings of celiac disease.
Another issue is the absence of a universal standard threshold across labs for a high antibody value. “Common assays used in North America differ in performance, and there are not many large multicenter studies looking at this issue. Hopefully, a standard will be developed in the near future. Before this serologic pathway can enter into our guidelines, this question needs to be addressed.”
Study Details
The multicenter retrospective study by Dr. Chang’s team looked at patients younger than 18 years from three pediatric hospitals in Canada and nine in the US who had an elevated tTG-IgA within 6 months of an esophagogastroduodenoscopy from January 2016 to December 2021. Biopsy-confirmed celiac disease was determined by the presence of intraepithelial lymphocytosis and villous atrophy. The primary outcomes were the PPV of an elevated tTG-IgA and a tTG-IgA at least 10 times the upper limit of normal (10x ULN).
The study cohort included 4019 children (63.3% female, 9% with type 1 diabetes, and 2% with Down syndrome). Histologic findings were consistent with celiac disease for 3321 children, for a PPV of 82.6% (95% CI, 81.4%-83.8%).
Among the 1739 (43.2%) children with tTG-IgA of at least 10x ULN, 1651 had biopsy-confirmed celiac disease, for a PPV 10x ULN of 94.9% (95% CI, 93.8%-95.9%). About 5% (n = 88) of positive-testing children did not have histologic findings of celiac disease, including 2% (n = 41) with normal histology.
Diagnostic accuracy of tTG-IgA varied widely among the assays used in North America, with a PPV range of 71.5%-88.8% and a PPV 10x ULN range of 89.3%-97.3%. Assays did not perform as well in children with type 1 diabetes: PPV 10x ULN of 89% (95% CI, 83.5%-92.8%).
In other notable findings, the EMA blood test only marginally improved specificity, as 76% of children without celiac disease, but with a tTG-IgA of at least 10x ULN had a positive EMA in the same sample.
While the study lends credence to the notion that a highly positive tTG-IgA correlates with enteropathy in most children, the 1 in 20 with a tTG-IgA greater than 10x ULN who did not have histologic findings diagnostic of celiac disease cannot be ignored. “This included 2% who had normal small intestinal biopsies on a gluten-containing unrestricted diet, highlighting the limitations of making a celiac disease diagnosis based solely upon a single, highly positive tTG-IgA level,” Chang and colleagues wrote.
Does this mean that substantial numbers of children with suspected celiac disease are being unnecessarily placed on gluten-restricted diets to no avail? “That’s a good question, but our retrospective data do not provide an answer to that,” Chang said. And what causes elevated autoantibodies in children who are not diagnosed with celiac disease? “That is also a question that will require further research,” he said.
Commenting on the study but not involved in it, Supriya Nair, MD, a pediatric gastroenterologist at UTHealth Houston, called it “very interesting because it highlights for primary care physicians that we may need endoscopic evaluation more than we thought.” This is particularly true given the lack of standardized laboratory values noted in the study.
Nair said that some children with high seromarker levels but no discernible lesions may develop celiac disease later. “It may be that the markers are not yet causing inflammation in the bowel. These patients must be monitored to see if levels stay high or come down.”
In her practice, she has seen some children who have been put on gluten-free diets prematurely. “But it’s very important to get an accurate, official confirmation with endoscopy because of the ramifications of a celiac diagnosis,” she said. “This is a lifelong condition, and the diet is not easy to follow, especially in North America.” And for children, especially, there are restrictive social impacts and the constant need to be aware of what they’re eating and the danger of cross-contamination in foods, she said.
Chang hopes these data will be pivotal in helping medical societies develop new North American guidelines. In the meantime, pediatricians and primary doctors need to be aware that a high number on a tTG-IgA test does not always mean the presence of celiac disease, although it could be a harbinger of its future development. “Further confirmation by a specialist is essential.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Chang and Nair reported having no competing interests. Several study authors reported receiving research support from and serving as consultants or members of data safety monitoring boards for pharmaceutical companies.
A version of this article appeared on Medscape.com.
, a large pediatric cohort study in North America found.
Because tTG-IgA assay performance varied widely across labs, diagnostic confirmation by a specialist is essential before gluten-targeted dietary changes are made, according to Denis Chang, MD, MS, of the Division of Gastroenterology and Nutrition at Boston Children’s Hospital in Boston, and colleagues reported in Pediatrics.
“Currently, small intestinal biopsy is the gold standard for diagnosing pediatric celiac disease, but recent European diagnostic criteria allow a nonbiopsy pathway for serologic diagnosis,” Chang told GI & Heaptology News. The European guidelines allow this pathway when a very high tTG-IgA is confirmed by a positive endomysial IgA antibody (EMA) in a second blood sample.
Those guidelines have not been adopted on this continent, however, so Chang’s group assessed the positive predictive value (PPV) of the North American tTG-IgA assay to identify histologic findings of celiac disease.
Another issue is the absence of a universal standard threshold across labs for a high antibody value. “Common assays used in North America differ in performance, and there are not many large multicenter studies looking at this issue. Hopefully, a standard will be developed in the near future. Before this serologic pathway can enter into our guidelines, this question needs to be addressed.”
Study Details
The multicenter retrospective study by Dr. Chang’s team looked at patients younger than 18 years from three pediatric hospitals in Canada and nine in the US who had an elevated tTG-IgA within 6 months of an esophagogastroduodenoscopy from January 2016 to December 2021. Biopsy-confirmed celiac disease was determined by the presence of intraepithelial lymphocytosis and villous atrophy. The primary outcomes were the PPV of an elevated tTG-IgA and a tTG-IgA at least 10 times the upper limit of normal (10x ULN).
The study cohort included 4019 children (63.3% female, 9% with type 1 diabetes, and 2% with Down syndrome). Histologic findings were consistent with celiac disease for 3321 children, for a PPV of 82.6% (95% CI, 81.4%-83.8%).
Among the 1739 (43.2%) children with tTG-IgA of at least 10x ULN, 1651 had biopsy-confirmed celiac disease, for a PPV 10x ULN of 94.9% (95% CI, 93.8%-95.9%). About 5% (n = 88) of positive-testing children did not have histologic findings of celiac disease, including 2% (n = 41) with normal histology.
Diagnostic accuracy of tTG-IgA varied widely among the assays used in North America, with a PPV range of 71.5%-88.8% and a PPV 10x ULN range of 89.3%-97.3%. Assays did not perform as well in children with type 1 diabetes: PPV 10x ULN of 89% (95% CI, 83.5%-92.8%).
In other notable findings, the EMA blood test only marginally improved specificity, as 76% of children without celiac disease, but with a tTG-IgA of at least 10x ULN had a positive EMA in the same sample.
While the study lends credence to the notion that a highly positive tTG-IgA correlates with enteropathy in most children, the 1 in 20 with a tTG-IgA greater than 10x ULN who did not have histologic findings diagnostic of celiac disease cannot be ignored. “This included 2% who had normal small intestinal biopsies on a gluten-containing unrestricted diet, highlighting the limitations of making a celiac disease diagnosis based solely upon a single, highly positive tTG-IgA level,” Chang and colleagues wrote.
Does this mean that substantial numbers of children with suspected celiac disease are being unnecessarily placed on gluten-restricted diets to no avail? “That’s a good question, but our retrospective data do not provide an answer to that,” Chang said. And what causes elevated autoantibodies in children who are not diagnosed with celiac disease? “That is also a question that will require further research,” he said.
Commenting on the study but not involved in it, Supriya Nair, MD, a pediatric gastroenterologist at UTHealth Houston, called it “very interesting because it highlights for primary care physicians that we may need endoscopic evaluation more than we thought.” This is particularly true given the lack of standardized laboratory values noted in the study.
Nair said that some children with high seromarker levels but no discernible lesions may develop celiac disease later. “It may be that the markers are not yet causing inflammation in the bowel. These patients must be monitored to see if levels stay high or come down.”
In her practice, she has seen some children who have been put on gluten-free diets prematurely. “But it’s very important to get an accurate, official confirmation with endoscopy because of the ramifications of a celiac diagnosis,” she said. “This is a lifelong condition, and the diet is not easy to follow, especially in North America.” And for children, especially, there are restrictive social impacts and the constant need to be aware of what they’re eating and the danger of cross-contamination in foods, she said.
Chang hopes these data will be pivotal in helping medical societies develop new North American guidelines. In the meantime, pediatricians and primary doctors need to be aware that a high number on a tTG-IgA test does not always mean the presence of celiac disease, although it could be a harbinger of its future development. “Further confirmation by a specialist is essential.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Chang and Nair reported having no competing interests. Several study authors reported receiving research support from and serving as consultants or members of data safety monitoring boards for pharmaceutical companies.
A version of this article appeared on Medscape.com.
, a large pediatric cohort study in North America found.
Because tTG-IgA assay performance varied widely across labs, diagnostic confirmation by a specialist is essential before gluten-targeted dietary changes are made, according to Denis Chang, MD, MS, of the Division of Gastroenterology and Nutrition at Boston Children’s Hospital in Boston, and colleagues reported in Pediatrics.
“Currently, small intestinal biopsy is the gold standard for diagnosing pediatric celiac disease, but recent European diagnostic criteria allow a nonbiopsy pathway for serologic diagnosis,” Chang told GI & Heaptology News. The European guidelines allow this pathway when a very high tTG-IgA is confirmed by a positive endomysial IgA antibody (EMA) in a second blood sample.
Those guidelines have not been adopted on this continent, however, so Chang’s group assessed the positive predictive value (PPV) of the North American tTG-IgA assay to identify histologic findings of celiac disease.
Another issue is the absence of a universal standard threshold across labs for a high antibody value. “Common assays used in North America differ in performance, and there are not many large multicenter studies looking at this issue. Hopefully, a standard will be developed in the near future. Before this serologic pathway can enter into our guidelines, this question needs to be addressed.”
Study Details
The multicenter retrospective study by Dr. Chang’s team looked at patients younger than 18 years from three pediatric hospitals in Canada and nine in the US who had an elevated tTG-IgA within 6 months of an esophagogastroduodenoscopy from January 2016 to December 2021. Biopsy-confirmed celiac disease was determined by the presence of intraepithelial lymphocytosis and villous atrophy. The primary outcomes were the PPV of an elevated tTG-IgA and a tTG-IgA at least 10 times the upper limit of normal (10x ULN).
The study cohort included 4019 children (63.3% female, 9% with type 1 diabetes, and 2% with Down syndrome). Histologic findings were consistent with celiac disease for 3321 children, for a PPV of 82.6% (95% CI, 81.4%-83.8%).
Among the 1739 (43.2%) children with tTG-IgA of at least 10x ULN, 1651 had biopsy-confirmed celiac disease, for a PPV 10x ULN of 94.9% (95% CI, 93.8%-95.9%). About 5% (n = 88) of positive-testing children did not have histologic findings of celiac disease, including 2% (n = 41) with normal histology.
Diagnostic accuracy of tTG-IgA varied widely among the assays used in North America, with a PPV range of 71.5%-88.8% and a PPV 10x ULN range of 89.3%-97.3%. Assays did not perform as well in children with type 1 diabetes: PPV 10x ULN of 89% (95% CI, 83.5%-92.8%).
In other notable findings, the EMA blood test only marginally improved specificity, as 76% of children without celiac disease, but with a tTG-IgA of at least 10x ULN had a positive EMA in the same sample.
While the study lends credence to the notion that a highly positive tTG-IgA correlates with enteropathy in most children, the 1 in 20 with a tTG-IgA greater than 10x ULN who did not have histologic findings diagnostic of celiac disease cannot be ignored. “This included 2% who had normal small intestinal biopsies on a gluten-containing unrestricted diet, highlighting the limitations of making a celiac disease diagnosis based solely upon a single, highly positive tTG-IgA level,” Chang and colleagues wrote.
Does this mean that substantial numbers of children with suspected celiac disease are being unnecessarily placed on gluten-restricted diets to no avail? “That’s a good question, but our retrospective data do not provide an answer to that,” Chang said. And what causes elevated autoantibodies in children who are not diagnosed with celiac disease? “That is also a question that will require further research,” he said.
Commenting on the study but not involved in it, Supriya Nair, MD, a pediatric gastroenterologist at UTHealth Houston, called it “very interesting because it highlights for primary care physicians that we may need endoscopic evaluation more than we thought.” This is particularly true given the lack of standardized laboratory values noted in the study.
Nair said that some children with high seromarker levels but no discernible lesions may develop celiac disease later. “It may be that the markers are not yet causing inflammation in the bowel. These patients must be monitored to see if levels stay high or come down.”
In her practice, she has seen some children who have been put on gluten-free diets prematurely. “But it’s very important to get an accurate, official confirmation with endoscopy because of the ramifications of a celiac diagnosis,” she said. “This is a lifelong condition, and the diet is not easy to follow, especially in North America.” And for children, especially, there are restrictive social impacts and the constant need to be aware of what they’re eating and the danger of cross-contamination in foods, she said.
Chang hopes these data will be pivotal in helping medical societies develop new North American guidelines. In the meantime, pediatricians and primary doctors need to be aware that a high number on a tTG-IgA test does not always mean the presence of celiac disease, although it could be a harbinger of its future development. “Further confirmation by a specialist is essential.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Chang and Nair reported having no competing interests. Several study authors reported receiving research support from and serving as consultants or members of data safety monitoring boards for pharmaceutical companies.
A version of this article appeared on Medscape.com.