User login
Time to Reconsider Tramadol for Chronic Pain?
Time to Reconsider Tramadol for Chronic Pain?
Tramadol, a commonly prescribed opioid often viewed as a safer option for chronic pain, provided limited pain relief while increasing the risk for serious adverse effects, results of a new analysis showed.
In a systematic review and meta-analysis, investigators found that tramadol offered clinically insignificant pain relief, while doubling the likelihood of serious adverse events, most commonly cardiac complications.
"Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered," Jehad Ahmad Barakji, MD, of the Centre for Clinical Intervention Research at Rigshospitalet in Copenhagen, Denmark, told Medscape Medical News.
"Across different chronic pain conditions, tramadol's pain-relieving effect appears modest, and while some patients may experience relief, most will not gain substantial benefit," he added.
However, the researchers cautioned that the certainty of the evidence was low-to-moderate and that the quality of the underlying trials varied substantially.
The study was published on October 7 in BMJ Evidence-Based Medicine.
Popularity Outpacing Proof
Tramadol, a dual-action opioid that modulates serotonin and norepinephrine pathways, has long been promoted as a middle-ground analgesic - less addictive than morphine but stronger than nonopioid medications. It is approved for moderate-to-severe pain, including postoperative and chronic conditions.
Prescriptions have risen sharply worldwide, fueled by perceptions of safety and a belief that tramadol carries a lower risk for dependence. A recent global analysis estimated that nearly 18% of adults have used tramadol in their lifetime, and > 80% of those users combined it with at least 1 other substance.
Despite its widespread use, evidence supporting tramadol's long-term effectiveness and safety in chronic pain has been limited and inconsistent. Previous research has largely focused on short-term or condition-specific outcomes, such as osteoarthritis or neuropathic pain, leaving uncertainty about the drug's overall risk-benefit profile.
Small Benefit, Big Risk
The current study is the first comprehensive systematic review to evaluate tramadol alone for chronic pain using both meta-analysis and trail sequential analysis, provided a broader view of efficacy and safety across pain types.
"We sought to fill this gap by evaluating the totality of evidence to guide clinical practice," Barakji said.
The analysis included 19 randomized, placebo-controlled trials with 6569 adults. The average participant age was 56 years, and study durations ranged from 4 to 16 weeks. Pain intensity was typically assessed with the 0-10 numeric rating scale (NRS), while function and quality of life were measured with validated patient-reported tools.
Across the pooled analysis, participants receiving tramadol experienced an average pain reduction of 0.9 points on the NRS compared with placebo - a difference below the 1-point threshold considered clinically meaningful. About 7% more patients in the tramadol groups achieved noticeable pain relief, but investigators said the benefit was modest and uncertain.
Serious adverse events were twice as common among tramadol users, most often involving cardiac complications such as chest pain, coronary artery disease, or heart failure. Nonserious adverse effects, including nausea, dizziness, constipation, and drowsiness, were frequent and contributed to higher discontinuation rates among tramadol recipients.
The researchers acknowledged that most included trials were at a high risk for bias due to incomplete outcome reporting, small sample sizes, and inconsistent assessment methods, factors that may have exaggerated benefits and underestimated harms.
Reevaluating Tramadol's Role
Commenting on the research, Jessica Otte, MD, clinical associate professor in the Department of Family Medicine at The University of British Columbia, Vancouver, British Columbia, Canada, said the new review stands out for examining tramadol's use across a range of chronic pain conditions, an area where clinicians often struggle to help patients achieve meaningful and sustained relief.
Otte, who has studied the drug's safety and effectiveness through The University of British Columbia's Therapeutics Initiative, said the Danish team's analysis expands on earlier research that largely focused on single pain conditions. The findings, she said, add weight to growing evidence that challenges tramadol's perceived advantages over other analgesics.
"This review doesn't change the narrative but strengthens it: Tramdol's reputation as a safer or uniquely effective opioid is increasingly difficult to defend," she told Medscape Medical News.
While she believes the study makes an important contribution, Otte said the results should be interpreted with caution because of gaps in the underlying evidence. The Danish authors noted similar concerns, and Otte agreed that many of the included trials had methodological shortcomings.
"A lot of the studies had biases that made use less certain about what was reported," she said. "Many outcomes that matter to patients - like quality of life, functional improvement, or withdrawal - were either inconsistently measured or not reported at all."
She added that patients assigned to tramadol were more likely to discontinue early, both overall and because of adverse effects, raising concern about tolerability and attrition bias.
Also commenting, Houman Danesh, MD, professor and medical director of pain management at the Icahn School of Medicine at Mount Sinai in New York City, said the review provides moderate-certainty evidence that tramadol increases the risk for serious adverse events; but its broad approach - evaluating efficacy and safety across multiple chronic pain conditions - could be a confounding factor.
"Tramadol may benefit some conditions more than others," he noted, which could alter the overall risk-benefit profile.
In his clinical experience, Danesh said severe complications such as cardiac events are uncommon. He explained that heart rhythm disturbances occasionally associated with tramadol generally arise when patients are taking other medications that affect cardiac conduction.
Danesh emphasized that clinicians should weigh the study alongside other research and their own experience when deciding whether to prescribe the drug.
"It's important to take this study into consideration," he said, "but there are multiple studies that support the use of tramadol, and we have to look at the totality of the evidence."
Written by Carla Cantor.
The authors declared no competing interests and received no specific grant from any funding agency. Otte and Danesh reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Tramadol, a commonly prescribed opioid often viewed as a safer option for chronic pain, provided limited pain relief while increasing the risk for serious adverse effects, results of a new analysis showed.
In a systematic review and meta-analysis, investigators found that tramadol offered clinically insignificant pain relief, while doubling the likelihood of serious adverse events, most commonly cardiac complications.
"Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered," Jehad Ahmad Barakji, MD, of the Centre for Clinical Intervention Research at Rigshospitalet in Copenhagen, Denmark, told Medscape Medical News.
"Across different chronic pain conditions, tramadol's pain-relieving effect appears modest, and while some patients may experience relief, most will not gain substantial benefit," he added.
However, the researchers cautioned that the certainty of the evidence was low-to-moderate and that the quality of the underlying trials varied substantially.
The study was published on October 7 in BMJ Evidence-Based Medicine.
Popularity Outpacing Proof
Tramadol, a dual-action opioid that modulates serotonin and norepinephrine pathways, has long been promoted as a middle-ground analgesic - less addictive than morphine but stronger than nonopioid medications. It is approved for moderate-to-severe pain, including postoperative and chronic conditions.
Prescriptions have risen sharply worldwide, fueled by perceptions of safety and a belief that tramadol carries a lower risk for dependence. A recent global analysis estimated that nearly 18% of adults have used tramadol in their lifetime, and > 80% of those users combined it with at least 1 other substance.
Despite its widespread use, evidence supporting tramadol's long-term effectiveness and safety in chronic pain has been limited and inconsistent. Previous research has largely focused on short-term or condition-specific outcomes, such as osteoarthritis or neuropathic pain, leaving uncertainty about the drug's overall risk-benefit profile.
Small Benefit, Big Risk
The current study is the first comprehensive systematic review to evaluate tramadol alone for chronic pain using both meta-analysis and trail sequential analysis, provided a broader view of efficacy and safety across pain types.
"We sought to fill this gap by evaluating the totality of evidence to guide clinical practice," Barakji said.
The analysis included 19 randomized, placebo-controlled trials with 6569 adults. The average participant age was 56 years, and study durations ranged from 4 to 16 weeks. Pain intensity was typically assessed with the 0-10 numeric rating scale (NRS), while function and quality of life were measured with validated patient-reported tools.
Across the pooled analysis, participants receiving tramadol experienced an average pain reduction of 0.9 points on the NRS compared with placebo - a difference below the 1-point threshold considered clinically meaningful. About 7% more patients in the tramadol groups achieved noticeable pain relief, but investigators said the benefit was modest and uncertain.
Serious adverse events were twice as common among tramadol users, most often involving cardiac complications such as chest pain, coronary artery disease, or heart failure. Nonserious adverse effects, including nausea, dizziness, constipation, and drowsiness, were frequent and contributed to higher discontinuation rates among tramadol recipients.
The researchers acknowledged that most included trials were at a high risk for bias due to incomplete outcome reporting, small sample sizes, and inconsistent assessment methods, factors that may have exaggerated benefits and underestimated harms.
Reevaluating Tramadol's Role
Commenting on the research, Jessica Otte, MD, clinical associate professor in the Department of Family Medicine at The University of British Columbia, Vancouver, British Columbia, Canada, said the new review stands out for examining tramadol's use across a range of chronic pain conditions, an area where clinicians often struggle to help patients achieve meaningful and sustained relief.
Otte, who has studied the drug's safety and effectiveness through The University of British Columbia's Therapeutics Initiative, said the Danish team's analysis expands on earlier research that largely focused on single pain conditions. The findings, she said, add weight to growing evidence that challenges tramadol's perceived advantages over other analgesics.
"This review doesn't change the narrative but strengthens it: Tramdol's reputation as a safer or uniquely effective opioid is increasingly difficult to defend," she told Medscape Medical News.
While she believes the study makes an important contribution, Otte said the results should be interpreted with caution because of gaps in the underlying evidence. The Danish authors noted similar concerns, and Otte agreed that many of the included trials had methodological shortcomings.
"A lot of the studies had biases that made use less certain about what was reported," she said. "Many outcomes that matter to patients - like quality of life, functional improvement, or withdrawal - were either inconsistently measured or not reported at all."
She added that patients assigned to tramadol were more likely to discontinue early, both overall and because of adverse effects, raising concern about tolerability and attrition bias.
Also commenting, Houman Danesh, MD, professor and medical director of pain management at the Icahn School of Medicine at Mount Sinai in New York City, said the review provides moderate-certainty evidence that tramadol increases the risk for serious adverse events; but its broad approach - evaluating efficacy and safety across multiple chronic pain conditions - could be a confounding factor.
"Tramadol may benefit some conditions more than others," he noted, which could alter the overall risk-benefit profile.
In his clinical experience, Danesh said severe complications such as cardiac events are uncommon. He explained that heart rhythm disturbances occasionally associated with tramadol generally arise when patients are taking other medications that affect cardiac conduction.
Danesh emphasized that clinicians should weigh the study alongside other research and their own experience when deciding whether to prescribe the drug.
"It's important to take this study into consideration," he said, "but there are multiple studies that support the use of tramadol, and we have to look at the totality of the evidence."
Written by Carla Cantor.
The authors declared no competing interests and received no specific grant from any funding agency. Otte and Danesh reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Tramadol, a commonly prescribed opioid often viewed as a safer option for chronic pain, provided limited pain relief while increasing the risk for serious adverse effects, results of a new analysis showed.
In a systematic review and meta-analysis, investigators found that tramadol offered clinically insignificant pain relief, while doubling the likelihood of serious adverse events, most commonly cardiac complications.
"Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered," Jehad Ahmad Barakji, MD, of the Centre for Clinical Intervention Research at Rigshospitalet in Copenhagen, Denmark, told Medscape Medical News.
"Across different chronic pain conditions, tramadol's pain-relieving effect appears modest, and while some patients may experience relief, most will not gain substantial benefit," he added.
However, the researchers cautioned that the certainty of the evidence was low-to-moderate and that the quality of the underlying trials varied substantially.
The study was published on October 7 in BMJ Evidence-Based Medicine.
Popularity Outpacing Proof
Tramadol, a dual-action opioid that modulates serotonin and norepinephrine pathways, has long been promoted as a middle-ground analgesic - less addictive than morphine but stronger than nonopioid medications. It is approved for moderate-to-severe pain, including postoperative and chronic conditions.
Prescriptions have risen sharply worldwide, fueled by perceptions of safety and a belief that tramadol carries a lower risk for dependence. A recent global analysis estimated that nearly 18% of adults have used tramadol in their lifetime, and > 80% of those users combined it with at least 1 other substance.
Despite its widespread use, evidence supporting tramadol's long-term effectiveness and safety in chronic pain has been limited and inconsistent. Previous research has largely focused on short-term or condition-specific outcomes, such as osteoarthritis or neuropathic pain, leaving uncertainty about the drug's overall risk-benefit profile.
Small Benefit, Big Risk
The current study is the first comprehensive systematic review to evaluate tramadol alone for chronic pain using both meta-analysis and trail sequential analysis, provided a broader view of efficacy and safety across pain types.
"We sought to fill this gap by evaluating the totality of evidence to guide clinical practice," Barakji said.
The analysis included 19 randomized, placebo-controlled trials with 6569 adults. The average participant age was 56 years, and study durations ranged from 4 to 16 weeks. Pain intensity was typically assessed with the 0-10 numeric rating scale (NRS), while function and quality of life were measured with validated patient-reported tools.
Across the pooled analysis, participants receiving tramadol experienced an average pain reduction of 0.9 points on the NRS compared with placebo - a difference below the 1-point threshold considered clinically meaningful. About 7% more patients in the tramadol groups achieved noticeable pain relief, but investigators said the benefit was modest and uncertain.
Serious adverse events were twice as common among tramadol users, most often involving cardiac complications such as chest pain, coronary artery disease, or heart failure. Nonserious adverse effects, including nausea, dizziness, constipation, and drowsiness, were frequent and contributed to higher discontinuation rates among tramadol recipients.
The researchers acknowledged that most included trials were at a high risk for bias due to incomplete outcome reporting, small sample sizes, and inconsistent assessment methods, factors that may have exaggerated benefits and underestimated harms.
Reevaluating Tramadol's Role
Commenting on the research, Jessica Otte, MD, clinical associate professor in the Department of Family Medicine at The University of British Columbia, Vancouver, British Columbia, Canada, said the new review stands out for examining tramadol's use across a range of chronic pain conditions, an area where clinicians often struggle to help patients achieve meaningful and sustained relief.
Otte, who has studied the drug's safety and effectiveness through The University of British Columbia's Therapeutics Initiative, said the Danish team's analysis expands on earlier research that largely focused on single pain conditions. The findings, she said, add weight to growing evidence that challenges tramadol's perceived advantages over other analgesics.
"This review doesn't change the narrative but strengthens it: Tramdol's reputation as a safer or uniquely effective opioid is increasingly difficult to defend," she told Medscape Medical News.
While she believes the study makes an important contribution, Otte said the results should be interpreted with caution because of gaps in the underlying evidence. The Danish authors noted similar concerns, and Otte agreed that many of the included trials had methodological shortcomings.
"A lot of the studies had biases that made use less certain about what was reported," she said. "Many outcomes that matter to patients - like quality of life, functional improvement, or withdrawal - were either inconsistently measured or not reported at all."
She added that patients assigned to tramadol were more likely to discontinue early, both overall and because of adverse effects, raising concern about tolerability and attrition bias.
Also commenting, Houman Danesh, MD, professor and medical director of pain management at the Icahn School of Medicine at Mount Sinai in New York City, said the review provides moderate-certainty evidence that tramadol increases the risk for serious adverse events; but its broad approach - evaluating efficacy and safety across multiple chronic pain conditions - could be a confounding factor.
"Tramadol may benefit some conditions more than others," he noted, which could alter the overall risk-benefit profile.
In his clinical experience, Danesh said severe complications such as cardiac events are uncommon. He explained that heart rhythm disturbances occasionally associated with tramadol generally arise when patients are taking other medications that affect cardiac conduction.
Danesh emphasized that clinicians should weigh the study alongside other research and their own experience when deciding whether to prescribe the drug.
"It's important to take this study into consideration," he said, "but there are multiple studies that support the use of tramadol, and we have to look at the totality of the evidence."
Written by Carla Cantor.
The authors declared no competing interests and received no specific grant from any funding agency. Otte and Danesh reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Time to Reconsider Tramadol for Chronic Pain?
Time to Reconsider Tramadol for Chronic Pain?
Combining Upper-Lower GI Screening Feasible, Effective
BERLIN — , including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.
“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.
While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.
The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”
Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.
Mixed Rates of GI Cancers Across Europe and the US
These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.
However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”
The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy.
A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.
Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.
Neoplasia and Preneoplasia Found
A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.
A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”
Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.
Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.
Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.
“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.
“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”
PROSPERO: Early Detection of Upper GI Conditions in a UK Population
Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”
“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.
“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”
Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”
TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.
Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.
A version of this article first appeared on Medscape.com.
BERLIN — , including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.
“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.
While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.
The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”
Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.
Mixed Rates of GI Cancers Across Europe and the US
These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.
However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”
The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy.
A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.
Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.
Neoplasia and Preneoplasia Found
A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.
A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”
Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.
Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.
Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.
“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.
“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”
PROSPERO: Early Detection of Upper GI Conditions in a UK Population
Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”
“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.
“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”
Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”
TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.
Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.
A version of this article first appeared on Medscape.com.
BERLIN — , including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.
“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.
While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.
The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”
Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.
Mixed Rates of GI Cancers Across Europe and the US
These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.
However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”
The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy.
A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.
Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.
Neoplasia and Preneoplasia Found
A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.
A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”
Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.
Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.
Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.
“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.
“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”
PROSPERO: Early Detection of Upper GI Conditions in a UK Population
Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”
“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.
“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”
Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”
TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.
Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.
A version of this article first appeared on Medscape.com.
Real-World Pros & Cons of the New Liver Disease Nomenclature
VIENNA – Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.
In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.
Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.
However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.
“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.
MASLD, MetALD, or ALD?
“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol?
If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.
Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.
Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.
“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”
Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”
On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”
Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.
Cancer, Cirrhosis, CVD
MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.
In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.
Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.”
One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”
During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”
Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”
Remaining Questions
And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”
The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.
No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.
A version of this article first appeared on Medscape.com.
VIENNA – Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.
In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.
Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.
However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.
“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.
MASLD, MetALD, or ALD?
“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol?
If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.
Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.
Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.
“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”
Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”
On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”
Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.
Cancer, Cirrhosis, CVD
MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.
In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.
Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.”
One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”
During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”
Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”
Remaining Questions
And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”
The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.
No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.
A version of this article first appeared on Medscape.com.
VIENNA – Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.
In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.
Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.
However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.
“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.
MASLD, MetALD, or ALD?
“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol?
If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.
Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.
Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.
“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”
Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”
On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”
Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.
Cancer, Cirrhosis, CVD
MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.
In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.
Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.”
One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”
During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”
Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”
Remaining Questions
And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”
The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.
No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.
A version of this article first appeared on Medscape.com.
FDA OKs Simponi for Pediatric Ulcerative Colitis
Of the more than 1 million people in the US living with UC, roughly 20% are children, Johnson & Johnson noted in a statement announcing approval.
The pediatric indication for golimumab in UC was supported by the open-label PURSUIT 2 phase 3 study evaluating the efficacy, safety, and pharmacokinetics of subcutaneously administered golimumab in children aged 2 years and older with moderately to severely active UC.
In the trial, the primary endpoint of clinical remission at week 6 was achieved by 32% of children. Clinical remission was defined as a Mayo score ≤ 2 points, with no individual subscore > 1.
The secondary endpoints of clinical response at week 6 was achieved by 58%, and endoscopic improvement at week 6 was achieved by 40% of patients receiving golimumab.
Clinical response was defined as a decrease from baseline in the Mayo score by > 30% and > 3 points, with either a decrease from baseline in the rectal bleeding subscore of > 1 or a rectal bleeding subscore of 0 or 1. Endoscopic remission was defined as an endoscopy subscore of 0 or 1 based on local endoscopy.
Among children treated with golimumab who were in clinical remission at 6 weeks, 57% maintained clinical remission of symptoms at week 54. Safety results in children were consistent with clinical trials of golimumab in adults with UC, the company said.
The recommended dose of golimumab for pediatric patients weighing at least 40 kg is 200 mg at week 0, followed by 100 mg at weeks 2, 6, and every 4 weeks thereafter; for those weighing at least 15 kg to less than 40 kg, golimumab is administered at 100 mg at week 0, followed by 50 mg at weeks 2, 6, and every 4 weeks thereafter.
Golimumab is administered as a prefilled syringe; children aged 12 and older can self-administer it after proper training by a healthcare provider.
This is the first pediatric approval for golimumab, which is already approved for four indications, including adults living with moderate-to-severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderately to severely active UC.
Full prescribing information and medication guide is available online.
A version of this article first appeared on Medscape.com.
Of the more than 1 million people in the US living with UC, roughly 20% are children, Johnson & Johnson noted in a statement announcing approval.
The pediatric indication for golimumab in UC was supported by the open-label PURSUIT 2 phase 3 study evaluating the efficacy, safety, and pharmacokinetics of subcutaneously administered golimumab in children aged 2 years and older with moderately to severely active UC.
In the trial, the primary endpoint of clinical remission at week 6 was achieved by 32% of children. Clinical remission was defined as a Mayo score ≤ 2 points, with no individual subscore > 1.
The secondary endpoints of clinical response at week 6 was achieved by 58%, and endoscopic improvement at week 6 was achieved by 40% of patients receiving golimumab.
Clinical response was defined as a decrease from baseline in the Mayo score by > 30% and > 3 points, with either a decrease from baseline in the rectal bleeding subscore of > 1 or a rectal bleeding subscore of 0 or 1. Endoscopic remission was defined as an endoscopy subscore of 0 or 1 based on local endoscopy.
Among children treated with golimumab who were in clinical remission at 6 weeks, 57% maintained clinical remission of symptoms at week 54. Safety results in children were consistent with clinical trials of golimumab in adults with UC, the company said.
The recommended dose of golimumab for pediatric patients weighing at least 40 kg is 200 mg at week 0, followed by 100 mg at weeks 2, 6, and every 4 weeks thereafter; for those weighing at least 15 kg to less than 40 kg, golimumab is administered at 100 mg at week 0, followed by 50 mg at weeks 2, 6, and every 4 weeks thereafter.
Golimumab is administered as a prefilled syringe; children aged 12 and older can self-administer it after proper training by a healthcare provider.
This is the first pediatric approval for golimumab, which is already approved for four indications, including adults living with moderate-to-severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderately to severely active UC.
Full prescribing information and medication guide is available online.
A version of this article first appeared on Medscape.com.
Of the more than 1 million people in the US living with UC, roughly 20% are children, Johnson & Johnson noted in a statement announcing approval.
The pediatric indication for golimumab in UC was supported by the open-label PURSUIT 2 phase 3 study evaluating the efficacy, safety, and pharmacokinetics of subcutaneously administered golimumab in children aged 2 years and older with moderately to severely active UC.
In the trial, the primary endpoint of clinical remission at week 6 was achieved by 32% of children. Clinical remission was defined as a Mayo score ≤ 2 points, with no individual subscore > 1.
The secondary endpoints of clinical response at week 6 was achieved by 58%, and endoscopic improvement at week 6 was achieved by 40% of patients receiving golimumab.
Clinical response was defined as a decrease from baseline in the Mayo score by > 30% and > 3 points, with either a decrease from baseline in the rectal bleeding subscore of > 1 or a rectal bleeding subscore of 0 or 1. Endoscopic remission was defined as an endoscopy subscore of 0 or 1 based on local endoscopy.
Among children treated with golimumab who were in clinical remission at 6 weeks, 57% maintained clinical remission of symptoms at week 54. Safety results in children were consistent with clinical trials of golimumab in adults with UC, the company said.
The recommended dose of golimumab for pediatric patients weighing at least 40 kg is 200 mg at week 0, followed by 100 mg at weeks 2, 6, and every 4 weeks thereafter; for those weighing at least 15 kg to less than 40 kg, golimumab is administered at 100 mg at week 0, followed by 50 mg at weeks 2, 6, and every 4 weeks thereafter.
Golimumab is administered as a prefilled syringe; children aged 12 and older can self-administer it after proper training by a healthcare provider.
This is the first pediatric approval for golimumab, which is already approved for four indications, including adults living with moderate-to-severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderately to severely active UC.
Full prescribing information and medication guide is available online.
A version of this article first appeared on Medscape.com.
Anti-TNF Exposure Influences Efficacy of Subsequent Therapies in UC
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Making Surgery Safer for Patients With Cirrhosis
, according to an updated guideline from the American College of Gastroenterology.
Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology.
“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.
“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.
The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.
Three conditional recommendations:
- For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
- For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
- For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.
The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis.
What’s New and Notable?
New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.
The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.
Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.
“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.
These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.
Tackling Clinical Challenges
The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.
“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.
“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.
For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.
The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose.
A version of this article appeared on Medscape.com
, according to an updated guideline from the American College of Gastroenterology.
Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology.
“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.
“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.
The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.
Three conditional recommendations:
- For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
- For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
- For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.
The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis.
What’s New and Notable?
New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.
The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.
Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.
“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.
These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.
Tackling Clinical Challenges
The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.
“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.
“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.
For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.
The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose.
A version of this article appeared on Medscape.com
, according to an updated guideline from the American College of Gastroenterology.
Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology.
“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.
“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.
The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.
Three conditional recommendations:
- For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
- For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
- For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.
The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis.
What’s New and Notable?
New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.
The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.
Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.
“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.
These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.
Tackling Clinical Challenges
The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.
“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.
“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.
For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.
The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose.
A version of this article appeared on Medscape.com
Formula Type May Fuel NEC in Premature Infants
DENVER – , according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.
Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.
The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.
Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.
Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.
Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis.
Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.
The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.
Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.
Younger Babies at Greater Risk
Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.
“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.
“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.
The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.
Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.
However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.
Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.
The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
DENVER – , according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.
Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.
The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.
Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.
Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.
Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis.
Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.
The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.
Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.
Younger Babies at Greater Risk
Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.
“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.
“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.
The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.
Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.
However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.
Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.
The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
DENVER – , according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.
Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.
The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.
Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.
Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.
Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis.
Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.
The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.
Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.
Younger Babies at Greater Risk
Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.
“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.
“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.
The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.
Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.
However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.
Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.
The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Prevention and Risk-Based Surveillance Key to Curbing HCC
BERLIN — according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).
The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
BERLIN — according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).
The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
BERLIN — according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).
The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
FROM UEG WEEK 2025
‘At-Need’ Endoscopy Equal to Standard Surveillance in Barrett’s Patients?
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Linerixibat Reduces Itching in PBC
BERLIN — , according to phase 3 results from the GLISTEN trial.
The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
BERLIN — , according to phase 3 results from the GLISTEN trial.
The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
BERLIN — , according to phase 3 results from the GLISTEN trial.
The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.