This Week in Gastroenterology — Oct 6, 2026

This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.

Welcome to This Week in Gastroenterology. This week we're covering 10 notable papers spanning cirrhosis, transplantation and viral hepatitis, the evolving picture of steatotic liver disease, ulcerative colitis therapeutics, and a cluster of luminal and anorectal questions. Let's dive in.

We start with advanced liver disease, where this week brought a new guideline, a prospective transplant cohort, and a trial that could simplify hepatitis C care. In the American Journal of Gastroenterology, Tapper and colleagues present the ACG clinical guideline on preventive care for patients with cirrhosis, built around 18 GRADE-assessed recommendations and 6 key concept statements across four domains [1]. The strong recommendations include carvedilol or variceal ligation for high-risk esophageal varices, semiannual hepatocellular carcinoma surveillance, hepatitis A testing and vaccination, immunization against influenza, SARS-CoV-2 and respiratory syncytial virus, and smoking-cessation counseling. Conditional recommendations cover lactulose for minimal hepatic encephalopathy, adjunctive rifaximin after hospitalization, short-course antibiotic prophylaxis in upper GI bleeding, post-discharge behavioral therapy for alcohol use disorder, dietitian-guided nutrition, structured exercise, and bisphosphonates for osteoporosis. The authors are candid that most of the underlying evidence is of low certainty, so the guideline's real contribution is in organizing preventive care into a deliverable framework rather than in settling individual questions. At the sickest end of the cirrhosis spectrum, Gustot and colleagues report in the Journal of Hepatology on a prospective study across 63 transplant centers worldwide examining outcomes after liver transplantation in acute-on-chronic liver failure [2]. Among patients with two or more organ failures who were declined for transplant, mortality at one year was stark: nearly three quarters of patients with ACLF grade 2 and close to nine in ten patients with grade 3 died. By contrast, among the 612 transplanted patients, about one in eight died within the year. Patients transplanted with ACLF grade 3 had a case-fatality rate of about one in five, roughly double that of patients without ACLF, while grade 2 carried a risk similar to no ACLF. The important caveat is the subgroup with five or six organ failures, in whom post-transplant mortality reached about 42 percent, and the authors caution against routine transplantation in that group. Being transplanted in Asia was also independently associated with higher mortality. This is observational and the declined group is not a randomized comparator, but it strengthens the case that severe ACLF alone is not a reason to withhold transplant, while drawing a line at extreme organ failure burden.

Staying with viral liver disease, the Lancet published RESOLVE, a multicentre, open-label non-inferiority trial from five publicly funded hospitals in India, led by Goel [3]. Investigators randomized 880 treatment-naive adults with non-cirrhotic hepatitis C to sofosbuvir-velpatasvir for either 8 or 12 weeks. Sustained virological response at 12 weeks was essentially identical, close to 99 percent in both arms on per-protocol analysis, and the shorter regimen also met non-inferiority on intention-to-treat analysis. No participant had a drug-related serious adverse event. The population was young, with a median age of 35, and drawn from a single country, so generalizability to older patients or other genotype distributions is an open question, but the authors conclude the result supports shortening treatment in non-cirrhotic, treatment-naive patients, with obvious implications for cost and programme scale-up.

Our second theme is metabolic dysfunction-associated steatotic liver disease, where two papers challenge assumptions about who gets sick and who responds to treatment. In JAMA, de Avila and colleagues analyzed more than 18,000 patients with biopsy-confirmed MASLD from 41 countries in the Global MASLD project [4]. Lean patients made up roughly 7 percent of the cohort by body mass index, and lean disease was most common in Asia. Lean patients had less diabetes, less advanced fibrosis and milder histologic activity, yet after adjustment, lean status was not associated with any difference in mortality or liver-related events. What did predict outcomes was fibrosis: advanced fibrosis roughly doubled the risk of death and more than tripled the risk of clinical events. Notably, the FIB-4 score performed somewhat less well in lean patients, while transient elastography performed better. This is retrospective, but the message is that body habitus should not be read as reassurance, and that fibrosis staging, with elastography holding up well in lean individuals, carries the prognostic weight. In the Journal of Hepatology, Chalasani and colleagues report a pre-specified genetic analysis of 738 patients in the MAESTRO-NASH phase three trial of resmetirom [5]. Patients carrying high-risk variants in genes such as PNPLA3 and HSD17B13 had fewer metabolic risk factors at baseline, which fits the idea of genetically driven disease. Resmetirom's effects on MASH resolution, fibrosis improvement, liver fat and biomarkers were not significantly altered by any single risk genotype or by a composite genetic risk score. The authors acknowledge the analysis was not powered to detect small effects, so this is reassuring rather than definitive, but it argues against genotype as a reason to expect a weaker response.

Turning to ulcerative colitis, two papers in Clinical Gastroenterology and Hepatology converge on the Janus kinase inhibitor upadacitinib. Olivera, Singh and colleagues updated their network meta-analysis of advanced therapies for induction in moderate-to-severe disease, pooling 33 phase three trials of 17 therapies [6]. Upadacitinib ranked highest for both clinical remission and endoscopic improvement, with high confidence for remission. In patients naive to advanced therapy, obefazimod and upadacitinib ranked highest, while in experienced patients upadacitinib, ustekinumab and tofacitinib led. The anti-p19 agents, risankizumab, subcutaneous guselkumab and mirikizumab, had the most favorable profiles for serious adverse events and discontinuations, though confidence in the safety estimates was lower. Network rankings are indirect and do not replace head-to-head trials, but they frame the efficacy-safety trade-off clearly. Gilmore and colleagues then looked at the acute severe setting in a retrospective cohort of 150 patients across 13 Australian centres treated with a JAK inhibitor [7]. Overall about a third of patients underwent colectomy by one year, but the rate with upadacitinib was roughly half that with tofacitinib, at about 23 versus 43 percent, a difference that emerged only by week 52. Using a JAK inhibitor as sequential salvage after failed rescue therapy produced a numerically higher colectomy rate than first-line rescue, but that difference was not statistically significant. Taken together, the two papers point the same direction on upadacitinib's potency, though the acute severe colitis data are non-randomized and susceptible to selection effects, and prospective comparison is still lacking.

Our final theme gathers three papers on eosinophilic, neoplastic and functional disorders of the gut. In Alimentary Pharmacology and Therapeutics, Dellon and colleagues present a post hoc subgroup analysis of the LIBERTY EoE TREET trial of dupilumab in eosinophilic oesophagitis [8]. Dupilumab increased histological remission over placebo at week 24 in every subgroup examined, including those defined by weight, disease duration, atopic comorbidities, prior or concurrent elimination diets, proton pump inhibitor use and prior dilation, with similar gains in dysphagia scores and endoscopic findings, maintained to week 52. As post hoc work it cannot establish subgroup-specific effects with precision, but it finds no subgroup in which benefit was absent. In the American Journal of Gastroenterology, Rex and colleagues offer a review and consensus statement from the United States Multi-Society Task Force on serrated polyposis syndrome [9], which they describe as the most common polyposis syndrome yet often unrecognized. The statement emphasizes meticulous inspection, clearing of the colon and frequent surveillance colonoscopy, reserves surgery for cancer or polyp burden beyond expert endoscopic control, notes there is no common germline variant, limits genetic testing to patients meeting criteria for known hereditary syndromes, and recommends colonoscopic screening for first-degree relatives. Finally, back in Clinical Gastroenterology and Hepatology, Bharucha and colleagues report the FIT trial, which randomized 200 patients with fecal incontinence refractory to medical and behavioral therapy to dextranomer-hyaluronate injection or anorectal biofeedback [10]. Neither approach was superior: only a little over a quarter of patients in each arm achieved at least a 75 percent reduction in episodes. Adverse events were uncommon in both groups, but injections cost payers roughly fifteen hundred dollars more per patient. This is a negative trial on efficacy, and the authors conclude that biofeedback is the less expensive option, while the modest response rates underline how much room remains for better therapies.

If you only have time for one paper this week, make it the RESOLVE trial in the Lancet [3]. It provides randomized evidence that an 8-week sofosbuvir-velpatasvir course matches the 12-week standard in non-cirrhotic, treatment-naive hepatitis C, reopening the question of how short and simple elimination-scale treatment can be.

Here is what this week's evidence adds up to in Gastroenterology. First, a randomized trial now supports an 8-week sofosbuvir-velpatasvir course for treatment-naive patients without cirrhosis, although data come from a young Indian population and confirmation elsewhere would strengthen it. Second, prospective transplant data show that patients with severe acute-on-chronic liver failure fare far better with transplant than without, except at five or six organ failures, where mortality remains prohibitive; the comparison is observational. Third, in MASLD, fibrosis rather than body weight tracks with outcomes, elastography performs well in lean patients, and resmetirom's benefit does not appear to depend on common risk genotypes, within the limits of an underpowered analysis. Fourth, upadacitinib ranks highest for ulcerative colitis induction in network analysis and was linked to fewer colectomies than tofacitinib in acute severe colitis, but no head-to-head randomized data exist yet. Fifth, for refractory fecal incontinence, injection and biofeedback performed equally and modestly, with biofeedback costing less.

That's your roundup for This Week in Gastroenterology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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