This Week in Gastroenterology — Jul 7, 2026

Welcome to This Week in Gastroenterology. This week we're covering 9 notable papers spanning advanced hepatology and portal hypertension, safety and long-term outcomes in inflammatory bowel disease, innovations in interventional endoscopy, and emerging therapies for advanced biliary tract cancer. Let's dive in.

We begin with critical updates in hepatology, starting with a major comparative effectiveness study published in the Annals of Internal Medicine. Nonselective beta-blockers are a cornerstone of therapy in patients with cirrhosis to reduce hepatic portal pressure and prevent clinical decompensation. While carvedilol has increasingly become the preferred agent, direct comparative evidence against other nonselective beta-blockers like nadolol and propranolol has been limited. To address this, researchers conducted a large database cohort study using a United States administrative claims database from 2013 to 2025, evaluating adults with cirrhosis who initiated carvedilol, nadolol, or propranolol [1]. After using inverse probability of treatment weighting to account for one hundred and twenty-nine preexposure covariates, the study revealed that patients initiating carvedilol had a meaningfully lower risk of major decompensation events at six months compared to those starting nadolol or propranolol. Specifically, carvedilol reduced the risk of major decompensation by twenty percent compared to nadolol, and by seventeen percent compared to propranolol. This risk reduction was consistent across individual decompensation events, including a significantly lower risk of variceal hemorrhage, and a combined endpoint of ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. These findings provide robust, real-world evidence supporting carvedilol as the preferred nonselective beta-blocker to prevent decompensation in patients with cirrhosis.

Remaining in the field of hepatology, we turn to the long-term management of chronic hepatitis B. A study published in the Journal of Hepatology evaluated the long-term outcomes of patients treated with high-barrier nucleoside or nucleotide analogues, such as entecavir or tenofovir, beyond ten years of therapy [4]. Utilizing data from the PAGE-B cohort, which included over sixteen hundred Caucasian patients, researchers followed more than nine hundred patients beyond the ten-year mark, with a mean follow-up of fourteen years. The study found that the cumulative incidence of hepatocellular carcinoma at ten and fifteen years was approximately eleven percent and thirteen percent, respectively. Although the risk of developing liver cancer persists even after a decade of antiviral therapy, the incidence rate declined significantly, dropping from one and a quarter cases per one hundred person-years before year ten to just over half a case per one hundred person-years after year ten. Notably, the overall rate of liver-related death or liver transplantation remained stable across both periods, and hepatocellular carcinoma development remained the primary driver of mortality. On a positive note, the rate of hepatitis B surface antigen loss actually increased after ten years of therapy, rising from under one percent to nearly one and a half percent per one hundred person-years. These results emphasize that while long-term antiviral therapy successfully lowers liver cancer risk over time, clinicians must maintain vigilant, lifelong surveillance for hepatocellular carcinoma, even in patients who have been stable on therapy for more than a decade.

Our final paper in this hepatology section, published in Clinical Gastroenterology and Hepatology, explores the metabolic side of liver disease, focusing on the relationship between metabolic dysfunction-associated steatotic liver disease, or MASLD, and type 2 diabetes [8]. While MASLD is a well-established risk factor for diabetes, the impact of the age at which MASLD first develops has not been well understood. Using the large, prospective Kailuan Study cohort, researchers analyzed over nineteen thousand patients with newly diagnosed MASLD and matched them to an equal number of controls without the disease, following them for a median of nearly twelve years. To avoid reverse causality, the researchers excluded any participants who developed diabetes within the first two years of follow-up. The study demonstrated that while MASLD onset at any age increases the risk of developing type 2 diabetes, the risk is dramatically higher when the disease develops earlier in life. Compared to those without MASLD, individuals diagnosed with the condition before the age of forty had more than a six-fold increased risk of developing diabetes. This elevated risk gradually attenuated in older age groups, dropping to roughly a three-fold risk for those diagnosed in their forties, fifties, and sixties, and a two-fold risk for those diagnosed at seventy years of age or older. This striking gradient underscores the critical importance of early screening and aggressive lifestyle interventions to prevent or delay the onset of MASLD in young adults, as early-onset disease carries a disproportionately high metabolic burden.

Next, we transition to inflammatory bowel disease, where two new studies provide essential data on long-term treatment strategies and safety. First, in Clinical Gastroenterology and Hepatology, we have the five-year follow-up results of the randomized TISKids trial, which compared first-line infliximab to conventional therapy in pediatric Crohn's disease [2]. The initial trial showed that first-line infliximab was highly effective at achieving clinical remission at one year. In this five-year follow-up of one hundred children with moderate-to-severe Crohn's disease, patients had been randomized to receive either five initial infusions of infliximab followed by discontinuation, or conventional treatment with exclusive enteral nutrition or oral prednisolone, with both groups receiving azathioprine maintenance. At five years, the primary outcome of sustained clinical remission without any additional Crohn's-related therapy was extremely low in both groups, occurring in only six percent of the first-line infliximab group and two percent of the conventional treatment group. Ultimately, the vast majority of patients in both groups required additional therapy over the five-year period. However, first-line infliximab did significantly delay the median time required to restart a biologic, extending it to sixty-five weeks compared to only thirty-one weeks in the conventional group. The clinical takeaway here is clear: while a short, initial course of infliximab provides early benefits, moderate-to-severe pediatric Crohn's disease is a progressive condition that almost always requires early, continuous, and maintained biologic therapy rather than a temporary induction strategy.

In terms of therapeutic safety, clinicians often worry about the long-term oncogenic potential of combination therapies in inflammatory bowel disease. A retrospective cohort study published in Inflammatory Bowel Diseases addressed this concern by comparing the risk of cancer in patients receiving combination therapy with an anti-TNF agent and methotrexate versus those on anti-TNF monotherapy [7]. While the elevated cancer risk associated with combining anti-TNFs with thiopurines is well established, data regarding methotrexate combination therapy has been sparse. Analyzing over twenty-three hundred patients on monotherapy and nearly five hundred and fifty patients on combination therapy within a large integrated healthcare system, researchers found no significant difference in cancer rates over a mean follow-up of more than three years. The incidence of all cancers was seven point four per one thousand person-years in the combination group compared to six point four in the monotherapy group, which was not a statistically significant difference. There was also no increased risk detected specifically for skin or non-skin cancers. The only factors independently associated with an increased risk of cancer were an age of sixty years or older and prior exposure to thiopurines. These findings offer reassuring safety data for clinicians, suggesting that adding methotrexate to anti-TNF therapy to optimize drug levels and prevent immunogenicity does not carry the same oncogenic concerns as thiopurine combination regimens.

Moving into the endoscopy suite, we highlight two studies that offer practical guidance for improving patient comfort and optimizing post-procedure surveillance. Published in Gastrointestinal Endoscopy, the U-POEM trial is a multicenter, single-blinded randomized controlled trial comparing the effect of underwater versus carbon dioxide insufflation during peroral endoscopic myotomy on post-procedural pain [3]. Thirty-six patients with subtype one or two achalasia were randomized to either saline immersion, known as underwater POEM, or standard carbon dioxide insufflation. While both techniques achieved one hundred percent technical and clinical success with no adverse events, the underwater approach dramatically reduced patient discomfort. The immediate post-procedure pain score was cut in half in the underwater group compared to the carbon dioxide group, with a mean score of one point six compared to three point three on a ten-point scale. Furthermore, only about seventeen percent of patients in the underwater group experienced moderate-to-severe pain, compared to over fifty-five percent in the carbon dioxide group. This translated directly into a ten-fold reduction in the need for post-operative opioid analgesics, with only five point five percent of the underwater group requiring opioids compared to fifty percent of the carbon dioxide group. This pain reduction persisted up to seventy-two hours post-procedure. By eliminating the tension and stretch associated with gas insufflation, underwater POEM represents a safe, highly effective modification that significantly improves the patient experience.

Also in Gastrointestinal Endoscopy, a large international Western multicenter study provides much-needed data on local recurrence rates after colorectal endoscopic submucosal dissection, or ESD, to help guide surveillance recommendations [5]. While Asian databases have robust data on this topic, Western data has been limited. Analyzing over twenty-one hundred patients who underwent colorectal ESD across thirteen centers, researchers evaluated the risk of local recurrence at the ESD site during surveillance colonoscopy. Overall, the en-bloc and R0 resection rates were high, at approximately ninety-four percent and eighty-one percent, respectively. Among the patients who underwent surveillance, local recurrence was remarkably low, occurring in only one point five percent of patients at a median of fourteen months. For very low-risk lesions, defined as those under forty millimeters in size with only low-grade dysplasia on histology, the recurrence rate was a mere zero point eight percent. Multivariable analysis revealed that severe submucosal fibrosis more than doubled the risk of local recurrence, while achieving an R0 resection reduced the likelihood of recurrence by seventy percent. These results strongly support current guidelines recommending a first surveillance colonoscopy at twelve months after colorectal ESD, and they suggest that we might safely extend this surveillance interval even further for patients with very low-risk lesions.

Finally, we turn to oncology, where advanced biliary tract cancer remains a highly challenging malignancy with a poor prognosis. Two new studies in the Journal of Hepatology explore novel first-line therapeutic combinations to improve patient outcomes. The first is the phase three-b TOURMALINE study, which evaluated the safety and efficacy of adding the PD-L1 inhibitor durvalumab to seven different gemcitabine-based chemotherapy regimens in a real-world patient population [6]. This trial aimed to build on the success of the TOPAZ-1 trial by testing durvalumab with a wider variety of chemotherapy backbones used globally, including in patients with a poorer prognosis. Among one hundred and forty-two participants, about half experienced severe treatment-related adverse events within six months, which was considered manageable and consistent with the known safety profile of these regimens. The median progression-free survival was seven point four months, and the median overall survival was thirteen point five months, with an objective response rate of thirty-three percent. These findings confirm that durvalumab can be safely and effectively combined with alternative gemcitabine-based backbones, offering clinicians valuable flexibility in tailoring chemotherapy regimens for diverse patient populations.

In another clinical trial in the Journal of Hepatology, researchers investigated a novel bi-specific antibody, ivonescimab, which targets both PD-1 and VEGF, combined with gemcitabine and cisplatin as a first-line treatment for advanced biliary tract cancer [9]. In this multicenter, open-label phase two trial, thirty treatment-naive patients received the combination therapy. The results were highly encouraging, with an objective response rate of nearly sixty-seven percent and a disease control rate of one hundred percent. The median progression-free survival reached eight point five months, and the median overall survival was sixteen point eight months. While treatment-related adverse events occurred in all patients, with hematologic toxicities like anemia and decreased white blood cell counts being the most common, there were no treatment-related deaths. Furthermore, exploratory proteomic analyses identified a protein called MAP2K7 as a potential biomarker of resistance, showing that its suppression could enhance the anti-tumor activity of ivonescimab. While these phase two results are promising and suggest that dual targeting of PD-1 and VEGF may offer a survival advantage over standard immunotherapy combinations, larger phase three trials are needed to confirm these findings.

If you only have time for one paper this week, make it the comparative effectiveness study of carvedilol versus other nonselective beta-blockers in cirrhosis, published in the Annals of Internal Medicine [1]. This large-scale, real-world study provides the most definitive evidence to date that carvedilol should be our first-line beta-blocker, demonstrating a clear, clinically meaningful reduction in major decompensation events and variceal hemorrhage compared to nadolol and propranolol.

Here are the key takeaways from this week in Gastroenterology. First, carvedilol is associated with a significantly lower risk of major cirrhosis decompensation and variceal hemorrhage at six months compared to nadolol or propranolol, reinforcing its role as the preferred nonselective beta-blocker. Second, while long-term antiviral therapy with entecavir or tenofovir significantly reduces the incidence of hepatocellular carcinoma in hepatitis B patients after ten years, a persistent risk remains, necessitating lifelong, continuous surveillance. Third, metabolic dysfunction-associated steatotic liver disease diagnosed before the age of forty carries a more than six-fold risk of developing type 2 diabetes, highlighting the urgent need for early aggressive intervention in young adults. Fourth, a short, first-line course of infliximab in pediatric Crohn's disease only delays the time to restarting biologics, confirming that moderate-to-severe disease requires early and continuously maintained biologic therapy. Finally, performing peroral endoscopic myotomy using an underwater technique rather than carbon dioxide insufflation cuts immediate post-procedure pain in half and reduces opioid requirements ten-fold, without compromising safety or procedural efficiency.

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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