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[Viewpoint] Ulcerative colitis: moving beyond the mucosal dogma

Ulcerative colitis has traditionally been regarded as a non-fibrotic, solely mucosal disease, whereas Crohn's disease is characterised by transmural inflammation and fibrosis. However, more recent evidence supports the existence of disease involvement beyond the mucosa in ulcerative colitis. Intestinal ultrasound has allowed for dynamic, in-vivo characterisation of the transmural alterations that occur in ulcerative colitis, such as increased bowel wall thickness, submucosal thickening, loss of bowel wall stratification, haustral loss, and mesenteric fibrofatty proliferation.

[Review] Current and emerging therapeutic landscape for metabolic dysfunction-associated steatohepatitis

Globally, metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease, affecting up to one in three people in the general population, with an estimated increase in prevalence of more than 50% in the last three decades. The rise in prevalence of MASLD will result in substantial increases in the number patients with decompensated cirrhosis and those developing liver cancer by 2030. Despite the complex pathobiology of MASLD, two major breakthroughs in phase 3 clinical trials now herald an era of licensed therapies for MASLD.

[In Focus] The label of a diagnosis

To suddenly and unexpectedly feel unwell is not welcome in our busy day-to-day lives. For the physical symptoms to persist longer than you know they should is even worse. The desperation to feel better is palpable. To constantly feel unwell is draining. And, of course, nobody wants to admit that there may be an underlying cause. The denial that you may need to seek medical help and the fear of the unknown are real and strong. But, eventually and probably inevitably, it seems that seeking professional help is the only sensible option, the only way forward.

[News] Research in Brief

Perioperative camrelizumab plus rivoceranib shows benefit in patients with hepatocellular carcinoma at intermediate or high risk of relapse, according to the CARES-009 phase 2/3 trial. Zheng Wang and colleagues randomly assigned patients to receive either perioperative therapy comprising two cycles of neoadjuvant camrelizumab plus rivoceranib, followed by surgery and adjuvant camrelizumab plus rivoceranib (n=148), or surgery alone (n=146). At a prespecified interim analysis, with a median follow-up of 21·3 months, median EFS was 42·1 months (95% CI 23·2–not estimable [NE]) in the perioperative group versus 19·4 months (14·9–NE) in the surgery-alone group (hazard ratio [HR] 0·59, 95% CI 0·41–0·85; p=0·0040).

[Corrections] Correction to Lancet Gastroenterol Hepatol 2025; 10: 431–41

Hugova K, Mares J, Hakanson B, et al. Per-oral endoscopic myotomy versus laparoscopic Heller's myotomy plus Dor fundoplication in patients with idiopathic achalasia: 5-year follow-up of a multicentre, randomised, open-label, non-inferiority trial. Lancet Gastroenterol Hepatol 2025; 10: 431–41—In this Article, Prof Alessandro Repici's affiliations should have been “Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy” and “Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy”.

[Corrections] Correction to Lancet Gastroenterol Hepatol 2019; 4: 364–75

Hurt C, Ramaraj R, Farr A, et al. Feasibility and economic assessment of chromocolonoscopy for detection of proximal serrated neoplasia within a population-based colorectal cancer screening programme (CONSCOP): an open-label, randomised controlled non-inferiority trial. Lancet Gastroenterol Hepatol 2019; 4: 364–75—The appendix of this Article had been inadvertently switched with that of another paper; the correct appendix has now been supplied, as of Dec 2, 2025.

[Correspondence] Clinical remission in ulcerative colitis: restoring precision in trial terminology

The term remission is a fundamental descriptor of therapeutic success in clinical medicine, denoting the abatement of symptoms and a return towards normal function. In ulcerative colitis, the term clinical remission can be traced back to the first modern randomised controlled trial in gastroenterology, the landmark cortisone versus placebo study, in which remission was defined strictly by symptom resolution.1 Endoscopic disease activity was reported separately, indicating early recognition that these outcomes represent separate dimensions of disease control.

[Correspondence] Endoscopic palliation of malignant gastric outlet obstruction: harmonising outcomes

Three recent randomised controlled trials (RCTs)—two of which were published in The Lancet Gastroenterology & Hepatology—have defined endoscopic ultrasonography-guided gastroenterostomy as a transformative advance for malignant gastric outlet obstruction.1–3 Each trial represents a major technical and methodological accomplishment, collectively positioning endoscopic ultrasonography-guided gastroenterostomy as a credible and increasingly accessible alternative to surgical bypass or duodenal stent palliation.

[Correspondence] Efficacy differentiation of sterile faecal filtrates in Clostridioides difficile infection

We congratulate Dina Kao and colleagues on their elegant and methodologically rigorous non-inferiority trial comparing lyophilised sterile faecal filtrate (LSFF) with lyophilised faecal microbiota transplantation (LFMT) in patients with recurrent Clostridioides difficile infection.1 This work represents the first adequately powered attempt to test whether live microbes are indispensable for the efficacy of microbiota-based therapy in this important indication.

[Comment] Colorectal cancer screening in LGBTQIA+ people: an urgent call for equity

Worldwide, colorectal cancer is the second leading cause of cancer-related mortality and the third most common cancer, with incidence rates increasing among individuals younger than 50 years.1 Although there are multiple effective colorectal cancer screening modalities, uptake is variable. Disparities in screening participation are driven, in part, by social determinants of health, including educational attainment, income, and living environment. For example, in the USA, screening rates are lowest among non-White individuals, the uninsured, those with low income, and individuals without a high school degree.

[Comment] Closing the Middle East and north Africa representation gap in clinical trials in inflammatory bowel disease

Inflammatory bowel disease (IBD) has expanded beyond its initial confines of early industrialised countries in North America, Europe, and Oceania and now constitutes a global illness. Once rare in the Middle East and north Africa region, analyses using the Global Burden of Disease 2019 Study database showed a 30% increase in age-standardised IBD incidence from 1990 to 2019, with prevalence estimates at 48·3 per 100 000 people;1 a study by Hracs and colleagues analysing the global epidemiological evolution of IBD indicates that the Middle East and north Africa region is currently at stage 2, with growing incidence and rising prevalence.

[Comment] Expanding the therapeutic arsenal for paediatric ulcerative colitis

Interleukin-23 (IL-23) plays a pivotal role in the complex pathogenesis of both ulcerative colitis and Crohn's disease, making it a promising therapeutic target.1 Mirikizumab is a humanised IgG4 monoclonal antibody that selectively inhibits IL-23 by binding to its p19 subunit. The drug has been approved for moderate-to-severe adult ulcerative colitis; however, clinical trials in the paediatric population are still in earlier stages of development. In The Lancet Gastroenterology & Hepatology, Jess L Kaplan and colleagues report data from SHINE-1, the first phase 2 trial of mirikizumab in children with moderate-to-severe ulcerative colitis.

[Editorial] ACIP's HBV birth-dose vaccine recommendations: a fiasco

The Advisory Committee on Immunization Practices (ACIP), a panel that advises the US Centers for Disease Control and Prevention (CDC) on national vaccine policy, voted on Dec 5, 2025, to abandon recommendations for universal hepatitis B vaccination in newborns, revoking guidance that had seen the number of childhood cases of hepatitis B virus (HBV) infection in the USA fall by 99% since being adopted in 1991.

[Review] Fatigue in people with primary biliary cholangitis: a position paper from the European Reference Network for Rare Liver Diseases

Given the unmet need of fatigue in primary biliary cholangitis (PBC), the PBC working group of the European Reference Network for Rare Liver Diseases assessed and summarised the current evidence relating to fatigue in PBC to provide guidance for clinical practice and identify knowledge gaps to shape the future research agenda. Six key questions regarding PBC-related fatigue were summarised through systematic review and meta-analyses. Fatigue is highly prevalent in PBC and substantially affects health-related quality of life.

[Review] Age-related changes of the gastrointestinal tract

Disorders of the gastrointestinal tract are common in those aged 65 years or older, impairing their quality of life and potentially increasing morbidity and mortality risk. Unlike many organ systems, the luminal gastrointestinal tract does not undergo much natural degeneration. However, age-related anatomical and functional changes of the gastrointestinal tract might promote pathophysiology and explain some atypical presentations of gastrointestinal disorders in older adults. This Review summarises current knowledge of major anatomical and functional changes that occur in the gastrointestinal tract during ageing.