Reviews & Analysis

Gastric and gastroesophageal junction adenocarcinoma remains a major global health challenge, with a rising incidence among younger individuals worldwide despite advances in biomarker-directed targeted therapies and immunotherapy. Current breakthroughs include perioperative immunotherapy, HER2-directed therapy sequencing and a decisive shift towards biomarker-driven treatment.

Chronic hepatitis B infection remains the dominant aetiology of liver-related complications and hepatocellular carcinoma. In 2025, key evidence emerged supporting the expansion of treatment criteria, confirming the feasibility of an RNA interference-based combination regimen to boost functional cure rate, and identifying low-risk individuals who might not require liver cancer surveillance.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

In this Review, Altier and colleagues describe the mechanisms of chronic abdominal pain in inflammatory bowel disease (IBD). In addition, they discuss implications for IBD treatment and identify directions for future research.

In summary, 2025 has seen a shift in focus from pure therapeutic management to active disease prevention. The message is unambiguous. The next breakthrough in IBD will not emerge solely from new drugs or biologics, but from reimagining how we live, eat and engage with the microbial ecosystems that define our health.

Individuals living with human immunodeficiency virus infection are experiencing an increase in liver disease burden. This Review summarizes current knowledge on the burden of liver diseases in this population and provides insights into clinical management and future directions.

In this Review, Luedde and colleagues describe the complex role of regulated necrosis pathways, including necroptosis, pyroptosis and ferroptosis, in liver disease and cancer development. Potential therapeutic approaches modulating regulated cell death pathways in liver disease are explored.

Despite the high incidence and mortality rates of hepatopancreatobiliary cancers in the African continent, epidemiological and clinical data are scarce. This Roadmap article describes the efforts of the Africa HepatoPancreatoBiliary Cancer Consortium to establish cancer registries in the region.

This Review examines how advances in tumour biology, immunogenomics and graft preservation are redefining surgical management of hepatocellular carcinoma. Malik et al. describe the shift from anatomical to biology-informed paradigms to individualize surgical decision-making.

A new case report of successful treatment of refractory ulcerative colitis with CD19-directed chimeric antigen receptor T cell therapy sheds light on the role of B lineage cells in disease pathogenesis and the possibility of an ‘immune reset’. This approach could reshape therapeutic strategies, although its long-term efficacy, safety and positioning remain open questions.

The liver is a key metabolic organ that influences metabolic homeostasis by communicating with the central nervous system. This Review discusses the role of gut–liver–brain communication in chronic liver disease, highlighting underlying mechanisms and signalling pathways.

In this Review, the authors discuss the role of the main IL-1 family members in gastrointestinal and liver diseases, focusing on preclinical and clinical research. Opportunities for therapeutic interventions are also outlined.

The gut virome is a complex ecosystem and has a critical role in human health. This Review outlines gut virome composition and functional relevance, and its role in human health and disease. Methodological challenges in advancing our knowledge of the gut virome are also discussed.

The year 2025 has seen substantial advances in the understanding and management of metabolic dysfunction-associated steatotic liver disease, providing new insights into its systemic effects. Emerging evidence in 2025 supports integrated heart–liver co-management, translating the concept into actionable clinical strategies.

The gut microbiome presents in a multi-kingdom form and tunes host health in various ways. Studies published in 2025 have further pushed this frontier by unveiling the enigmatic roles of the gut fungi and bacteria in cross-organ regulations of host homeostasis through metabolite and immune cell-mediated pathways.

This Review explores the different types of sensory nerves involved in gut–brain communication, detailing the locations of these nerve endings in the gut and their mechanisms of activation. Insights and new information regarding spinal and vagal afferents alongside viscerofugal neurons are detailed.

In this Review, Deraison and Vergnolle describe the role of extracellular proteases and protease inhibitors in gastrointestinal physiology and in diseases including inflammatory bowel disease, irritable bowel syndrome and colorectal cancer. They also explore emerging therapeutic options for restoring proteolytic balance.

This Roadmap presents and outlines the creation of the Human Liver Cell Atlas as a reference map and resource for the liver community, providing an overview of the steps needed to build the atlas, as well as outlining the major challenges and potential of this venture.

Advances in organoid culture have enabled the modelling of many aspects of organs in vitro, transforming experimental biology. This Review provides a comprehensive overview of the current and emerging liver and pancreas organoid technologies and discusses current limitations and future directions.

WNT–β-catenin activation is common in hepatocellular carcinoma (HCC). In this Review, the authors summarize our understanding of the role of WNT–β-catenin activation in HCC — based on results from in vitro and in vivo models — and implications for precision treatment of HCC via targeting β-catenin.