Reviews & Analysis

Increasing evidence shows a role of cellular stress responses in nonalcoholic steatohepatitis (NASH) and liver fibrosis pathogenesis. This Review provides a comprehensive overview of the molecular mechanisms involved in cellular stress in fibrogenesis and their role in NASH progression.

Hormones released in the gut orchestrate pivotal physiological processes. In this Review, the authors present an overview of gut hormones that are involved in the regulation of metabolism, and discuss their action in the gastrointestinal system and beyond.

In this Review, Arrese and colleagues discuss the intersection of nonalcoholic fatty liver disease and alcohol-related liver disease, including their pathophysiology, clinical management and suggestions for future research.

Hepatic stellate cells (HSCs) drive liver fibrosis and are closely linked to liver cancer development. This comprehensive Review provides an in-depth analysis of the specific characteristics of HSCs in cancer, highlighting therapeutic implications based on progress in clarifying HSC biology.

In this Review, Huang et al. discuss the current status of hepatocellular carcinoma surveillance, the remaining challenges, including the changing aetiology of liver disease, and strategies to improve the utilization and quality of surveillance.

The importance of commensal fungi in health and disease is becoming increasingly clear. In this Review, Ost and Round discuss the involvement of the mycobiota in intestinal diseases, and consider potential opportunities to target fungi and their interactions for therapeutic purposes.

Nonalcoholic fatty liver disease (NALFD) prevalence, including in children and adolescents, is rising worldwide. This Review offers a comprehensive overview of the lifestyle interventions available for NAFLD, including dietary and physical-activity strategies.

Liver inflammation is a key process that orchestrates intrahepatic injury. This Review offers a comprehensive overview of the inflammatory mechanisms of hepatic fibrosis and discusses current advances and therapeutic implications.

This Review discusses the role of the circadian clock in liver homeostasis, and how dysfunction of the liver circadian clock is associated with several liver-related diseases, including nonalcoholic fatty liver disease, type 2 diabetes mellitus and hepatocellular carcinoma.

Currently, systematic care for adults and adolescents with oesophageal atresia–tracheoesophageal fistula (EA-TEF) as they transition into adulthood is lacking. A multidisciplinary group of experts structured this Consensus Statement offering guidelines for the care of adolescents and adults with EA-TEF during transition.

Tackling fibrosis in patients with nonalcoholic steatohepatitis (NASH), one of the major causes of liver cirrhosis, is critical in improving patient outcomes. This Perspective discusses potential strategies to develop better antifibrotic therapies in NASH, from the discovery process to future clinical trials.

Up to one-third of people with irritable bowel syndrome (IBS) also experience anxiety or depression. In this Review, we highlight common challenges that arise when managing patients with IBS and co-occurring anxiety and depression, and provide recommendations for tailoring clinical assessment and treatment.

Single-cell profiling studies of the human gastrointestinal tract are increasing, offering an excellent opportunity to generate the first Human Gut Cell Atlas. This Roadmap presents a structured direction towards this goal and provides a detailed overview of the major challenges.

Recent clinical trials have demonstrated efficacy and safety of etrasimod, a new sphingosine-1-phosphate receptor modulator, in the treatment of patients with moderately-to-severely active ulcerative colitis. Etrasimod is a promising new oral treatment option for ulcerative colitis, although long-term efficacy and safety data should be accumulated.

Advances in single-cell technologies and lineage tracing have improved our understanding of liver development. In this Review, Hoodless and colleagues discuss the formation of liver parenchymal and non-parenchymal cell types, and describe emerging parallels between early liver development and the pathogenesis of liver injury.

A new study has found that a strain of the gut bacterium Lactiplantibacillus plantarum activates a NOD2–type I interferon–insulin-like growth factor 1 pathway in young mice to partially protect against the deleterious growth effects of a diet deficient in protein and fat. Could live biotherapeutic products or their derivatives unlock the full potential of nutritional interventions against childhood stunting?

Increased intestinal permeability owing to tight junction barrier loss could be targeted in gastrointestinal diseases associated with increased permeability. In this Review, the authors discuss the molecular components and regulation of the tight junction, and consider the relevance to gut diseases and therapeutic opportunities.

In this Review, Pabst and colleagues discuss the gut–liver axis, with an emphasis on the establishment and regulation of structural and functional barriers, dynamics within the axis (immune responses and microbiome) and clinical implications.

The appendix is thought to have a role in the pathogenesis of ulcerative colitis but the association remains unclear. In this Perspective, the authors consider the biology of the appendix with respect to its immunological function and the microbiome, and how this relates to its possible involvement in ulcerative colitis.

A prospective study suggests that the risk of liver fibrosis with methotrexate treatment has been overestimated. The findings suggest the need to reconsider the intensive strategies and the screening tools that are recommended for monitoring liver fibrosis in patients receiving methotrexate.