This Review describes inter-organ ammonia metabolism in liver disease and mechanisms underlying the pathogenic effect of hyperammonaemia in hepatic encephalopathy, liver disease progression in metabolic dysfunction-associated steatotic liver disease, immune dysfunction and hepatocellular carcinoma. It also addresses the principles of treating hyperammonaemia.

In this Review, Ma and colleagues discuss the evolution in clinical trial designs for inflammatory bowel disease (IBD), their implications for clinical care, and identify future directions for the next generation of IBD studies.

Metabolic dysfunction-associated steatohepatitis (MASH), a primary cause of chronic liver disease (CLD), often leads to advanced CLD stages such as cirrhosis. This Roadmap summarizes the current landscape and challenges of MASH-related compensated cirrhosis clinical trials and explores a way forward for future studies.

Probiotics might prevent some necrotizing enterocolitis, late-onset sepsis and mortality in preterm infants. However, clinical practice varies widely, and families are often excluded from shared decision making. This Clinical Outlook highlights current evidence, clinical practice guidelines and the future outlook of probiotics in the neonatal intensive care unit.

Twenty years since the launch of Nature Reviews Gastroenterology & Hepatology, developments in research and clinical practice continue apace. In our anniversary issue, we focus on the past, present and future of gastroenterology and hepatology.