To define the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and identify therapeutic options, it is crucial to understand the sources of hepatic fat accumulation. In patients with MASLD, it is estimated that hepatic triglycerides are primarily derived from adipose tissue as free fatty acids (~59%), followed by de novo lipogenesis (~26%) and diet (~15%). However

To mark the twentieth anniversary of Nature Reviews Gastroenterology & Hepatology, we asked three experts to comment on how the gut microbiome has transformed our understanding of biology and the strengths and limitations of microbiome research today as well as to look ahead at what the next 20 years of microbiome research and clinical applications might look like. In this Viewpoint, Maria Carmen Collado

Subsets of human tuft cells retain their proliferative capacity throughout life and can act as a damage-induced pool of regenerative stem cells, report Huang et al. in Nature. Organoids containing all human intestinal cell types were generated by the researchers from a single mature proliferating human tuft cell. Organoids engineered to lack tuft cells did not regenerate after irradiation, unlike those

Consumption of no and low-alcohol (NoLo) beverages is now commonplace in modern society. However, the debate surrounding the relative risks and benefits of these products is nuanced and evolving, particularly in patients with a history of alcohol use disorder or alcohol-related liver disease. This Comment summarizes the major individual and public health implications of NoLo drinks in order to help

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.

From 12–15 October, United European Gastroenterology (UEG) Week was held in person in Vienna, Austria, and online simultaneously. According to the organizers, there were 11,377 total registrants from 114 countries or territories, of whom 11% were registered for the virtual congress, with 4,701 individuals registered for the Postgraduate Teaching Programme, of whom 19% were registered for virtual attendance

Apical sodium-dependent bile acid transporter inhibitors have revolutionized care for children with genetic cholestasis. This Clinical Outlook discusses how this new class of drugs came into clinical practice and how they might benefit transplant-free survival for a multitude of indications.

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-00981-6, published online 2 October 2024.

A phase IIIa trial tested the safety and efficacy of liraglutide, a glucagon-like peptide 1 receptor agonist, in 82 children (6 to <12 years) with obesity. The children were randomly assigned (2:1) to receive a daily dose of 3 mg liraglutide (or the maximum tolerated dose) or placebo and follow lifestyle interventions. The treatment lasted 56 weeks with a 26-week follow-up. In week 56, the primary

A multicentre, open-label, prospective, randomized controlled trial (TransMet) assessed liver transplantation plus chemotherapy in 94 patients (intention-to-treat population) with permanently unresectable colorectal liver metastases from resected BRAF-non-mutated colorectal cancer and with no extrahepatic disease. The trial took place in 20 tertiary centres in Europe between 2016 and 2021. Patients

We thank Avades and colleagues for the opportunity to expand on our expert panel consensus statement (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. Nat. Rev. Gastroenterol. Hepatol. 21, 626–645 (2024))1 to highlight the important role of persons with lived experience of alcohol use disorder (AUD) and/or

We fully support the consensus statement on designing clinical trials to address alcohol use in people with alcohol-associated liver disease (ALD), which aims to standardize and improve the design of ALD trials (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. Nat. Rev. Gastroenterol. Hepatol. 21, 626–645 (2024))1

Management of anticoagulation in cirrhosis is challenging because of the concomitant risk of both thromboembolism and bleeding complications. Randomized controlled studies are lacking. Direct oral anticoagulants seem to be the most manageable option. However, for patients with Child C cirrhosis, the only safer anticoagulant strategy, currently, is low-molecular-weight heparin.

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-00974-5, published online 5 September 2024.

To coincide with the 20th anniversary of Nature Reviews Gastroenterology & Hepatology, we asked three experts to reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management. They comment on how MASLD research and clinical management has changed over the past 20 years, the strengths and limitations of the MASLD field today

New research published in Nature Genetics shows how neoadjuvant chemotherapy and radiotherapy affect the tumour microenvironment (TME) in pancreatic ductal adenocarcinoma using single-cell spatial transcriptomics. To this end, the researchers developed a computational tool (namely, spatially constrained optimal transport interaction analysis (SCOTIA)) to map ligand–receptor interactions within the

Nature Reviews Gastroenterology & Hepatology is launching a new Series on justice, equity, diversity and inclusion in an effort to increase awareness and advance equitable health.

The food we eat includes complex microbiomes, but the diversity of these food microbiomes has not been explored fully. In a new study published in Cell, the microbial diversity of >2,500 food metagenomes has been assessed and analysed in connection with the human microbiome, generating a new open access resource, the curatedFoodMetagenomicData (cFMD). “We all knew how food microbes are important for

The current state of microbiome research in Africa can be leveraged to encourage the development and implementation of standardized processes for data collection and management. In this Comment, we provide some recommendations to enable the research community to fully harness the richness of the microbiome of African populations and potential opportunities therein.

Gastroenterology as a specialty can make a substantial contribution to reducing the carbon footprint of the health-care system. Concrete actions are needed to increase awareness, education and evidence-based knowledge on eco-sustainable diagnostic and therapeutic approaches to digestive diseases.

A study published in Nature elucidates the genomic landscape of colorectal cancer (CRC). Researchers performed whole-genome sequencing of CRC samples from participants in the UK 100,000 Genomes Project. Analysis of the samples (n = 2,023) identified >250 putative driver genes of CRC and characterized subgroups of CRC. For example, the researchers clustered microsatellite-stable CRC into four distinct

In a study published in Nature Medicine, researchers report an artificial intelligence (AI)-based digital pathology tool for scoring metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis (NASH)) histology. MASH clinical trial enrollment and endpoint assessment are based on histological criteria. The tool, which is termed AIM-MASH, produced predictions

New research has mapped neuroimmune interactions in the mouse gut, revealing that TRPV1-expressing nociceptor neurons (involved in visceral pain) control and suppress regulatory T (Treg) cells in the gut, increasing susceptibility to colitis in mouse models. The findings potentially link pain signalling with immunomodulatory mechanisms in the gut. In their screen, eight distinct neuronal subsets were

From 26–29 June 2024, Nature Reviews Gastroenterology & Hepatology attended the 56th meeting of the European Pancreatic Club (EPC) in Santiago de Compostela, Spain. The hybrid meeting featured sessions that traversed basic, translational and clinical science, with sessions dedicated to the latest research into acute and chronic pancreatitis, cystic pancreatic lesions and pancreatic cancer, among others

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-00955-8, published online 17 July 2024.

A multicenter, open-label, controlled phase IIIb clinical trial (SEQUENCE) published in the New England Journal of Medicine, compared the efficacy and safety of risankizumab (a monoclonal antibody that targets IL-23A) versus ustekinumab (a monoclonal antibody that targets IL-12 and IL-23) in patients with moderate-to-severe Crohn's disease who previously did not respond to anti-tumour necrosis factor

In June 2024, Nature Reviews Gastroenterology & Hepatology attended in person the European Association for the Study of the Liver (EASL) Congress 2024 in Milan, Italy. This was the third year the international liver conference was in person and virtual, with the session recordings available for 3 months. According to the organizers, 7,809 people attended the meeting, 7,108 onsite and 701 online. There

A recent study in Nature Medicine describes a multi-parametric profile of a pre-metastatic signature using liver biopsy samples to predict metastatic outcomes in early-stage pancreatic cancer (PaC). The investigators obtained liver biopsy samples during pancreatectomy from patients with localized PaC (n = 49) and without cancerous lesions (n = 19). The liver samples were analysed by combining imaging

Mother-to-child transmission of hepatitis B virus remains a mode of transmission in high-burden regions where there are gaps in antenatal screening, limited hepatitis B virus birth-dose vaccination and variable access to antiviral prophylaxis. Policymakers, governments and relevant stakeholders must ensure equitable access to necessary interventions to achieve elimination targets.

The countdown to the 2030 viral hepatitis elimination goal continues, but time is running out and progress is not keeping pace. Viral hepatitis remains a major public health challenge; we need to take action now to mobilize resources and focus efforts.

Two phase III trials of new drugs for eosinophilic oesophagitis (EoE) have been reported in The New England Journal of Medicine. The findings not only highlight new treatments for the condition, but also potentially shift the emphasis for future therapeutic targets and diagnostic criteria. In the first trial (EoE KIDS), Mirna Chehade and colleagues assessed dupilumab, a human monoclonal antibody that

Globally, one in six people have a disability, and individuals with disabilities often experience a narrow margin of health, less financial security and health disparities. We call for action to improve access to health care for people with disabilities and show how this plan might be achieved.