Nature Reviews Gastroenterology &Hepatology最新文献

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.

Alongside the usual variety of sessions on basic, translational and clinical science across the fields of gastroenterology and hepatology, there was an expansion in the scope of the topics covered, and indeed how they were delivered (so-called silent sessions with attendees listening on headphones). Sessions on metabolism and nutrition were noticeably prominent, highlighting the current interest in food as medicine and the new obesity management medications. A whole session was dedicated to the role of nutrition in the pathogenesis and treatment of lower gastrointestinal disease and a late-breaker abstract presented positive data for the ‘Tasty&Healthy’ flexible diet in children and young adults with mild–moderate Crohn’s disease. Attendees were also guided through the underlying mechanisms for GLP1 agonists and the ever-expanding list of dual and triple agonists for the management of obesity, as well as given practical advice on the therapeutic management of obesity, which included lifestyle interventions and surgery.

The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally.

Thyroid hormones (triiodothyronine and thyroxine) are pivotal for metabolic balance in the liver and entire body. Dysregulation of the hypothalamus–pituitary–thyroid axis can contribute to hepatic metabolic disturbances, affecting lipid metabolism, glucose regulation and protein synthesis. In addition, reductions in circulating and intrahepatic thyroid hormone concentrations increase the risk of metabolic dysfunction-associated steatotic liver disease by inducing lipotoxicity, inflammation and fibrosis. Amelioration of hepatic metabolic disease by thyroid hormones in preclinical and clinical studies has spurred the development of thyromimetics that target THRB (the predominant thyroid hormone receptor isoform in the liver) and/or the liver itself to provide more selective activation of hepatic thyroid hormone-regulated metabolic pathways while reducing thyrotoxic side effects in tissues that predominantly express THRA such as the heart and bone. Resmetirom, a liver and THRB-selective thyromimetic, recently became the first FDA-approved drug for metabolic dysfunction-associated steatohepatitis (MASH). Thus, a better understanding of the metabolic actions of thyroid hormones and thyromimetics in the liver is timely and clinically relevant. Here, we describe the roles of thyroid hormones in normal liver function and pathogenesis of MASH, as well as some potential clinical issues that might arise when treating patients with MASH with thyroid hormone supplementation or thyromimetics.

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 endpoint was reached, which was the percentage change in body mass index (BMI) from baseline: in the liraglutide group, mean BMI percentage change was –5.8% versus 1.6% in the placebo group (95% CI –11.6 to –3.2, P < 0.001). The secondary endpoint was a BMI reduction of at least 5% and was observed in 46% of the children who received liraglutide and 9% of the children in the placebo group (adjusted odds ratio 6.3, 95% CI 1.4–28.8, P = 0.02).

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 were randomly assigned (1:1) to the liver transplantation group plus chemotherapy (group A) or chemotherapy alone (group B). Overall, 74 patients were included in the per-protocol analysis. In the intention-to-treat population, 5-year overall survival was 56.6% for group A and 12.6% for group B (HR 0.37; 95% CI 0.21–0.65; P = 0.0003), whereas in the per-protocol analysis population, it was 73.3% and 9.3%, respectively (HR 0.36; 95% CI 0.07–0.33; P = 0.0001).

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. The authors highlight the global burden of ALD and the paucity of clinical trials of interventions to reduce or eliminate alcohol use in people with alcohol use disorder (AUD) — a set of recommendations for this field is crucial.

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 alcohol-associated liver disease (ALD), their caregivers and their advocates in clinical trials (Avades, T. et al. An expert panel Consensus Statement on ALD without experts by experience. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/10.1038/s41575-024-00994-1 (2024))². Including these voices is critical to guide the design of clinical trials, recruitment and retention efforts, and, most importantly, the implementation of findings for the individuals most affected by these diseases.

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