Nature Reviews Gastroenterology &Hepatology最新文献

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.