Uncouplers of mitochondrial oxidation in non-alcoholic fatty liver disease

In parallel to the obesity and type 2 diabetes epidemics, the prevalence of non-alcoholic fatty liver disease (NAFLD), newly designated metabolic dysfunction-associated steatotic liver disease, is estimated to be approximately 30% globally. 1 Henry L Paik J Younossi ZM Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment Pharmacol Ther. 2022; 56: 942-956 Crossref PubMed Scopus (59) Google Scholar When left undiagnosed and untreated, NAFLD and its inflammatory progressive subtype, non-alcoholic steatohepatitis (NASH), are associated with high all-cause and liver-related mortality. 2 Simon TG Roelstraete B Khalili H Hagström H Ludvigsson JF Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. 2021; 70: 1375-1382 Crossref PubMed Scopus (248) Google Scholar Although lifestyle remains the primary treatment approach, pharmacotherapy is urgently needed to augment the therapeutic effect size obtained with lifestyle changes. Additionally, the multiple mechanisms of NAFLD and NASH that contribute to disease progression will probably require different treatments to maximise the resolution of steatohepatitis and fibrosis regression. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trialHU6 could be a promising pharmacological agent for treating patients with obesity and NAFLD and its metabolic complications. Full-Text PDF