Rifaximin-α in alcohol-associated liver disease

Alcohol-associated liver disease is the most common cause of cirrhosis and a leading indication for liver transplantation in the USA and worldwide. 1 Huang DQ Mathurin P Cortez-Pinto H Loomba R Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors. Nat Rev Gastroenterol Hepatol. 2023; 20: 37-49 Crossref PubMed Scopus (38) Google Scholar , 2 Singal AK Mathurin P Diagnosis and treatment of alcohol-associated liver disease: a review. JAMA. 2021; 326: 165-176 Crossref PubMed Scopus (111) Google Scholar A public health concern, the morbidity and mortality of alcohol-associated liver disease has accelerated globally since the COVID-19 pandemic due to rising alcohol consumption. 3 Deutsch-Link S Curtis B Singal AK COVID-19 and alcohol associated liver disease. Dig Liver Dis. 2022; 54: 1459-1468 Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar Alcohol causes liver fibrosis directly by reactive oxygen species generated via its hepatic metabolism, and indirectly through its effect on the gut–liver axis, leading to dysbiosis and increased gut permeability resulting in bacterial translocation. Together, these effects alter innate immune responses, resulting in a hepatic and systemic inflammatory milieu with the release of cytokines and chemokines, which cross talk with hepatic cells (sinusoidal endothelial and stellate cells) to promote fibrosis via hepatic stellate cell activation (figure). 2 Singal AK Mathurin P Diagnosis and treatment of alcohol-associated liver disease: a review. JAMA. 2021; 326: 165-176 Crossref PubMed Scopus (111) Google Scholar Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trialIn patients with alcohol-related liver disease, rifaximin-α might reduce progression of liver fibrosis. These findings warrant confirmation in a multicentre phase 3 trial. Full-Text PDF Open Access