Exercise Training Decreases Alcohol Consumption and Tissue Injury by an FGF21-dependent Mechanism

Who can take part

• • Adults age 18 years or older, of either sex; Clinical diagnosis of alcohol use disorder (AUD) / alcohol-related liver disease (ALD); Meets NIAAA hazardous-drinking criteria: at least 7 drinks/week for women or 14 drinks/week for men for more than 6 months, with ongoing alcohol use within 2 months of evaluation; MELD score less than 21; Able to safely participate in exercise testing and endurance exercise; Able to provide informed consent; No concurrent renal, cardiac, pulmonary, cerebrovascular, or malignant illness that affects skeletal muscle mass; no diabetes mellitus; and no use of medications that affect skeletal muscle mass/protein turnover as described in the protocol, including anabolic steroids, high-dose corticosteroids, or anticoagulants

Who cannot take part

• • Pedal edema above the ankle or grade 2 pedal edema; Liver transplant; Active malignancy; Gastrointestinal bleed within the previous 4 weeks; Hepatic encephalopathy within the previous 6 months; Grade 2 or greater active esophageal varices; Active infection; Large ascites by clinical and/or imaging criteria; Advanced cardiac disease (NYHA class 3 or 4) or advanced pulmonary disease (GOLD class 3 or 4); Use of medications affecting muscle protein turnover, including corticosteroids, or medications used to prevent clotting; Prior orthopedic surgery or chronic joint pain that, in the opinion of the PI, may inhibit participation; INR greater than 1.7 or platelet count less than 60,000/mL; Unable to provide informed consent; judged likely to be unable to perform exercise or unlikely to complete the study in the opinion of the investigators; End-stage kidney disease defined as eGFR less than 15 mL/min/1.73 m² or dialysis; Considered unsafe for exercise in the opinion of the PI; Failure to pass the exercise stress test