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

Inclusion Criteria:

• • 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.

Exclusion Criteria:

• • 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.