Current Medical Treatment for Alcohol-Associated Liver Disease

Abstract

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Keywords: AC, Amoxicillin/clavulanate; ACLF, Acute-on-Chronic Liver Failure; ADLs, Activities of Daily Living; AH, Alcohol-Associated Hepatitis; AKI-HRS, Acute Kidney Injury - Hepatorenal Syndrome; ALD; ALD, Alcohol-Associated Liver Disease; ASH, Alcoholic Steatohepatitis; AUD, Alcohol Use Disorder; AWS, Alcohol Withdrawal Syndrome; BCAAs, Branched-Chain Amino Acids; CDC, Center for Disease Control; CI, Confidence Interval; COVID-19, Coronavirus Disease 2019; CT, Computerized Tomography; GABA, gamma-aminobutyric acid agonist; HBV, Hepatitis B Virus; HCC, Hepatocellular Carcinoma; HCV, Hepatitis C Virus; HE, Hepatic Encephalopathy; HIV, Human Immunodeficiency Virus; HR, Hazard Ratio; IBW, Ideal Body Weight; ICA, International Club of Ascites; IL-1β, Interleukin-1β; IL-22, Interleukin-22; KPS, Karnofsky Performance Status; LB, Liver Biopsy; LPS, Lipopolysaccharide; LSM, Liver Stiffness Measurement; LT, Liver Transplantation; MDF, Maddrey’s Discriminant Function; MELD, Model of End-Stage Liver Disease; MRI, Magnetic Resonance Imaging; MUST, Malnutrition Universal Screening Tool; NIAAA, National Institute on Alcohol Abuse and Alcoholism; NRS-2002, Nutritional Risk Screening-2002; OR, Odds Ratio; PAMPs, Pathogen-Activated Molecular Patterns; PMI, Psoas Muscle Index; PTX, Pentoxifylline; RAI, Relative Adrenal Insufficiency; RCT, Randomized Clinical Trials; RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool; ROS, Reactive Oxygen Species; RR, Relative Risk; SIRS, Systemic Inflammatory Response Syndrome; TNF, Tumor Necrosis Factor; WKS, Wernicke-Korsakoff Syndrome; alcohol; alcohol use disorders; alcohol-associated hepatitis; cirrhosis; fatty liver disease; steatosis.

Algorithm 1

General management of alcohol-associated hepatitis. AST: aspartate aminotransferase;ALT: alanine aminotransferase; MELD: Model of End-Stage Liver Disease; GI: gastrointestinal; HCV: hepatitis C virus.