Alcohol-Associated Liver Disease

Alcohol associated liver disease is liver injury caused by chronic heavy alcohol use, spanning steatosis, alcoholic hepatitis, fibrosis and cirrhosis.

• Risk threshold: more than 40 g daily in men and 20 g daily in women for 5 years or more (one drink is about 10 g of ethanol).
• Steatosis occurs in almost all heavy drinkers; 10 to 20 percent develop steatohepatitis, and 10 to 20 percent develop cirrhosis.
• Cofactors: female sex, obesity, hepatitis B or C, HIV, iron overload, genetic variants (PNPLA3), smoking and binge drinking. Local brews may contain methanol and other toxins.

Steatosis and early disease: asymptomatic, hepatomegaly, raised gamma-glutamyl transferase.

• Alcoholic hepatitis: fever, jaundice, tender hepatomegaly, ascites, malnutrition, leucocytosis, within weeks of heavy drinking; severe disease may present with encephalopathy and renal failure.
• Cirrhosis: spider naevi, palmar erythema, Dupuytren contracture, parotid enlargement, gynaecomastia, testicular atrophy, ascites, variceal bleeding, encephalopathy.
• Differential diagnosis: viral hepatitis, metabolic associated fatty liver disease, drug-induced liver injury, autoimmune hepatitis, haemochromatosis, Wilson disease, biliary obstruction, sepsis, cholangitis.
• Complications: decompensated cirrhosis, hepatocellular carcinoma, infection (spontaneous bacterial peritonitis), acute kidney injury, alcohol withdrawal (seizures, delirium tremens), Wernicke encephalopathy, pancreatitis, malnutrition and sarcopenia.

Alcohol history (quantity, pattern, duration); structured questionnaire; collateral history; phosphatidylethanol testing where available.

• AST greater than ALT (ratio above 2, AST seldom above 300 IU/L), raised gamma-glutamyl transferase, macrocytosis, thrombocytopenia, bilirubin, INR, albumin, neutrophilia.
• Alcoholic hepatitis: rapid onset jaundice, bilirubin above 50 micromol/L, AST above 50 IU/L, recent heavy drinking, exclusion of other causes; biopsy if doubt (transjugular route when coagulopathic).
• Severity: discriminant function (from prothrombin time and bilirubin) above 32 indicates severe disease.
• Ultrasound, elastography, hepatitis B and C serology, HIV, iron profile, autoimmune markers; ascitic fluid analysis; endoscopy for varices in cirrhosis.

Supportive

• Alcohol abstinence is the single most important intervention; brief intervention, motivational counselling, mutual help groups, and addiction services.
• Nutrition: 35 to 40 kcal/kg/day and protein 1.2 to 1.5 g/kg/day, late evening snack; enteral feeding if intake is poor; thiamine 100 mg orally three times daily (200 to 300 mg IV daily or high dose IV vitamin B complex if Wernicke risk), folic acid 5 mg daily, multivitamin, correct hypokalaemia, hypomagnesaemia, hypophosphataemia.

Pharmacological

• Withdrawal: chlordiazepoxide 10 to 30 mg orally every 4 to 6 hours reducing over 5 to 7 days, or diazepam 5 to 10 mg; lorazepam 1 to 2 mg every 4 to 6 hours in severe liver disease or elderly patients; seizures need lorazepam 4 mg IV.
• Severe alcoholic hepatitis (discriminant function above 32, no active infection, bleeding or renal failure): prednisolone 40 mg once daily for 28 days (stop earlier if bilirubin has not fallen by day 7); treat infection first (ceftriaxone 2 g IV daily) and screen daily; N-acetylcysteine adds benefit in selected patients.
• Relapse prevention: acamprosate 666 mg three times daily (avoid if creatinine clearance below 30 mL/min), naltrexone 50 mg daily (avoid in decompensated disease), baclofen 5 to 10 mg three times daily increasing to a maximum of 30 mg daily (safe in cirrhosis), disulfiram not advised in liver disease.
• Complications of cirrhosis: treat ascites, variceal bleeding and encephalopathy.

Procedures: endoscopic variceal band ligation; hepatocellular carcinoma surveillance every 6 months in cirrhosis; liver transplantation for abstinent patients with decompensation and for selected severe alcoholic hepatitis unresponsive to steroids.

Special groups: women (develop disease at lower intake), HIV and hepatitis coinfection (specialist care), pregnancy (abstinence and nutrition).

Red flags: encephalopathy, bilirubin rising, INR above 1.5, creatinine rise, gastrointestinal bleeding, sepsis, withdrawal seizures.

Follow-up: liver profile and weight monthly, then every 3 to 6 months; alcohol relapse review; vaccination against hepatitis A and B, pneumococcus and influenza.