Key Facts

Alcoholic liver disease (ALD) is the leading cause of liver-related morbidity and mortality in the UK. The spectrum ranges from simple steatosis (fatty liver) to end-stage cirrhosis. Early identification and abstinence can halt and even reverse disease.

Epidemiology

ALD accounts for >60% of liver disease deaths in the UK. Approximately 8,000 alcohol-related deaths per year. Cirrhosis mortality has increased 400% since the 1970s in the UK (compared with reductions in Southern Europe). ~25% of heavy drinkers develop cirrhosis.

Aetiology

• Alcohol consumption: >14 units/week sustained; significant disease risk with >35 units/week in men, >28 in women over >10 years
• Cofactors increasing susceptibility: obesity (synergistic with alcohol), hepatitis B/C co-infection, genetic factors (PNPLA3 polymorphism), female sex, malnutrition

Pathophysiology

Steatosis: alcohol metabolism generates NADH (via ADH and ALDH), shifting hepatic metabolism towards fatty acid synthesis and away from fatty acid oxidation → triglyceride accumulation.

Steatohepatitis: acetaldehyde (toxic metabolite) causes lipid peroxidation, mitochondrial damage, and generation of reactive oxygen species. Gut-derived endotoxin (LPS) activates Kupffer cells → TNF-α, IL-1, IL-6 → hepatocyte necrosis, neutrophilic infiltration, Mallory-Denk bodies.

Fibrosis/Cirrhosis: activated hepatic stellate cells produce collagen → progressive fibrosis → nodular regeneration → cirrhosis. Portal hypertension develops when hepatic venous pressure gradient exceeds 10 mmHg.

Alcoholic Steatosis

• Often asymptomatic
• Hepatomegaly, mild RUQ discomfort
• Abnormal LFTs (raised GGT, mildly raised ALT/AST)

Alcoholic Hepatitis (Acute)

• Rapid onset jaundice, malaise, anorexia
• Tender hepatomegaly
• Fever (low-grade, sterile)
• Coagulopathy (raised INR)
• Ascites (in severe cases)
• Signs of decompensated liver disease

Alcoholic Cirrhosis

• Stigmata of chronic liver disease: spider naevi, palmar erythema, gynaecomastia, testicular atrophy, caput medusae, Dupuytren's contracture
• Decompensation: jaundice, ascites, variceal bleeding, hepatic encephalopathy
• Parotid enlargement: bilateral, non-tender

Red Flags

• Rapidly worsening jaundice (alcoholic hepatitis)
• Coagulopathy (INR >1.5) with jaundice
• Encephalopathy (confusion, asterixis)
• Variceal bleeding
• Hepatorenal syndrome (rising creatinine with liver failure)

Bedside

• Alcohol history: AUDIT/AUDIT-C questionnaire; units per week; duration; pattern
• Examination: stigmata of CLD, hepatomegaly, ascites, encephalopathy

Bloods

• LFTs: AST:ALT ratio >2 (characteristic of ALD); raised GGT (often markedly); raised bilirubin in hepatitis/cirrhosis
• FBC: macrocytosis (MCV >100 fL — direct toxic effect + folate deficiency), thrombocytopaenia (hypersplenism)
• Coagulation (INR/PT): raised in severe disease (synthetic failure)
• Albumin: low in advanced disease
• U&Es: hepatorenal syndrome screening
• CRP: raised in alcoholic hepatitis (but must exclude infection)
• Discriminant function (Maddrey DF): 4.6 × (patient PT − control PT) + bilirubin (μmol/L)/17.1; DF ≥32 = severe alcoholic hepatitis
• MELD score: ≥21 predicts poor prognosis
• Lille score: at day 7 of steroid treatment; >0.45 = non-responder → stop steroids
• Exclude other causes: hepatitis B/C serology, autoantibodies (ANA, SMA, anti-LKM), immunoglobulins, iron studies, caeruloplasmin, alpha-1 antitrypsin

Imaging

• USS abdomen: hepatic steatosis (bright/echogenic liver), hepatomegaly, features of cirrhosis (irregular surface, splenomegaly, ascites)
• Transient elastography (FibroScan): liver stiffness measurement; >12.5 kPa suggests significant fibrosis/cirrhosis; also measures CAP (controlled attenuation parameter) for steatosis
• CT/MRI: cirrhosis morphology, HCC screening, portal hypertension features

Special Tests

• Liver biopsy: not routinely required; indicated for diagnostic uncertainty; shows steatosis, Mallory-Denk bodies, ballooning degeneration, neutrophilic infiltration, pericellular fibrosis
• Enhanced liver fibrosis (ELF) test: serum biomarker panel for fibrosis staging
• AFP: HCC screening in cirrhotics

Non-pharmacological

• Alcohol abstinence: single most important intervention — improves survival at ALL stages including decompensated cirrhosis; brief intervention, motivational interviewing, referral to alcohol services
• Nutritional support: high-calorie, high-protein diet (1.2-1.5 g/kg/day protein); avoid protein restriction even in encephalopathy (outdated practice)
• Thiamine (vitamin B1): Pabrinex IV (2 pairs TDS for 3-5 days) in all ALD admissions to prevent Wernicke's encephalopathy; then oral thiamine 100 mg TDS

Pharmacological

• Severe alcoholic hepatitis (DF ≥32 or MELD ≥21):
  • Prednisolone 40 mg OD for 28 days — STOPAH trial: improved 28-day survival (8% vs 14% mortality); no benefit at 90 days
  • Assess response with Lille score at day 7: ≤0.45 continue steroids; >0.45 stop (non-responder)
  • Contraindications to steroids: active infection, GI bleeding, renal failure, pancreatitis
  • Pentoxifylline: no longer recommended (STOPAH showed no benefit)
• Alcohol withdrawal management: chlordiazepoxide reducing regimen (symptom-triggered or fixed dose); monitor with CIWA-Ar score
• Cirrhosis management: see portal hypertension, ascites, encephalopathy entries as applicable
• Baclofen 10-30 mg TDS: may reduce alcohol craving in patients with liver disease (safer than naltrexone/acamprosate)

Surgical/Interventional

• Liver transplantation: for decompensated ALD cirrhosis; typically requires 6 months abstinence (variable between centres); increasingly considered for severe alcoholic hepatitis not responding to medical therapy (ACCELERATE trial evidence for early transplant)
• TIPSS: for refractory ascites or variceal bleeding in ALD cirrhosis

Referral Criteria

• Hepatology referral: all ALD with fibrosis/cirrhosis, alcoholic hepatitis, decompensation
• Alcohol services: all patients with harmful/dependent drinking
• Liver transplant assessment: decompensated cirrhosis with abstinence
• Nutritional/dietitian support

Alcoholic steatosis is fully reversible with abstinence. Alcoholic hepatitis: 28-day mortality is ~15-20% for severe disease (DF ≥32) even with steroids; higher if Lille non-responder. Compensated ALD cirrhosis: 5-year survival ~80% WITH abstinence, ~60% without. Decompensated ALD cirrhosis: median survival 2-4 years without transplant. Abstinence improves survival at all stages. HCC risk in ALD cirrhosis: ~2-3% per year. Post-transplant outcomes for ALD are excellent (>70% 5-year survival).

Maddrey Discriminant Function

• Formula: DF = 4.6 × (patient PT − control PT) + bilirubin (μmol/L) / 17.1
• DF ≥32 = severe alcoholic hepatitis → consider steroids

Lille Score (Day 7)

• Incorporates: age, albumin, bilirubin at day 0, bilirubin at day 7, creatinine, PT
• ≤0.45: responder → complete 28-day course
• >0.45: non-responder → stop steroids (futile + risk of infection)

Spectrum of ALD