Key Facts

Alcoholic liver disease (ALD) is a major public health problem in the UK. It is the 3rd commonest cause of premature death in working-age adults. The rising trend in alcohol consumption has led to increasing rates of liver disease, in contrast to most other European countries.

Epidemiology

• >60% of liver disease deaths in the UK are alcohol-related
• Cirrhosis develops in approximately 10-20% of heavy drinkers after 10-20 years
• Risk increases significantly above 14 units/week; risk dose-dependent
• Women are more susceptible at lower levels of consumption (lower body water, reduced gastric ADH)
• Liver disease mortality has increased >400% since the 1970s in the UK
• Mean age at death from ALD: ~55 years

Aetiology

• Threshold: risk increases above 21 units/week (men) and 14 units/week (women) over prolonged periods
• Cofactors increasing risk: obesity (synergistic with alcohol), hepatitis B/C co-infection, genetic factors (PNPLA3 gene variant), iron overload, smoking
• Pattern of drinking: binge drinking may be more hepatotoxic than steady consumption

Pathophysiology

• Steatosis: alcohol metabolism generates excess NADH → shifts hepatic metabolism towards fat synthesis; reversible with abstinence
• Steatohepatitis: oxidative stress (CYP2E1, reactive oxygen species) + acetaldehyde toxicity → hepatocyte injury → neutrophilic inflammation; Mallory-Denk bodies on histology
• Fibrosis: activation of hepatic stellate cells → excess collagen deposition; initially pericentral/perivenular (zone 3)
• Cirrhosis: progressive fibrosis → nodular regeneration → architectural distortion → portal hypertension

Alcoholic Fatty Liver (Steatosis)

• Often asymptomatic or vague right upper quadrant discomfort
• Hepatomegaly: smooth, non-tender liver
• Abnormal LFTs on routine blood tests
• Completely reversible with abstinence

Alcoholic Hepatitis

• Acute presentation: jaundice, fever, right upper quadrant pain, hepatomegaly
• Systemic inflammatory response: tachycardia, pyrexia, leucocytosis
• Hepatic decompensation: ascites, coagulopathy, encephalopathy
• Tender hepatomegaly with hepatic bruit in severe cases
• Features of chronic liver disease may coexist

Alcoholic Cirrhosis

• Chronic liver disease signs: spider naevi (>5 is significant), palmar erythema, gynaecomastia, testicular atrophy, Dupuytren contracture, parotid enlargement
• Portal hypertension: splenomegaly, ascites, caput medusae, oesophageal varices
• Hepatic decompensation: jaundice, ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome

Red Flags

• Maddrey DF ≥32: severe alcoholic hepatitis with high mortality
• Hepatic encephalopathy: confusion, asterixis, fetor hepaticus — indicates significant hepatocellular failure
• Variceal haemorrhage: haematemesis/melaena — 15-20% mortality per episode
• Spontaneous bacterial peritonitis: fever, abdominal pain, deterioration in patient with ascites
• Hepatorenal syndrome: rising creatinine in cirrhotic patient without other cause — very poor prognosis
• New hepatic mass: risk of hepatocellular carcinoma in cirrhosis

Bedside

• Clinical assessment: stigmata of chronic liver disease, nutritional status, signs of decompensation
• BMI and nutritional screening: MUST score
• Alcohol history: AUDIT, SADQ
• Abdominal examination: hepatomegaly, splenomegaly, ascites (shifting dullness, fluid thrill)

Bloods

• LFTs: AST:ALT ratio >2 (classic); GGT markedly elevated; bilirubin raised in hepatitis/cirrhosis
• FBC: macrocytosis (MCV), thrombocytopenia (hypersplenism/marrow suppression), leucocytosis (alcoholic hepatitis)
• Clotting: prolonged PT/INR (impaired synthetic function)
• Albumin: low in chronic liver disease (impaired synthesis)
• U&Es and creatinine: hepatorenal syndrome assessment
• CRP: elevated in alcoholic hepatitis
• Liver screen: hepatitis B/C serology, autoantibodies (ANA, SMA, AMA), immunoglobulins, ferritin, caeruloplasmin (if <40 years), alpha-1 antitrypsin

Scoring Systems

• Maddrey Discriminant Function: 4.6 × (patient PT − control PT) + serum bilirubin (μmol/L)/17.1; ≥32 = severe alcoholic hepatitis
• Glasgow Alcoholic Hepatitis Score (GAHS): age, WCC, urea, PT ratio, bilirubin; ≥9 = poor prognosis
• MELD score: Model for End-stage Liver Disease; used for transplant prioritisation
• Child-Pugh score: A (5-6), B (7-9), C (10-15); predicts survival in cirrhosis

Imaging

• Liver ultrasound: steatosis (echobright liver), cirrhotic morphology, portal hypertension (splenomegaly, ascites), hepatocellular carcinoma screening
• FibroScan: non-invasive fibrosis assessment; >8 kPa significant fibrosis, >12.5 kPa cirrhosis
• CT abdomen: staging, portal hypertension, HCC characterisation
• MRI with contrast: gold standard for characterising liver lesions

Special Tests

• Upper GI endoscopy: variceal screening — all patients with new diagnosis of cirrhosis
• Ascitic tap: diagnostic if new ascites — cell count, albumin (SAAG ≥11 g/L = portal hypertension), culture
• Liver biopsy: if diagnostic uncertainty; histology shows steatosis, Mallory-Denk bodies, neutrophilic infiltrate, pericellular fibrosis

Non-pharmacological

• Alcohol abstinence: single most important intervention; improves survival at all stages
• Nutritional support: high-protein, high-calorie diet (35-40 kcal/kg/day, 1.2-1.5 g protein/kg/day); nasogastric feeding if unable to eat
• Fluid and sodium restriction: for ascites management (sodium <2 g/day)
• Weight management: address co-morbid obesity
• Hepatocellular carcinoma surveillance: 6-monthly USS and AFP in cirrhosis (NICE CG49)

Pharmacological

• Alcoholic hepatitis (Maddrey DF ≥32):
  • Prednisolone 40 mg OD for 28 days then taper — STOPAH trial (2015): showed trend towards reduced 28-day mortality (OR 0.72) but no benefit at 90 days or 1 year
  • Assess response with Lille score at day 7: score >0.45 = non-responder → stop steroids
  • Pentoxifylline: no longer recommended (STOPAH showed no benefit)
  • Contraindications to steroids: active GI bleeding, uncontrolled sepsis, hepatorenal syndrome, hepatitis B
• Ascites management:
  • Spironolactone 100 mg OD (up to 400 mg) ± furosemide 40 mg OD (up to 160 mg) — aim weight loss 0.5-1 kg/day
  • Therapeutic paracentesis with albumin replacement (6-8 g/L drained) for tense/diuretic-resistant ascites
• Variceal prophylaxis:
  • Primary: propranolol (titrate to HR 55-60) or carvedilol 6.25-12.5 mg OD
  • Variceal band ligation: for large varices or intolerance to beta-blockers
• Hepatic encephalopathy: lactulose 15-30 ml TDS (aim 2-3 soft stools/day) ± rifaximin 550 mg BD (NICE TA612)
• Spontaneous bacterial peritonitis: IV cefotaxime 2 g BD (or co-amoxiclav); prophylaxis with ciprofloxacin 500 mg OD if prior SBP episode

Surgical

• Liver transplantation: definitive treatment for end-stage ALD; 5-year survival ~70-75%; traditionally requires 6 months abstinence (increasingly flexible for selected patients with severe alcoholic hepatitis)
• TIPSS: for refractory ascites or recurrent variceal haemorrhage

Referral Criteria

• Hepatology: all patients with suspected cirrhosis, severe alcoholic hepatitis, decompensated liver disease
• Transplant centre: end-stage liver disease, MELD ≥15, decompensated cirrhosis with poor quality of life
• Alcohol services: all patients with ALD for relapse prevention
• Dietitian: nutritional assessment and management
• Palliative care: if not transplant candidate with progressive decompensated disease

Mortality and Survival

• Steatosis: excellent prognosis with abstinence; complete reversibility
• Alcoholic hepatitis (Maddrey DF ≥32): 28-day mortality 30-50%; 1-year mortality ~40-50%
• Compensated cirrhosis: median survival ~12 years with abstinence; ~6 years if drinking continues
• Decompensated cirrhosis: median survival ~2 years without transplant
• Child-Pugh C cirrhosis: 1-year survival ~45%
• Post-transplant: 5-year survival ~70-75%

Complications

• Portal hypertension: varices, ascites, splenomegaly, hepatorenal syndrome, hepatopulmonary syndrome
• Hepatocellular carcinoma: annual incidence 1-3% in established cirrhosis
• Spontaneous bacterial peritonitis: occurs in ~10-30% of patients with ascites; in-hospital mortality ~20%
• Hepatorenal syndrome: type 1 (rapid, median survival 2 weeks without treatment) and type 2 (gradual)
• Hepatic encephalopathy: graded I-IV; precipitated by infection, GI bleed, constipation, medications
• Alcohol-related brain damage: concurrent Wernicke-Korsakoff, cerebellar degeneration

Child-Pugh Score

Child-Pugh Classification

Landmark Trials in Alcoholic Liver Disease