Liver disease - alcoholic
Description
- Spectrum, and the stages overlap rather than progressing in lockstep
| Stage | Features | Reversible? |
|---|---|---|
| Steatosis | In ~90% of heavy drinkers. Asymptomatic, hepatomegaly | Yes - within weeks of abstinence |
| Alcohol-related (steato)hepatitis | Jaundice, tender hepatomegaly, fever, leucocytosis, AST:ALT >2 | Partly |
| Fibrosis -> cirrhosis | In 10-20% of heavy drinkers | Fibrosis can regress with abstinence |
| Decompensated cirrhosis / HCC | No |
- *Only a minority of heavy drinkers get cirrhosis - genetics (PNPLA3*), sex, obesity and coexisting liver disease decide who
- New nomenclature: MetALD where metabolic risk factors coexist with alcohol 20-50 g/day (F) or 30-60 g/day (M); ALD above those thresholds
Epidemiology
- Alcohol and MASLD have overtaken viral hepatitis as the leading causes of cirrhosis and transplant listing in Australia
- Women are more susceptible at lower intakes - lower body water, lower gastric alcohol dehydrogenase, oestrogen effects
- Australian guideline: no more than 10 standard drinks/week and no more than 4 on any one day (a standard drink = 10 g alcohol)
- Aboriginal and Torres Strait Islander peoples: higher rates of alcohol-related liver death, earlier onset
Aetiopathogenesis
Risk factors for alcohol-related liver injury
- Amount and duration - >80 g/day for >5 years is the classic threshold (but injury occurs well below it, particularly in women)
- Drinking pattern: daily > binge; drinking outside meals; spirits
- Diet high in pork and fat
- Viral hepatitis co-infection (HCV especially) - synergistic
- Iron overload
- Other hepatotoxins; obesity and metabolic syndrome (multiplicative, not additive)
- Female sex; PNPLA3 I148M, TM6SF2, MBOAT7
Mechanism
- Alcohol -> alcohol dehydrogenase and CYP2E1 -> acetaldehyde -> acetate
- inc NADH:NAD+ ratio -> inc lipogenesis, dec fatty acid oxidation, dec gluconeogenesis (hypoglycaemia), inc lactate (dec urate excretion -> gout)
- CYP2E1 induction -> inc reactive oxygen species, and inc paracetamol conversion to NAPQI (hepatotoxicity at therapeutic doses)
- Acetaldehyde -> protein adducts -> immune response
- Gut-derived endotoxin -> Kupffer cell TNF-alpha -> neutrophilic inflammation
- Histology: steatosis, ballooning, Mallory-Denk bodies, neutrophil infiltrate, pericellular "chicken-wire" fibrosis - indistinguishable from MASH; the history makes the diagnosis
Diagnosis
History is the diagnosis
- Quantify in standard drinks/week; AUDIT-C for screening; corroborate with family where possible
- CAGE; assess dependence, withdrawal history, previous seizures or delirium tremens
Bloods
- AST:ALT >2 (often >3) - the reverse of MASLD; pyridoxine deficiency impairs ALT synthesis, and mitochondrial AST is released
- ALT rarely exceeds ~300 U/L in pure alcohol-related disease - higher suggests another cause
- inc GGT (sensitive, non-specific); inc MCV (macrocytosis)
- FBC: macrocytosis, thrombocytopenia (marrow suppression + hypersplenism), leucocytosis in alcohol-related hepatitis
- INR and albumin - synthetic function
- inc IgA; inc ferritin (check transferrin saturation before calling it haemochromatosis)
- Assess thiamine and nutritional status
- Carbohydrate-deficient transferrin, urinary ethyl glucuronide - objective markers of recent intake
Imaging
- Liver ultrasound - steatosis, nodularity, splenomegaly, portal flow, ascites, focal lesions
- Elastography - unreliable during acute alcohol-related hepatitis and while still drinking (inflammation falsely raises stiffness); repeat after weeks of abstinence
Always exclude coexisting disease
- Viral hepatitis B and C, haemochromatosis, autoimmune, Wilson (if young), alpha-1 antitrypsin
- MASLD frequently coexists - the metabolic risk factors do not disappear because someone drinks
Alcohol-related hepatitis - the acute syndrome
- Rapid-onset jaundice (<8 weeks), tender hepatomegaly, fever, leucocytosis, in the context of heavy ongoing use
- Maddrey discriminant function = 4.6 x (PT - control PT) + bilirubin (mg/dL); >=32 = severe
- MELD and the Glasgow alcoholic hepatitis score also used
- Biopsy (transjugular) if the diagnosis is uncertain before committing to corticosteroids
- Always culture - infection is present in ~25% at presentation and is the main reason a steroid decision goes wrong
Spur cell (acanthocyte) haemolytic anaemia
- A recognised complication of severe alcohol-related liver disease/cirrhosis
- Altered red cell membrane lipid composition from hepatocellular dysfunction -> spiculated cells removed by the spleen
- Often accompanied by thrombocytopenia from hypersplenism
- Ominous - usually indicates advanced disease and predicts poor survival
Management
1. Abstinence - the only intervention that changes the natural history
- Improvement occurs even in decompensated cirrhosis - steatosis reverses in weeks, and fibrosis can regress
- Pharmacotherapy for alcohol use disorder:
- Naltrexone - avoid in acute hepatitis and decompensated disease
- Acamprosate - renally cleared, safe in liver disease
- Baclofen - the best-studied option in cirrhosis
- Disulfiram is contraindicated in significant liver disease
- Withdrawal management: diazepam (or lorazepam/oxazepam if significant liver impairment - no active metabolites), symptom-triggered
- Parenteral thiamine BEFORE any glucose-containing fluid - Wernicke prophylaxis
- Addiction medicine referral, counselling, peer support - the drug is an adjunct to the psychosocial care, not a substitute
2. Severe alcohol-related hepatitis (Maddrey >=32 or MELD >20)
- Prednisolone 40 mg daily for 28 days if no contraindication
- Contraindications: active infection, GI bleeding, hepatorenal syndrome, uncontrolled diabetes
- Screen for and treat infection first - then steroids
- Assess response at day 7 with the Lille score
- Lille >=0.45 = non-responder -> STOP steroids (no benefit, ongoing infection risk)
- N-acetylcysteine may be added; pentoxifylline is no longer recommended (STOPAH showed no benefit)
- Aggressive nutrition - the mortality benefit here is large and consistently underused
- Early liver transplantation for carefully selected non-responders is now offered in specialist programmes; the historic fixed 6-month abstinence rule has been superseded by individualised psychosocial assessment
3. Nutrition
- High protein 1.2-1.5 g/kg/day, frequent small meals, late-evening snack (protein restriction is obsolete and harmful)
- Thiamine, folate, pyridoxine, zinc, magnesium, vitamin D
- Watch for refeeding syndrome - phosphate, potassium, magnesium
4. Manage the cirrhosis
- Ascites, varices, encephalopathy, SBP, hepatorenal syndrome - as for any cirrhosis
- 6-monthly HCC surveillance; variceal screening
- Vaccinate: hepatitis A and B, influenza, pneumococcal, COVID
- Bone density; avoid NSAIDs and nephrotoxins
Associations
Other organ effects of alcohol - examined together
- Neurological: Wernicke-Korsakoff, cerebellar degeneration, peripheral neuropathy, alcohol-related dementia, seizures, central pontine myelinolysis (from over-rapid sodium correction)
- Cardiac: dilated cardiomyopathy, hypertension, AF ("holiday heart")
- Pancreas: acute and chronic pancreatitis, type 3c diabetes
- Haematological: macrocytosis, marrow suppression, thrombocytopenia, spur cell haemolysis, folate deficiency
- GI: Mallory-Weiss tear, oesophagitis, gastritis, oesophageal and oropharyngeal SCC
- Metabolic: hypoglycaemia, alcoholic ketoacidosis, lactic acidosis, hypomagnesaemia, hypophosphataemia, gout
- Musculoskeletal: myopathy, rhabdomyolysis, osteoporosis, avascular necrosis of the femoral head
- Malignancy: liver, oropharynx, oesophagus, breast, colorectum
- Foetal alcohol spectrum disorder
- Dupuytren contracture, parotid enlargement, facial telangiectasia, gynaecomastia, testicular atrophy
Natural history & complications
Progression
- Steatosis in ~90% of heavy drinkers; cirrhosis in 10-20%
- Steatosis reverses within weeks of abstinence
- Compensated alcohol-related cirrhosis with sustained abstinence: 5-year survival ~90%
- Continued drinking after decompensation: 5-year survival ~30% or less
- Alcohol-related hepatitis: 28-day mortality ~15% overall, up to 30-40% in severe disease
Prognostic markers
- Maddrey discriminant function, MELD, Lille score at day 7
- Bilirubin, INR, creatinine, encephalopathy, infection
- Spur cell haemolysis, hepatorenal syndrome, ongoing drinking - all ominous
Complications
- Portal hypertension and its complications
- HCC - risk persists after abstinence
- Infection and alcohol-related immune dysfunction
- Malnutrition, sarcopenia, Wernicke-Korsakoff
Monitor
- LFT, INR, albumin, FBE; fibrosis stage once abstinent
- 6-monthly ultrasound +/- AFP in cirrhosis
- Continued engagement with alcohol treatment - relapse is the rule, not a treatment failure
🔒
6 more sections, plus exam facts
Premium unlocks every note across every specialty, and the full exam fact library behind it.
Get premium access