GastroenterologyTier 1Disease (DEADMAN)

Hepatitis - alcohol induced

Description

Alcohol-related liver disease is a spectrum: steatosis -> alcoholic (steato)hepatitis -> fibrosis -> cirrhosis
- Steatosis is reversible in weeks; cirrhosis is not
Alcohol-associated hepatitis = a clinical syndrome, not a biopsy finding
- Rapid-onset jaundice (<8 weeks) in a patient with heavy alcohol use (>40-60 g/day for >6 months, abstinent <60 days)
- AST >50 but usually <400, AST:ALT >1.5-2, bilirubin >50 micromol/L
- No other cause of liver disease
Renamed "alcohol-associated" in newer nomenclature; MetALD describes coexisting metabolic and alcohol-related disease

Alcohol causes ~5-6% of Australian deaths; ~1 in 4 Australians drink at risky levels
Only ~10-20% of heavy drinkers develop cirrhosis - genetic and cofactor dependent
F>M for equivalent intake (lower gastric ADH, higher body fat fraction, lower volume of distribution)
Australian guideline: <=10 standard drinks/week AND <=4 on any day
Severe alcohol-associated hepatitis: 28-day mortality up to 30-50%

Ethanol -> acetaldehyde (ADH) -> acetate (ALDH2)
- inc NADH:NAD+ ratio -> inc fatty acid synthesis, dec beta-oxidation -> steatosis
- Also -> lactic acidosis, hypoglycaemia, hyperuricaemia (gout), ketosis
CYP2E1 induction -> ROS, lipid peroxidation, and inc paracetamol toxicity at therapeutic doses
Acetaldehyde - protein adducts -> neoantigens, mitochondrial injury
Gut dysbiosis + inc intestinal permeability -> portal endotoxin (LPS) -> Kupffer cell TLR4 -> TNF-alpha, IL-1, IL-8 -> neutrophil recruitment
Histology: steatosis, ballooning degeneration, MALLORY-DENK BODIES, neutrophilic infiltrate, pericentral/perisinusoidal ("chicken wire") fibrosis
Cofactors: obesity, hepatitis C, PNPLA3 I148M, female sex, smoking

Clinical

Jaundice, tender hepatomegaly, fever, anorexia, weight loss
Signs of chronic liver disease - spider naevi, palmar erythema, Dupuytren, parotidomegaly, gynaecomastia, testicular atrophy
Hepatic bruit (uncommon but characteristic)
Encephalopathy, ascites, variceal bleeding if decompensated
Withdrawal must be anticipated - CIWA-Ar scoring

Bloods

AST:ALT >2 with AST rarely >400 (a level >500 suggests another cause - paracetamol, ischaemia, viral)
inc GGT, macrocytosis (MCV >100), thrombocytopenia, inc INR, dec albumin
Neutrophil leucocytosis - but always culture: SBP, pneumonia and UTI are common and mimic
Carbohydrate-deficient transferrin - a more specific marker of sustained heavy intake
Exclude everything else: viral serology, autoimmune screen, ferritin, caeruloplasmin, paracetamol level

Severity scores

Score	Use
Maddrey discriminant function	>32 = severe; 1-month mortality 20-30%, 6-month 30-40% -> the threshold for considering steroids
MELD	>20 also defines severe; better discrimination; transplant listing
Glasgow alcoholic hepatitis score	>=9 = severe
Lille score	Calculated at day 7 of steroids - >0.45 = non-responder -> STOP steroids

Biopsy (transjugular) only if the diagnosis is uncertain - coagulopathy and ascites preclude percutaneous

1. Abstinence - the only intervention that changes long-term survival

*Nothing else matters as much.* Addiction medicine referral at the index admission
Naltrexone, acamprosate (avoid naltrexone in decompensated disease/opioid use); baclofen is the preferred agent in cirrhosis
Thiamine 300 mg IV/day BEFORE glucose - Wernicke prophylaxis
Withdrawal: diazepam, or oxazepam/lorazepam if significant liver impairment (directly glucuronidated - no active metabolites, no CYP oxidation)

2. Nutrition

*Malnutrition is near-universal and independently predicts death*
35-40 kcal/kg/day and 1.2-1.5 g/kg/day protein; nasogastric feeding if intake inadequate
Do NOT restrict protein, even in encephalopathy
Replace thiamine, folate, zinc, magnesium, phosphate; watch for refeeding syndrome

3. Corticosteroids - severe disease only

Prednisolone 40 mg daily for 28 days if Maddrey DF >32 or MELD >20, after excluding sepsis and GI bleeding
STOPAH: steroids gave a modest reduction in 28-day mortality only - not significant at the 1-year primary endpoint, because by then most patients had resumed drinking, diluting the effect
*STOPAH showed NO role for pentoxifylline* - it is no longer used
Day-7 Lille score >0.45 -> stop steroids (no benefit, ongoing infection risk)
N-acetylcysteine added to steroids improved 1-month survival in one RCT - reasonable adjunct
Contraindications: active infection, GI bleeding, AKI/hepatorenal syndrome, uncontrolled diabetes

4. Treat the complications

Infection screen at admission and any deterioration (ascitic tap, blood/urine cultures, CXR)
Hepatorenal syndrome - albumin + terlipressin; avoid NSAIDs, aminoglycosides, contrast
Ascites, variceal bleeding, encephalopathy (lactulose, rifaximin) as for cirrhosis
Volume expansion with albumin at diagnosis - reduces AKI

5. Transplant

Early transplant in carefully selected non-responders is now accepted, without the traditional arbitrary 6-month abstinence rule
- Requires strong psychosocial support, first presentation, and MDT selection
- The "6-month rule" has no evidence base and excludes patients who die within that window

Wernicke-Korsakoff, peripheral neuropathy, cerebellar degeneration, central pontine myelinolysis
Pancreatitis - acute and chronic
Cardiomyopathy, hypertension, AF ("holiday heart")
Malignancy - oesophageal SCC, head and neck, breast, colorectal, HCC
Haematology - macrocytosis, sideroblastic anaemia, Zieve syndrome (haemolysis + hyperlipidaemia + jaundice), thrombocytopenia
Metabolic - hypoglycaemia, hypomagnesaemia, hypophosphataemia, hypokalaemia, ketoacidosis, gout
Osteoporosis, myopathy, Dupuytren contracture
Coexisting MASLD (MetALD), hepatitis C - synergistic fibrosis

Abstinence is prognostic at every stage
- Compensated alcohol cirrhosis with abstinence: 5-yr survival ~85-90%; continued drinking ~60%
- Decompensated + continued drinking: 5-yr survival ~30%
Severe alcohol-associated hepatitis: 28-day mortality 20-50%; steroid non-responders (Lille >0.45) do worst
Steatosis reverses within weeks of abstinence; fibrosis may regress; cirrhosis does not
HCC risk persists after abstinence -> 6-monthly ultrasound surveillance once cirrhotic
Recurrent admissions with decompensation mark a poor trajectory - initiate advance care planning alongside transplant assessment

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