IM5.1-7 | Liver Disease Foundations — Summary & Reflection

KEY TAKEAWAYS

Liver disease pathophysiology can be organised around four themes:

1. Bilirubin metabolism: Pre-hepatic (unconjugated dominant, haemolysis) → hepatic conjugation failure (Gilbert, Crigler-Najjar — unconjugated) → intrahepatic cholestasis (conjugated dominant, mixed hepatocellular-cholestatic) → extrahepatic obstruction (conjugated dominant, ALP/GGT elevated, dark urine, pale stools).

2. Viral hepatitis: HAV (faecal-oral, no chronicity, no vaccine needed for lifelong protection after infection), HBV (parenteral/perinatal, 90% chronicity if neonatal, vaccine available), HCV (parenteral, 75–85% chronicity, NO vaccine), HEV (faecal-oral, severe in pregnancy). Pathomechanism: immune-mediated cytotoxicity, not direct viral injury.

3. Alcoholic liver disease: Ethanol → acetaldehyde (via ADH) → NAD+/NADH shift → steatosis; acetaldehyde → protein adducts + oxidative stress + Kupffer cell activation → alcoholic hepatitis (AST:ALT >2:1, Mallory-Denk bodies, neutrophilic infiltrate, zone 3 necrosis); persistent fibrosis → cirrhosis.

4. Cirrhosis complications:
- Child-Pugh (5 params: bilirubin, albumin, INR, ascites, encephalopathy; A/B/C 5–6/7–9/10–15).
- MELD (3 labs: bilirubin, creatinine, INR — NOT albumin).
- Portal hypertension → varices (HVPG ≥12 mmHg), ascites (SAAG ≥1.1 g/dL), SBP (PMN ≥250/mm³), HE (ammonia; West-Haven I–IV), HRS (Type 1 = rapid; terlipressin + albumin), HCC (screen 6-monthly USS).
- DILI: Intrinsic (paracetamol/NAPQI — treat with NAC per Rumack nomogram); idiosyncratic (INH, amiodarone, herbal medicines — RUCAM for causality).
- Cholelithiasis: Cholesterol stones (lithogenic bile, obesity, oestrogen); pigment stones (black = haemolysis, brown = biliary infection); complications: biliary colic, acute cholecystitis (Murphy's sign), choledocholithiasis (Charcot's triad = fever + jaundice + RUQ pain), ascending cholangitis, gallstone pancreatitis.

REFLECT

Returning to the opening cases: Rahul (alcoholic cirrhosis with Child-Pugh C, ascites, and grade II encephalopathy) and Priya (acute viral hepatitis A with high ALT and direct hyperbilirubinaemia). Their shared symptom — jaundice — arises through entirely different mechanisms: for Priya, conjugated bilirubin accumulates because acute immune-mediated hepatocyte necrosis disrupts canalicular excretion; for Rahul, jaundice reflects the synthetic failure and intrahepatic cholestasis of end-stage cirrhosis. One requires only supportive care and will resolve completely; the other carries a 1-year mortality that must be quantified by Child-Pugh and MELD. Think about this question: if Rahul develops confusion on the ward tonight and has asterixis, what is the first precipitating cause you would look for — and what would you do in the next 30 minutes? The answer to that question — and the reasoning behind it — is what this module equips you to provide.