A 58-year-old man with a 20-year history of heavy alcohol use presents with jaundice, ascites, and lower limb oedema. He reports no fever or abdominal pain. Examination reveals spider angiomata, palmar erythema, and splenomegaly. Laboratory findings: total bilirubin 5.4 mg/dL (direct 3.2 mg/dL, indirect 2.2 mg/dL), AST 180 IU/L, ALT 65 IU/L, ALP 95 IU/L, albumin 2.1 g/dL, INR 2.8. Ultrasound shows cirrhotic liver, ascites, and patent portal vein. What is the most likely cause of jaundice in this patient?

Explanation

## Pathophysiology of Jaundice in Cirrhosis **Key Point:** In advanced cirrhosis, jaundice results from **impaired hepatic conjugation and excretion** of bilirubin, combined with **cholestasis** — not biliary obstruction or hemolysis. ### Diagnostic Clues Pointing to Hepatic Jaundice | Feature | Finding | Significance | |---------|---------|---------------| | **Clinical signs** | Spider angiomata, palmar erythema, splenomegaly | Portal hypertension + cirrhosis | | **Bilirubin pattern** | Mixed (direct 3.2, indirect 2.2) | Both conjugation and excretion impaired | | **Transaminase pattern** | AST > ALT (AST:ALT ratio 2.8:1) | Alcoholic liver disease | | **ALP** | Normal (95 IU/L) | Rules out biliary obstruction | | **Albumin** | 2.1 g/dL (low) | Impaired synthetic function | | **INR** | 2.8 (prolonged) | Coagulopathy from liver failure | | **Imaging** | Cirrhotic liver, patent portal vein | No obstruction; hepatic cause confirmed | ### Why This Is Hepatic Jaundice **High-Yield:** Hepatic jaundice in cirrhosis is caused by: 1. **Impaired conjugation** — damaged hepatocytes cannot conjugate bilirubin efficiently. 2. **Impaired excretion** — cholestasis (intrahepatic obstruction) prevents conjugated bilirubin from entering bile canaliculi. 3. **Shunting** — portal hypertension causes portosystemic collaterals, bypassing the liver. The **AST > ALT pattern** is classic for alcoholic cirrhosis (AST released from mitochondria of necrotic hepatocytes; ALT is more specific to hepatocytes but less abundant in alcoholic liver disease). **Clinical Pearl:** In cirrhosis, a normal ALP *excludes* biliary obstruction. If ALP were markedly elevated, suspect superimposed obstruction (stone, stricture, or malignancy). ## Differential Diagnosis in Jaundiced Cirrhotic ```mermaid flowchart TD A[Cirrhotic patient with jaundice]:::outcome --> B{ALP normal?}:::decision B -->|Yes| C[Hepatic jaundice]:::outcome C --> D{AST > ALT?}:::decision D -->|Yes| E[Alcoholic cirrhosis]:::outcome B -->|No| F[Biliary obstruction]:::outcome F --> G[ERCP for stone/stricture/malignancy]:::action A --> H{Fever + RUQ pain?}:::decision H -->|Yes| I[Acute cholangitis]:::urgent H -->|No| J[Uncomplicated obstruction]:::outcome ``` **Citation:** Harrison 21e Ch 308, Robbins 10e Ch 18