Pathology

Pathology/C/50

Liver cirrhosis

肝硬変

1. Definition

  • Cirrhosis = diffuse process: fibrosis + conversion of normal liver architecture into structurally abnormal regenerative nodules (pseudolobules).
  • Final common outcome of all chronic liver diseases.

2. Causes

  • Alcoholic liver disease (toxic damage)
  • NAFLD → NASH (hepatocyte necrosis, inflammation)
  • Chronic viral hepatitis (HBV, HCV)
  • Biliary disease: PBC, PSC, extrahepatic biliary obstruction
  • Metabolic / inherited: hemochromatosis, Wilson, α1-AT deficiency
  • Cryptogenic (unknown)

3. Pathogenesis

  • Chronic cell death over a long time → fibrosis (scar formation).
  • Advanced disease: fibrous bands separate regenerative nodules.
  • Vascular changes:
    • Loss of sinusoidal endothelial fenestrations.
    • Portal vein ↔ hepatic vein and hepatic artery ↔ portal vein vascular shunts → defective hepatic function.
  • Collagen deposition converts sinusoids to high-pressure, fast-flow channels → no free solute exchange.
    • Deposited by activated stellate cells (Ito cells) in space of Disse.
    • Activators: ROS, growth factors, cytokines (normally store fat + vitamin A).

4. Morphology — by Nodule Size

Type Nodule size Septa Typical cause
Micronodular < 3 mm (~2 mm), uniform Thin Chemical / alcohol (diffuse uniform injury)
Macronodular > 3 mm, irregular Wider scars Infectious / viral hepatitis (non-uniform injury)

5. Stages

A) Compensated cirrhosis (asymptomatic)

  • No ascites, varices, encephalopathy, or jaundice.
  • Median survival > 12 yr.
  • Presence of esophageal varices = key prognostic factor.

B) Decompensated cirrhosis (symptomatic)

  • Ascites, variceal hemorrhage, hepatic encephalopathy, jaundice.
  • Median survival ~ 2 yr.
  • Can regress to compensated stage if underlying cause is removed (e.g., alcohol abstinence).

6. Consequences of Cirrhosis

A) Parenchymal failure → jaundice

  • Bilirubin metabolism is complex → sensitive marker of liver dysfunction.

B) Vascular failure → ascites (portal hypertension)

Consequences of portal hypertension:

1. **Ascites** formation
2. **Splenomegaly → hypersplenism** (thrombocytopenia)
3. **Portosystemic shunts** → **esophageal varices** (rupture is a common cause of death), caput medusae, hemorrhoids

C) Tumors

  • Hepatocellular carcinoma (HCC) — chief malignant complication.

💡 High-yield: Cirrhosis = diffuse fibrosis + regenerative pseudolobules; final common pathway of chronic liver disease. Micronodular = alcohol (uniform); macronodular = viral / post-necrotic. Stellate cells in space of Disse drive fibrosis. Compensated (asymptomatic, >12 yr) vs decompensated (ascites, varices, encephalopathy, jaundice; ~2 yr). Three consequences: jaundice (parenchymal), ascites/varices (portal HTN), HCC.