Cirrhosis and Its Complications

Cirrhosis Intro - The Scarred Liver

• Definition: An irreversible end-stage of chronic liver disease, with diffuse fibrosis, distorted architecture, and abnormal regenerative nodules.
• Etiology (India Focus):
  • Alcohol (leading cause in India)
  • Viral Hepatitis (Chronic Hep B, Hep C)
  • Non-Alcoholic Fatty Liver Disease (NAFLD/NASH)
  • 📌 VHANDS Mnemonic: Viral, Hemochromatosis/Wilson's, Alpha-1 antitrypsin, NASH/NAFLD, Drugs, Sclerosing cholangitis.
• Pathogenesis:
  • Persistent liver injury activates Hepatic Stellate Cells (Ito cells).
  • Activated stellate cells transform into myofibroblasts.
  • Myofibroblasts deposit excessive collagen (Type I & III), leading to fibrosis.
  • Key cytokine: TGF-β.

⭐ Hepatic stellate cells (Ito cells) are the primary collagen-producing cells in liver fibrosis.

Cirrhosis Features - Signs & Stages

• Morphology:
  • Micronodular: Nodules <3mm (e.g., alcohol, hemochromatosis, Wilson's disease)
  • Macronodular: Nodules >3mm (e.g., viral hepatitis, α1-antitrypsin deficiency)
• Gross & Microscopic:
  • Gross: Shrunken, firm, finely or coarsely nodular liver.
  • Micro: Bridging fibrous septa, parenchymal regenerative nodules, disruption of architecture.
• Clinical Features:
  • Compensated: Asymptomatic or non-specific symptoms (fatigue, weight loss).
  • Decompensated: Jaundice, ascites, variceal hemorrhage, hepatic encephalopathy.
• Stigmata of Chronic Liver Disease: Spider nevi, palmar erythema, gynecomastia, testicular atrophy, caput medusae, clubbing, Dupuytren's contracture.
• Scoring Systems:
  • Child-Pugh Score: Assesses prognosis. 📌 Mnemonic: ABEAP (Albumin, Bilirubin, Encephalopathy, Ascites, PT/INR).
    • Class A: 5-6 points (1-year survival ~100%)
    • Class B: 7-9 points (1-year survival ~80%)
    • Class C: 10-15 points (1-year survival ~45%)
  • MELD Score: Prioritizes for liver transplant. Parameters: Serum Bilirubin, INR, Serum Creatinine.

⭐ MELD score is preferred for predicting 3-month mortality and for prioritizing patients for liver transplantation (especially >15).

Portal Hypertension - Pressure Overload

• Definition: Hepatic Venous Pressure Gradient (HVPG) >5 mmHg; clinically significant if HVPG >10 mmHg.
  • $HVPG = \text{Portal Vein Pressure} - \text{Inferior Vena Cava Pressure}$
• Pathophysiology: Dual mechanism:
  • ↑ Intrahepatic resistance (due to fibrosis & regenerative nodules).
  • ↑ Splanchnic blood flow (due to splanchnic vasodilation).

• Consequences:
  • Esophageal/Gastric Varices (risk of bleeding if HVPG >12 mmHg)
  • Splenomegaly (thrombocytopenia, leukopenia)
  • Ascites
  • Caput Medusae
  • Hemorrhoids
  • Porto-systemic Encephalopathy (PSE)
• 📌 Mnemonic (Portosystemic Shunts): GUES (Gastro-esophageal, Umbilical, Rectal, Spleno-renal)

⭐ Bleeding from esophageal varices is a life-threatening complication of portal hypertension, occurring when HVPG exceeds 12 mmHg.

Major Complications - Systemic Fallout

• Ascites:

  • Pathophys: PHT → splanchnic vasodilation → ↓ effective arterial volume → RAAS activation → Na⁺/H₂O retention.
  • Dx: Paracentesis; SAAG ≥1.1 g/dL (indicates PHT).

• Spontaneous Bacterial Peritonitis (SBP):

  • Dx: Ascitic fluid PMN >250 cells/mm³.
  • Common bugs: E. coli, Klebsiella.

  ⭐ Suspect SBP in cirrhotics with ascites & clinical worsening; Dx: ascitic PMN >250/mm³.

• Hepatic Encephalopathy (HE):

  • Pathophys: ↑ NH₃, altered GABA transmission.
  • Precipitants: Infection, GI bleed, constipation, electrolyte imbalance, sedatives/opiates.
  • Grading: West Haven Criteria.

• Hepatorenal Syndrome (HRS):

  • Pathophys: Severe renal vasoconstriction due to intense splanchnic vasodilation & ↓ effective circulating volume.
  • Types: Type 1 (rapid, poor prognosis), Type 2 (slower, with refractory ascites).

• Hepatocellular Carcinoma (HCC):

  • Risk: ↑ in all cirrhotic patients.
  • Surveillance: Ultrasound (± AFP) q6mo. AFP = tumor marker.

High‑Yield Points - ⚡ Biggest Takeaways

• Cirrhosis is irreversible liver fibrosis with nodular regeneration, primarily caused by alcohol and viral hepatitis.
• Portal hypertension is a key consequence, leading to ascites, esophageal varices, and splenomegaly.
• Hepatic encephalopathy, marked by asterixis, results from ↑ ammonia.
• Spontaneous Bacterial Peritonitis (SBP) in ascites: diagnose with ascitic fluid PMN > 250/mm³.
• Risk of Hepatocellular Carcinoma (HCC) necessitates screening with AFP and ultrasound.
• Child-Pugh and MELD scores are crucial for prognosis and transplant listing.