Definition of Liver Cirrhosis
Cirrhosis is an end-stage form of chronic liver disease characterized by the gradual replacement of healthy liver tissue with annular fibrosis, destroying the architecture of the liver parenchyma and blocking intrahepatic portal blood flow, leading to portal hypertension and hepatic dysfunction. 1
Pathophysiologic Definition
The disease represents a marked distortion of hepatic architecture by extensive fibrosis, typically in a chicken-wire pattern, formation of regenerating nodules, and abnormal sinusoidal blood flow. 2 This architectural distortion fundamentally alters liver function through two key mechanisms:
Structural changes: Fibrosis development begins in the space of Disse, progressively maturing and enlarging over time, typically starting in the centrilobular region and extending toward the portal tract. 1, 3
Hemodynamic consequences: The fibrotic tissue and vascular distortion create increased intrahepatic resistance to portal flow, which is the primary factor in the development of portal hypertension. 1, 3
Clinical Staging Framework
Cirrhosis exists in two distinct clinical phases that determine prognosis and management:
Compensated Cirrhosis
Compensated cirrhosis is defined as histologic, imaging-proven cirrhosis and/or clinically significant sinusoidal portal hypertension with Child-Pugh class A, in a patient who has never experienced an episode of acute decompensation (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, or bacterial infection). 2 This represents a state of clinical stability with median survival exceeding 12 years. 1
Decompensated Cirrhosis
Acute decompensation is defined as the acute development of clinically significant ascites, hepatic encephalopathy, portal hypertensive-related gastrointestinal bleeding, or bacterial infection, or any combination thereof. 2 Decompensated cirrhosis reduces median survival to approximately 1.8-2 years. 1
Diagnostic Confirmation
While cirrhosis can be suspected clinically and through noninvasive methods (serum markers, elastography, imaging showing liver surface nodularity, atrophic right lobe, hypertrophied caudate lobe), it remains fundamentally a histologic term that requires liver biopsy for definitive diagnosis. 4, 5
Key Pathophysiologic Features
The disease process involves several critical elements:
Chronic inflammation: Advanced cirrhosis is characterized by a state of chronic inflammation with increased circulating pro-inflammatory cytokines and chemokines, likely caused by systemic spread of bacteria and bacterial products. 3
Portal hypertension threshold: A hepatic venous pressure gradient (HVPG) ≥10-12 mmHg represents a critical threshold beyond which chronic liver disease becomes a systemic disorder with involvement of other organs and systems. 6
Varices development: Portal hypertension drives gastroesophageal varices formation, present in 30-40% of patients with compensated cirrhosis and up to 85% with decompensated cirrhosis. 1, 3