Chapter 42: Cirrhosis and Liver Failure

Cirrhosis represents the irreversible, end-stage consequence of chronic hepatocellular injury, characterized by progressive fibrosis, nodular tissue regeneration, and architectural distortion that fundamentally compromises liver function. The condition develops when sustained hepatic damage triggers a pathological repair response, resulting in fibrous scar tissue and regenerative nodules that compress vascular and biliary structures, ultimately leading to portal hypertension and multi-system organ dysfunction. In the United States, the predominant etiologies are chronic alcohol use disorder and viral hepatitis, though nonalcoholic fatty liver disease has emerged as a major global contributor, particularly in populations with metabolic syndrome and obesity. Additional causative pathways include autoimmune and cholestatic disorders such as primary biliary cirrhosis and primary sclerosing cholangitis, alongside genetic metabolic conditions like hemochromatosis and Wilson's disease, as well as vascular obstruction syndromes. Histological classification based on nodule size distinguishes micronodular, macronodular, and mixed patterns, each carrying prognostic and etiological implications. Clinical manifestations encompass hepatocellular dysfunction manifested through synthetic failure and biochemical derangement, alongside portal hypertension-related sequelae including ascites formation, esophageal varices, and splenomegaly. The characteristic physical examination findings collectively termed stigmata of liver disease include spider angiomas, palmar erythema, caput medusae, and hepatic encephalopathy with characteristic asterixis. Diagnostic confirmation relies on laboratory assessment demonstrating synthetic dysfunction through prolonged prothrombin time, characteristic enzyme patterns including elevated aspartate aminotransferase with altered aminotransferase ratios, and imaging modalities supplemented by tissue biopsy when etiology remains uncertain. Management strategies focus on identifying and eliminating the underlying causative agent while addressing decompensating complications through targeted pharmacological and procedural interventions, including diuretic therapy for ascites, variceal band ligation for hemorrhage prevention, lactulose administration for encephalopathy management, and ultimately liver transplantation for end-stage irreversible disease. Patient outcomes depend substantially on early diagnosis, disease etiology, severity of portal hypertension, and access to advanced hepatological care and transplant services.