Cirrhosis

Cirrhosis is the advanced, diffuse stage of chronic liver disease in which sustained hepatocellular injury and a wound-healing response replace normal liver architecture with bands of fibrous tissue surrounding regenerative nodules. This structural distortion impairs hepatic function and obstructs blood flow through the liver, producing portal hypertension and progression from a compensated to a decompensated state.

Definition

A diffuse process of the liver characterised by fibrosis and the conversion of normal architecture into structurally abnormal regenerative nodules, representing the end stage of many chronic liver diseases and giving rise to hepatic insufficiency and portal hypertension.

Scope

This entry covers the pathology of cirrhosis: the fibrogenic response to chronic injury, the nodular-fibrotic architecture that defines it, the major aetiologies, and the consequences of portal hypertension and hepatocellular failure. It is a reference account of mechanism and morphology, not a management protocol.

Core questions

• How does chronic liver injury drive fibrogenesis and the formation of regenerative nodules?
• How does the cirrhotic architecture produce portal hypertension and its complications?
• What distinguishes compensated from decompensated cirrhosis?

Key concepts

• Hepatic fibrosis and regenerative nodules
• Hepatic stellate cell activation
• Portal hypertension
• Compensated versus decompensated cirrhosis
• Varices, ascites, and hepatic encephalopathy
• Aetiologies (viral, alcohol-related, metabolic)

Mechanisms

Cirrhosis is the common end point of chronic liver injury from causes such as chronic viral hepatitis, alcohol-related liver disease, and metabolic (fatty) liver disease. Persistent hepatocyte injury and inflammation activate hepatic stellate cells, which transform into myofibroblast-like cells and deposit excess extracellular matrix. Over time, diffuse fibrous septa partition the parenchyma into regenerative nodules, distorting the lobular architecture and the hepatic vasculature (Tsochatzis 2014). The resulting increase in intrahepatic vascular resistance, compounded by altered splanchnic blood flow, raises portal pressure; portal hypertension underlies the development of gastro-oesophageal varices, ascites, and contributes to hepatic encephalopathy (Garcia-Tsao 2010). Clinically, the disease is staged from a compensated phase to a decompensated phase marked by these complications (Tsochatzis 2014).

Clinical relevance

The pathology of cirrhosis explains the major complications of chronic liver disease and the rationale for staging liver fibrosis. Understanding the nodular-fibrotic architecture and portal hypertension supports interpretation of liver biopsies and imaging; this material is descriptive and educational and is not a basis for individualized treatment decisions (Tsochatzis 2014).

Epidemiology

Cirrhosis is a major global cause of liver-related morbidity and mortality, with the leading aetiologies—chronic viral hepatitis, alcohol-related liver disease, and metabolic-associated fatty liver disease—varying in their relative contribution by region and over time (Tsochatzis 2014).

Evidence & guidelines

The account here draws on a comprehensive review of liver cirrhosis (Tsochatzis 2014) and on a review of variceal complications of portal hypertension (Garcia-Tsao 2010). These are cited to support the descriptive pathophysiology and not as prescriptive guidance.

History

The term cirrhosis derives from the tawny colour of the diseased liver and is attributed to René Laennec in the early nineteenth century. Subsequent pathology distinguished its fibrotic and nodular character, and modern hepatology has clarified the cellular basis of fibrogenesis and the haemodynamics of portal hypertension that give the disease its clinical course (Tsochatzis 2014).

Key figures

• René Laennec
• Emmanuel Tsochatzis
• Jaime Bosch

Seminal works

• tsochatzis-2014
• garcia-tsao-2010

Frequently asked questions

What defines cirrhosis at the tissue level?

Cirrhosis is defined by diffuse fibrosis that surrounds regenerative nodules and replaces the normal liver architecture, the structural end stage of many chronic liver diseases.

Why does cirrhosis cause portal hypertension?

The fibrous septa and regenerative nodules distort the hepatic vasculature and increase resistance to blood flow through the liver, which raises pressure in the portal venous system and leads to varices and ascites.