Definition

• Irreversible replacement of the normal liver architecture by bands of fibrous tissue separating nodules of regenerating hepatocytes.

 Epidemiology

 • Common and increasing in incidence due to alcohol and obesity.

 Aetiology

• Alcohol, chronic viral hepatitis, and NAFLD are the most common causes.

• Less commonly, PBC, PSC, autoimmune hepatitis (AIH), Wilson’s disease, and haemochromatosis.

• In some cases, the cause remains unclear (cryptogenic cirrhosis) although many of these are thought to be secondary to NAFLD.

 Pathogenesis

 • Persistent liver injury causes Kupffer cells lining the vascular sinusoids to release cytokines which activate hepatic stellate cells.

 • Activated stellate cells proliferate and secrete large quantities of dense collagen, leading to irreversible liver fibrosis and hepatocyte loss.

• Cirrhosis causes a number of functional defects: reduced synthesis of coagulation factors; low glycogen reserves; reduced clearance of organisms by Kupffer cells; portal hypertension with hypersplenism and oesophageal varices; and splanchnic vasodilation → decreased renal blood flow →  secondary hyperaldosteronism →  ascites.

Presentation

 • Non- specific symptoms of tiredness and malaise.

 • Signs of chronic liver disease are usually present on clinical examination and LFts are usually abnormal.

 • Patients often present with a complication related to the presence of cirrhosis (e.g. upper GI haemorrhage).

Macroscopy

• the liver may be normal in size, enlarged, or shrunken.

 • the cut surface has a firm texture and shows diffuse nodularity (Fig. 1).

Histopathology

 • the entire liver is replaced by nodules of regenerating hepatocytes surrounded by fibrous bands.

• the size of the nodules is related to the cause: micronodular cirrhosis in alcoholic liver disease and macronodular cirrhosis secondary to viral hepatitis.

 • the fibrous bands contain a variable inflammatory infiltrate and reactive bile ductular proliferation.

• In some cases, the features may point to a particular aetiology.

Fig1. the cirrhotic liver. this liver was removed at post- mortem from a patient known to abuse alcohol. the whole of the liver is studded with nodules. Microscopically, the liver showed nodules of regenerating hepatocytes separated by dense bands of fibrosis, confirming established cirrhosis (see Plate 15). reproduced with permission from Clinical Pathology (Oxford Core texts), Carton, James, Daly, richard, and ramani, Pramila, Oxford university Press (2006), p. 168, Figure 9.9.

Prognosis

 • Generally poor, with a high risk of significant complications such as infections (including bacterial peritonitis), upper GI bleeding, renal failure, and HCC.

* Development of complications may tip the patient into terminal hepatic failure, characterized by deep jaundice, severe coagulopathy, hepatic encephalopathy, and high risk of mortality.