Patterns of hepatocyte injury in man

Three patterns of hepatocyte injury in man, direct, immunological, and cholestatic, are described. The characteristics of the direct pattern are predominantly mitochondrial damage, central (zone 3) necrosis, and, usually, fatty change. It can be subdivided into the alcohol type (also seen with obesity, in diabetes, as a reaction to perhexiline, in Wilson's disease, and in Indian childhood cirrhosis) and the Reye's syndrome type (also seen with tetracycline toxicity, fatty liver of pregnancy, and cytotoxic drugs). Reactive drug metabolites, metal poisoning, and anoxia are also associated with the direct pattern of hepatocyte injury. The immunological pattern is characterised by damage to cell membranes with piecemeal necrosis of periportal (zone 1) hepatocytes and mononuclear-cell infiltration. Examples include chronic active hepatitis, primary biliary cirrhosis, and drug reactions such as those to halothane. In the cholestatic pattern there is disturbance of the bile-secretory mechanism with retention of bile within the hepatocytes. Cholestatic liver injury may be intrahepatic, as in sex-hormone cholestasis, or extrahepatic, as in choledocholithiasis or carcinoma of the bile ducts. Identification of the type of hepatocyte injury is valuable in diagnosis, in assessing prognosis, and in selecting treatment.