Histopathology, grading and staging of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the liver disease associated with obesity, diabetes and the metabolic syndrome. Although steatosis is a key histological feature, liver biopsies of patients with NAFLD can show a wide range of other findings, including portal and lobular inflammation, ballooning and apoptotic hepatocellular injury, Mallory-Denk bodies, megamitochondria and fibrosis. Nonalcoholic steatohepatitis (NASH) is a progressive subtype of NAFLD first defined by analogy to alcoholic hepatitis. The characteristic finding in NASH is ballooning hepatocellular injury. The fibrosis pattern is distinctive, with perisinusoidal fibrosis around the central veins being the first manifestation of fibrosis. Young children may have an alternate pattern of progressive NAFLD characterized by a zone 1 distribution of steatosis, inflammation and fibrosis. Several grading and staging systems exist for use in natural history studies and clinical trials, each with some advantages and disadvantages. These include the Brunt system, the NASH CRN system and the SAF system. Each of these systems has been applied to clinical studies permitting correlation of laboratory and demographic observations with histological findings.