Nonalcoholic steatohepatitis: Definition and pathology

Nonalcoholic steatohepatitis (NASH) is a significant form of chronic liver disease in adults and children. The natural history of NASH ranges from ind olent to endstage liver disease. Current studies are focusing on identifica tion of histologic and/or clinical markers of progression. NASH may be an u nderlying cause of cryptogenic cirrhosis, and the lesions of NASH may recur in allograft livers. An expanding array of clinical conditions and pathoge netic mechanisms have been identified, but many cases remain "idio-pathic"; lack of significant alcohol use is, by definition, common to all cases. Ne ither clinical evaluation nor laboratory values can ensure either the diagn osis or the exclusion of NASH, and liver biopsy interpretation continues to be considered the "gold standard" for diagnosis. The lesions in NASH are s imilar but not identical to those of alcoholic steatohepatitis; exact, spec ific histologic criteria for the diagnosis are currently under discussion. The lesions most commonly accepted for NASH include steatosis, hepatocyte b allooning degeneration, mild diffuse lobular mixed acute and chronic inflam mation, and perivenular, perisinusoidal collagen deposition. Zone 3 accentu ation may be detected. Mallory's hyaline, vacuolated nuclei in periportal h epatocytes, lobular lipogranulomas, and PAS-diastase-resistant Kupffer cell s are common. In biopsy specimens from children, portal inflammation may be more prominent than in adults. Progression of fibrosis may result in bridg ing septa and cirrhosis. The lesions of steatohepatitis may be noted concur rently with other forms of chronic Liver disease. A histological "grading a nd staging" system has been developed to reflect the unique features of ste atohepatitis, gradations of severity and fibrosis, and to promote uniform r eporting of the histopathology.