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Nonalcoholic fatty liver disease (NAFLD) results in histologically complex specific and nonspecific injury patterns. In clinical research of NAFLD, the liver biopsy evaluation provides a wealth of information on the architectural arrangement and severity of a variety of histologic changes, including steatosis, inflammation, cellular injury, and fibrosis. This information is summarized as an overall diagnostic category, such steatosis or steatohepatitis and the severity of the injury can be graded and staged. Histopathologic disease classification in NAFLD is related to but separate from evaluation of individual histologic lesions. The patient population under study may affect the prevalence of histologic findings and in particular, pediatric patients with NAFLD may show a higher prevalence of zone 1 steatosis and periportal fibrosis as compared with adult populations. For the purposes of clinical research, it is important to provide the pathologist with biopsies that are adequate to classify the disease process as well as to grade and stage the changes. A current understanding of NAFLD pathologic classification, as well as nuances of grading and staging, is presented in this review.

Nonalcoholic steatohepatitis (NASH) is a significant form of chronic liver disease in adults and children. The natural history of NASH ranges from indolent to end-stage liver disease. Current studies are focusing on identification of histologic and/or clinical markers of progression. NASH may be an underlying cause of cryptogenic cirrhosis, and the lesions of NASH may recur in allograft livers. An expanding array of clinical conditions and pathogenetic mechanisms have been identified, but many cases remain "idiopathic"; lack of significant alcohol use is, by definition, common to all cases. Neither clinical evaluation nor laboratory values can ensure either the diagnosis or the exclusion of NASH, and liver biopsy interpretation continues to be considered the "gold standard" for diagnosis. The lesions in NASH are similar but not identical to those of alcoholic steatohepatitis; exact, specific histologic criteria for the diagnosis are currently under discussion. The lesions most commonly accepted for NASH include steatosis, hepatocyte ballooning degeneration, mild diffuse lobular mixed acute and chronic inflammation, and perivenular, perisinusoidal collagen deposition. Zone 3 accentuation may be detected. Mallory's hyaline, vacuolated nuclei in periportal hepatocytes, lobular lipogranulomas, and PAS-diastase-resistant Kupffer cells are common. In biopsy specimens from children, portal inflammation may be more prominent than in adults. Progression of fibrosis may result in bridging septa and cirrhosis. The lesions of steatohepatitis may be noted concurrently with other forms of chronic liver disease. A histological "grading and staging" system has been developed to reflect the unique features of steatohepatitis, gradations of severity and fibrosis, and to promote uniform reporting of the histopathology.