Transitions of histopathologic criteria for diagnosis of nonalcoholic fatty liver disease during the last three decades.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and is the most common type of chronic liver diseases in the majority of developed countries. NAFLD shows a wide spectrum of disorders including simple steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. While simple steatosis is recognized to be benign and stable, NASH is considered to be an aggressive form of the disease progressing to cirrhosis. Currently, differentiation between NASH and simple steatosis can be done only by liver biopsy. Despite many proposals and revisions, the histological criteria for the differentiation have not been perfected yet. In this review article, the changes in the histopathologic criteria of NAFLD during the last three decades are summarized, and perspectives of the future changes are demonstrated. The discussion focuses on how pathologists have been dealing with "hepatocellular ballooning". Loose criteria, in which hepatocellular ballooning was not required for the diagnosis of NASH, were applied in many clinical studies published in around 2000's, whereas a strict criterion based on the presence/absence of hepatocellular ballooning was approved recently. Hence, simple and reliable methods of identifying ballooned hepatocytes are being sought. Clinical and pathological predictors of NAFLD-related hepatocarcinogenesis will also be sought in the future.