Hepatocellular ballooning in nonalcoholic steatohepatitis: the pathologist’s perspective

Nonalcoholic fatty liver disease (NAFLD) is an important complication of the metabolic syndrome. The increasing prevalence of the metabolic syndrome is paralleled by an increasing prevalence of NAFLD, which has become one of the most common chronic liver diseases. NAFLD comprises a morphological spectrum ranging from nonalcoholic fatty liver (NAFL), characterized by accumulation of fat in hepatocytes, to nonalcoholic steatohepatitis (NASH). The key histological features of NASH accepted by most pathologists include steatosis, hepatocellular ballooning and lobular inflammation, whereas, like in other chronic liver diseases, the presence of fibrosis is not considered a requirement for the diagnosis. The diagnosis of NASH and the distinction from NAFL carries important prognostic and therapeutic implications because NASH, in contrast to NAFL, is associated with an increased risk of progression to cirrhosis and hepatocellular carcinoma. Hepatocellular ballooning is a key feature required for the diagnosis of NASH and a component of currently used histological grading and staging systems of NAFLD. However, it represents an ill-defined form of liver cell injury associated with cell swelling and rounding of the cytoplasm, the detection of which is prone to intra- as well as inter-observer variation. Some of the factors that may contribute to ballooning are the rearrangement of the intermediate filament cytoskeleton, accumulation of small-droplet fat in the cytoplasm and dilation of the endoplasmic reticulum. The rearrangement of the intermediate filament cytoskeleton can be demonstrated by the loss of keratin 8/18 immunostaining of the cytoplasm, and may thus be evaluated in the future as a marker for the more objective detection of hepatocellular ballooning in NASH.