The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis

Abstract

Steatohepatitis and metabolic syndrome are increasingly recognized as important risk factors for development of hepatocellular carcinoma. We have recently described a histologic subtype of hepatocellular carcinoma termed steatohepatitic hepatocellular carcinoma, which shows features resembling steatohepatitis in the nonneoplastic liver. The present study is undertaken to assess the association between the steatohepatitic hepatocellular carcinoma variant and underlying steatohepatitis and features of metabolic syndrome. We examined all hepatocellular carcinomas diagnosed on resections and explant specimens over a 3.5-year period at our institution. Tumors were classified as either conventional hepatocellular carcinoma or steatohepatitic hepatocellular carcinoma variant based on their predominant histopathologic pattern. The underlying chronic liver disease in each case was determined. The steatohepatitic hepatocellular carcinoma variant represented 13.5% (16/118) of cases. All but one case of steatohepatitic hepatocellular carcinoma occurred in patients with underlying steatohepatitis. Steatohepatitic hepatocellular carcinoma was diagnosed in 35.7% of patients with either nonalcoholic steatohepatitis or alcoholic liver disease compared with 1.3% of patient with other chronic liver diseases (P < .0001). The steatohepatitic hepatocellular carcinoma group had a significantly higher number of metabolic syndrome risk factors (2.44 versus 1.48, P = .01) and a higher percentage of patients with at least 3 metabolic syndrome components (50% versus 22.5%, P = .02). Immunohistochemically, there were diffuse loss of cytoplasmic CK8/18 and increased numbers of activated hepatic stellate cells within steatohepatitic hepatocellular carcinoma, in a pattern identical to that seen in steatohepatitis in nonneoplastic liver. Hepatocellular carcinomas showing a "steatohepatitic" histologic phenotype are strongly associated with underlying steatohepatitis and metabolic syndrome. This association further supports a possible role of steatohepatitis in human hepatocarcinogenesis.