Steatohepatitic Hepatocellular Carcinoma: A Novel Histologic Variant Associated with Steatohepatitis and Metabolic Syndrome.
Marcela Salomao, Abby Siegel, Jay H Lefkowitch, Roger K Moreira. Columbia University Medical Center, New York, NY
Background: We recently described a histologic subtype of hepatocellular carcinoma (HCC) termed “steatohepatitic HCC” (SH-HCC) with features resembling steatohepatitis (SH) in the non-neoplastic liver, including steatosis, hepatocyte ballooning, Mallory bodies, inflammation, and trabecular/pericellular fibrosis. Our initial SH-HCC cases were described in hepatitis C-related cirrhosis. The present study was undertaken to comprehensively assess the overall prevalence of SH-HCC among resected HCCs as well as possible associations with underlying SH and clinical features of metabolic syndrome (MS).
Design: We examined all HCCs diagnosed on partial hepatectomy or liver explant specimens obtained at our institution during a recent 3.5-year period, with special attention to the presence of “steatohepatitis-like” features within neoplastic tissue. A total of 119 viable HCC cases were reviewed. The underlying liver diseases included alcoholic and non-alcoholic cirrhosis, viral hepatitis and others. Tumors were classified as SH-HCC if all features of steatohepatitis were present in >50% of the tumor; otherwise, the tumor was classified as “typical” HCC. Clinical information regarding diagnostic criteria for MS (increased body mass index, hypertriglyceridemia, low HDL cholesterol, hypertension, and diabetes) was retrieved from medical records.
Results: SH-HCC was identified in a total of 16 of 119 cases (13.4%). Underlying SH (alcoholic or non-alcoholic) was found in 93.7% (15/16) of SH-HCC cases, compared to 27.5% (22/80) of typical HCC cases (P<0.0001). The SH-HCC group had a significantly higher MS score (2.44 vs 1.46; P=0.008) and a higher % of patients with > 3 MS components (50% vs 21.2%; P=0.03). Steatosis was present in the non-neoplastic liver of 81.2% of SH-HCC cases compared to 38.7% of typical HCCs (P=0.004), while SH was present in 68.7% and 10% of cases, respectively (P=0.0001). Immunohistochemically, there was diffuse loss of cytoplasmic CK8/18 and increased numbers of activated hepatic stellate cells within SH-HCC, in a pattern identical to that seen in steatohepatitis in non-neoplastic liver.
Conclusions: HCCs with the “steatohepatitic” histologic phenotype (SH-HCC) are strongly associated with underlying SH and MS. This association further suggests a possible direct role of SH/MS in human hepatocarcinogenesis. The impact of such a concept is considerable in light of the current global epidemic of obesity and fatty liver disease.
Category: Liver & Pancreas
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 259, Tuesday Morning