Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Hum Pathol. 2012 May;43(5):737-46. doi: 10.1016/j.humpath.2011.07.005. Epub 2011 Oct 20.
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.
脂肪性肝炎和代谢综合征正逐渐被视为肝细胞癌发展的重要危险因素。我们最近描述了一种被称为脂肪性肝炎型肝细胞癌的组织学亚型，其在非肿瘤性肝脏中表现出类似于脂肪性肝炎的特征。本研究旨在评估脂肪性肝炎型肝细胞癌变体与潜在的脂肪性肝炎和代谢综合征特征之间的关联。我们检查了我院在 3.5 年内切除和移植标本中诊断的所有肝细胞癌。根据其主要组织病理学模式，将肿瘤分为常规肝细胞癌或脂肪性肝炎型肝细胞癌变体。确定了每种情况下的潜在慢性肝病。脂肪性肝炎型肝细胞癌变体占 13.5%（16/118）的病例。除了一个病例外，所有的脂肪性肝炎型肝细胞癌都发生在有潜在脂肪性肝炎的患者中。与其他慢性肝病患者的 1.3%相比，非酒精性脂肪性肝炎或酒精性肝病患者中有 35.7%被诊断为脂肪性肝炎型肝细胞癌（P<0.0001）。脂肪性肝炎型肝细胞癌组有更多的代谢综合征危险因素（2.44 与 1.48，P=0.01）和更多的患者有至少 3 种代谢综合征成分（50%与 22.5%，P=0.02）。免疫组化显示，脂肪性肝炎型肝细胞癌中存在弥漫性细胞质 CK8/18 缺失和活化的肝星状细胞数量增加，这种模式与非肿瘤性肝脏中的脂肪性肝炎相同。表现出“脂肪性肝炎”组织学表型的肝细胞癌与潜在的脂肪性肝炎和代谢综合征密切相关。这种关联进一步支持了脂肪性肝炎在人类肝癌发生中的可能作用。
