Shiota G, Oyama K, Udagawa A, Tanaka K, Nomi T, Kitamura A, Tsutsumi A, Noguchi N, Takano Y, Yashima K, Kishimoto Y, Suou T, Kawasaki H
Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
J Med Virol. 2000 Oct;62(2):151-8. doi: 10.1002/1096-9071(200010)62:2<151::aid-jmv5>3.0.co;2-n.
Hepatitis B virus (HBV) genome was reported to be detected in serum or liver tissues in hepatocellular carcinoma (HCC) patients negative for hepatitis B surface antigen (HBsAg). Hepatitis B x (HBx) and p53 protein were reported to play an important role in HBV-related hepatocarcinogenesis. To clarify latent HBV infection in HBsAg- and anti-hepatitis C virus (anti-HCV)-negative HCC in a Japanese population and involvement of HBx and p53 protein in these patients, we performed the sensitive and specific nested polymerase chain reaction (PCR) and immunohistochemical analysis. Of 1,024 HCC patients we saw between 1974 and 1998, 66 (6.4%) were negative for HBsAg and anti-HCV. Serum DNA was amplified by nested PCR by using specific primers of surface (S), core (C) and X regions in 26 patients negative for HBsAg and anti-HCV. Eighteen (69%) patients were positive for either S, C, or X region and the results of PCR were confirmed by Southern blotting. Of 18 PCR-positive patients, 3 were positive for anti-HBs and 9 were positive for anti-HBc, however, one was negative for any HBV markers. In HBsAg-negative and PCR-positive patients, the positive rates of expression of HBx and p53 were 8/13 (62%) and 7/13 (54%), being comparable to those in HBsAg-positive HCC patients. The results of the present study suggest that high prevalence of HBV infection is observed in HBsAg-negative HCC in a Japanese population and expression of HBx and p53 is consistent with a role, in these patients, for the transforming ability of these proteins.
据报道，在乙肝表面抗原（HBsAg）呈阴性的肝细胞癌（HCC）患者的血清或肝组织中检测到了乙肝病毒（HBV）基因组。据报道，乙肝X蛋白（HBx）和p53蛋白在HBV相关的肝癌发生过程中发挥着重要作用。为了阐明日本人群中HBsAg和抗丙型肝炎病毒（抗-HCV）均呈阴性的HCC患者中的潜在HBV感染情况以及HBx和p53蛋白在这些患者中的作用，我们进行了灵敏且特异的巢式聚合酶链反应（PCR）和免疫组织化学分析。在1974年至1998年间我们诊治的1024例HCC患者中，66例（6.4%）HBsAg和抗-HCV均呈阴性。对26例HBsAg和抗-HCV均呈阴性的患者，使用表面（S）、核心（C）和X区域的特异性引物通过巢式PCR扩增血清DNA。18例（69%）患者的S、C或X区域呈阳性，PCR结果通过Southern印迹法得以证实。在18例PCR阳性患者中，3例抗-HBs呈阳性，9例抗-HBc呈阳性，然而，有1例所有HBV标志物均呈阴性。在HBsAg阴性且PCR阳性的患者中，HBx和p53的表达阳性率分别为8/13（62%）和7/13（54%），与HBsAg阳性的HCC患者相当。本研究结果表明在日本人群的HBsAg阴性HCC患者中观察到HBV感染的高流行率，并且HBx和p53的表达与这些蛋白在这些患者中的转化能力所起的作用是一致的。
