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在丙型肝炎病毒持续病毒学应答患者的肝细胞癌中频繁检测到乙型肝炎病毒DNA

Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus.

作者信息

Tamori Akihiro, Hayashi Takehiro, Shinzaki Mayumi, Kobayashi Sawako, Iwai Shuji, Enomoto Masaru, Morikawa Hiroyasu, Sakaguchi Hiroki, Shiomi Susumu, Takemura Shigekazu, Kubo Shoji, Kawada Norifumi

机构信息

Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

出版信息

J Med Virol. 2009 Jun;81(6):1009-14. doi: 10.1002/jmv.21488.

Abstract

Hepatocellular carcinoma (HCC) develops several years after the eradication of hepatitis C virus (HCV) by interferon therapy. Risk factors for the development of HCC are only partly understood. To elucidate the role of occult hepatitis B virus (HBV) infection in hepatocarcinogenesis in patients with sustained virologic response, the prevalences of HBV-related makers were examined. Study group comprised 16 patients with sustained virologic response (group A) and 50 with HCV (group B). Anti-HBc and anti-HBs in serum were examined by enzyme-linked immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction, using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA. Sequence of the amplified HBV DNA for 'a' determinant of HBsAg was determined in HCC. Anti-HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P = 0.044). In group A, HBV DNA in liver was detected frequently in patients without cirrhosis and in those with a longer period from the time of HCV eradication to the development of HCC. Mutation in 'a' determinant of HBsAg was found in three HCC of group A. Occult HBV infection may be one of the most important risk factors in hepatocarcinogenesis of Japanese patients with sustained virologic response.

摘要

肝细胞癌(HCC)在通过干扰素治疗清除丙型肝炎病毒(HCV)数年后发生。HCC发生的危险因素仅部分为人所知。为了阐明隐匿性乙型肝炎病毒(HBV)感染在病毒学应答持续患者肝癌发生中的作用,研究了HBV相关标志物的患病率。研究组包括16例病毒学应答持续的患者(A组)和50例HCV患者(B组)。采用酶联免疫吸附测定法检测血清中的抗-HBc和抗-HBs。使用针对编码HBx、HBsAg、HBcAg和HBV cccDNA的基因的引物,通过巢式聚合酶链反应检测肝脏中的HBV DNA。在HCC中测定扩增的HBV DNA针对HBsAg“a”决定簇的序列。A组16例中有10例抗-HBc阳性,B组50例中有25例抗-HBc阳性。A组16例中有12例检测到肝脏中的HBV DNA,B组50例中有21例检测到肝脏中的HBV DNA(P = 0.044)。在A组中,在无肝硬化的患者以及从HCV清除到HCC发生间隔时间较长的患者中,肝脏中HBV DNA的检测频率较高。在A组的3例HCC中发现了HBsAg“a”决定簇的突变。隐匿性HBV感染可能是日本病毒学应答持续患者肝癌发生的最重要危险因素之一。

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