Tamori Akihiro, Nishiguchi Shuhei, Kubo Shoji, Enomoto Masaru, Koh Noritoshi, Takeda Tadashi, Shiomi Susumu, Hirohashi Kazuhiro, Kinoshita Hiroaki, Otani Shuzo
Department of Hepatology, Osaka City University Graduate School of Medicine, Japan.
J Med Virol. 2003 Apr;69(4):475-81. doi: 10.1002/jmv.10334.
DNA of free hepatitis B viruses (HBV) has been detected in the liver of patients infected with hepatitis C virus (HCV). It is unknown whether HBV DNA is integrated into such livers; if so, it may affect hepatocarcinogenesis. Hepatocellular carcinomas (HCCs) from 34 patients without HBV surface antigen (HBsAg) and with anti-HCV, and from 7 patients with HBsAg and without anti-HCV as controls, were examined, using the cassette-ligation-mediated polymerase chain reaction and primers based on HBV DNA sequence. In the controls, HBV DNA had been integrated into human DNA of all HCCs. On the basis of HBV DNA in tumor tissue, 23 of the 34 patients with anti-HCV had occult infection. Junctions between human DNA and HBV DNA were detected in 10 of the 34 patients without HBsAg and with anti-HCV. HBV DNA was integrated into chromosome 11q in 4 of the 10 HCCs with junctions. The DNA to either side of the human-viral junctions was sequenced. Clinically, the mean tumor size of these 10 HCCs was 39 mm; that of the 24 HCCs without integrated HBV was 25 mm. The surrounding tissue was cirrhotic in 2 of the 10 former HCCs and in 16 of the latter 24 HCCs. In conclusion, integrated HBV was detected in some patients with HCV infection; in these patients, the integrated DNA was associated with accelerated hepatocarcinogenesis.
在丙型肝炎病毒(HCV)感染患者的肝脏中检测到了游离乙型肝炎病毒(HBV)的DNA。尚不清楚HBV DNA是否整合到此类肝脏中;如果是这样,它可能会影响肝癌的发生。使用盒式连接介导的聚合酶链反应和基于HBV DNA序列的引物,对34例无乙型肝炎表面抗原(HBsAg)且抗-HCV阳性的患者以及7例有HBsAg且抗-HCV阴性的患者的肝细胞癌(HCC)进行了检查。在对照组中,所有HCC的人类DNA中均已整合了HBV DNA。根据肿瘤组织中的HBV DNA,34例抗-HCV阳性患者中有23例存在隐匿性感染。在34例无HBsAg且抗-HCV阳性的患者中,有10例检测到人类DNA与HBV DNA之间的连接。在10例有连接的HCC中,有4例HBV DNA整合到了11号染色体q臂上。对人类-病毒连接点两侧的DNA进行了测序。临床上,这l O例HCC的平均肿瘤大小为39mm;24例未整合HBV的HCC的平均肿瘤大小为25mm。10例前者中的2例以及24例后者中的16例周围组织为肝硬化。总之,在一些HCV感染患者中检测到了整合的HBV;在这些患者中,整合的DNA与肝癌发生加速有关。