Toyoda Hidenori, Kumada Takashi, Kaneoka Yuji, Murakami Yoshiki
Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
J Hepatol. 2008 Jan;48(1):43-50. doi: 10.1016/j.jhep.2007.08.016. Epub 2007 Oct 24.
BACKGROUND/AIMS: We analyzed hepatitis B virus (HBV) X gene integration in hepatocytes of HBV-negative, chronic hepatitis C (CH-C) patients with mild fibrosis, and prospectively followed these patients for the development of hepatocellular carcinoma (HCC).
The study included 39 HBV-negative CH-C patients with mild fibrosis. HBV-X integration was determined by Alu-PCR analysis of liver specimens obtained by fine-needle biopsy.
Integration of HBV-X gene sequence into liver genome occurred in 9 of the 39 patients. Six of the 39 patients developed HCC during the 12-year follow-up period. No significant difference was found in the incidence of HCC between patients with and without HBV-X integration. However, the two patients with HBV-X integration who developed HCC did not have cirrhosis at the time when HCC was diagnosed, whereas the four patients without HBV-X integration who developed HCC did have cirrhosis.
Our findings suggest that HBV-X integration detected at the mild fibrosis stage might not indicate a high risk for HCC. HBV-X integration may be associated with HCC development in the absence of cirrhosis. However, we did not find evidence that HBV-X integration directly plays a role in hepatocarcinogenesis in CH-C patients. Further studies will be needed to clarify this point.
背景/目的：我们分析了乙肝病毒（HBV）X基因在轻度纤维化的HBV阴性慢性丙型肝炎（CH-C）患者肝细胞中的整合情况，并对这些患者发生肝细胞癌（HCC）的情况进行了前瞻性随访。
该研究纳入了39例轻度纤维化的HBV阴性CH-C患者。通过对细针穿刺活检获得的肝脏标本进行Alu-PCR分析来确定HBV-X整合情况。
39例患者中有9例出现HBV-X基因序列整合入肝脏基因组。在12年的随访期内，39例患者中有6例发生了HCC。HBV-X整合阳性和阴性患者的HCC发生率无显著差异。然而，发生HCC的2例HBV-X整合阳性患者在诊断HCC时没有肝硬化，而发生HCC的4例HBV-X整合阴性患者有肝硬化。
我们的研究结果表明，在轻度纤维化阶段检测到的HBV-X整合可能并不意味着HCC的高风险。在没有肝硬化的情况下，HBV-X整合可能与HCC的发生有关。然而，我们没有发现证据表明HBV-X整合在CH-C患者的肝癌发生中直接起作用。需要进一步的研究来阐明这一点。
