ASO：cccDNA/ih HBV DNA比值为HBV HCC患者生存预测因素

在2013年6月15日在线出版的《外科肿瘤学年鉴》(Annals of Surgical Oncology)杂志上，发表了美国西奈山医学院Spiros P. Hiotis博士等人的一项研究结果，该研究目的为，确定肝内总HBV(ih HBV)DNA和共价闭环DNA(cccDNA)与坏死性感染和纤维化的关系，及其对接受切除治疗的HBV HCC患者预后的影响。慢性乙肝病毒(HBV)感染可诱导患者产生持续但无效的免疫活化，造成坏死性感染、纤维化，并存在导致肝细胞癌(HCC)的风险。

该研究所用数据来源为在纽约西奈山医院(1991–2008)接受原发性肝脏切除治疗的111例HBV HCC患者。通过实时PCR方法，对ih HBV DNA及cccDNA进行定量分析。根据组织学活性指数(HAI)，对坏死性感染进行了分级，并通过改良的Ishak法，对肝脏纤维化进行了分期。

研究结果表明，分别有106 例(95 %)及89例(80 %)患者检测到ih HBV DNA 及cccDNA，同时有43 %的患者血清中检测到HBV DNA。在ih HBV DNA中，cccDNA的比例较低(中位cccDNA/ih HBV DNA 比值= 0.022)。较高水平的ih HBV DNA与较高的HAI和血清丙氨酸转移酶(ALT)有关，而较低的cccDNA/ih HBV DNA比值与较高的HAI、ALT及Ishak纤维化分期结果有关。ih HBV及cccDNA与患者生存无关，但cccDNA/ih HBV DNA比值最低结果(<0.0024)则为较差总生存率的独立相关因素。

研究人员最后认为，较低cccDNA/ih HBVDNA比值与较高的坏死性感染及肝脏纤维化有关，且为较差总生存率的独立相关因素。因此细胞内病毒载量及病毒DNA相对比例可反映出肝脏的组织损伤情况，并对HBV HCC患者的临床结局产生影响。

Impact of Intrahepatic Hepatitis B DNA and Covalently Closed Circular DNA on Survival After Hepatectomy in HBV-Associated Hepatocellular Carcinoma Patients
Background
Chronic hepatitis B virus (HBV) infection induces persistent but ineffective immune activation that contributes to necroinflammation, fibrosis, and risk of hepatocellular carcinoma (HCC). This study aims to determine the relationship of intrahepatic total HBV (ih HBV) DNA and covalently closed circular DNA (cccDNA) with necroinflammation and fibrosis, and their impact on prognosis after resection in HBV HCC patients.
Methods
Data are from 111 patients treated with primary liver resection for HBV HCC at Mount Sinai, New York (1991–2008). ih HBV DNA and cccDNA were quantitated by real-time PCR. Necroinflammation was graded according to histologic activity index (HAI), and liver fibrosis was staged by the modified Ishak method.
Results
A total of 106 (95 %) and 89 patients (80 %) had detectable ih HBV DNA and cccDNA, respectively, while 43 % had detectable serum HBV DNA. cccDNA made up a small proportion of ih HBV DNA (median cccDNA/ih HBV DNA ratio = 0.022). Higher levels of ih HBV DNA were associated with higher HAI and serum alanine aminotransferase (ALT), while a lower ratio of cccDNA/ih HBV DNA was associated with higher HAI, ALT, and Ishak fibrosis stage. ih HBV and cccDNA were not associated with survival, but the lowest quintile of cccDNA/ih HBV DNA ratio (<0.0024) was independently associated with poor overall survival.
Conclusions
A lower cccDNA/ih HBV DNA ratio was associated with greater necroinflammation and liver fibrosis, and was independently associated with poor overall survival. Thus, intracellular virus loads and relative proportions of virus DNA reflect histologic damage in the liver and influence the clinical outcome of HBV HCC patients.