Huang Chung-Feng, Yeh Ming-Lun, Huang Ching-I, Lin Yu-Ju, Tsai Pei-Chien, Lin Zu-Yau, Chan Soa-Yu, Chen Shinn-Cherng, Yang Hwai-I, Huang Jee-Fu, Lu Sheng-Nan, Dai Chia-Yen, Jen Chin-Lan, Yuan Yong, L'Italien Gilbert, Wang Li-Yu, Lee Mei-Hsuan, Yu Ming-Lung, Chuang Wan-Long, Chen Chien-Jen
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Oncotarget. 2017 Jul 4;8(27):43925-43933. doi: 10.18632/oncotarget.14937.
BACKGROUND/AIMS: Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethods: A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis.
Nineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15).
Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.
背景/目的：丙型肝炎病毒（HCV）的自然清除以及抗病毒治疗实现持续病毒学应答（SVR）均能大幅降低肝细胞癌（HCC）的发病率。本研究旨在比较这两组患者发生HCC的风险。
共纳入313例HCV自然清除（SC）的受试者以及564例年龄和性别匹配的治疗诱导SVR组患者进行分析。
在877例患者6963人年的随访期间，有19例（2.2%）发生了HCC。14例（2.5%）SVR患者和5例（1.6%）SC患者发生了HCC（P = 0.004）。对预测HCC的因素进行Cox回归分析，结果包括SVR（与SC相比：风险比[HR]/95%置信区间[CI]：5.83/1.27 - 26.88）、糖尿病（HR/CI：3.41/1.21 - 9.58）和年龄（HR/CI：1.07/1.01 - 1.14）。在564例SVR患者中，187例纤维化2 - 4期（F2 - 4）患者中有11例（5.9%）发生了HCC，226例F0 - 1期患者中有2例（0.9%）发生了HCC（P = 0.01）。与SC受试者相比，仅F2 - 4期的SVR患者（P < 0.001）而非F0 - 1期的SVR患者（P = 0.60）发生HCC的风险更高。以肝纤维化作为变量进行Cox回归分析表明，与HCC相关的因素包括F2 - 4期的SVR（与SC相比：HR/CI：10.06/2.20 - 45.98）、糖尿病（HR/CI：3.23/1.14 - 9.19）和年龄（HR/CI：1.08/1.02 - 1.15）。
与病毒自然清除的受试者相比，抗病毒治疗诱导HCV病毒清除的受试者发生HCC的风险仍然很高，尤其是在他们有显著肝纤维化时。这些结果可能为资源有限国家当前直接抗病毒药物的优先排序决策提供重要信息。
