Huang, Chung-FengYeh, Ming-LunHuang, Ching-ILin, Yu-JuTsai, Pei-ChienLin, Zu-YauChan, Soa-YuChen, Shinn-CherngYang, Hwai-IHuang, Jee-FuLu, Sheng-NanDai, Chia-YenJen, Chin-LanYuan, YongL’Italien, GilbertWang, Li-YuLee, Mei-HsuanYu, Ming-LungChuang, Wan-LongChen, Chien-Jen2017-11-212017Huang, C., M. Yeh, C. Huang, Y. Lin, P. Tsai, Z. Lin, S. Chan, et al. 2017. “Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.” Oncotarget 8 (27): 43925-43933. doi:10.18632/oncotarget.14937. http://dx.doi.org/10.18632/oncotarget.14937.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34375119Background/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 groups Methods: 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. Results: 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). Conclusions: 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.en-USHCVHCCspontaneous clearancetreatmentJournal Article2017-11-2110.18632/oncotarget.14937