Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance

// Chung-Feng Huang 1, 2 , Ming-Lun Yeh 1, 2 , Ching-I Huang 1 , Yu-Ju Lin 3 , Pei-Chien Tsai 1 , Zu-Yau Lin 1, 2 , Soa-Yu Chan 3 , Shinn-Cherng Chen 1, 2 , Hwai-I Yang 4 , Jee-Fu Huang 1, 2 , Sheng-Nan Lu 5, 6 , Chia-Yen Dai 1, 2 , Chin-Lan Jen 4 , Yong Yuan 7 , Gilbert L’Italien 8 , Li-Yu Wang 9 , Mei-Hsuan Lee 3 , Ming-Lung Yu 1, 2, 10, 12 , Wan-Long Chuang 1, 2 and Chien-Jen Chen 11 1 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 4 The Genomics Research Center, Academia Sinica, Taipei, Taiwan 5 The Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 6 Chang Gung University School of Medicine, Kaohsiung, Taiwan 7 The Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States of America 8 The Yale University School of Medicine, New Haven, CT, United States of America 9 MacKay Medical College, Taipei, Taiwan 10 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 11 Academia Sinica, Taipei, Taiwan 12 Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America Correspondence to: Mei-Hsuan Lee, email: meihlee@ym.edu.tw Ming-Lung Yu, email: fish6069@gmail.com Keywords: HCV, HCC, spontaneous clearance, treatment Received: October 15, 2016     Accepted: December 27, 2016     Published: February 01, 2017 ABSTRACT 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 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.