Research Papers:

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

Chung-Feng Huang _, Ming-Lun Yeh, Ching-I Huang, Yu-Ju Lin, Pei-Chien Tsai, Zu-Yau Lin, Soa-Yu Chan, Shinn-Cherng Chen, Hwai-I Yang, Jee-Fu Huang, Sheng-Nan Lu, Chia-Yen Dai, Chin-Lan Jen, Yong Yuan, Gilbert L'Italien, Li-Yu Wang, Mei-Hsuan Lee, Ming-Lung Yu, Wan-Long Chuang and Chien-Jen Chen

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Oncotarget. 2017; 8:43925-43933. https://doi.org/10.18632/oncotarget.14937

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Chung-Feng Huang1,2, Ming-Lun Yeh1,2, Ching-I Huang1, Yu-Ju Lin3, Pei-Chien Tsai1, Zu-Yau Lin1,2, Soa-Yu Chan3, Shinn-Cherng Chen1,2, Hwai-I Yang4, Jee-Fu Huang1,2, Sheng-Nan Lu5,6, Chia-Yen Dai1,2, Chin-Lan Jen4, Yong Yuan7, Gilbert L’Italien8, Li-Yu Wang9, Mei-Hsuan Lee3, Ming-Lung Yu1,2,10,12, Wan-Long Chuang1,2 and Chien-Jen Chen11

1Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

4The Genomics Research Center, Academia Sinica, Taipei, Taiwan

5The Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

6Chang Gung University School of Medicine, Kaohsiung, Taiwan

7The Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States of America

8The Yale University School of Medicine, New Haven, CT, United States of America

9MacKay Medical College, Taipei, Taiwan

10Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

11Academia Sinica, Taipei, Taiwan

12Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America

Correspondence to:

Mei-Hsuan Lee, email: [email protected]

Ming-Lung Yu, email: [email protected]

Keywords: HCV, HCC, spontaneous clearance, treatment

Received: October 15, 2016    Accepted: December 27, 2016    Published: February 01, 2017


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.

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