title: Time-Degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among Hepatitis C Virus Patients: A Model for Prioritization of Treatment.
abstract: Purpose:Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular carcinoma among chronic hepatitis C (CHC) patients.Experimental Design:A total of 1,281 biopsy-proven CHC patients receiving IFN-based therapy were followed for a mean period of 5.5 years.Results:The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-sustained virological response (SVR) and SVR patients who were <40 years old (7.7% vs. 0.5%,P= 0.1) but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%,P< 0.001) and >55 years old (15.1% vs. 7.9%,P= 0.03). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients 40 to 55 years old [HR/95% confidence intervals (CI), 10.92/3.78-31.56;P< 0.001] and >55 years old (HR/CI, 1.96/1.06-3.63;P= 0.03) but not in patients <40 years old (HR/CI, 2.76/0.41-18.84;P= 0.3). The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%,P= 0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%,P< 0.001) or F4 (33.5% vs. 8.4%,P= 0.002). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients with F2-3 (HR/CI, 4.36/2.10-9.03;P< 0.001) and F4 (HR/CI, 3.84/1.59-9.30;P= 0.03) but not in those with F0-1 (HR/CI, 1.53/0.49-4.74;P= 0.47).Conclusions:Delayed hepatitis C virus clearance for patients with CHC >40 years old or with a fibrosis stage >2 increases the risk of hepatocellular carcinoma over time.Clin Cancer Res; 23(7); 1690-7. ©2016 AACR.
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.|Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ching-I
authors.initials: CI
authors.lastname: Huang
authors.affiliation: Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Hsieh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. d820195@gmail.com waloch@kmu.edu.tw.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. d820195@gmail.com waloch@kmu.edu.tw.|Faculty of Internal Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha