title: Individualized treatment strategies and predictors of virological response for chronic hepatitis C: a multicenter prospective study from China.
abstract: Combination therapy comprising pegylated interferon-alpha (PegIFNα) and ribavirin (RBV) has been the standard of care for the chronic hepatitis C patients for more than a decade. Recently, direct antiviral agents show better efficacy, tolerance, and shorter treatment duration. However, the prohibitive costs of the regimens limit their use in developing countries where most of the HCV infection exists. Optimizing the treatment and understanding the host- and virus-factors associated with viral clearance were necessary for individualizing therapy to maximize sustained virologic response. To explore individualized antiviral strategies with PegIFNα-2a/IFNα-2b plus ribavirin for CHC patients, and to clarify predictive factors for virological response. A cohort of 314 patients were included in this open-label, prospective clinical trial, which received individualized doses of PegIFNα-2a or IFNα-2b combined with RBV according to body weight, disease status and complications, with the duration of 44 weeks after HCV RNA undetectable. All the IL-28B (rs8099917), IL-17A (rs8193036), IL-17B (rs2275913) and PD-1.1 SNPs were genotyped using the TaqMan system. The sustained virological response (SVR) in PegIFNα-2a group was significantly higher than that in IFNα-2b (85.8% vs 75.0%, P = 0.034), especially in HCV genotype 1 (84.0% vs 64.3%, P = 0.022). However, no significant differences were found in rapid virological response (RVR), complete early virological response (cEVR) and SVR between PegIFNα-2a and IFNα-2b according to different doses, respectively. The genotype frequency of IL-28B TT in patients with cEVR, SVR was higher than that in non-responsed patients (93.8% vs 78.1%, χ(2) = 7.827, P = 0.005; 95.9% vs 80.4%, χ(2) = 9.394, P = 0.002). No significant correlation between the genotype distribution of IL-17A, IL-17B and PD-1.1 with virological response. Individualized regimens of PegIFNα-2a/RBV and IFNα-2b/RBV could achieve satisfied virological response in Chinese HCV patients. The IL-28B (rs8099917) TT genotype is a clinical usefully marker for cEVR and SVR.
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Nan
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, The Fifth Hospital of Shijiazhuang City Shijiazhuang, China.
authors.forename: Huan-Wei
authors.initials: HW
authors.lastname: Zheng
authors.affiliation: Department of Traditional and Western Medical Hepatology, People's Hospital of Xingtai City Xingtai, China.
authors.forename: Chun-Mian
authors.initials: CM
authors.lastname: An
authors.affiliation: Department of Liver Disease, Infectious Diseases Hospital of Handan City Handan, China.
authors.forename: You-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of Liver Disease, Infectious Diseases Hospital of Cangzhou City Cangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Liver Disease, Bethune International Peace Hospital Shijiazhuang, China.
authors.forename: Dian-Xing
authors.initials: DX
authors.lastname: Sun
authors.affiliation: Department of Liver Disease, Infectious Diseases Hospital of Cangzhou City Cangzhou, China.
authors.forename: Cang-You
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Liver Disease, Infectious Diseases Hospital of Handan City Handan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Liver Disease, The First Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Tong
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Kong
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Su-Xian
authors.initials: SX
authors.lastname: Zhao
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Rong-Qi
authors.initials: RQ
authors.lastname: Wang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Meng
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Su
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University Shijiazhuang, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Niu
keywords: Chronic hepatitis C; interferon; pegylated interferon; ribavirin; single nucleotide polymorphisms; virological response