title: Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C.
abstract: OBJECTIVE
  To evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older.
  
  
  METHODS
  The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment.
  
  
  RESULTS
  Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7%vs66.7%, respectively,P< 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups (91.6%vs81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160; 95%CI: 1.593-41.804,P= 0.012) and the adherence of RBV (> 60%) (OR = 11.052; 95%CI: 1.160-105.273,P= 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger (81.1%) and older (82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes (77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR (OR = 9.677; 95%CI: 1.114-84.087,P= 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively.
  
  
  CONCLUSIONS
  Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Waguri
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Sugitani
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Wakabayashi
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ohkoshi
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsukishiro
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
keywords: Aged patients; Hepatitis C virus genotype 1b; Interleukin 28B; Simeprevir; Telaprevir