title: Favorable efficacy of daclatasvir plus asunaprevir in treatment of elderly Japanese patients infected with HCV genotype 1b aged 70 and older.
abstract: The combination of daclatasvir and asunaprevir is efficacious in the treatment of hepatitis C virus (HCV) infection, but its efficacy and predictors of efficacy in the elderly (≥70 years) remain unclear. In this study, 844 patients with chronic HCV genotype 1b infection, were treated with daclatasvir (60 mg once daily) plus asunaprevir (100 mg twice daily) for 24 weeks. Using the intention-to-treat analysis, the sustained virological response (SVR) rates were 87% and 88% for all 844 patients and 411 elderly (>70 years of age), respectively. In both groups, multivariate analysis identified NS5A-Y93H mutation (<20%), pretreatment (failure of treatment except for triple therapy with simeprevir, or treatment naive), and level of viremia (<6.0 log IU/ml) as independent predictors of SVR. Direct sequencing showed a significantly higher rate of NS3-D168 mutation at baseline in non-responders to triple therapy with simeprevir (44%) than others (2%). Alfa-fetoprotein (AFP) level and liver stiffness were significantly lower after end of treatment than at baseline, in both the SVR and non-SVR groups. In conclusion, daclatasvir-asunaprevir combination achieved high SVR in HCV genotype 1b patients, including elderly patients. Viral factors negatively influenced the response to treatment. Treatment improved AFP level and liver stiffness (surrogate markers of hepatocellular carcinoma), regardless of treatment efficacy. J. Med. Virol. 89:91-98, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Hepatology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D002219:Carbamates; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007546:Isoquinolines / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012189:Retrospective Studies; D013449:Sulfonamides / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D000509:alpha-Fetoproteins; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: AFP; HCV; NS3; NS5A; asunaprevir; daclatasvir; elderly; liver stiffness; resistance-associated variant