Mixed HCV Infection of Genotype 1B and Other Genotypes Influences Non-response during Daclatasvir + Asunaprevir Combination Therapy

• Published in: Acta medica Okayama Vol. 72; no. 4; pp. 401 - 406
• Main Authors: Wada, Nozomu, Ikeda, Fusao, Mori, Chizuru, Takaguchi, Koichi, Fujioka, Shin-Ichi, Kobashi, Haruhiko, Morimoto, Yoichi, Kariyama, Kazuya, Sakaguchi, Kosaku, Hashimoto, Noriaki, Moriya, Akio, Kawaguchi, Mitsuhiko, Miyatake, Hirokazu, Hagihara, Hiroaki, Kubota, Junichi, Takayama, Hiroki, Takeuchi, Yasuto, Yasunaka, Tetsuya, Takaki, Akinobu, Iwasaki, Yoshiaki, Okada, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Japan 01.08.2018
• Subjects: Adult; Aged; Aged, 80 and over; Antiviral Agents - administration & dosage; Drug Therapy, Combination; Female; Genotype; Hepacivirus - classification; Hepacivirus - genetics; Hepatitis C - drug therapy; Hepatitis C - virology; Humans; Imidazoles - administration & dosage; Isoquinolines - administration & dosage; Male; Middle Aged; Sulfonamides - administration & dosage; Young Adult; HCV; serogrouping 1 infection; asunaprevir; mixed genotype; daclatasvir
• ISSN: 0386-300X
• DOI: 10.18926/amo/56178

Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure.