Viral and host factors are associated with retreatment failure in hepatitis C patients receiving all‐oral direct antiviral therapy

• Published in: Hepatology research 2020-04, Vol.50 (4), p.453-465
• Main Authors: Mawatari, Seiichi, Oda, Kohei, Kumagai, Kotaro, Tabu, Kazuaki, Ijuin, Sho, Fujisaki, Kunio, Inada, Yukiko, Uto, Hirofumi, Saisyoji, Akiko, Hiramine, Yasunari, Hori, Takeshi, Taniyama, Ohki, Toyodome, Ai, Sakae, Haruka, Hashiguchi, Masafumi, Kure, Takeshi, Sakurai, Kazuhiro, Tamai, Tsutomu, Moriuchi, Akihiro, Ido, Akio
• Format: Article
• Language: English
• Subjects: Alleles; Antiretroviral drugs; Antiviral agents; direct‐acting antiviral; Gene deletion; Gene polymorphism; Hepatitis; Hepatitis C; IL28B SNP; Multivariate analysis; resistance‐associated substitutions; Response rates; retreatment; Risk factors; Single-nucleotide polymorphism
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.13474

Aim Direct‐acting antiviral (DAA) therapy for hepatitis C virus is associated with high sustained virologic response rates. However, patients for whom DAA therapy fails acquire resistance‐associated substitutions (RASs). We therefore evaluated the efficacy of DAA retreatment and factors associated with retreatment failure. Methods Non‐structural 5A RASs were investigated at the start of DAA therapy and at treatment failure in 64 patients with hepatitis C virus genotype 1b for whom DAA combination therapy had failed. A total of 59 patients were introduced to DAA retreatment. The factors associated with retreatment failure were investigated. Results A total of 20 of 43 (46.5%) daclatasvir + asunaprevir‐treated patients with virologic failure had no RASs at baseline, and three (15%) acquired P32 deletion RASs. Four of seven sofosbuvir/ledipasvir‐treated patients with virologic failure had more than two RASs of NS5A at baseline. The sustained virologic response rates on retreatment were as follows: sofosbuvir/ledipasvir, 81.8%; with elbasvir + grazoprevir, 0%; and glecaprevir/pibrentasvir, 87.5%. Patients for whom sofosbuvir/ledipasvir or elbasvir + grazoprevir failed achieved sustained virologic response with glecaprevir/pibrentasvir. Two of three patients for whom glecaprevir/pibrentasvir retreatment failed had Q24/L28/R30 and A92K RASs; the other had P32 deletion RAS at baseline. Interestingly, 10 of 11 patients with retreatment failure had the interleukin (IL)‐28B single‐nucleotide polymorphism (SNP) minor allele. A multivariate analysis showed that the IL28B SNP minor allele (P = 0.005, odds ratio 28.291) was an independent risk factor for retreatment failure. Conclusions In addition to viral factors (e.g. Q24, L28, R30, and A92 or P32 deletion RASs), host factors (e.g. IL28B SNP) are associated with DAA retreatment failure.