부산대학교 도서관

Aims: Ledipasvir/sofosbuvir (LDV/SOF) with ribavirin (RBV) demonstrated high SVR rates in patients with chronic hepatitis C (HCV) genotype (GT) 1 or 4 infection who have decompensated cirrhosis or who have undergone liver transplantation. Here we evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized the viral resistance in all virologic failures. Methods: Deep sequencing with a 1% assay cut-off was performed for NS5A and NS5B at baseline for all the patients and at the time of virologic failure for those who relapsed. Results: Out of 625, 622, and 619 samples were analyzed for baseline NS5A and NS5B respectively. Table 1 summarizes SVR12 rates by treatment duration and the presence or absence of baseline NS5A RAVs. NS5B RAVs at baseline were uncommon, occurring in 4.8% (28/586) GT1 patients and 3.2% (1/31) GT 4 patients. Of these 29 patients, only one GT1 patient with CPT C cirrhosis who had L159F at baseline and was treated for 24 weeks with LDV/SOF+RBV did not achieve SVR12. NS5A RAVs at positions 24, 28, 30, 31, 58, and 93 were enriched or emerged in 20/22 (91%) GT1 and 1/3 GT4 infected patients with virologic failure. The NS5B NI RAV E237G emerged in 3 GT1a patients and 1 GT4d patient at the time of relapse (4/23, 17%). Conclusions: The presence of baseline NS5A or NS5B RAVs did not impact the treatment outcome to 12 or 24 weeks of LDV/SOF+RBV in GT1 or GT4 HCV patients with liver ransplantation without decompensated liver disease, or 24 weeks of LDV/SOF+RBV in patients with decompensated cirrhosis. Lower SVR rates were observed among the limited number of patients with decompensated cirrhosis and baseline NS5A RAVs who received 12 weeks of LDV/SOF+RBV treatment.