Influencing factors for direct-acting antiviral therapy failure in treatment of hepatitis C / 临床肝胆病杂志

Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.

Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents / 中华肝脏病杂志

Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.