Ribavirin facilitates early viral kinetics in chronic hepatitis C patients receiving daclatasvir/asunaprevir

Abstract

Background and AimRibavirin (RBV) remains crucial in difficult‐to‐cure chronic hepatitis C patients receiving directly acting antivirals (DAAs). The current study aimed to address whether RBV enhanced early viral kinetics in patients with DAAs.MethodsHepatitis C virus (HCV) genotype‐1b patients were allocated to daclatasvir/asunaprevir +weight‐based RBV (1000–1200 mg/day) for 12–24 weeks. HCV RNA levels were compared at day 1, week 1, week 2, and week 4 of treatment.ResultsThe sustained virological response rate was 100% (67/67) and 96.7% (59/61) in the RBV and non‐RBV group, respectively. The HCV RNA levels at treatment week 2 (W2) were significantly lower in the RBV group than in the non‐RBV group (0.42 ± 0.81 log IU/mL vs 0.79 ± 1.03 log IU/mL, P = 0.04). Among the intermediate responders who remained to have detectable RNA after W1 of treatment, patients with RBV had a significantly higher rate of undetectable HCV RNA (71.4% vs 36.0%, P = 0.003) and lower HCV RNA level at W2 (0.55 ± 0.89 log IU/mL vs 1.32 ± 1.04 log IU/mL, P = 0.001). A more significant magnitude of HCV RNA reduction was also noted from baseline to day 1 (3.15 ± 0.38 log IU/mL vs 2.80 ± 0.70 log IU/mL, P = 0.009) and W1 to W2 (1.40 ± 0.65 log IU/mL vs 0.88 ± 0.78 log IU/mL, P = 0.007) in the RBV group compared to the non‐RBV group among the intermediate responders. Logistic regression analysis revealed that adding RBV independently predicted undetectable HCV RNA at W2 (odds ratio/confidence interval: 4.74/1.54–14.57, P = 0.007) in the intermediate responders.ConclusionsAdding RBV to DAAs improved early viral kinetic, in particular, for intermediate responders.

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy

“…The role of ribavirin in the improvement in DAA efficacy is not fully understood, 14 and whether it improves early kinetics and promotes immune modulations to diminish the chance of relapse following viral mutation awaits further identification. 15 It should be noted that the failure to attain an SVR in a significant proportion of decompensated patients was due to adverse events or mortality-related treatment discontinuation rather than to virological failure in the trials, [11][12][13] which reflected the difficulty in the management of the fragile subjects in the clinical setting. For example, a recent study using SOF/VEL plus ribavirin in the treatment of 23 patients with Child-Pugh class C resulted in an SVR12 of only 70% (16/23) in an intention-to-treat analysis.…”

“…Adding ribavirin to DAAs in the population is warranted to ascertain treatment efficacy. The role of ribavirin in the improvement in DAA efficacy is not fully understood [ 14 ], and whether it improves early kinetics and promotes immune modulations to diminish the chance of relapse following viral mutation awaits further identification [ 15 ]. It should be noted that the failure to attain an SVR in a significant proportion of decompensated patients was due to adverse events or mortality-related treatment discontinuation rather than to virological failure in the trials [ 11 - 13 ], which reflected the difficulty in the management of the fragile subjects in the clinical setting.…”

IL28B-Gene Polymorphisms (rs12979860) in HCV Liver Parenchymal changes legitimize Screening for SNPs before DAAs Therapy

“…The highest prevalence of active HCV genotype 4 (G4) infection (10%) is found among Egyptians, including the non-viremic anti-HCV IgG antibody seropositive and occult viral infections [2,3]. Introduction of rst and second generation direct-acting antiviral therapies (DAAs) [4][5][6][7][8][9] improved HCV treatment outcomes with oral therapy and provided considerable advantage in evaluating host-related factors that may affect HCV-induced hepatic damage and response to medications [10,11].…”

“…Therefore, further research is needed to study the relationship between gene SNPs and occurrence of various grades of hepatic parenchymal changes before proposing the antiviral therapeutic regimens.HCV RNA detection in serum is used to determine post-DAAs response; either as SVR, no response or relapse. SVR is assessed at the end of the 12 th week after end of treatment (EOT) when serum HCV-PCR turns negative[4][5][6][7][8][9]. When adding PBMCs-PCR to HCV diagnostic protocol, other researchers suggested different de nitions of nonresponse, relapse, and SVR given the persistent detection of intracellular HCV-RNA genomic strands[34,38].…”