Is an 8‐week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real‐world experience?

Abstract

Background and Aims:The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). Methods: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. Results: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = À0.14, P < 0.001) were independent predictors of nonresponse. Conclusions: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.

Genotype-specific versus pangenotypic regimens in patients infected with HCV genotype 1b in real-world settings

“…Our findings on the very high effectiveness of GLE/PIB regardless of the history of previous therapies and liver fibrosis status supported the results of numerous clinical trials [33][34][35][36]. The excellent efficacy of 99-100% in GT1b patients, both noncirrhotic and cirrhotic, as well as treatmentnaïve and experienced, was also documented in published RWE studies [37][38][39][40][41]. Importantly, this option can be administered in renally impaired patients; two patients with kidney failure stage 4 and 5 treated within the current study responded to the therapy, which is consistent with published data [42].…”

Glecaprevir/pibrentasvir for 8 weeks in patients with compensated cirrhosis: Safety and effectiveness data from the German Hepatitis C‐Registry

“…Rates of SVR12 were similar in the PP analysis of GT3‐ vs non‐GT3‐infected patients (97.9% vs 98.8%, respectively); GT3 patients had lower SVR12 in the ITT analysis (82.1% vs 88.8%) with equal patients LTFU. Another real‐world study evaluating 8‐week G/P therapy showed similar results in GT3 cirrhotics with 71.5% of F4 patients achieving SVR12% vs 98.5% of non‐GT3 infected patients; in F0‐F3 patients, 96.3% of GT3‐infected patients achieved SVR12% vs 98.6% of non‐GT3‐infected patients 11 . However, only seven GT3‐infected, F4 patients were included in the modified intention‐to‐treat (mITT) analysis vs 65 non‐GT3 patients.…”

Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics

“…The same effectiveness was documented by Lampertico et al following the 8-week GLE/PIB treatment duration in 19 cirrhotic patients with GT3 infection from seven small RWE studies included in the summary analysis [ 34 , 35 ]. A much lower SVR of 72% in PP analysis was demonstrated in nine GT3 infected cirrhotics in our previous study from the EpiTer-2 database, but it was due to a small subset of patients [ 36 ]. In the current study, 16 patients treated for 8 weeks achieved SVR, which gives an unsatisfactory rate of 84% in PP analysis, lower than demonstrated for a 12-week regimen with statistical significance for ITT analysis (80% vs. 95.4%, p = 0.05), however, it should be noted that a number of patients on 8-week regimen was still low.…”