Comparison of three therapeutic regimens for genotype‐3 hepatitis C virus infection in a large real‐life multicentre cohort

Abstract

Background & Aims In the direct‐acting antiviral era, treatment of genotype‐3 HCV (HCV‐GT3) is still challenging. Real‐life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. Methods Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV‐GT3 patients consecutively treated within the Lombardia web‐based Navigatore HCV‐Network; differences in SVR12 across regimens were evaluated by logistic regression. Results Of the 2082 subjects with HCV‐GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV‐positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV‐RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10HCV‐RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV‐RNA were independently associated with SVR12. Conclusions In a large real‐life setting of HCV‐GT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier‐to‐treat patients allows ribavirin‐free and shorter schedules without mining SVR12 in this <<difficult‐to‐treat>> genotype.

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

“…The reported efficacy rates were 89% for SOF/VEL ± RBV (8/9) regimen and 67% (2/3) for GLE/PIB option [ 37 ]. The second available RWE study comparing SOF/VEL ± RBV, GLE/PIB, and SOF/DCV regimens in GT3 infected patients was made by Soria et al in a multicentre cohort of Italian patients [ 38 ]. Ninety-nine of 2082 individuals included in the study had liver cirrhosis, and despite the difference in SVR rates with 100% in 21 patients treated with GLE/PIB and 93.6% among 78 those receiving SOF/VEL ± RBV regimen, no statistical significance was demonstrated.…”

High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV‐infected patients treated in a real‐life setting

“…HCV genotype 3 has been initially considered as a difficult‐to‐treat virus, with lower responses to the first approved DAA regimens 26 . With the development of pan‐genotypic regimens (i.e., SOF/VEL, GLE/PIB), SVR12 rates have become similar in all genotypes 14,15,27‐31 …”

Resistance analysis and treatment outcomes in hepatitis C virus genotype 3‐infected patients within the Italian network VIRONET‐C

“…The addition of RBV was relevant only in SOF/DAC, while cirrhosis reduced the success rate only in SOF/VEL, and a higher baseline HCV-RNA load and male gender were the only features independently associated with lower response. 16 Considering DAA-failures, the presence of RASs is an important issue in the retreatment of GT3-infected patients particularly in those with cirrhosis. 11 For instance, GT3 was the only factor associated with low retreatment response with SOF/VEL/VOX, in patients with cirrhosis showing lowest SVR12 rates (69%) compared to 97% in non-GT3 cirrhotic patients.…”

“…In a recent Italian large real‐life setting of HCVGT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable and similar across groups: 94.8% in SOF/DAC, 97.6% in SOF/VEL and 96.7% in G/P ( P = .065). The addition of RBV was relevant only in SOF/DAC, while cirrhosis reduced the success rate only in SOF/VEL, and a higher baseline HCV‐RNA load and male gender were the only features independently associated with lower response 16 …”