Treatment Outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir in Direct-Acting Antiviral-Experienced Hepatitis C Virus Patients: A Systematic Review and Meta-Analysis

Abstract

About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions (p < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.

Uncovering Novel Roles of miR-122 in the Pathophysiology of the Liver: Potential Interaction with NRF1 and E2F4 Signaling

“…This pioneering achievement proved highly effective in suppressing viral replication in individuals suffering from chronic hepatitis C virus (HCV) infections [ 53 ]. Nevertheless, the introduction of innovative and potent pharmaceutical agents for hepatitis C treatment [ 54 ] has considerably diminished the emphasis on therapeutic strategies involving miR-122 inhibition. The findings presented within this study, coupled with our recently published research [ 40 ], propose an intriguing potential physiological role for the reduction in miR-122 in response to inflammation.…”

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives

“…The main challenge with DAA treatment is resistance-associated substitution (RAS), the leading cause of DAA resistance [154][155][156]. This treatment resistance is an inevitable and intrinsic problem, as HCV is highly adaptable [154][155][156].…”

“…The main challenge with DAA treatment is resistance-associated substitution (RAS), the leading cause of DAA resistance [154][155][156]. This treatment resistance is an inevitable and intrinsic problem, as HCV is highly adaptable [154][155][156]. These mutations are due to the lack of correction of HCV polymerase, leading to base mutations for each viral replication [154][155][156].…”

“…This treatment resistance is an inevitable and intrinsic problem, as HCV is highly adaptable [154][155][156]. These mutations are due to the lack of correction of HCV polymerase, leading to base mutations for each viral replication [154][155][156]. SARs occur because of different treatment regimens, the various HCV genotypes and subtypes, and the geographic distribution.…”

Real‐life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir

“…Several real‐world studies have also evaluated SOF/VEL/VOX as a rescue therapy 7–12 . The majority of them included a small proportion of patients who had previously received SOF/VEL or GLE/PIB and were predominantly infected by GT1 HCV 13 . Even the most recent study, which assessed SOF/VEL/VOX in 746 European patients, mainly included individuals who had failed to HCV regimens not currently recommended in Europe, only 17% failed to SOF/VEL and 8% to GLE/PIB 14 .…”