Diseases (Apr 2025)

Efficacy and Safety of Adding Ribavirin to Sofosbuvir-Based Direct-Acting Antivirals (DAAs) in Re-Treating Non-Genotype 1 Hepatitis C—A Systematic Review and Meta-Analysis

  • Shahd Hamran,
  • Amani A. Al-Rajhi,
  • Kawthar Jasim,
  • Majed A. Al-Theyab,
  • Mohamed Elahtam,
  • Mooza K. Al-Hail,
  • Wadha Al-Fahaidi,
  • Yaman A. Khamis,
  • Yara Dweidri,
  • Abdel-Naser Elzouki,
  • Tawanda Chivese

DOI
https://doi.org/10.3390/diseases13050138
Journal volume & issue
Vol. 13, no. 5
p. 138

Abstract

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Background: There is still debate whether ribavirin should be added to direct-acting antivirals (DAAs) for the management of treatment-experienced individuals with non-genotype-1 hepatitis C. This study compared the efficacy and safety of adding ribavirin to sofosbuvir-based combinations compared to sofosbuvir-based regimens alone in treating non-genotype 1 hepatitis C virus (HCV) in individuals who have been previously treated. Methods: We searched Cochrane CENTRAL, PubMed, SCOPUS, CINAHL and preprint databases from inception to September 2023 for randomized controlled trials (RCTs) that compared sofosbuvir-based regimens with ribavirin to sofosbuvir-based regimens alone in previously treated individuals with non-genotype 1 HCV infection. Data extraction and quality of study assessments were performed by two independent authors, and synthesis was performed using bias-adjusted models, heterogeneity using I2, and publication bias using funnel plots. Results: Eight RCTs compared sofosbuvir-based combinations with and without ribavirin were included. Overall, the addition of ribavirin to sofosbuvir, compared to sofosbuvir alone, did not show a benefit in achieving sustained virological response (SVR) (OR 0.91, 95% CI 0.26–3.17, I2 = 70.0%) with moderate certainty in Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence. In subgroup analysis, there was no benefit of adding ribavirin to sofosbuvir in individuals with non-genotype 1 HCV. The additional ribavirin was associated with increased adverse events (OR 2.03, 95% CI 1.58–2.6, I2 = 8.0%) and treatment discontinuation (OR 1.81, 95% CI 0.78–4.28, I2 = 0.0%). Conclusions: The moderate certainty evidence suggests that adding ribavirin to sofosbuvir-based regimens may not confer benefit in achieving SVR in previously treated individuals with non-genotype 1 HCV but increases the odds of adverse events and treatment discontinuation. More evidence is needed on the effect of additional ribavirin in achieving SVR in individuals with decompensated cirrhosis. Registration: The protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022368868).

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