Efficacy and safety of adding ribavirin to direct-acting antivirals (DAAs) in re-treating non-genotype1 hepatitis C- a systematic review and meta-analysis.

Shahd Hamran; Amani Al-Rajhi; Kawther Jasim; Majed Al-Theyab; Mohamed Elahtam; Mooza Al-Hail; Wadha Al-fahaidi; Yaman Khamis; Abdel-Naser Elzouki; Tawanda Chivese

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Efficacy and safety of adding ribavirin to direct-acting antivirals (DAAs) in re-treating non-genotype1 hepatitis C- a systematic review and meta-analysis.

Shahd Hamran

^{1, 2},

Amani A. Al-Rajhi

¹,

Kawther Jasim

³,

Majed A, Al-Theyab

¹,

Mohamed Elahtam

¹,

Mooza K. Al-Hail

¹,

Wadha Al-fahaidi

¹,

Yaman Khamis

¹,

Abdel-Naser Elzouki

⁴,

Tawanda Chivese

^{*

5}

¹ College of Medicine, QU Health, Qatar University, Doha, Qatar
² Hamad Medical Corporation, Doha, Qatar
³ College of Dental medicine, QU Health, Qatar university, Doha, Qatar
⁴ Internal Medicine, Hamad Medical Corporation, Doha, Qatar
⁵ School of Interdisciplinary Arts and Sciences, University of Washington Tacoma, Washington, USA

Academic Editor: Omar Cauli

Published: 04 September 2025 by MDPI in The 1st International Online Conference on Diseases session Infectious Diseases

Abstract:

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 HCV in individuals who have been previously treated. 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 done by two independent authors and synthesis using bias-adjusted models, heterogeneity using I2, and publication bias using funnel plots. Eight RCTs, which compared sofosbuvir-based combinations with and without ribavirin were included. Overall, the addition of ribavirin to sofosbuvir, compared to sofosbuvir alone, did not show benefit in achieving sustained virological response (SVR) (OR 0.91, 95% CI 0.26-3.17, I2 = 70.0%) with moderate certainty GRADE evidence. In subgroup analysis, there was no benefit of adding ribavirin to sofosbuvir in individuals with different HCV genotypes. The additional ribavirin showed increased odds of developing adverse events (OR 2.03, 95%CI 1.58-2.6, I 2 = 8.0%) and treatment discontinuation (OR 1.81, 95%CI 0.78-4.28, I 2 = 0.0%). 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).

Keywords: Hepatitis C virus (HCV); Ribavirin (RBV); Direct-acting Antivirals (DAAs); HCV genotype; Sustained virological response (SVR); Systematic review and meta-analysis.

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