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. 2020 Jan 5:18:100237.
doi: 10.1016/j.eclinm.2019.12.007. eCollection 2020 Jan.

Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis

Michael J Zoratti  1   2 , Ayesha Siddiqua  2   3 , Rita E Morassut  4 , Dena Zeraatkar  2 , Roger Chou  5 , Judith van Holten  6 , Feng Xie  2 , Eric Druyts  7
Affiliations

Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis

Michael J Zoratti et al. EClinicalMedicine. .

Abstract

Background: Recent approval and adoption of pangenotypic direct acting antivirals (DAAs) necessitated a revision of the 2015 World Health Organization guidelines for the management of persons with hepatitis C virus (HCV) infection.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and relevant conference proceedings to identify randomized and non-randomized trials, as well as prospective observational studies of DAAs. The proportions of persons with events were pooled for sustained virological response at 12 weeks post-treatment (SVR12), discontinuations due to adverse events (DAEs), serious adverse events (SAEs), and all-cause mortality. Analyses were stratified by HCV genotype and antiviral treatment experience, with subgroup analyses based on presence of cirrhosis and HIV-HCV coinfection.

Findings: The evidence base consisted of 238 publications describing 142 studies. In the overall analysis, which included all persons irrespective of treatment experience or comorbidities, the pooled proportion achieving SVR12 exceeded 0.94 for all pangenotypic regimens across genotypes 1, 2, and 4. Some heterogeneity may have led to lower SVR rates in persons with genotype 3 infection. High SVR12 (>0.90) was observed in persons with genotype 1 infection with cirrhosis, though evidence varied and was limited for genotypes 2-4. Evidence was sparse for persons with HIV-HCV coinfection. All regimens were associated with small proportions of persons with DAEs, SAEs, or all-cause mortality.

Interpretation: Based on this and other supporting evidence, the WHO issued updated guidelines with a conditional recommendation, based on moderate quality evidence, for the use of pangenotypic DAA regimens for persons with chronic HCV infection aged 18 years and older (July 2018).

Funding: This study was funded by the World Health Organization.

Keywords: Direct-acting antivirals; Hepatitis C; Pangenotypic; SVR12; Systematic review.

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Conflict of interest statement

Mr. Zoratti reports that he is a shareholder of Zoratti HEOR Consulting Inc. which was contracted to conduct this study. Ms. Siddiqua reports personal fees from Zoratti HEOR Consulting Inc. during the conduct of the study. Ms. Morassut reports personal fees from Zoratti HEOR Consulting Inc. during the conduct of the study. Ms. Zeraatkar reports personal fees from Zoratti HEOR Consulting Inc. during the conduct of the study. Dr. Chou reports serving as methodologist for the World Health Organization hepatitis C guideline, during the conduct of the study and grants from Agency for Healthcare Research and Quality outside the submitted work on hepatitis C screening and treatment. Mr. Druyts reports that he is a shareholder of Pharmalytics Consulting Group Inc. (“Pharmalytics Group”), registered in the province of British Columbia, Canada, which provides consulting services to the healthcare and pharmaceutical industries. No other author has anything to disclose.

Figures

Fig 1
Fig. 1
Study selection.
Fig 2
Fig. 2
Illustration of findings from the all-comer analyses, stratified by genotype, all treatment experience.
Fig 3
Fig. 3
Illustration of findings from the analyses of persons with cirrhosis, stratified by genotype, all treatment experience.
Fig 4
Fig. 4
Illustration of findings from the analyses of persons with HIV–HCV coinfection, stratified by genotype, all treatment-experience.
Fig 5
Fig. 5
Illustration of findings from the analyses of harms, all treatment-experience.
See this image and copyright information in PMC

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