Chronic hepatitis C: current status of the issue, epidemiological trends, and clinical outcomes in the era of directacting antiviral therapy (a systematic review and meta-analysis)

Abstract

The paper aims to present a comprehensive analysis of the global burden of chronic hepatitis C (CHC) and assess the evolution of epidemiological indicators, the efficacy and safety of modern direct-acting antiviral (DAA) regimens, and long-term clinical outcomes over the period 2021–2026. Materials and Methods. A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. The search was performed in the PubMed, Embase, Scopus, Cochrane Library, and Google Scholar databases for the period from January 1, 2021 to March 1, 2026. Reports from the World Health Organization (WHO), data from the Polaris Observatory, and the EASL and AASLD registries were additionally included. Of the 2,486 records initially identified, 147 studies (population-based cohorts, randomized controlled trials (RCTs), systematic reviews, and meta-analyses) were included in the final analysis after screening. Random-effects models were used for quantitative synthesis, and heterogeneity was assessed using I². Results. The global prevalence of hepatitis C virus (HCV) infection declined from 1.0% (2015) to 0.7% (2024); however, the absolute number of infected individuals remains at 50-56 million. The highest concentration of infection persists in Eastern Europe, Central Asia, and sub-Saharan Africa. Sustained virologic response at 12 weeks after the end of therapy (SVR12) with pangenotypic regimens (sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) exceeds 96% in the general population, 94% in patients with compensated cirrhosis, and 88% in decompensated cirrhosis (portal-invasive regimens). The rate of virologic failure is associated with baseline NS5A-Y93H resistance mutations (OR 4.5; 95% CI 2.9-7.0) and prior interferon-based therapy experience. Achieving SVR reduces the risk of hepatocellular carcinoma (HCC) by 72% (RR 0.28; 0.22-0.35), but does not eliminate it entirely: the cumulative 5-year incidence of HCC after SVR is 2.1% in the general cohort and 4.8% in patients with cirrhosis. The implementation of elimination programs, including simplified treatment regimens and decentralized screening, led to a 34% increase in treatment coverage in 2021–2025; however, the WHO's global goal of HCV elimination by 2030 has been achieved in only 11 of the 102 countries analyzed. Conclusions. CHC remains a significant medical and social problem despite the high efficacy of DAAs. The main barriers to elimination are insufficient screening coverage, late diagnosis, and limited access to therapy in low-income countries. A personalized approach that accounts for HCC risk factors and drug resistance, along with the expansion of simplified care models, could accelerate progress toward achieving global targets.