Contemporary Insights into Hepatitis C Virus: A Comprehensive Review

Abstract

Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.

Keywords: HCV; drug resistance; genotype; hepatology; prevention; viral hepatitis; virology.

Figure 1

The evolutionary history of HCV genotypes (GTs) based on (Sallam, 2017) [66]. The phylogeny was constructed using the neighbor-joining (NJ) method with bootstrap test for evaluation of topology (1000 replicates). Internal branches with bootstrap values ≥ 0.9 are highlighted in black. The evolutionary distances were computed using the TN93 method. The rate variation among sites was modelled with a gamma distribution (shape parameter = 4). The analysis involved 147 NS5B sequences (1495 bases) downloaded from the Los Alamos Hepatitis C sequence and immunology databases (https://hcv.lanl.gov/content/index, accessed on 30 April 2024). Evolutionary analyses were conducted in MEGA6 [68].

Figure 2

Schematic illustration of HCV genome and polyprotein. The nucleotide positions are in accordance with strain H77 numbering (GenBank accession number: AF009606) based on (Sallam, 2017) [66].

Figure 3

The prevalence of HCV per country based on the Polaris Observatory data [174]. The map was generated in Microsoft Excel, powered by Bing, © Australian Bureau of Statistics, GeoNames, Microsoft, Navinfo, Open Places, OpenStreetMapTomTom, Zenrin. The map of Australia was generated by an older version of Microsoft Excel, powered by Bing, © GeoNames, Microsoft, Navinfo, TomTom, Wikipedia. We are neutral with regard to jurisdictional claims in this map.