Hepatitis C virus: Virology, diagnosis and treatment

Abstract

More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000s, pegylated interferon plus ribavirin became the standard anti-HCV treatment. However, this therapy is not ideal. To 2014, boceprevir, telaprevir, simeprevir, sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral, interferon-free, pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these anti-viral treatments. However, not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus, an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.

Keywords: Diagnosis; Direct acting antivirals; Enzyme immunoassay; Hepatitis C virus; Hepatocellular carcinoma; Host-targeted agents; Interferon; Nucleic acid test; Sofosbuvir; Treatment.

Figure 1

The hepatitis C virus poly-protein is processed co- and posttranslationally by host and viral proteases into at least 10 different proteins, which are arranged in the order of NH2-C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH. Host signal peptidase is required for the cleavages at C-E1, E1-E2, E2-p7, and p7-NS2 junctions. NS2 cleaves the site between NS2 and NS3; NS3/4A serine protease cleaves the sites at NS3-NS4A, NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B junctions. Several new DAAs (e.g., boceprevir, simeprevir, and telaprevir) specifically designed to inhibit the NS3/4A protease are now becoming available. The wavy lines mark the un-translated regions (UTR) of hepatitis C virus genomic RNA while the rectangle represents the poly-protein derived from the long open reading frame.

Figure 2

Hepatitis C virus NS5B acts as RNA-dependent RNA polymerase and plays an important role in the synthesis of new RNA genomes. As the central component of the hepatitis C virus replication complex, NS5B has emerged as a major target for antiviral treatment. New direct acting antivirals, specifically designed to inhibit the NS5B are now becoming available (e.g., sofosbuvir).

Figure 3

Assays to detect anti-hepatitis C virus antibody, viral core antigen, and viral genomic RNA are used to diagnose HCV infection in clinical practice. HCV: Hepatitis C virus; POCT: Point-of-care test; EIA: Enzyme immuno-assay; RIBA: Recombinant immunoblot assays; RT-PCR: Reverse transcription-polymerase chain reaction; TMA: Transcription-mediated amplification; bDNA: Branched DNA.

Figure 4

Possible diagnostic results for hepatitis C virus infection. Individuals are in high risk, e.g., persons who have been exposed to HCV; persons with elevated alanine aminotransferase; persons who are immunocompromised. HCV: Hepatitis C virus.