Chronic hepatitis C

Abstract

The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma.

Keywords: Chronic hepatitis C; Therapeutics; Virology.

Fig. 1

Geographic distribution of hepatitis C infection worldwide, 2007 (Data from International Travel and Health [Internet]. Geneva: World Health Organization; 2007 [cited 2009 Mar 11]. Available from: http://www.who.int/ith/maps/hepatitisc2007.jpg).

Fig. 2

Hepatitis C virus (HCV) sequences have been classified into six major genotypes with approximately 65% sequence identity. Within each genotype, sequences are further classified into subtypes with 78% sequence identity. Different isolates within the same subtype share 91% to 99% sequence identity. Within a host, HCV particles circulate as a population of very closely related, but not identical, variants referred to as quasispecies. Genotypes are denoted by numbers (1-6), and subgenotypes are denoted by lower case letters (Adapted from Fishman SL, et al. Infect Genet Evol 2009;9:1158-1167).

Fig. 3

Genomic structure of hepatitis C virus (HCV). HCV is a plus-stranded RNA virus. The total viral protein is 3011 amino acids (aa) in length. It consists of structural and nonstructural proteins processed from a single polyprotein by host and viral proteases.

Fig. 4

Molecular processes that signal the host response to hepatitis C virus infection (Adapted from Gale M Jr, et al. Nature 2005;436:939-945).

Fig. 5

Percentage of sustained virologic response (SVR) by rs12979860 genotypes (Adapted from Ge D, et al . Nature 2009; 461:399-401).

Fig. 6

Graphic display of virological responses (Adapted from AASLD Practice Guideline: Diagnosis, Management, and Treatment of Hepatitis C. An Update).

Fig. 7

Rates of viral clearance predict sustained virologic response in patients with PEG-RBV treatment (Adapted from Ferenci P, et al. J Hepatol 2005;43:425-433).

Fig. 8

End-of-treatment and sustained virological responses in patients with a rapid virological response (undetectable HCV RNA) at week 4. The number of patients in each group is presented at the base of each bar (Adapted from Jensen DM, et al. Hepatology 2006;43:954-960). LD, low dose; SD, standard dose.

Fig. 9

Treatment algorithm for the management of acute hepatitis C (Adapted from Maheshwari A, et al. Clin Liver Dis 2010;14:169-176).

Fig. 10

Telaprevir increases sustained virologic response rates in patients with hepatitis C virus genotype 1 infection (Data from McHutchison JG, et al. N Engl J Med 2009;360:1827-1838).