Hepatitis C virus (HCV) infection is the major etiology of chronic liver disease, liver cirrhosis, and hepatocellular carcinoma. According to an estimate from the World Health Organization, there are more than 180 million chronic HCV-infected persons worldwide; hence, effective treatment of chronic hepatitis C (CHC) is important. Nevertheless, the current standard of care for CHC using pegylated (Peg) IFN plus ribavirin is expensive, is effective in only a certain proportion of patients who have CHC, and has many unpleasant adverse effects. Therefore, identifying predictive factors of therapeutical response in patients with CHC is important.
Several factors have been linked to the therapeutical response of patients who have CHC, including viral factors, host factors, metabolic factors, histological factors, types of regimens, and duration of infection. Among these factors, viral kinetics following antiviral therapy has become widely accepted in both clinical trials and daily practice and is increasingly recognized as the most outweighing predictor of sustained virological response (SVR) to IFN-based therapy.
Pharmacotherapeutic success is evaluated based on viral RNA negativity 24 weeks after completion of the treatment, which is defined as a sustained virological response (SVR). Only 40-50% of patients infected with HCV genotype 1 (HCV-1) had SVR after 48 weeks of treatment, whereas 75% of patients infected with HCV genotypes 2 or 3 (HCV-2/ 3) typically achieved SVR after 24 weeks of therapy. In HCV-1 cases, additional treatment with protease inhibitors (PI) has improved the SVR rate to about 80%.
Recently, it has been documented that there was a strong association of two SNPs of the IL28B gene encoding IFN-λ-3, with treatment outcomes of Peg-IFNα-2a plus ribavirin therapy. These variations in the IL28B gene correlated well with natural clearance of HCV and with SVR, and they may explain the difference in treatment response rates among African-Americans, Europeans, and Asians.
