Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

Chronically hepatitis C virus (HCV) infects about 180 million people worldwide and it is a major cause of serious liver disease. As sustained virological response (SVR) to anti-HCV therapy avoids progression of liver fibrosis, decreases the risk of hepatocellular carcinoma and improve the survival of patients, antiviral therapy is considered as a crucial option in the management of chronic HCV infection. After approval of boceprevir and telaprevir, the standard of care treatment for genotype-1 infection is now peginterferon plus ribavirin and a protease inhibitor. However, in the area where these direct-acting antiviral agents are not available, combination therapy with peginterferon plus ribavirin has still become the standard of care in the treatment of patients with chronic hepatitis C virus infection. Although ribavirin has only a transient effect on HCV clearance in the absence of interferon, it greatly enhances SVR rate when given in combination with interferon alfa. Ribavirin significantly accelerates the second/third phase of HCV clearance in patients treated with peginterferon, and combination therapy with peginterferon and ribavirin enhances the rates of early virological response (EVR), end of treatment response (ETR), and SVR relative to that with peginterferon alone. The causes for ribavirin dose reduction are anemia, fatigue, rash, depression, anxiety, confusion or insomnia, etc. Anemia is a frequent complication of peginterferon plus ribavirin therapy for which ribavirin dose reduction is the primary management strategy. However, lower SVR rates have been reported in patients who undergo ribavirin dose reduction. Therefore, many clinicians have concerns to improve anemia related symptoms while maintaining ribavirin dose. Hematologic toxicities of ribavirin with subsequent ribavirin dose reduction may impair response to combination therapy. Reduced ribavirin exposure may be correlated with increased rates of relapse. Combination therapy yields SVR in approximately 40-45% of patients with HCV genotype 1 and 80% of patients with genotype 2 or 3. Even in genotype 1 patients, SVR occurs more frequently in patients who are able to maintain near full doses of these medications and is reduced substantially in patients who require reduction in the doses of these medications. In contrast, dose reduction does not appear to influence adversely SVR in patients with genotype 2 or 3. The genotype 1 patients who received at least 80% of their total expected cumulative dose of peginterferon and/or ribavirin for at least 80% of the planned duration of therapy (38 weeks) had SVR of 51% compared with only 34% for patients who received Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients