Nonresponse to treatment for hepatitis C: current management strategies.

Chronic hepatitis C affects >170 million people worldwide, causing cirrhosis and liver cancer in a sizeable proportion of patients. Substantial progress has been made in the treatment of chronic hepatitis C. More than 50% of patients can achieve sustained virological response after 24-48 weeks of interferon and ribavirin combination therapy, making chronic hepatitis C a potentially curable disease. However, a large proportion of patients with chronic hepatitis C do not clear the virus after current standard therapy. Hepatitis C virus develops two pathways to counteract the antiviral effect of interferon. Some chronic hepatitis C patients may have a virus that is more resistant to interferon therapy, while other patients appear to have defective immune responses or poor tolerance or compliance to interferon-based antiviral therapy. The possible strategies to improve antiviral efficiency in these nonresponders are to increase the dosage, prolong the duration of treatment and improve the compliance of patients. A total of 6-15% of prior nonresponders to standard interferon plus ribavirin therapy will respond to re-treatment with peginterferon plus ribavirin, while 32-50% of patients who have relapsed will respond to re-treatment. New small molecules are under development to treat chronic hepatitis C and may be important particularly in the treatment of prior nonresponders to current standard therapy.