Limitation of combination therapy of Interferon and Ribavirin for older patients with chronic hepatitis C

A new Japanese study examining the effects of combination therapy on older patients with hepatitis C found more adverse effects necessitating discontinuation of treatment, lowering of dosages, and lower long-term benefits in this age group.

The results of this study appear in the January 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.

Chronic hepatitis C virus (HCV), the most common cause of liver disease, affects approximately 300 million people worldwide. The virus was seen in the Japanese population decades before the U.S., with the result that HCV patients in Japan are 10 to 15 years older than patients in western countries. The standard treatment is combination therapy with interferon or pegylated interferon (a newer form of the drug that is thought to be more effective) and the antiviral drug ribavirin. However, this treatment tends to be associated with adverse effects that lead to either a dose reduction or discontinuation of therapy in up to 28 percent of patients.

Researchers led by Yoshiaki Iwasaki of the Department of Gastroenterology and Hepatology at Okayama University in Okayama, Japan conducted a study involving 208 HCV patients between December 2001 and July 2003. They classified the patients into three groups: younger than 50 years of age, 50 to 59 years old, and 60 years of age or older and scheduled them for 24 weeks of combination therapy with interferon and ribavirin. Of the 208 patients, 56 percent had to discontinue therapy or reduce their dosage due to adverse effects such as decreased appetite, retinal hemorrhage, and low white blood cell count and the older the patient, the more likely it was that this was the case. In addition, there was a tendency toward a lower sustained virological response (SVR, the absence of HCV for more than 6 months after completing therapy) in the older patient group.

The dose reductions and discontinuation of therapy in this study were much more frequent than in previous studies, which the researchers attribute to the more advanced age of the patients. The fact that older patients had higher rates of impaired kidney function and high blood pressure may have led to more frequent adverse effects. In addition, they note that patients were given high-dose induction therapy of standard interferon, which may render them more susceptible to adverse effects than HCV patients in western countries, where lower doses of interferon or pegylated interferon are the norm.

The results also indicated that for more than 70 percent of the patients, dose reduction and discontinuation of therapy was necessary within the first 12 weeks of therapy, which had a negative impact on SVR, especially in older patients and in cases where the doses of both drugs were reduced. Of the two drugs, reducing ribavirin during the first 12 weeks of therapy seemed to have a greater impact on SVR than reducing interferon.

"The present data demonstrated the importance of considering patient age when treating hepatitis C via combination therapy, especially for patients more than 60 years old," the authors state. "The treatment schedule should be modified, or other therapeutic modalities should be considered for older patients with chronic hepatitis C." They stress the importance of patient education and support to maximize patient compliance in completing the treatment regimen. Although the study involved only Japanese patients, it should be noted that approximately 35,000 new HCV infections occur each year in the U.S.; the proper treatment of older patients with chronic hepatitis C may therefore become an emerging problem in this country.