Interferon-alpha-2a: a review of its use in chronic hepatitis C.
Interferon-alpha-2a, a single interferon-alpha subtype manufactured by use of recombinant DNA technology, has immmunomodulatory, antiviral and antiproliferative properties. It is a beneficial treatment for about 30% of patients with well-compensated chronic hepatitis C. Biochemical responses [defined as normalisation of serum alanine aminotransferase (ALT) levels] are achieved in 37 to 76% of patients at the end of treatment with interferon-alpha-2a at dosages of 3 to 6MU 3 times weekly (given intramuscularly or subcutaneously) for 6 to 12 months. In contrast, evidence of disease remission is seldom observed in untreated patients. Improvements in liver histology in patients receiving interferon-alpha-2a are associated with complete biochemical responses to the drug. Virological responses (defined as an absence of hepatitis C-RNA in the serum) occur in up to 86% of patients after treatment with interferon-alpha-2a 3 to 6MU 3 times weekly for 12 months. After cessation of interferon-alpha-2a therapy, a considerable proportion of treatment responders experience disease reactivation. Rates of sustained biochemical response are generally higher after 12 months' therapy (27 to 57%) than after 6-month courses of treatment (27 to 30%). The long term efficacy of interferon-alpha-2a in patients with chronic hepatitis C is improved by the concomitant administration of ribavirin. Interferon-alpha-2a shows efficacy similar to that of interferon-alpha-2b or interferon-alpha-n1 in patients with chronic hepatitis C. During the first few days of therapy with interferon-alpha-2a (or other forms of interferon-alpha), most patients experience a transient 'influenza-like' reaction, characterised by fatigue, fever, chills and headache. These symptoms are usually alleviated by paracetamol (acetaminophen). Lethargy, mild myelosuppression, alopecia and neuropsychiatric symptoms are dose-limiting adverse effects that may occur during longer term therapy. Severe adverse effects, experienced by <2% of interferon-alpha-2a recipients, include severe depression, seizures and generalised bacterial infections. Autoimmune thyroid dysfunction develops in 3 to 12% of patients during treatment with interferon-alpha-2a. Conclusion. Interferon-alpha-2a produces sustained responses in about 30% of adults with chronic hepatitis C. Its efficacy appears to be similar to that of other interferon-alpha products. Thus, the drug remains a useful first-line treatment option for adults with well-compensated chronic hepatitis C. Further research into the optimal dosage of interferon-alpha-2a and its role in combination with other agents is likely to contribute towards future advances in the management of chronic hepatitis C.
Perry
C M
CM
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Wilde
M I
MI