Interferon-alpha-n1: a review of its pharmacological properties and therapeutic efficacy in the management of chronic viral hepatitis.

Interferon-alpha-n1 (lymphoblastoid interferon-alpha) is a nonrecombinant 'natural' interferon derived from lymphoblastoid cells exposed to Sendai virus. In common with endogenous and recombinant interferon-alpha molecules, interferon-alpha-n1 has antiviral, immunomodulatory and antiproliferative properties. Interferon-alpha-n1 shows some efficacy in immunocompetent adults with well-compensated chronic viral hepatitis B. Rates of complete virological response (defined as an absence of detectable hepatitis B virus-DNA in the serum) ranged from 5 to 79% of adults who received various dosage regimens of interferon-alpha-n1 in monotherapy trials. Clearance of hepatitis B 'e' antigen was reported in 5 to 70% of patients treated with the drug. Spontaneous virological responses occurred in 0 to 48% of untreated patients. The clinical efficacy of interferon-alpha-n1 in patients with chronic hepatitis B is not improved by concomitantly administered deflazacort, zidovudine or levamisole, but may be increased by a course of corticosteroid pretreatment in some patients. Interferon-alpha-n1 also shows therapeutic benefit in adults with chronic hepatitis C. Complete biochemical responses (defined as normalisation of serum ALT levels) were achieved in 27 to 60% of adult patients treated with the drug, whereas spontaneous normalisation of serum ALT levels occurred in up to 11% of untreated patients. Responses to interferon-alpha-n1 were temporary in 27 to 78% of treatment responders but were sustained in 6 to 40% of patients. Emerging data delineating baseline factors predictive of a positive response to interferon-alpha-n1 treatment may aid in the selection of patients with hepatitis B or C most likely to benefit from treatment with this drug. Most patients receiving interferon-alpha-n1 experience a transient 'influenza-like' syndrome during the first week of treatment. The syndrome, which is dose related and alleviated by paracetamol (acetaminophen), is characterised by fever, chills, and arthralgia. Dose-limiting adverse effects occurring during longer term interferon-alpha-n1 therapy include fatigue, myalgia, headache, depression, pruritus and seizures. Neutropenia and thrombocytopenia may also occur during interferon-alpha-n1 treatment. Autoimmune thyroid disease may develop in up to 9% of patients treated with interferon-alpha-n1 for >or=6 months. At present, interferon-alpha-n1 and the recombinant forms of interferon-alpha are the only drugs available for the treatment of adults with well-compensated hepatitis B or C. Interferon-alpha-n1 produces moderate response rates in adults with well-compensated chronic hepatitis B or C. Thus, it is positioned alongside recombinant interferon-alpha products as a useful first-line treatment option for patients with chronic hepatitis B or C.