Chronic hepatitis C - What treatment for nonresponders to recombinant interferon-alpha?

In this paper we describe a study in which 150 patients with chronic hepatitis C virus infection who did not respond to 6 months' treatment with recombinant interferon-alpha (rIFN alpha) 3MU 3 times weekly were randomly allocated to 1 of 5 groups of 30 patients each: group A continued the same dose of rIFN alpha 3MU 3 times weekly; group B was treated with the same rIFN alpha but received a double dose (6MU 3 times weekly); group C received lymphoblastoid interferon (L-IFN) 3MU 3 times weekly; group D received natural interferon-alpha (N-IFN alpha) 3MU 3 times weekly; and group E stopped interferon-alpha therapy and did not receive any treatment. The patients were treated for a further 6 months. All patients who achieved normalisation of alanine aminotransferase (ALT) levels were followed up for at least 6 months after withdrawal of interferon therapy. A statistical analysis was carried out at the beginning and at the end of the study. The 5 groups were homogeneous. No patient discontinued therapy because of adverse effects. A biochemical response was defined as a simple normalisation of ALT levels, while a complete response was defined as normalisation of ALT levels with disappearance of serum HCV-RNA. After the additional 6-month treatment period, a biochemical response was seen in 5 (17%) patients in group A, 9 (30%) in group B, 6 (20%) in group C and 7 (23%) in group D (none in group E). A complete response was seen in 2 (7%) patients in group A, 5 (17%) in group B and 3 (10%) each in groups C and D (none in group E). At the end of the treatment-free follow-up period, 8 (7%) of 120 treated patients and 3 (10%) controls had a biochemical response, while 5 (3%) patients, all in the treated groups, also had undetectable serum HCV-RNA, without a statistically significant difference among the 4 treatment groups and between the type of response (biochemical or complete). A higher dose of rIFN alpha given for a longer period produced the best results, but there was no statisically significant difference between the double-dose rIFN alpha, N-IFN alpha, L-IFN and control groups, Therefore it can be concluded that there is no really satisfactory treatment for patients who do not respond to a course of rIFN alpha therapy, even if in our study a second course of double-dosed rIFN alpha seemed to be the most advantageous therapeutic protocol.