RESPONSE TO INTERFERON THERAPY - INFLUENCE OF HUMAN-LEUKOCYTE ANTIGENALLELES IN PATIENTS WITH CHRONIC HEPATITIS-C

The response to interferon (IFN) therapy in patients with chronic hepa titis C is characterized by normalization bf the serum alanine aminotr ansferase (ALT) activity during treatment, but relapse within 6 months of cessation of therapy is common. Viral characteristics, such as the genotype and viral load, may influence the patient response to IFN, T he aim of this study was to examine host factors, namely the genetical ly determined human leucocyte antigen (HLA) class II alleles, in patie nts with chronic hepatitis C, and their relationship to the response t o IFN therapy. Seventy white patients with chronic hepatitis C, treate d with IFN-c( for 6 months, were enrolled in the study, Serum ALT was measured at the end of treatment to assess short-term response and aga in 6 months post-treatment to assess sustained response. Sequence-spec ific primers were used in the polymerase chain reaction (PCR) to ampli fy genomic DNA isolated from peripheral mononuclear cells, HLA class I I alleles were determined by analysis of the amplicon by gel electroph oresis and hybridization of sequence-specific oligonucleotide probes. At the end of treatment, 25 of the 70 patients (36%) had a normal ALT. By 6 months post-treatment, only six patients (9%) had a sustained no rmalization of ALT The frequency of the allele DRB10404 was significa ntly higher in patients with a sustained response as compared to those lacking such a response (25.0% vs 2.3%, with a Bonferonni-corrected P -value of 0.019), There was no difference in the frequency of other cl ass II alleles at the DRB1 and DQB1 loci in responders as compared wit h non-responders. Therefore, we conclude that the maintenance of a res ponse to IFN in chronic hepatitis C may be, in part, determined by gen etic factors in the host.