Response to interferon therapy: influence of human leucocyte antigen alleles in patients with chronic hepatitis C

Abstract

The response to interferon (IFN) therapy in patients with chronic hepatitis C is characterized by normalization of the serum alanine aminotransferase (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. The aim of this study was to examine host factors, namely the genetically determined human leucocyte antigen (HLA) class II alleles, in patients with chronic hepatitis C, and their relationship to the response to IFN therapy. Seventy white patients with chronic hepatitis C, treated with IFN-alpha for 6 months, were enrolled in the study. Serum ALT was measured at the end of treatment to assess short-term response and again 6 months post-treatment to assess sustained response. Sequence-specific primers were used in the polymerase chain reaction (PCR) to amplify genomic DNA isolated from peripheral mononuclear cells. HLA class II alleles were determined by analysis of the amplicon by gel electrophoresis 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 normalization of ALT. The frequency of the allele DRB1*0404 was significantly 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 class II alleles at the DRB1 and DQB1 loci in responders as compared with non-responders. Therefore, we conclude that the maintenance of a response to IFN in chronic hepatitis C may be, in part, determined by genetic factors in the host.

The H63D Mutation of the Hemochromatosis Gene is Associated with Sustained Virological Response in Chronic Hepatitis C Patients Treated with Interferon-Based Therapy: A Meta-Analysis

“…The precise role of these haplotypes, however, has yet to be elucidated (Porto et al 1998). It is interesting to note that several MHC class I and class II loci appear to contribute to SVR under interferon treatment conditions (Puppo et al 1995;Miyaguchi et al 1997;Almarri et al 1998;Kikuchi et al 1998;Sim et al 1998;Thursz et al 1999). In addition, some genes for the interferon regulatory factors, such as IRF4, located in the same chromosomal region and not very far from the HFE gene, may also contribute to this phenotype (Lebray et al 2004).…”

A comparative review of HLA associations with hepatitis B and C viral infections across global populations

“…Also, HLA class Ⅱ does not influence response to interferon treatment in this population [87] . HLA DRB1*0404 is associated with responsiveness in the HCV infected Caucasian population [88] . Piekarsha et al [89] did not find any association of HLA DRB1* alleles with response to Interferon alpha 2b treatment of Polish HCV subjects, but in other populations these alleles are reported to influence the response (Table 9).…”

Host genetic determinants in hepatitis C virus infection

“…While the Kikuchi study examined Japanese patients, the Sim paper studied Caucasians from Canada. 73,82 Both studies defined response based on biochemical parameters. Geographic variations in viral genotype also exist, with genotype 1 predominating in North American countries such as Canada, and genotypes 2 and 6, in addition to genotype 1, also existing in parts of eastern Asia, and it is possible that viral genotypic differences may mask host genetic associations.…”