title: Mutations in the X region and core promoter are rare and have little impact on response to interferon therapy for chronic hepatitis B.
abstract: Therapy for chronic hepatitis B with interferon-alpha (IFN) may result in viral clearance and hepatitis B e seroconversion in 30-40% of patients. It is still unclear whether viral genetic variability influences response rates. However, certain core promoter mutations were recently associated with a better response to IFN. In the present study, the entire X region, including the core promoter, of hepatitis B virus (HBV) from 26 HBeAg-positive patients treated with IFN for 12 weeks, was sequenced. Serum samples pre-treatment, at end-of-treatment, and at follow-up of 18 sustained and 8 nonsustained responders were analyzed. Most patients were of European origin and had moderate aminotransferase elevation (mean 2.4 x upper limit of normal) and genotype A infection. Before treatment, 16 patients had an X region identical to a consensus sequence of the corresponding genotype; in the remaining 10 patients, a median of 1.5 mutations were found. After treatment, 1-4 new mutations (mean 1.8) had emerged in 5 patients. There was no association between specific mutations, or the number of mutations, and response to IFN. The low frequency of mutations indicates that analysis of this region is of limited clinical value and that emerging mutations in this region are not major determinants of response to treatment with IFN-alpha.
authors.affiliation: Department of Clinical Virology, Göteborg University, Göteborg, Sweden.
authors.forename: Charles
authors.initials: C
authors.lastname: Hannoun
authors.forename: Peter
authors.initials: P
authors.lastname: Horal
authors.forename: Kim
authors.initials: K
authors.lastname: Krogsgaard
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D016896:Treatment Outcome; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D016898:Interferon-alpha; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein