title: Precore/core promoter mutations and hepatitis B virus genotype in hepatitis B and C dually infected patients treated with interferon-based therapy.
abstract: We studied the prevalence and distribution of precore/basal core promoter (BCP) mutations and hepatitis B virus (HBV) genotypes in HBV/hepatitis C virus (HCV) dually-infected patients, and evaluated their impact on long-term HBV response of interferon (IFN)-based therapy. The HBV genotypes and sequences of the precore/BCP regions were determined in 180 HBV/HCV dually-infected patients and were compared with 90 age, sex and hepatitis B e antigen-matched chronic hepatitis B controls. Serum HBV DNA and hepatitis B surface antigen (HBsAg) were assessed every 3-6 months after therapy with IFN or pegylated-IFN plus ribavirin in 135 dually-infected patients with active hepatitis C. Dually-infected patients had a higher prevalence of genotype C HBV (P=0.022) and a lower frequency of G1896A mutation (P=0.004) as compared with controls. Among dually-infected patients, genotype C was associated with a higher frequency of A1762T/G1764A mutation (P<0.001), but with lower HBV DNA (P<0.001) and a lower frequency of A1752T/G (P=0.008), C1799G (P<0.001) and G1896A mutation (P<0.001) than genotype B. Based on Cox proportional hazards model, young age (hazard ratio (HR)=0.952, P=0.001), sustained virological response to HCV (HR=4.638, P=0.044), C1766T mutation (HR=5.216, P=0.003) and A1846T mutation (HR=2.332, P=0.031) correlated with HBV DNA reactivation (⩾2000IU/ml) after therapy. Age (HR=1.068, P=0.020), G1896A mutation (HR=0.140, P=0.01) and A1846T mutation (HR=0.086, P=0.018) were associated with HBsAg seroclearance independently. In conclusion, specific mutations in the precore/BCP regions could be useful in predicting long-term HBV response in HBV/HCV dually-infected patients treated with IFN-based therapy.
authors: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Chao-Hung
authors: CH
authors: Hung
authors: Chien-Hung
authors: CH
authors: Chen
authors: Sheng-Nan
authors: SN
authors: Lu
authors: Jing-Houng
authors: JH
authors: Wang
authors: Tsung-Hui
authors: TH
authors: Hu
authors: Chao-Min
authors: CM
authors: Huang
authors: Ming-Chao
authors: MC
authors: Tsai
authors: Chuan-Mo
authors: CM
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000187:drug effects; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D012254:Ribavirin; D007372:Interferons