title: The effects of cytokines on spontaneous hepatitis B surface antigen seroconversion in chronic hepatitis B virus infection.
abstract: We examined the role of human cytokines in the natural course of hepatitis B surface Ag (HBsAg) seroconversion in chronic hepatitis B virus (HBV) infection. The clinical course of spontaneous HBsAg seroconversion was assessed in 296 chronically HBV-infected patients. Single nucleotide polymorphisms (SNPs) in IL-1β, IL-2, IL-4, IL-10, IL-12β, IL-13, IL-27, and IFN-γ genes were examined in 296 chronically HBV-infected patients and another 193 HBV recoverers. The HBsAg a determinant sequence of chronically HBV-infected subjects with and without HBsAg seroconversion was also analyzed. The start of the immune-clearance phase (serum alanine aminotransferase levels > 30 IU/l) before the age of 48 mo and hepatitis B e Ag (HBeAg) seroconversion before the age of 10 y predicted spontaneous HBsAg seroconversion in chronically HBV-infected patients (odds ratios 17.7 and 5.0; p < 0.001 and p < 0.002, respectively). The A-allele of IL-10 SNP rs1800872 was associated with higher IL-10 serum levels, and the G-allele of IL-12β SNP rs3212217 was associated with sustained high serum IL-12p70 levels during the immune-clearance phase. Both were predictors of spontaneous HBsAg seroconversion and HBV recovery (odds ratios 4.0 and 26.3; p = 0.002 and p < 0.001, respectively). Spontaneous HBsAg seroconversion was not related to sex, HBV genotype, or HBsAg a determinant mutation. The start of immune-clearance phase, age at HBeAg seroconversion, and serum IL-10 and IL-12 levels are associated with the course of the immune-clearance phase in chronic HBV infection, and are predictive of spontaneous HBsAg seroconversion and HBV recovery.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan;
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan;
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan;
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei 10041, Taiwan; and.
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan; Department of Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan.
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei 10041, Taiwan; and changmh@ntu.edu.tw.
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D016207:Cytokines; D006513:Hepatitis B e Antigens