The Effects of Cytokines on Spontaneous Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B Virus Infection

• Published in: The Journal of immunology (1950) Vol. 194; no. 2; pp. 690 - 696
• Main Authors: Wu, Jia-Feng, Hsu, Hong-Yuan, Chiu, Yu-Chun, Chen, Huey-Ling, Ni, Yen-Hsuan, Chang, Mei-Hwei
• Format: Journal Article
• Language: English
• Published: United States 15.01.2015
• Subjects: Adult; Cross-Sectional Studies; Cytokines - genetics; Cytokines - immunology; Female; Follow-Up Studies; Hepatitis B e Antigens - genetics; Hepatitis B e Antigens - immunology; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B, Chronic - genetics; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - pathology; Humans; Immunity, Cellular - genetics; Male; Middle Aged; Mutation; Polymorphism, Single Nucleotide; Retrospective Studies
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1401659

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.