Serum Levels of Interleukin-10 and Interleukin-12 Predict Early, Spontaneous Hepatitis B Virus e Antigen Seroconversion

BACKGROUND & AIMS: This prospective cohort study aimed to determine the effect of cytokines on spontaneous hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B virus (HBV) infection. METHODS: Polymorphisms in interleukin (IL)-2, IL-4, IL-10, IL-12 beta, and interferon-gamma were evaluated in 288 HBeAg-positive chronic HBV patients (median initial age, 8.6 years; median follow-up duration, 19.3 years). Serum cytokine levels were determined in 154 subjects (53.5%) before and after HBeAg seroconversion by enzyme-linked immunosorbent assay analysis. Peripheral blood mononuclear cells (PBMC) were isolated from patients with chronic HBV infection and Stimulated with HBV core antigen (HBcAg); data on cytokine genotypes and phenotypes were compared. RESULTS: The IL-10-1082 GIG and IL-12 beta -10993C/G genotypes predicted early) spontaneous HBeAg seroconversion (hazard ratio [HRs] = 3.43 and 1.54; P < .001, and P < .004, respectively), based on multivariate survival analysis. The IL-10 -1082 GIG genotype was associated with higher serum levels of IL-10 and IL-12, the IL-12 beta-10993 C/G genotype predicted higher levels OF IL-12 secretion by PBMC after in vitro HBcAg stimulation (P = .04). Higher levels of serum IL-12 (>45 pg/mL) and IL-10 (>70 pg/mL) were associated with early, spontaneous HBeAg seroconversion (HR = 1.52 and 1.48; P = .04 and .02, respectively), CONCLUSIONS: The IL-10-1082 GIG is associated with higher serum IL-10 and IL-12 levels and IL-12 beta -10993 C/G is associated with increased secretion of IL-12 in response to HBcAg stimulation of PBMC. Both genotypes are associated with early, spontaneous HBeAg seroconversion. Higher serum levels of IL-10 and IL-12 in HBeAg-positive patients are correlated with early, spontaneous HBeAg seroconversion.