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-12β, and interferon-γ 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 G/G and IL-12β -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 G/G genotype was associated with higher serum levels of IL-10 and IL-12; the IL-12β -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 G/G is associated with higher serum IL-10 and IL-12 levels and IL-12β -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.

Abbreviations used in this paper: ALT, alanine aminotransferase, HBcAg, HBV core antigen, HBeAg, hepatitis B e antigen, HBV, hepatitis B virus, HR, hazard ratio, IL, interleukin, PBMC, peripheral blood mononuclear cells, PCR, polymerase chain reaction, SNP, single nucleotide polymorphism, Th1 and Th2, types 1 and 2 helper T lymphocyte