Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion.
OBJECTIVE
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-12beta, 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 G/G and IL-12beta -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-12beta -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-12beta -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.
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Jia-Feng
JF
Wu
Tzee-Chung
TC
Wu
Chien-Hung
CH
Chen
Yen-Hsuan
YH
Ni
Huey-Ling
HL
Chen
Hong-Yuan
HY
Hsu
Mei-Hwei
MH
Chang
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics*; D053762:Interleukin-12 Subunit p40 / Q000097:blood* / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019562:Viral Load; D055815:Young Adult
D006513:Hepatitis B e Antigens; C508609:IL10 protein, human; C508598:IL4 protein, human; D053762:Interleukin-12 Subunit p40; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma