Effect of Puberty Onset on Spontaneous Hepatitis B Virus e Antigen Seroconversion in Men

Background

Male predominance is a remarkable phenomenon in hepatitis B virus (HBV)−related liver disease. This study elucidated the effects of puberty on spontaneous hepatitis B virus e antigen (HBeAg) seroconversion in boys.

Methods

One-hundred HBeAg-positive chronic HBV-infected males recruited at younger than 10 years of age who had been followed for >10 years were selected randomly from our long-term followed cohort into this study. Serum testosterone levels, androgen receptor exon-1 CAG repeat number and steroid 5α reductase type II (SRD5A2, valine vs leucine alleles) polymorphism were determined. Serial clinical data, HBV genotype, and spontaneous HBeAg seroconversion age were also analyzed.

Results

Seventy-two subjects had spontaneous HBeAg seroconversion during the follow-up period. Subjects with serum testosterone levels ≥2.5 ng/mL at 15 years old (earlier-onset puberty, n = 87) had earlier HBeAg seroconversion (median age, 13.2 vs 22.5 years; hazard ratio = 2.95; P = .005), higher peak alanine aminotransferase levels when HBeAg positive (305.7 ± 372.7 vs 154.8 ± 126.0 IU/L; P = .006), and a greater HBV viral load reduction from 10 to 20 years of age (1.6 ± 2.4 vs 0.2 ± 1.4 log10 copies/mL; P = .009) than those with serum testosterone levels <2.5 ng/mL (later-onset puberty, n = 13). Valine allele carrier at the SRD5A2 V89L polymorphism was also associated with earlier spontaneous HBeAg seroconversion (median age, 11.7 vs 18.7 years; hazard ratio = 1.88; P = .028).

Conclusion

Earlier-onset puberty and increased SRD5A2 enzyme activity are associated with earlier HBeAg seroconversion, higher serum alanine aminotransferase levels, and a greater HBV viral load decrement in chronic HBV infected males.

Keywords: Hepatitis B Virus e Antigen, Puberty, Steroid 5α Reductase Type II, Testosterone

Abbreviations used in this paper: ALT, alanine aminotransferase, AR, androgen receptor, HBeAg, hepatitis B virus e antigen, HBsAg, hepatitis B virus surface antigen, HBV, hepatitis B virus, HCC, hepatocellular carcinoma, HR, hazard ratio, PCR, polymerase chain reaction, RFLP, restriction fragment length polymorphism, SD, standard deviation, SRD5A2, steroid 5 α-reductase type II