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 5alpha 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 > or =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).


CONCLUSIONS
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.
Wu
Jia-Feng
JF
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Tsai
Wen-Yu
WY
Hsu
Hong-Yuan
HY
Ni
Yen-Hsuan
YH
Chen
Huey-Ling
HL
Tsuei
Daw-Jen
DJ
Chang
Mei-Hwei
MH
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D005091:Exons; D005500:Follow-Up Studies; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011627:Puberty / Q000097:blood*; D011944:Receptors, Androgen / Q000235:genetics; D018570:Risk Assessment; D013624:Taiwan; D013739:Testosterone / Q000097:blood*; D013997:Time Factors; D018911:Trinucleotide Repeats; D019562:Viral Load; D055815:Young Adult
C410798:AR protein, human; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D011944:Receptors, Androgen; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000410:Alanine Transaminase