Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Gastroenterology. 2010 Mar;138(3):942-8.e1. doi: 10.1053/j.gastro.2009.11.051. Epub 2009 Dec 4.
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.
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.
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).
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.
乙型肝炎病毒（HBV）相关肝病中男性优势是一个显著的现象。本研究阐明了青春期对男孩自发性乙型肝炎病毒 e 抗原（HBeAg）血清学转换的影响。
从我们长期随访的队列中随机选择了 100 名年龄小于 10 岁时被诊断为慢性 HBV 感染的 HBeAg 阳性男性，这些患者随访时间超过 10 年。测定了血清睾酮水平、雄激素受体外显子 1 CAG 重复数和类固醇 5α 还原酶 II（SRD5A2，缬氨酸对亮氨酸等位基因）多态性。还分析了连续的临床数据、HBV 基因型和自发性 HBeAg 血清学转换年龄。
72 例患者在随访期间自发发生 HBeAg 血清学转换。15 岁时血清睾酮水平≥2.5ng/mL（早发性青春期，n=87）的患者 HBeAg 血清学转换更早（中位年龄 13.2 岁比 22.5 岁；风险比=2.95；P=0.005），HBeAg 阳性时的丙氨酸氨基转移酶峰值更高（305.7±372.7IU/L 比 154.8±126.0IU/L；P=0.006），10 至 20 岁时 HBV 病毒载量下降更多（1.6±2.4log10 拷贝/mL 比 0.2±1.4log10 拷贝/mL；P=0.009），而血清睾酮水平<2.5ng/mL（晚发性青春期，n=13）的患者则不然。SRD5A2 V89L 多态性的缬氨酸等位基因携带者也与自发性 HBeAg 血清学转换更早（中位年龄 11.7 岁比 18.7 岁；风险比=1.88；P=0.028）相关。
早发性青春期和增加的 SRD5A2 酶活性与慢性 HBV 感染男性的 HBeAg 血清学转换更早、血清丙氨酸氨基转移酶水平更高以及 HBV 病毒载量下降更多有关。
