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Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen,  Hong-Yuan Hsu, Mei-Hwei Chang

Androgen Factors on Spontaneous HBeAg Seroconversion and HBV Viral Load Pattern in Men -A Long-Term Prospective Cohort Study in Taiwan. Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen,  Hong-Yuan Hsu, Mei-Hwei Chang Department of Pediatrics, National Taiwan University Hospital 2009/09/26.

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Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen,  Hong-Yuan Hsu, Mei-Hwei Chang

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  1. Androgen Factors on Spontaneous HBeAg Seroconversion and HBV Viral Load Pattern in Men -A Long-Term Prospective Cohort Study in Taiwan Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen,  Hong-Yuan Hsu, Mei-Hwei Chang Department of Pediatrics, National Taiwan University Hospital 2009/09/26

  2. Background ♠ HBeAg seroconversion is considered as an important indicator of subsidence of disease activity and decrease of active viral replication. Hepatology 1986; 6: 167-72 ♠ During the course of chronic HBV infection, persistent HBeAg is regarded as an important risk factor of hepatocellular carcinoma. (HBeAg(+) > 30y/o with OR 6.27 as compared with HBeAg(-) B carrier) N Engl J Med 2002; 347: 168-74.

  3. Background and Aims • Male predominance was a remarkable phenomenon in HBV related liver disease. • Difference between males and females, especially the androgen related factors, may be candidate host factors to make the difference. Cancer 1999;86:1143-1150 Hepatology 1995;22:1027-1033 • Aims: To determine the effects of androgen related factors on spontaneous HBeAg seroconversion in chronic HBV infected men.

  4. Methods • 100 HBeAg-positive male subjects with chronic HBV infection under 10 years of age and followed in our institute for more than 10 years were included. -Serial serum testosterone levels (10-, 15-, and 20-years of age) assessed by Immunoassay -Serial HBV viral load (10-, 15-, and 20-years of age) by real-time PCR J Hepatol 2004;41:659-666. - HBV genotyping by melting temperature curve analysis -HBV seromarker and serum aminotransferase levels determined every 3-6 months

  5. Methods Genomic DNA extraction: PUREGENE kit -Androgen receptor (AR) exon-1 CAG repeat number *The fewer the CAG repeat number imply the stronger the AR potency in mediating the androgen signal. J Nat Cancer Inst 2000;92:2023-2028 -Steroid 5 alpha-reductase type II (SRD5A2) V89L polymorphism (by RFLP) *Type II steroid 5α-reductase is responsible for the conversion of testosterone to more potent androgen. *V allele carriers at the SRD5A2 V89L SNP sites have higher enzyme activity. J Nat Cancer Inst 2002;93:1644-1651

  6. Definition of Puberty Onset in this study Subjects (n=13) with serum testosterone less than 2.5 ng/mL (one SD below mean) at 15 years of age are grouped as later-onset of puberty, while others (n=87) as earlier-onset of puberty group.

  7. Earlier- vs. Later-puberty onset By student’s t test Subjects with earlier–onset of puberty were associated with higher peak ALT and more HBV viral load decrement from puberty to young adulthood (10 to 20 years of age).

  8. Earlier puberty onset and higher SRD5A2 activity predict earlier HBeAg Seroconversion Cox’s survival analysis adjusted by HBV genotype and viral load at baseline AR exon-1 CAG repeat number is insignificant (P>0.05) in the survival analysis.

  9. HBeAg Seroconversion Age • Subjects with earlier-onset of puberty had spontaneous HBeAg seroconversion age younger than those with later-onset of puberty (median age, 13.2 vs. 22.5 years, P, 0.005) • Subjects with VV and VL genotype at SRD5A2 V89L polymorphism site were associated with earlier spontaneous HBeAg seroconversion (median age, 11.7 years) than those with LL genotype (median age, 18.7 years) (P, 0.03)

  10. Discussions • Higher serum testosterone levels at adolescence suggests an earlier onset of puberty in men, and have higher cumulative testosterone exposure before the serum androgen level begin to decline (3rd decade of life). Hormone Res 2004;62:110-114 • The correlations between serum testosterone levels and elevated ALT levels is similar to the hepatitis induced by use of anabolic androgenic steroid. • Elevation of ALT also indicate the breakthrough of host immune tolerance.

  11. Limitations • In this study, only the effects of androgen related factors from the puberty to young adulthood in men were investigated. • Other host, viral, and environmental factors need further investigations to clarify their effects on the course of chronic HBV infection.

  12. Conclusion • Earlier-onset of puberty and increased SRD5A2 enzyme activity are associated with earlier HBeAg seroconversion age, higher serum ALT levels before spontaneous HBeAg seroconversion, and more HBV viral load decrement from puberty to young adulthood in chronic HBV infected men.

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