SUMMARY: Boys with chronic hepatitis B virus (HBV) infection may experience hepatitis B "e" antigen (HBeAg) seroconversion and see a reduction in HBV DNA levels when they reach puberty, according to a study published in the March 2010 issue of Gastroenterology. These findings shed further light on sex differences in the natural history of hepatitis B.

By Liz Highleyman

Given that male predominance is a "remarkable phenomenon" in HBV-related liver disease, J.F. Wu and colleagues from the National Taiwan University Hospital in Taipei sought to determine the effects of puberty on spontaneous (without treatment) HBeAg seroconversion in boys.

It has long been recognized that women with chronic viral hepatitis tend to experience slower and milder liver disease progression than men. This might be due to protective effects of the female sex hormone estrogen or detrimental effects of the male hormone testosterone.

The study included 100 initially HBeAg positive male children with chronic HBV infection who were recruited when they were less than 10 years old and followed for more than 10 years; participants were selected at random from a long-term follow-up cohort.

The researchers measured serum testosterone levels, as well as genetic polymorphisms (variations) in androgen receptor exon-1 CAG repeat number and steroid 5 alpha reductase type II (SRD5A2, valine vs leucine alleles). They compared outcomes among 87 boys with earlier onset of puberty (defined as serum testosterone >2.5 ng/mL at age 15) versus 13 with later puberty.

Results

	72 participants (72%) experienced spontaneous HBeAg seroconversion during follow-up.
	Boys with earlier-onset puberty experienced significantly earlier HBeAg seroconversion on average than those with later puberty (at a median age of 13.2 vs 22.5 years; hazard ratio 2.95).
	The early puberty onset group also had significantly higher peak alanine aminotransferase (ALT) levels while they were HBeAg positive (306 vs 155 IU/L).
	Finally, the early puberty group experienced significantly greater HBV viral load reduction between 10 and 20 years of age than the late puberty group (1.6 vs 0.2 log10 copies/mL).
	Having the valine allele at the SRD5A2 V89L polymorphism site was also associated with earlier spontaneous HBeAg seroconversion (at a median age of 11.7 vs 18.7 years; hazard ratio 1.88).

Based on these findings, the study authors concluded, "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."

Since earlier puberty -- with its increase in testosterone -- led to HBeAg conversion and lower HBV DNA, both of which are associated with milder liver disease, these findings do not explain faster disease progression in men.

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

3/12/10

Reference
JF Wu, WY Tsai, HY Hsu, and others. Effect of Puberty Onset on Spontaneous Hepatitis B Virus e Antigen Seroconversion in Men. Gastroenterology 138(3): 942-948.e1 (Abstract). March 2010.