Gender Difference in the Natural Course of HBeAg Positive Chronic Hepatitis B

Some prior cross-sectional studies from Taiwan -- where hepatitis B virus (HBV) infection is endemic -- have produced evidence suggesting that men may experience earlier spontaneous hepatitis B “e” antigen (HBeAg) seroconversion than women, but nevertheless have worse prognosis for liver disease progression. Other recent studies have shown that patients with HBV genotype B have earlier HBeAg seroconversion and better prognosis than those with genotype C.

As reported at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007), Taiwanese researchers conducted a longitudinal study to clarify gender-related differences in the natural history of hepatitis B, taking into account HBV genotype.

Patients with HBeAg seropositive chronic hepatitis B (454 men and 110 women) were recruited from 1977 through 1998. All met the following criteria:

·   Histological and biochemical confirmation of chronic hepatitis B.

·   Follow-up every 3-6 months for at least 2 years.

·   No coinfection with hepatitis C (HCV) or hepatitis delta virus (HDV).

·   No anti-HBV treatment during the follow-up period.

Age, baseline serum alanine aminotransferase (ALT) levels, and HBV genotype distribution were comparable between men and women. Clinical course and biochemical and serological changes were compared between male and female patients.

Results

·  During a mean follow-up period of 12 years, there was no significant difference in the timing or cumulative incidence of spontaneous HBeAg seroconversion between men and women (97.6% vs 100%; P = 0.915).

·  To minimize the influence of other confounding factors, the 110 women were compared 1-to-1 with a group of men matched for age (within 2 years), baseline ALT (within 20 U/L), and duration of follow-up (within 1 year); HBV genotype distribution was comparable.

·  There was no significant difference between male and female patients in the incidence of hepatitis flares with ALT over 5 x the upper limit of normal (66.4% vs 72.5%; P = 0.326).

·  There was also no difference by gender in the 12-year cumulative incidence of HBeAg seroconversion (85.5% vs 74.4 %; P = 0.129).

·  However, 47.7% of the men showed persistent ALT elevation, with or without ALT flares, compared with just 14.5% of the women (P < 0.0001).

Conclusion

“This longitudinal study showed that there was no difference in the occurrence of hepatitis flare and spontaneous HBeAg seroconversion between males and females with active chronic hepatitis B,” the investigators concluded.

However, they added, “Male patients were found to have a higher propensity for persistent ALT elevation, which may be responsible for a more progressive course.”

Liver Research Unit, Chang Gung Memorial Hospital & Chang Gung University, Taipei, Taiwan; Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.

11/13/07