Gender difference in the natural course of HBeAg-positive chronic hepatitis B

[[abstract]]PURPOSE: Cross-sectional age-specific seroprevalence studiesfrom Taiwan have provided evidence to suggest that malepatients have earlier spontaneous hepatitis B e antigen (HBeAg)seroconversion but, paradoxically, bear a worse prognosis indisease progression when compared to their female counterparts.On the other hand, recent studies have shown thatpatients infected with genotype B hepatitis B virus (HBV) haveearlier HBeAg seroconversion and better prognosis than genotypeC infected patients. This longitudinal study was conductedto clarify this gender-related paradox while taking account theHBV genotype factor. METHODS: HBeAg seropositive patientsfrom 1977 to 1998 were recruited if they met the following criteria:(1) Histologic and biochemical confirmation of chronichepatitis B; (2) Follow-up every 3-6 months and ≥2 years; (3)No concomitant hepatitis C or D virus infection; (4) No drugtreatment during follow-up. The clinical course and biochemical/serological changes were compared between male andfemale patients using t test, X2 and Kaplan-Meir survival analysis.RESULTS: There were 454 males and 110 females who metour entry criteria. The age, baseline serum alanine aminotransferase(ALT) level and HBV genotype distribution were comparablebetween male and female patients. During a meanfollow-up period of 12 years, there was no significant differencein the timing and the cumulative incidence of spontaneousHBeAg seroconversion between male and female patients(97.6 vs 100%; P=0.915). To minimize the influence of otherconfounding factors, the 110 female patients were comparedwith a 1:1 group of male patients well matched for age (±2years), baseline ALT (±20 U/L) and duration of follow-up (±1year). The HBV genotype distribution in the female and thematched male patients was comparable (P=0.864). There wasno significant difference in the incidence of hepatitis flare withALT over 5 times the upper limit of normal (66.4 vs 72.5%;P=0.326) and in the 12-year cumulative incidence of HBeAgseroconversion (85.5 vs 74.4 %; P=0.129). However, 47.7%of the male patients showed persistent ALT elevation, with orwithout ALT flare, in contrast to 14.5% of the female patients(P