Increase risk of HBeAg-negative chronic hepatitis B with older age at HBeAg seroconversion

Background: Recent evidence suggests that delayed HBeAg seroconversion is associated with poorer outcome. We aim to determine the incidence of HBeAg-negative chronic hepatitis B (CHB) according to the age at which HBeAg seroconversion occurs. Methods: Chronic hepatitis B patients with natural HBeAg seroconversion and over 12 months follow-up after HBeAg-seroconversion, and without complications, were included. Patients were followed 3−6 monthly with liver biochemistry. HBV DNA and liver stiffness measurements by transient elastography were determined at the time of last follow-up. HBeAgnegative CHB was defined as a combination of ALT elevation above the upper limit of normal on more than one occasion for the entire duration of follow-up after HBeAg seroconversion, and HBV DNA >5 log copies/mL. Results: In total, 228 patients were included with a median follow-up (after HBeAg seroconversion) of 103 months (range, 12–247), of which 118 (52%) were male. The median age was 42 years (range, 21−74). The median age at HBeAg-seroconversion was 32 years (range, 6−64). Seventy-five (33%) and 137 (60%) patients had HBV DNA >5 log and >4 log copies/mL respectively. HBeAg-negative CHB was identified in 51 (22%) patients. In patients with evidence of HBeAg-negative CHB, the median age at HBeAg conversion was significantly higher compared to those with persistently normal ALT or HBV DNA <5 log copies/mL (38 vs 31 years respectively, p<0.001). In patients who seroconverted at age 20, 21−30, 31−40, 41−50, and >50, the rate of HBeAg-negative CHB was 12%, 15%, 21%, 39%, and 75% respectively (p = 0.002). There was no significant difference between males and females with respect to the age at HBeAg seroconversion (34 vs 32 years respectively, p = 0.90), and rate of HBeAg-negative CHB (25% vs 19% respectively, p = 0.25). Patients with HBeAg-negative CHB had higher median liver stiffness compared to those with persistently normal ALT or HBV DNA level <5 log copies/mL (9.0 vs 5.5 kPa respectively, p