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HBeAg seroconversion in childhood predicts lower risk for HBeAg-negative hepatitis in later life

Recent findings published in Hepatology showed that hepatitis B e antigen seroconversion during childhood — as well as male sex, hepatitis B virus genotype C infection and prior lamivudine therapy — were indicative of a lower risk for hepatitis B e antigen-negative hepatitis in later life. In addition, interferon-alpha therapy may effectively treat patients with chronic hepatitis B.

“This large-scale, long-term, prospective follow-up cohort study (from young children to adults) indicated that the age-specific annual incidences of [hepatitis B e antigen (HBeAg)] negative hepatitis were .29% and .64% in subjects with spontaneous HBeAg seroconversion before versus after 18 years of age, respectively,” the researchers wrote. “[In addition], HBeAg-negative hepatitis subjects carried more HBV [basal core promoter] and precore/core gene mutations immediately after HBeAg seroconversion. Selecting for these mutations during HBeAg seroconversion might lead to breakthrough in our understanding of alterations from the inactive phase to the HBeAg-negative hepatitis phase after HBeAg seroconversion.”

Although HBeAg seroconversion is indicative of reduced hepatitis activity in patients with chronic hepatitis B virus, HBeAg seroconversion after age 40 years has reportedly increased the risk for chronic liver insufficiency, liver cirrhosis, and hepatocellular carcinoma, the researchers wrote. In addition, between 2% and 4% of adult patients with HBV have HBeAg-negative hepatitis.

To determine the predictors of developing HBeAg-negative hepatitis in patients with chronic HBV from childhood to adulthood, the researchers performed a prospective cohort study of 434 HBeAg-positive patients with chronic HBV, with a median age of 7.22 years. Seroconversion occurred in 359 patients at a median age of 13.93 years and 75 patients developed seroconversion after antiviral therapy and were then followed for a median of 14.4 years. In addition, the researchers evaluated the HBV basal core promotor and precore/core gene sequences in patients both with and without HBeAg-negative hepatitis.

The annual incidence of HBeAg-negative hepatitis in all patients was 0.37%, which increased to 2.64% in patients treated with lamivudine, but remained at 0.58% in patients treated with interferon alpha. The researchers found that male sex, HBV genotype C, HBeAg seroconversion after age 18 years, and lamivudine therapy prior to HBeAg seroconversion were predictors of HBeAg-negative hepatitis in HBeAg seroconverters (P < .05). In addition, patients with HBeAg-negative hepatitis carried more A1762T/G1764A, C2063A, and A2131C HBV gene mutations than those without HBeAg-negative hepatitis. – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.