Predictors of hepatitis B e antigen‐negative hepatitis in chronic hepatitis B virus‐infected patients from childhood to adulthood

• Published in: Hepatology (Baltimore, Md.) Vol. 63; no. 1; pp. 74 - 82
• Main Authors: Wu, Jia‐Feng, Chiu, Yu‐Chun, Chang, Kai‐Chi, Chen, Huey‐Ling, Ni, Yen‐Hsuan, Hsu, Hong‐Yuan, Chang, Mei‐Hwei
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health, Inc 01.01.2016
• Subjects: Adolescent; Age; Age Factors; Antigens; Antiviral agents; Antiviral Agents - therapeutic use; Child; Childhood; Children; Chronic infection; Cohort Studies; Data processing; Female; Follow-Up Studies; Health risk assessment; Hepatitis; Hepatitis B; Hepatitis B e antigen; Hepatitis B e Antigens - blood; Hepatitis B virus; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Hepatology; Humans; Interferon; Interferon-alpha - therapeutic use; Lamivudine; Lamivudine - therapeutic use; Male; Prospective Studies; Risk Factors; Seroconversion; Young Adult; α-Interferon
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.28222

Hepatitis B e antigen (HBeAg)‐negative hepatitis is a clinical indicator of poor outcome for chronic hepatitis B viral (HBV) infection. This long‐term prospective cohort study aimed to elucidate the predictors of developing HBeAg‐negative hepatitis in chronic HBV‐infected subjects followed from childhood to adulthood. We followed 434 HBeAg‐positive chronic HBV‐infected patients from a median age of 7.22 years (interquartile range 4.31‐10.21 years). Spontaneous HBeAg seroconversion occurred in 359 subjects at a median age of 13.93 years (interquartile range 8.76‐20.59 years), and 75 subjects developed HBeAg seroconversion after antiviral therapy. These patients were followed for a median of 14.40 years (interquartile range 6.14‐22.02 years) after HBeAg seroconversion. Clinical data were analyzed to delineate the predictors of developing HBeAg‐negative hepatitis. The HBV basal core promoter and precore/core gene sequences were also evaluated in subjects with and without HBeAg‐negative hepatitis. The overall annual incidence of HBeAg‐negative hepatitis was 0.37% (95% confidence internal 0.35‐0.39) in spontaneous HBeAg seroconverters. The overall annual incidence of HBeAg‐negative hepatitis increased to 2.64% in lamivudine‐treated subjects but did not increase in those treated with interferon‐alpha (0.58%). Male gender (hazard ratio = 3.15), HBV genotype C (hazard ratio = 4.40), HBeAg seroconversion after 18 years of age (hazard ratio = 2.46), and lamivudine therapy prior to HBeAg seroconversion (hazard ratio = 1.42) were predictors of HBeAg‐negative hepatitis in HBeAg seroconverters (P < 0.05). HBeAg‐negative hepatitis subjects carried more A1762T/G1764A, C2063A, and A2131C HBV gene mutations than those without HBeAg‐negative hepatitis. Conclusions: HBeAg seroconversion during childhood predicts a lower risk of HBeAg‐negative hepatitis in later life. Interferon‐alpha therapy may be an effective antiviral therapy beneficial in chronic HBV‐infected children with severe inflammation that facilitates HBeAg seroconversion in earlier life. (Hepatology 2016;63:74–82)