JIA-FENG WUYU-CHUN CHIUKAI-CHI CHANGHUEY-LING CHENYEN-HSUAN NIHONG-YUAN HSUMEI-HWEI CHANGChen, Huey-LingHuey-LingChenYen-Hsuan NiNi, Yen-HsuanYen-HsuanNiHsu, Hong-YuanHong-YuanHsuChang, Mei-HweiMei-HweiChangChen, Chi-LingChi-LingChen倪衍玄陳惠玲張美惠許宏遠吳嘉?張凱琪邱郁淳2018-09-102018-09-102016-01http://europepmc.org/abstract/med/26389515http://scholars.lib.ntu.edu.tw/handle/123456789/396195Hepatitis 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. ? 2016 by the American Association for the Study of Liver Diseases.[SDGs]SDG1[SDGs]SDG3alpha interferon; entecavir; hepatitis B(e) antigen; lamivudine; antivirus agent; hepatitis B(e) antigen; adolescent; adult; adulthood; antiviral therapy; Article; child; childhood; chronic hepatitis B; cohort analysis; controlled study; disease severity; drug efficacy; female; gender; gene mutation; gene sequence; Hepatitis B virus; Hepatitis B virus genotype B; Hepatitis B virus genotype C; human; incidence; major clinical study; male; nonhuman; priority journal; prospective study; risk assessment; seroconversion; age; blood; follow up; Hepatitis B, Chronic; immunology; risk factor; young adult; Adolescent; Age Factors; Antiviral Agents; Child; Cohort Studies; Female; Follow-Up Studies; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Male; Prospective Studies; Risk Factors; Seroconversion; Young Adultjournal article10.1002/hep.28222