Hartono Gunardi1, Melanie Y Iskandar1, Susan I Ie2, Pramita G Dwipoerwantoro1, Rino A Gani3, David H Muljono4,5,6. 1. Department of Child Health, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 2. Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. 3. Department of Internal Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. 4. Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. davidhm@eijkman.go.id. 5. Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. davidhm@eijkman.go.id. 6. Sydney Medical School, University of Sydney, Sydney, NSW, Australia. davidhm@eijkman.go.id.
Abstract
BACKGROUND: HBV-infected patients are potential sources of intra-familial transmission. We studied HBV transmission and molecular characteristics within families of HBV-related chronic liver disease (CLD) patients. METHODS: Family members [index cases (ICs), spouses, and 1-18-year-old children] of HBV-related CLD patients were tested for HBsAg, anti-HBc, and anti-HBs. HBsAg-positive subjects were tested for HBeAg/anti-HBe. Anti-HBc-positive children together with their family members were further investigated for HBV DNA. Sequences of positive isolates were analyzed over surface, precore (PC) and basal core promoter (BCP) regions. RESULTS: Among 94 children of 46 ICs, the prevalence of HBsAg, anti-HBc, and anti-HBs was 10 (10.6 %), 19 (20.2 %), and 46 (48.9 %), respectively. Thirty-eight (40.4 %) children were seronegative, indicating susceptibility to HBV infection. HBV DNA was identified in all ICs, 4 spouses, and 16 children. Having both parents with HBsAg positive and at least two HBV carriers in the households were significant risk factors of intra-familial transmission. HBV genotype/subtype distributions were comparable between children and ICs/spouses, with predominance of genotype B. The majority of HBV DNA sequences found in children were identical to their corresponding ICs-particularly mothers-including mutation patterns in the surface, PC, and BCP regions. Recognized mutations associated with HBsAg detection and/or vaccination failure, T140I, T143S/M, G145R, and Y161F, were identified in 20 subjects; while mutations linked to HBeAg-defective variants, PC G1896A and BCP A1762T/G1764A, were found in 7 and 11 subjects, respectively. CONCLUSIONS: Children of HBV-related CLD patients were at increased risk of HBV infection through multi-modal transmission routes despite negative parental HBsAg and HBeAg status.
BACKGROUND:HBV-infectedpatients are potential sources of intra-familial transmission. We studied HBV transmission and molecular characteristics within families of HBV-related chronic liver disease (CLD) patients. METHODS: Family members [index cases (ICs), spouses, and 1-18-year-old children] of HBV-related CLD patients were tested for HBsAg, anti-HBc, and anti-HBs. HBsAg-positive subjects were tested for HBeAg/anti-HBe. Anti-HBc-positive children together with their family members were further investigated for HBV DNA. Sequences of positive isolates were analyzed over surface, precore (PC) and basal core promoter (BCP) regions. RESULTS: Among 94 children of 46 ICs, the prevalence of HBsAg, anti-HBc, and anti-HBs was 10 (10.6 %), 19 (20.2 %), and 46 (48.9 %), respectively. Thirty-eight (40.4 %) children were seronegative, indicating susceptibility to HBV infection. HBV DNA was identified in all ICs, 4 spouses, and 16 children. Having both parents with HBsAg positive and at least two HBV carriers in the households were significant risk factors of intra-familial transmission. HBV genotype/subtype distributions were comparable between children and ICs/spouses, with predominance of genotype B. The majority of HBV DNA sequences found in children were identical to their corresponding ICs-particularly mothers-including mutation patterns in the surface, PC, and BCP regions. Recognized mutations associated with HBsAg detection and/or vaccination failure, T140I, T143S/M, G145R, and Y161F, were identified in 20 subjects; while mutations linked to HBeAg-defective variants, PC G1896A and BCP A1762T/G1764A, were found in 7 and 11 subjects, respectively. CONCLUSIONS:Children of HBV-related CLD patients were at increased risk of HBV infection through multi-modal transmission routes despite negative parental HBsAg and HBeAg status.
Entities:
Keywords:
Hepatitis B in children; Hepatitis B virus; Intra-familial transmission; Mutation; Transmission modes of HBV