Meta Dewi Thedja1,2, Susan Irawati Ie3, Alida Roswita Harahap4,5, Korri Elvanita El-Khobar6, Martono Roni7, David Handojo Muljono8,9,10. 1. Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. mdewi@eijkman.go.id. 2. Eijkman Winkler Institute, Utrecht Medical Centre, Utrecht, The Netherlands. mdewi@eijkman.go.id. 3. Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. sii@eijkman.go.id. 4. Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. alida@eijkman.go.id. 5. Clinical Pathology Department, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. alida@eijkman.go.id. 6. Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. korri@eijkman.go.id. 7. Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. martono@eijkman.go.id. 8. Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. davidhm@eijkman.go.id. 9. Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. davidhm@eijkman.go.id. 10. Sydney Medical School, University of Sydney, Sydney, NSW, Australia. davidhm@eijkman.go.id.
Abstract
INTRODUCTION: Chronic hepatitis B (CHB) is a state of complex interactions between the hepatitis B virus (HBV) and host. We studied the changes in hepatitis B surface antigen (HBsAg), hepatitis B 'e' antigen (HBeAg) and HBV DNA levels, considering the implications of HBV genotype, basal core promoter (BCP) A1762T/G1764A and precore G1896A mutations in CHB. METHODS: One hundred fifty-two treatment-naïve CHB patients were classified into immune-tolerant (IT), immune-clearance (IC), low/non-replicative (LR) and 'e'-negative hepatitis B (ENH) phases, based on HBeAg status, HBV DNA and ALT levels. HBV DNA was detected and quantified by polymerase chain reaction, then analyzed by sequencing. HBsAg and HBeAg levels were measured serologically. RESULTS: HBsAg and HBV DNA levels varied between CHB phases, with HBsAg highest in IT and lowest in LR, and HBV DNA high in IT and IC, and lowest in LR. Both markers increased in ENH. Correlation between HBsAg and HBV DNA was significant in IT and IC, modest in ENH, but missing in LR. HBeAg and HBV DNA levels were dissociated in HBeAg-positive patients. Genotypes B and C were similarly distributed, with precore mutations higher in HBeAg-negative patients and BCP mutations comparable in all phases. Temporal association between HBeAg seroconversion and an increase of BCP/precore mutations was observed. CONCLUSION: HBsAg and HBV DNA levels were high and correlated in early CHB phases and dissociated after HBeAg seroconversion, indicating different controls affecting HBV replication and HBsAg production. Selection of BCP/precore mutants may affect disease course and explain the HBeAg-HBV DNA dissociation, a precaution for clinical application of quantitative HBeAg.
INTRODUCTION:Chronic hepatitis B (CHB) is a state of complex interactions between the hepatitis B virus (HBV) and host. We studied the changes in hepatitis B surface antigen (HBsAg), hepatitis B 'e' antigen (HBeAg) and HBV DNA levels, considering the implications of HBV genotype, basal core promoter (BCP) A1762T/G1764A and precore G1896A mutations in CHB. METHODS: One hundred fifty-two treatment-naïve CHB patients were classified into immune-tolerant (IT), immune-clearance (IC), low/non-replicative (LR) and 'e'-negative hepatitis B (ENH) phases, based on HBeAg status, HBV DNA and ALT levels. HBV DNA was detected and quantified by polymerase chain reaction, then analyzed by sequencing. HBsAg and HBeAg levels were measured serologically. RESULTS: HBsAg and HBV DNA levels varied between CHB phases, with HBsAg highest in IT and lowest in LR, and HBV DNA high in IT and IC, and lowest in LR. Both markers increased in ENH. Correlation between HBsAg and HBV DNA was significant in IT and IC, modest in ENH, but missing in LR. HBeAg and HBV DNA levels were dissociated in HBeAg-positive patients. Genotypes B and C were similarly distributed, with precore mutations higher in HBeAg-negative patients and BCP mutations comparable in all phases. Temporal association between HBeAg seroconversion and an increase of BCP/precore mutations was observed. CONCLUSION: HBsAg and HBV DNA levels were high and correlated in early CHB phases and dissociated after HBeAg seroconversion, indicating different controls affecting HBV replication and HBsAg production. Selection of BCP/precore mutants may affect disease course and explain the HBeAg-HBV DNA dissociation, a precaution for clinical application of quantitative HBeAg.
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