title: HBsAg, HBeAg and HBV DNA level changes and precore/basal core promoter mutations in the natural history of chronic hepatitis B in Indonesian patients.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. yadi@eijkman.go.id.
authors.lastname: Turyadi
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. mdewi@eijkman.go.id.|Eijkman Winkler Institute, Utrecht Medical Centre, Utrecht, The Netherlands. mdewi@eijkman.go.id.
authors.forename: Meta Dewi
authors.initials: MD
authors.lastname: Thedja
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. sii@eijkman.go.id.
authors.forename: Susan Irawati
authors.initials: SI
authors.lastname: Ie
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. alida@eijkman.go.id.|Clinical Pathology Department, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. alida@eijkman.go.id.
authors.forename: Alida Roswita
authors.initials: AR
authors.lastname: Harahap
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. korri@eijkman.go.id.
authors.forename: Korri Elvanita
authors.initials: KE
authors.lastname: El-Khobar
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. martono@eijkman.go.id.
authors.forename: Martono
authors.initials: M
authors.lastname: Roni
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta, 10430, Indonesia. davidhm@eijkman.go.id.|Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. davidhm@eijkman.go.id.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia. davidhm@eijkman.go.id.
authors.forename: David Handojo
authors.initials: DH
authors.lastname: Muljono
keywords: Basal core promoter; Chronic hepatitis B; HBV DNA; HBeAg; HBsAg; Natural history; Precore mutation; Quantitative serology