title: Predominance of precore mutations and clinical significance of basal core promoter mutations in chronic hepatitis B virus infection in Indonesia.
abstract: Chronic hepatitis B virus (HBV) infection is a major health problem worldwide, with a particularly high prevalence in the Asian-Pacific region. During chronic hepatitis B virus (HBV) infection, mutations commonly occur in the basal core promoter (BCP) and precore (PC) regions of HBV, affecting HBeAg expression, particularly following HBeAg serocon-version. Mutations in the B- and T-cell epitopes of the HBV core have also been observed during disease progression. The clinical significance of HBV genome variability has been demonstrated, however the results are a subject of controversy. Considering the characteristics of the virus associated with geographical location, the profiles of BCP, PC and core mutations and their clinical implications in patients with chronic HBV infection in Surabaya, Indonesia, were investigated. The BCP, PC and core mutations and HBV genotypes were detected by direct sequencing. The HBeAg/anti-HBe status and HBV DNA levels were also assessed. This study enrolled 10 patients with chronic HBV infection (UC) from Dr Soetomo General Hospital and Indonesian Red Cross, Surabaya, East Java, Indonesia, 10 patients with chronic hepatitis B and liver cirrhosis (LC) and 4 patients with chronic hepatitis B and hepatocellular carcinoma (HCC) from Dr Soetomo General Hospital. The PC mutation A1896 was predominant in all the groups (60-100%), together with the PC variant T1858, which was associated with HBV genotype B. The number of detected core mutations (Thr/Ser130) was higher in HCC patients (50%). However, the BCP mutations T1762/A1764 were predominant in LC patients (50-60%). The LC and HCC patients carried HBV isolates with additional mutations, at least at BCP or PC, mainly following HBeAg seroconversion. In the majority of anti-HBe-positive samples, the BCP T1762/A1764 mutations were associated with a high viral load, regardless of the PC 1896 status. In conclusion, the PC mutations were found to be predominant in all the groups. However, the BCP mutations were mainly detected in the LC group and may be considered as a critical indicator of a poor clinical outcome.
authors.affiliation: Department of Microbiology, School of Medicine, Airlangga University, Surabaya, East Java 60131; ; Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University;
authors.lastname: Juniastuti
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University; ; Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan ;
authors.forename: Takako
authors.initials: T
authors.lastname: Utsumi
authors.affiliation: Institute of Tropical Disease, Airlangga University, Surabaya, East Java 60115, Indonesia ;
authors.forename: Eduardus Bimo
authors.initials: EB
authors.lastname: Aksono
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan ;
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University; ; Department of Biochemistry, School of Medicine, Airlangga University;
authors.lastname: Soetjipto
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan ;
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan ;
authors.forename: Hak
authors.initials: H
authors.lastname: Hotta
authors.affiliation: Institute of Tropical Disease, Airlangga University, Surabaya, East Java 60115, Indonesia ;
authors.forename: Fedik Abdul
authors.initials: FA
authors.lastname: Rantam
authors.affiliation: Department of Internal Medicine, Dr Soetomo General Hospital, Surabaya, East Java 60131, Indonesia.
authors.forename: Hernomo Ontoseno
authors.initials: HO
authors.lastname: Kusumobroto
authors.affiliation: Department of Microbiology, School of Medicine, Airlangga University, Surabaya, East Java 60131; ; Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University;
authors.forename: Maria Inge
authors.initials: MI
authors.lastname: Lusida
keywords: basal core promoter mutations; chronic hepatitis B virus infection; core mutations; hepatitis B virus; precore mutations