title: Low prevalence of hepatitis B virus pre-S deletion mutation in Indonesia.
abstract: The molecular epidemiological study of hepatitis B virus (HBV) in Indonesia is still limited. This study was aimed to identify the prevalence of HBV pre-S deletion/insertion mutations, and to assess the association of pre-S deletion mutation with liver disease progression in Indonesia. Pre-S mutations were identified by direct sequencing. Of the 265 subjects, 32 samples (12.1%) harbored pre-S deletion/insertion mutations. The prevalence of those pre-S mutations was 2.7% (2/75), 12.9% (8/62), 16.7% (11/66), and 17.7% (11/62) in asymptomatic carrier, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma groups, respectively. Statistical analysis showed significant difference among them (P = 0.024). In HBV genotype B (HBV/B), pre-S1, pre-S1/S2, and pre-S2 deletion mutations were detected respectively in 3 (17.6%), 4 (23.5%), and 9 (52.9%) of 17 samples. On the other hand, in HBV/C, 12 of 15 samples (80.0%) showed a pre-S2 deletion mutation, and only 2 samples (13.3%) demonstrated a pre-S1/S2 deletion mutation. These results suggest that in HBV/B deletion mutation tends to occur in pre-S1 or pre-S1/S2 region, while in HBV/C the deletion mutation usually occurs in the pre-S2 region. Analysis of complete genome of four viruses confirmed that 3 isolates were classified into HBV/B3, and 1 isolate was HBV/C1. However, SimPlot and BootScan analyses showed that isolate 08.10.002 was an intragenotypic recombinant between HBV/B3 and HBV/B4. As conclusion, the prevalence of HBV pre-S mutations was relatively low in Indonesian patients compared to those from Taiwan, Japan, and other Asian countries. There was a weak association between pre-S deletion mutation and progressive liver disease.
authors.affiliation: Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang, Indonesia. autama@mrinstitute.org
authors.forename: Andi
authors.initials: A
authors.lastname: Utama
authors.forename: Marlinang Diarta
authors.initials: MD
authors.lastname: Siburian
authors.forename: Ismail
authors.initials: I
authors.lastname: Fanany
authors.forename: Mariana Destila Bayu
authors.initials: MD
authors.lastname: Intan
authors.forename: Rama
authors.initials: R
authors.lastname: Dhenni
authors.forename: Tri Shinta
authors.initials: TS
authors.lastname: Kurniasih
authors.forename: Syafruddin A R
authors.initials: SA
authors.lastname: Lelosutan
authors.forename: Wenny Astuti
authors.initials: WA
authors.lastname: Achwan
authors.lastname: Arnelis
authors.forename: Benyamin
authors.initials: B
authors.lastname: Lukito
authors.forename: Irawan
authors.initials: I
authors.lastname: Yusuf
authors.forename: Laurentius Adrianus
authors.initials: LA
authors.lastname: Lesmana
authors.forename: Ali
authors.initials: A
authors.lastname: Sulaiman
authors.forename: Susan
authors.initials: S
authors.lastname: Tai
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen