title: Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection.
abstract: We investigated 168 children and analysed the virological characterization and association with disease progression in children with hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutants. Among 168 patients with HBV infection (aged 0.5-18 years old, mean 10.1), 86 of them had HBV-related liver cirrhosis (LC) and 82 had HBV-related chronic hepatitis B (CHB). A direct sequencing method was employed to determine the HBV genotypes and the mutations in BCP/PC regions. In all, 133 of them were infected with genotype C viruses (79.17%); only 35 patients (20.83%) were infected with genotype B viruses. Both LC patients and CHB patients had significantly higher ratios of genotype C when compared with the ratios of genotype B (83.7%-16.3% versus 74.4%-25.6%). For patients with CHB, the prevalence of BCP/PC wild-type viruses was 52.4%; but this was only 4.7% in patients with LC. The C1653T, T1753C, A1762T/G1764A and G1896A mutations had a significantly higher prevalence in patients with LC. Among all the patients with genotype B viruses, those with LC had lower HBV DNA levels and higher G1899A mutation frequency than patients with CHB. Among all the patients with genotype C viruses, the patients with LC had higher prevalence of C1653T, A1762T/G1764A and G1896A mutation frequency, higher hepatitis B e antigen (HBeAg) -negative rates, lower viral load, lower elevated alanine aminotransferase and lower anti-HBe positive rates than CHB patients. The HBV BCP/PC variants were more common in HBeAg-negative LC patients than in the CHB group (BCP, 53.4% versus 15.6%; PC, 18.6% versus 3.7%, respectively, p < 0.001). Patients with HBV genotype C viruses, high viral load and C1653T, A1762T/G1764A, G1896A mutant viruses, were more susceptible to developing LC.
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China. Electronic address: zhongyanwei@126.com.
authors.forename: Y W
authors.initials: YW
authors.lastname: Zhong
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: F L
authors.initials: FL
authors.lastname: Di
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: HeBei North University, Zhangjiakou, China. Electronic address: zhangxiuchang302@163.com.
authors.forename: X C
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Bi
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Wu
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: L M
authors.initials: LM
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Shi
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China. Electronic address: zhanghongfei302@163.com.
authors.forename: H F
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Institute of Infectious Diseases, Pediatric Liver Disease Therapy and Research Centre, Beijing 302 Hospital, Beijing, China. Electronic address: zhangmin302@163.com.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000473:pathology / Q000821:virology*; D006801:Humans; D007223:Infant; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D059645:Mutation Rate; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D014758:Viral Core Proteins
keywords: Basal core promoter; genotype; hepatitis B virus; infant; mutation; precore