Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.
Hepatology
; 73(5): 1637-1651, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-32860463
ABSTRACT
BACKGROUND AND AIMS:
Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (>50%) were reported. APPROACH ANDRESULTS:
Median age was 36.3 years (range, 2-80), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and/or BCP variants increased from 14.4% in the first two decades to 51% after 40 years of age. Among those aged 2-18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001).CONCLUSIONS:
PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(-) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Virus de la Hepatitis B
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Hepatitis B Crónica
Tipo de estudio:
Observational_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Año:
2021
Tipo del documento:
Article