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Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes
Author(s) -
Lau Daryl T.Y.,
GanovaRaeva Lilia,
Wang Junyao,
Mogul Douglas,
Chung Raymond T.,
LiskerMelman Mauricio,
Chang KyongMi,
Shaikh Obaid S.,
Janssen Harry L.A.,
Wahed Abdus S.,
Lok Anna S.
Publication year - 2021
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31506
Subject(s) - hepatitis b virus , hbeag , genotype , virology , medicine , hepatitis b , population , orthohepadnavirus , biology , sanger sequencing , hepadnaviridae , virus , mutation , genetics , gene , hbsag , environmental health
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 and Results 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.