Public Release Type:
Journal
Publication Year: 2014
Authors:
Lisker-Melman M,
Chung RT,
Chang KM,
Ganova-Raeva L,
Janssen HL,
Johnson G,
Lau D,
Lok AS,
Shaikh OS,
Wahed AS
Studies:
Hepatitis B Research Network
The distribution of HBV genotypes vary geographically. HBV Precore (PC) mutation (G1896A) and dual basal core promoter (BCP) mutations (A1762T, G1764A) halt and downregulate HBeAg production respectively and contribute to disease outcomes. Aim/ Methods: We sought to characterize the PC and BCP variants by Sanger chromatograms in ethnically diverse, adult pts in North America and to examine the association of these variants with their HBV genotypes and clinical phenotypes. Baseline samples in the HBRN Cohort Study from 21 centers in US and Canada between 2011 and 2013 were included. Pts on antiviral therapy were excluded. By continent of birth, the 1349 pts (51% males) included 926 (69%) from Asia, 108 (8%) from Africa and 259 (19%) from North America. The majority (60%) had HBeAg -ve disease and 14% had Indeterminate phenotypes. Results: Pts born in Asia most commonly had genotype B (48%) or C (39%). African born pts had genotype A (53%: A1 44%, A2 4%, A3 2%), followed by E (25%) and D (10%). Those born in North America had genotype A (45%: A1 5%, A2 38%), C (23%), B (19%) and rarely D (6%). Dual BCP variants were present across all genotypes and were most common with genotype C (37%) and D (27%) [Table]. The G1896A PC variant was present in 16% of genotype A (both A1, A2) HBeAg -ve disease, an unexpected finding since the G1896A mutation is usually incompatible with genotype A. BCP variants were found in similar frequency among HBeAg +ve and -ve pts. The PC variant was common among inactive carriers and HBeAg -ve chronic hepatitis B (CHB). About 10% of the immune tolerant and HBeAg +ve CHB pts also had the PC variant; all but one with this variant had genotype B or C reflecting the association of the PC variant among Asians with HBeAg +ve disease. Conclusions:1. PC and BCP HBV variants occur with high frequency in this predominantly HBeAg -ve cohort living in North America. 2. Presence of the BCP, and especially PC, variants in HBeAg +ve phenotypes suggests co-existence of wild type and variant viruses and evolution of genomic mutations over time. 3. The finding of G1896A mutation in genotype A HBeAg -ve disease from both Africa and North America origins implies the presence of compensatory mutations to ensure its survival. The HBV molecular epidemiology may have important therapeutic implications.