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Impact of HBV genotype and mutations on HBV DNA and qHBsA g levels in patients with HB eAg‐negative chronic HBV infection
Author(s) -
Kuhnhenn L.,
Jiang B.,
Kubesch A.,
Vermehren J.,
Knop V.,
Susser S.,
Dietz J.,
Carra G.,
Finkelmeier F.,
Grammatikos G.,
Zeuzem S.,
Sarrazin C.,
Hildt E.,
Peiffer K.H.
Publication year - 2018
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.14636
Subject(s) - hbeag , hbsag , genotype , virology , hepatitis b virus , medicine , polymerase chain reaction , mutation , biology , gene , virus , genetics
Summary Background HBV DNA and quantitative (q)H B sAg levels as prognostic markers for HBV ‐related disease are mostly validated in Asia and their significance in Western populations is uncertain. Aim To analyse the impact of the HBV genotype and frequent mutations in precore ( PC ), basal core promoter ( BCP ) and preS on HBV DNA and qHBsA g levels. Methods HBV DNA and qHBsA g serum levels of 465 patients with HB eAg‐negative chronic HBV infection were correlated with the HBV genotype and mutations in PC , BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HB sAg release in cell culture. Results While no impact of the HBV genotype on HBV DNA levels was observed, qHBsA g levels differed up to 1.4 log among the genotypes ( P  < 0.001), reflected by large differences regarding the 1000 IU/mL HB sAg cut‐off. While PC mutations were associated with higher ( P  < 0.001), BCP mutations were associated with lower HBV DNA levels ( P  < 0.001). Higher qHBsA g levels were associated with preS and lower levels with PC mutations ( P  < 0.001 and P  = 0.001, respectively). The cell culture experiments revealed a higher HB sAg release and shorter filaments in case of a HBV genome harbouring a preS deletion. In contrast, a perinuclear HB sAg accumulation was detected for the PC and BCP ‐variants, reflecting an impaired HB sAg release. Conclusions qHB sAg serum levels depend on the HBV genotype and together with HBV DNA levels on frequent mutations in PC , BCP and preS in HB eAg‐negative patients. qHB sAg cut‐offs when used as prognostic markers require genotype‐dependent validation.

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