Chronic hepatitis B carriers with acute on chronic liver failure show increased HBV surface gene mutations, including immune escape variants

dc.contributor.authorGao, Shan
dc.contributor.authorJoshi, Shivali S
dc.contributor.authorOsiowy, Carla
dc.contributor.authorChen, Y.
dc.contributor.authorCoffin, Carla S
dc.contributor.authorDuan, Z-P.
dc.date.accessioned2018-09-26T12:10:32Z
dc.date.available2018-09-26T12:10:32Z
dc.date.issued2017-10-24
dc.date.updated2018-09-26T12:10:31Z
dc.description.abstractAbstract Background The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is not well understood. The aim of this study was to investigate whether there is an association between HBV polymerase (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC) variants and development of ACLF in CHB. Methods Two CHB patient cohorts were compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12 HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9 genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each group. Results Our data showed the incidence of IE and clusters of mutations in the HBV S region was significantly greater in ACLF patients vs. treatment naïve CHB patients (p < 0.05). Additionally, a significantly higher frequency of G1896A and A1762T/G1764A mutations were found in HBeAg negative than in ACLF patients (p < 0.0001). Conclusion In our study, ACLF was not associated with a specific genomic mutation. However, higher frequency of IE mutations along with various mutations clustering in the HBV S region could contribute to or be an outcome of ACLF in CHB infection. (words 226).
dc.identifier.citationVirology Journal. 2017 Oct 24;14(1):203
dc.identifier.doihttps://doi.org/10.1186/s12985-017-0870-x
dc.identifier.urihttp://hdl.handle.net/1880/108020
dc.identifier.urihttps://doi.org/10.11575/PRISM/44397
dc.language.rfc3066en
dc.rights.holderThe Author(s).
dc.titleChronic hepatitis B carriers with acute on chronic liver failure show increased HBV surface gene mutations, including immune escape variants
dc.typeJournal Article
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