Molecular characterization of intrahepatic and extrahepatic hepatitis B virus (HBV) reservoirs in patients on suppressive antiviral therapy.

Journal of Viral Hepatitis
Carla S CoffinNorah A Terrault

Abstract

The hepatitis B virus (HBV) replicates via an error-prone reverse transcriptase generating potential drug-resistant quasispecies. The degree of HBV variability in liver vs peripheral blood mononuclear cells (PBMC) in patients on long-term suppressive antivirals is unclear. We characterized HBV replication, drug resistance and molecular diversity in patients with plasma HBV DNA undetectable by clinical assays. Explant liver (n=9), PBMC (n=6) and plasma (n=7) from nine such patients undergoing liver transplantation were evaluated for HBV genomes by sensitive PCR/nucleic acid hybridization assay. Cases with HBV DNA in liver and PBMC were tested for covalently closed circular DNA (HBV cccDNA). HBV polymerase (P) amplicons were cloned, sequenced and both P and overlapping surface (S) gene sequences were analysed. HBV DNA was detected in 43% (3/7) of plasma, 100% (9/9) of liver and 83% (5/6) of PBMC samples. HBV cccDNA was detected in all liver and one PBMC sample. Four patients had a clinical diagnosis of resistance. HBV P gene sequencing revealed 100% wild type (wt) in plasma (2/2), 83% wt in PBMC (5/6) but livers of 3/9 (33%) contained wt and 6/9 (66%) carried resistance to lamivudine and/or adefovir. The translated S gene reveale...Continue Reading

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Citations

Jan 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Guoxin LiangMasamichi Muramatsu
Jun 3, 2014·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Carla S CoffinM John Gill
Oct 11, 2014·Nucleic Acids Research·Hei-Man Vincent TangDong-Yan Jin
Aug 28, 2013·Expert Review of Anti-infective Therapy·John E TavisYuan Hu
Oct 13, 2015·Journal of Gastroenterology and Hepatology·Guo Qing Yin, Bei Zhong
Jan 5, 2016·Liver International : Official Journal of the International Association for the Study of the Liver·Rajneesh KumarFabien Zoulim
Dec 19, 2015·Diagnostic Microbiology and Infectious Disease·Yanzhong PengJianxin Li
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Aug 24, 2021·Frontiers in Microbiology·Carla S CoffinTomasz I Michalak
Jun 14, 2019·Journal of Advanced Research·Nathalie MenthaDulce Alfaiate

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