The central nervous system is a potential reservoir and possible origin of drug resistance in hepatitis B infection

• Published in: Journal of Virus Eradication 2023-09, Vol.9 (3), p.100348
• Main Authors: Xu, Lijun, Zhou, Minghan, Peng, Xiuming, Xu, Yufan, Huang, Fan, Wang, Linyun, Peng, Xiaorong, Yang, Zongxing, Tao, Ran, Lang, Guanjing, Cao, Qing, Li, Minwei, Huang, Ying, Zhu, Biao, Xu, Yan
• Format: Article
• Language: English
• Subjects: Cerebrospinal fluid; HBV; Mutation; Original Research; Sequence
• ISSN: 2055-6640; 2055-6659
• DOI: 10.1016/j.jve.2023.100348

Background: The significance of hepatitis B virus (HBV) in cerebrospinal fluid (CSF) is unclear. Methods: Synchronous serum and CSF samples were collected from 13 patients. HBV DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of the reverse transcriptase (RT) region were performed based on PCR and sequencing methods. Results: HBV DNA was detected in the CSF of 3 antiviral-naïve individuals and 1 individual after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 individuals, including 2 with undetectable serum HBV DNA. Ten individuals exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 lamivudine/entecavir-associated resistance mutations only in the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV-HBV-coinfected individuals than in the HBV-monoinfected ones (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P