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Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure

1
Central Research Institute of Epidemiology, Moscow 111123, Russia
2
National Research Centre, Institute of Immunology, Federal Medical Biological Agency, Moscow 115478, Russia
3
I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russia, Moscow 119146, Russia
*
Author to whom correspondence should be addressed.
Genes 2018, 9(10), 483; https://doi.org/10.3390/genes9100483
Received: 1 September 2018 / Revised: 30 September 2018 / Accepted: 3 October 2018 / Published: 5 October 2018
Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text
Keywords: hepatitis B virus; chronic hepatitis B; pre-genomic RNA; splice variants; covalently closed circular DNA; monitoring; treatment end-points; nucleot(s)ide analogues; interferon; prediction; liver disease hepatitis B virus; chronic hepatitis B; pre-genomic RNA; splice variants; covalently closed circular DNA; monitoring; treatment end-points; nucleot(s)ide analogues; interferon; prediction; liver disease
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Kostyusheva, A.; Kostyushev, D.; Brezgin, S.; Volchkova, E.; Chulanov, V. Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure. Genes 2018, 9, 483.

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