Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy.
Autor: | Erken R; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism; Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: r.erken@amsterdamumc.nl., Zaaijer HL; Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: h.l.zaaijer@amsterdamumc.nl., Willemse SB; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism. Electronic address: s.b.willemse@amsterdamumc.nl., Bakker E; Sanquin Blood Supply Foundation, Plesmanlaan 125, Amsterdam, the Netherlands.. Electronic address: e.bakker@sanquin.nl., Takkenberg BB; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism. Electronic address: r.b.takkenberg@amsterdamumc.nl., Reesink HW; Amsterdam UMC, location AMC, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address: h.w.reesink@lumc.nl., Kootstra NA; Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.. Electronic address: n.a.kootstra@amc.uva.nl. |
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Jazyk: | angličtina |
Zdroj: | Annals of hepatology [Ann Hepatol] 2021 Dec; Vol. 26, pp. 100540. Date of Electronic Publication: 2021 Sep 25. |
DOI: | 10.1016/j.aohep.2021.100540 |
Abstrakt: | Introduction and Objectives: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment. Materials and Methods: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364). Results: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p < 0.001), intrahepatic HBV-DNA (ρ 0.73, p < 0.001) and plasma/serum HBV-DNA (ρ 0.80, p < 0.001), HBV-pgRNA (ρ 0.80, p < 0.001), and to lesser extend HBsAg (ρ 0.56, p < 0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up. Conclusions: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime. Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest. (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.) |
Databáze: | MEDLINE |
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