联合治疗前后与肝内和循环病毒标志物相关的乙型肝炎核心相关抗原
Robin Erken 1、Hans L Zaaijer 2、Sophie B Willemse 3、Ed Bakker 4、Bart B Takkenberg 5、Henk W Reesink 6、Neeltje A Kootstra 7
隶属关系
隶属关系
Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy
Robin Erken 1 , Hans L Zaaijer 2 , Sophie B Willemse 3 , Ed Bakker 4 , Bart B Takkenberg 5 , Henk W Reesink 6 , Neeltje A Kootstra 7
Affiliations
Affiliations
1
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism; Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.. Electronic address: [email protected].
2
Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: [email protected].
3
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism. Electronic address: [email protected].
4
Sanquin Blood Supply Foundation, Plesmanlaan 125, Amsterdam, the Netherlands.. Electronic address: [email protected].
5
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism. Electronic address: [email protected].
6
Amsterdam UMC, location AMC, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address: [email protected].
7
Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.. Electronic address: [email protected].
PMID: 34583061 DOI: 10.1016/j.aohep.2021.100540
Abstract
Introduction & 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 & 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.