TY - JOUR
T1 - Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy
T2 - HBcrAg in chronic hepatitis B
AU - Erken, Robin
AU - Zaaijer, Hans L.
AU - Willemse, Sophie B.
AU - Bakker, Ed
AU - Takkenberg, Bart B.
AU - Reesink, Henk W.
AU - Kootstra, Neeltje A.
N1 - Funding Information: We express our gratitude to Fujirebio for providing the test kits in an unrestricted grant and technical support for the HBcrAg measurements. We would also like to thank Margo Gorissen from Sanquin Blood Supply for technical support in performing the HBcrAg test and Sanquin Blood Supply Foundation for the use of their test facilities. The study was conducted according to the guidelines of the Declaration of Helsinki and the principles of good clinical practice, and was approved by local ethics committees (ISRCTN 77073364). All patients gave written informed consent. HBcrAg test-materials were funded by Fujirebio in a unrestricted grant. Publisher Copyright: © 2021 Fundación Clínica Médica Sur, A.C.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Adefovir
KW - HBV pgRNA
KW - HBcrAg
KW - Hepatitis B Virus
KW - Pegylated interferon
KW - Viral markers
UR - http://www.scopus.com/inward/record.url?scp=85121014497&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.aohep.2021.100540
DO - https://doi.org/10.1016/j.aohep.2021.100540
M3 - Article
C2 - 34583061
SN - 1665-2681
VL - 26
JO - Annals of hepatology
JF - Annals of hepatology
M1 - 100540
ER -