Performance of serum HBcrAg in chronic hepatitis B patients with 8-year nucleos(t)ide analogs therapy

Deng, Rong; Chen, En‐Qiang; Tao, Chuanmin; Liao, Juan; Zhou, Tong; Wang, Juan; Tang, Hong

doi:10.1016/j.clinre.2018.10.020

“…Additionally, baseline HBcrAg level is an independent predictor of long-term HBcrAg below the limit of detection [ 52 ]. Wang et al [ 52 ] investigated the long-term kinetics of serum HBcrAg and its correlation with serum HBsAg in CHB patients positive or negative for HBeAg with NA therapy over 8 years.…”

Section: Surrogate Marker Of Intrahepatic Hbv Replication: Hbcragmentioning

confidence: 99%

“…Additionally, baseline HBcrAg level is an independent predictor of long-term HBcrAg below the limit of detection [ 52 ]. Wang et al [ 52 ] investigated the long-term kinetics of serum HBcrAg and its correlation with serum HBsAg in CHB patients positive or negative for HBeAg with NA therapy over 8 years. At 8 years from the start of NA treatment, 21.3% of patients achieved a serum HBcrAg level of <3 log 10 U/mL, and only baseline HBcrAg was an independent predictor [ 52 ].…”

Section: Surrogate Marker Of Intrahepatic Hbv Replication: Hbcragmentioning

confidence: 99%

Novel biomarkers for the management of chronic hepatitis B

Inoue

¹

2020

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Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus <i>Lens culinaris</i> agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.

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“…The baseline HBcrAg level is an independent predictor of long-term HBcrAg below the limit of detection [71]. Wang et al investigated the long-term kinetics of serum HBcrAg and its correlation with serum HBsAg in CHB patients with NA therapy over 8 years.…”

Section: Anti-hbv Treatmentmentioning

confidence: 99%

“…Among 94 patients, serum HBcrAg gradually decreased from baseline to year 8 in HBeAg-negative and -positive patients. At eight years from the start of NA treatment, 21.3% of patients achieved a serum HBcrAg level of <3 log10 U/mL, and only baseline HBcrAg was an independent predictor [71].…”

Section: Anti-hbv Treatmentmentioning

confidence: 99%

The Role of Hepatitis B Core-Related Antigen

Tanaka

¹

2019

Genes

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Hepatitis B virus (HBV) cannot be completely eliminated from infected hepatocytes due to the existence of intrahepatic covalently closed circular DNA (cccDNA). Serological biomarkers reflect intrahepatic viral replicative activity as non-invasive alternatives to liver biopsy. Hepatitis B core-related antigen (HBcrAg) is a novel biomarker that has an important role in chronic hepatitis B (CHB), because it correlates with serum HBV DNA and intrahepatic cccDNA. In clinical cases with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with promising outcomes for CHB patients. HBcrAg can predict spontaneous or treatment-induced hepatitis B envelope antigen (HBeAg) seroconversion, persistent responses before and after cessation of nucleos(t)ide analogues, potential HBV reactivation, HBV reinfection after liver transplantation, and risk of hepatocellular carcinoma progression or recurrence. In this review, the clinical applications of HBcrAg in CHB patients based on its virological features are described. Furthermore, new potential therapeutic anti-HBV agents that affect intrahepatic cccDNA are under development, and the monitoring of HBcrAg might be useful to judge therapeutic effects. In conclusion, HBcrAg might be a suitable surrogate marker beyond other HBV markers to predict the disease progression and treatment responses of CHB patients.

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“…[ 11 , 12 ] During antiviral therapy, HBcrAg presented a gradually decreasing trend, similar to HBV DNA, HBsAg, and intrahepatic cccDNA, in both HBeAg-positive and -negative patients. [ 13 ] A decline in HBcrAg also correlated with declines in HBV DNA, HBsAg, and intrahepatic cccDNA, [ 14 ] but correlations between HBcrAg and other virological markers after antiviral therapy were inconsistent. [ 14 , 15 ] The relationships between HBcrAg and grade of inflammation, stage of fibrosis, and their degrees of change before and after antiviral therapy also differed.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

Li

¹

,

Zhao

²

,

Wang

³

2021

Chinese Medical Journal

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Background: Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables. Methods: One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods. Results: HBeAg-positive patients ( n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log 10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log 10 U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive ( r = 0.641, P < 0.001) and -negative patients ( r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients ( r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score ( r = −0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive ( r = −0.263, P = 0.014) and HBeAg-negative patients ( r = −0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA ( r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg ( r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients ( r = 0.329, P = 0.001). Patients with HBeAg loss ( n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. ...

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Performance of serum HBcrAg in chronic hepatitis B patients with 8-year nucleos(t)ide analogs therapy

Cited by 18 publications

References 26 publications

Novel biomarkers for the management of chronic hepatitis B

Novel biomarkers for the management of chronic hepatitis B

The Role of Hepatitis B Core-Related Antigen

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

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