Relationship between hepatitis B core‐related antigen levels and sustained <scp>HB</scp>eAg seroconversion in patients treated with nucleo(s)tide analogues

Sonneveld, Milan J.; Oord, Gertine W. van; Campenhout, Margo J.H. van; Man, Robert A. de; Janssen, Harry L.A.; Knegt, Robert J. de; Boonstra, André; Eijk, Annemiek A. van der

doi:10.1111/jvh.13097

Cited by 18 publications

(22 citation statements)

References 16 publications

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“…Several studies have shown that baseline levels and changes in HBcrAg while on antiviral therapy may predict HBeAg loss or seroconversion after patients receive nucleos(t)ide analog or peginterferon therapy. [ 18 , 19 , 36 ] Wang et al [ 18 ] discovered that a combination of HBcrAg and HBsAg levels at month 6 (with AUROC 0.769) or month 12 (with AUROC 0.807) had the greatest predictive value for HBeAg seroconversion, in which 36.4% (43/118) of patients achieved HBeAg seroconversion after a median of 39 months of treatment. This study also showed that a decline in HBcrAg was the only predictor of HBeAg loss after 78 weeks of therapy.…”

Section: Discussionmentioning

confidence: 99%

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

Zhao

Wang

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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Section: Discussionmentioning

confidence: 99%

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

Zhao

Wang

2021

Chinese Medical Journal

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“…This observation suggests a possible role of serial monitoring of HBcrAg in clinical practice. In fact, in a study reporting serial HBcrAg levels among 50 patients undergoing HBeAg seroconversion on nucleos(t)ide analog therapy, the mean HBcrAg at the time of HBeAg seroconversion was 5.34 log U/mL 14 . Similarly, in a study in the United Kingdom, an HBcrAg level of < 5.5 log U/mL at 12 months of nucleos(t)ide analog treatment could best predict HBeAg seroconversion in 43 patients after a median of 39 months' treatment 15 …”

Section: Discussionmentioning

confidence: 99%

“…mean HBcrAg at the time of HBeAg seroconversion was 5.34 log U/mL. 14 Similarly, in a study in the United Kingdom, an HBcrAg level of < 5.5 log U/mL at 12 months of nucleos(t)ide analog treatment could best predict HBeAg seroconversion in 43 patients after a median of 39 months' treatment. 15 HBcrAg levels have been shown to be higher among patients with HBeAg-negative chronic hepatitis than those with HBeAg-negative chronic infection in previous studies.…”

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confidence: 94%

Use of hepatitis B virus core‐related antigen to evaluate natural history of chronic hepatitis B

Chan

Yasuda

Wong

et al. 2020

J of Gastro and Hepatol

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Background and Aim: Hepatitis B core-related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B. Methods: Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in three serial serum samples for each patient. Patients were divided into six groups for analysis: hepatitis B e antigen (HBeAg)-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI), and HBsAg seroclearance (SS). Results: In total, 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with hepatitis B virus DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cutoff of ≥ 6.0 log U/mL could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve of 0.99, P < 0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg ≥ 4.0 log U/mL could best differentiate ENH from ENI (area under receiver operating characteristic curve of 0.81; P < 0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63%, and 89% patients in ENH, ENI, and SS groups at the last visit, respectively. Conclusions: HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease. Echosens, Gilead Sciences, Janssen, and Roche. Vincent Wong has served as an advisory committee member for 3V-BIO, AbbVie, Allergan, Echosens, Gilead Sciences, Janssen, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, and Terns and as a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences, and Merck. He has also received a research grant from Gilead Sciences. Takashi Kumada served as a speaker for Gilead and MSD. Hidenori Toyoda has served as a speaker for AbbVie, Bayer, Gilead, and MSD. The other authors declare that they have no competing interests.

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“…22 HBV DNA was undetected. 30 HBcrAg >5.7 log 10 U/mL was an independent predictor of recurrence during HBeAg seroconversion (adjusted Hazard Ratio 1.855, P = .021; 95% CI: 1.099-3.133) 31 and could be detected even if HBsAg lost. 32 In immunosuppressive patients with haematologic malignancies, both HBsAg and HBV DNA were negative, HBcrAg was positive and significantly associated with HBV reactivation (HRs 3.65, P = .011, 95% CI: 1.35-9.86).…”

Section: Empty Virusmentioning

confidence: 97%

Insights for clinical diagnostic indicators of virus and host in chronic hepatitis B infection

Guo

Zeng

et al. 2020

Journal of Viral Hepatitis

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Covalently closed circular DNA (cccDNA), which is stably present in the nucleus of hepatocytes, is an important indicator for evaluating antiviral efficacy. Since cccDNA quantification requires an invasive procedure, serum biological markers that can effectively reflect the transcriptional activity of intrahepatic virus and the efficacy of treatment are required. Here, from the aspects of virus and host, we outline the focus of clinical research of HBV in recent years, including HBV RNA, empty virus, hepatitis B core‐related antigen and changes in the immune response. We briefly discuss their significance in predicting disease activity and monitoring treatment response in chronic hepatitis B. On this basis, some issues worthy of attention in laboratory diagnosis are proposed.

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Relationship between hepatitis B core‐related antigen levels and sustained HBeAg seroconversion in patients treated with nucleo(s)tide analogues

Cited by 18 publications

References 16 publications

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

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

Use of hepatitis B virus core‐related antigen to evaluate natural history of chronic hepatitis B

Insights for clinical diagnostic indicators of virus and host in chronic hepatitis B infection

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