Comparison of hepatitis B virus core-related antigen and hepatitis B surface antigen for predicting HBeAg seroconversion in chronic hepatitis B patients with pegylated interferon therapy

Liao, Juan; Wei, Bing; Zhang, Dongmei; He, Ming; Tao, Ming-Chuan; Chen, En‐Qiang; Tang, Hong

doi:10.1080/23744235.2018.1442018

Cited by 13 publications

(3 citation statements)

References 28 publications

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“…Like HBeAg, p22cr is also a processed product of the precore protein, but with protein processing at both the N‐ and C‐terminals . In our previous studies, early on‐treatment serum HBcrAg level was found to be a good biomarker for predicting off‐treatment HBeAg seroconversion in patients receiving peginterferon therapy, and as compared to serum HBsAg level, serum HBcrAg has a better correlation with intrahepatic cccDNA . In addition, patients with low HBcrAg and HBsAg levels are also reported to have a low relapse risk after cessation of antiviral therapy …”

Section: Introductionmentioning

confidence: 99%

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Chen

Wang

Tao

et al. 2019

Journal of Viral Hepatitis

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Summary The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg‐positive and HBeAg‐negative CHB patients. In this study, 85 HBeAg‐positive and 25 HBeAg‐negative patients who have never received antiviral therapy were included. Among HBeAg‐positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg‐negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (β = −0.563, P < 0.001), HBsAg (β = −0.328, P < 0.001) and HBV RNA (β = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg‐positive patients, but only serum HBcrAg was associated with cccDNA level (β = 0.774, P = 0.000) among HBeAg‐negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg‐positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg‐positive and HBeAg‐negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.

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Section: Introductionmentioning

confidence: 99%

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Chen

Wang

Tao

et al. 2019

Journal of Viral Hepatitis

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“…HBV core-related antigen (HBcrAg) is another new valuable marker of HBV infection, which consists of three species of related proteins, including hepatitis B core antigen, hepatitis B e antigen, and a truncated 22KDa precore protein [15]. Serum HBcrAg was also considered to be correlated with cccDNA activity and was a good biomarker in predicting HBeAg seroconversion in patients treated with peg-IFN [16,17].…”

Section: Introductionmentioning

confidence: 99%

Serum HBV RNA Correlated with Intrahepatic cccDNA More Strongly than other HBV Markers During Peg-Interferon Treatment

Wang

Chi

et al. 2020

Preprint

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Background: Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, whether HBV RNA is superior to other HBV markers reflecting cccDNA profile in HBeAg-positive patients during peg-interferon (peg-IFN) treatment was still unclear.Methods: Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. The intrahepatic cccDNA was detected at baseline and week 48, respectively. The individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were then statistically analyzed.Results: HBV RNA levels in patients with HBeAg seroconversion decreased more rapidly compared with those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks of treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. For subsequent analysis, cccDNA positively correlated with HBV RNA and HBcrAg whereas did not correlate with HBV DNA and HBsAg in patients with HBeAg seroconversion. However, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, while no correlation was observed between cccDNA and HBsAg in patients without HBeAg seroconversion.Conclusion: Serum HBV RNA correlated more strongly than HBcrAg, HBV DNA, and HBsAg with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment.Trial registration: ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530&cntry=&state=&city=&dist=

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“…This finding implies that repeated measurements of qHBcrAg would be needed in order to continuously and more accurately gauge the risk of HBeAgseroclearance. Indeed, other studies focusing on time-specific measurements of serum qHBcrAg levels have involved peg-IFN treatment in HBV mono-infected patients, with qHBcrAg measured at 12 weeks representing an important milestone for treatment response and stopping rules [18,29,41]. These studies have also demonstrated higher Se, but modest Sp when using qHBcrAg to predict HBeAg-seroconversion.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Hepatitis B Core–Related Antigen and Anti–Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus–Hepatitis B Coinfection

Dezanet

Maylin

Gabassi

et al. 2020

The Journal of Infectious Diseases

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Background The aim of the current study was to describe the kinetics of quantified hepatitis B core–related antigen (qHBcrAg) and quantified anti–hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus. Methods Serum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6–12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves. Results During a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (−0.051 and −0.011 log10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33–.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08–2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg <6.5 log10 U/mL at month 24 (Se, 1; Sp, 0.58) and baseline qAnti-HBc ≥4.1 log10 Paul Ehrlich Institute units/mL (Se, 0.42; Sp, 0.81). Conclusions In coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance.

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Comparison of hepatitis B virus core-related antigen and hepatitis B surface antigen for predicting HBeAg seroconversion in chronic hepatitis B patients with pegylated interferon therapy

Abstract: Early on-treatment qHBcrAg may be a good biomarker for predicting off-treatment HBeAg seroconversion in patients receiving PEG-IFN therapy.

Cited by 13 publications

References 28 publications

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Serum HBV RNA Correlated with Intrahepatic cccDNA More Strongly than other HBV Markers During Peg-Interferon Treatment

Kinetics of Hepatitis B Core–Related Antigen and Anti–Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus–Hepatitis B Coinfection

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