Association of Hepatitis B Core-Related Antigen With Hepatitis B Virus Reactivation in Occult Viral Carriers Undergoing High-Risk Immunosuppressive Therapy

Seto, Wai‐Kay; Wong, Danny Ka‐Ho; Chan, Thomas S. Y.; Hwang, Y.; Fung, James; Liu, Kevin Sze-Hang; Gill, Harinder; Lam, Yuk-Fai; Cheung, Ka‐Shing; Lie, Albert K. W.; Lai, Ching–Lung; Kwong, Yok–Lam; Yuen, Man‐Fung

doi:10.1038/ajg.2016.436

Cited by 66 publications

(44 citation statements)

References 34 publications

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“…In this regard, a recent study has shown that positivity to HBV core‐related antigen (HBcrAg) is a significant risk factor for HBV reactivation in anti‐HBc‐positive/HBsAg‐negative patients. This biomarker can potentially have a role in identifying patients who will benefit from anti‐HBV treatment …”

Section: Discussionmentioning

confidence: 99%

A snapshot of virological presentation and outcome of immunosuppression‐driven HBV reactivation from real clinical practice: Evidence of a relevant risk of death and evolution from silent to chronic infection

Salpini

Battisti

Colagrossi

et al. 2019

Journal of Viral Hepatitis

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The study was undertaken in order to provide a snapshot from real clinical practice of virological presentation and outcome of patients developing immunosuppression‐driven HBV reactivation. Seventy patients with HBV reactivation were included (66.2% treated with rituximab, 10% with corticosteroids and 23.8% with other immunosuppressive drugs). Following HBV reactivation, patients received anti‐HBV treatment for a median (IQR) follow‐up of 31(13‐47) months. At baseline‐screening, 72.9% of patients were HBsAg‐negative and 27.1% HBsAg‐positive. About 71.4% had a diagnosis of biochemical reactivation [median (IQR) HBV DNA and ALT: 6.9 (5.4‐7.8) log IU/mL and 359 (102‐775) U/L]. Moreover, 10% of patients died from hepatic failure. Antiviral prophylaxis was documented in 57.9% and 15.7% of HBsAg‐positive and HBsAg‐negative patients at baseline‐screening (median [IQR] prophylaxis duration: 24[15‐33] and 25[17‐36] months, respectively). Notably, HBV reactivation occurred 2‐24 months after completing the recommended course of anti‐HBV prophylaxis in 35.3% of patients. By analysing treatment outcome, the cumulative probability of ALT normalization and of virological suppression was 97% and 69%, respectively. Nevertheless, in patients negative to HBsAg at baseline‐screening, only 27% returned to HBsAg‐negative status during prolonged follow‐up, suggesting the establishment of chronic infection. In conclusion, most patients received a diagnosis of HBV reactivation accompanied by high ALT and 10% died for hepatic failure, supporting the importance of strict monitoring for an early HBV reactivation diagnosis. Furthermore, HBV reactivation correlates with high risk of HBV chronicity in patients negative for HBsAg at baseline‐screening, converting a silent into a chronic infection, requiring long‐term antiviral treatment. Finally, a relevant proportion of patients experienced HBV reactivation after completing the recommended course of anti‐HBV prophylaxis, suggesting the need to reconsider proper duration of prophylaxis particularly in profound immunosuppression.

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Section: Discussionmentioning

confidence: 99%

A snapshot of virological presentation and outcome of immunosuppression‐driven HBV reactivation from real clinical practice: Evidence of a relevant risk of death and evolution from silent to chronic infection

Salpini

Battisti

Colagrossi

et al. 2019

Journal of Viral Hepatitis

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“…This aberrant protein was also named HBcrAg. In the literature, the term “HBcrAg” has been used to describe a combination of HBc and HBe [13,86,87,88]; the supposedly aberrant p22cr [47]; and a combination of all three entities, HBc, HBe, and p22cr [89,90,91]. As discussed above, the so-called p22cr probably does not really exist and the current HBcrAg ELISA kit most likely detects a combination of HBcAg (released from virions) and HBeAg.…”

Section: Potential Applications Of Hbv Particles In Clinical Managmentioning

confidence: 99%

“…It was also found to predict liver cancer development and recurrence in HBV-infected patients, and was an even better predictor than serum HBV DNA [92,94]. Serum HBcrAg was also found to associate with reactivation of occult hepatitis B following immunosuppressive therapy [91]. …”

Section: Potential Applications Of Hbv Particles In Clinical Managmentioning

confidence: 99%

Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application

Liu

2017

Viruses

231

245

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Hepatitis B virus (HBV) is a para-retrovirus or retroid virus that contains a double-stranded DNA genome and replicates this DNA via reverse transcription of a RNA pregenome. Viral reverse transcription takes place within a capsid upon packaging of the RNA and the viral reverse transcriptase. A major characteristic of HBV replication is the selection of capsids containing the double-stranded DNA, but not those containing the RNA or the single-stranded DNA replication intermediate, for envelopment during virion secretion. The complete HBV virion particles thus contain an outer envelope, studded with viral envelope proteins, that encloses the capsid, which, in turn, encapsidates the double-stranded DNA genome. Furthermore, HBV morphogenesis is characterized by the release of subviral particles that are several orders of magnitude more abundant than the complete virions. One class of subviral particles are the classical surface antigen particles (Australian antigen) that contain only the viral envelope proteins, whereas the more recently discovered genome-free (empty) virions contain both the envelope and capsid but no genome. In addition, recent evidence suggests that low levels of RNA-containing particles may be released, after all. We will summarize what is currently known about how the complete and incomplete HBV particles are assembled. We will discuss briefly the functions of the subviral particles, which remain largely unknown. Finally, we will explore the utility of the subviral particles, particularly, the potential of empty virions and putative RNA virions as diagnostic markers and the potential of empty virons as a vaccine candidate.

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“…Serum HBcrAg levels were measured using a CLEIA HBcrAg Assay Kit (Fujirebio, Inc, Tokyo, Japan) according to the manufacturer's instructions on a Lumipulse G1200 Automated Analyzer (Fujirebio, Tokyo, Japan). The HBcrAg value was expressed as log U/mL, and the lower limit of detection was 2 log U/mL …”

Section: Methodsmentioning

confidence: 99%

The role of hepatitis B core‐related antigen in predicting hepatitis B virus recurrence after liver transplantation

Liu

et al. 2019

Aliment Pharmacol Ther

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Summary Background Hepatitis B core‐related antigen (HBcrAg) is a viral marker for the development of cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, the relationship between HBcrAg and HBV recurrence after liver transplantation (LT) is unclear. Aim To investigate the correlation of serum HBcrAg level with HBV recurrence post‐LT to evaluate the prognostic role of the pre‐LT HBcrAg level. Methods This retrospective cohort study enrolled 357 CHB patients who received LT for a median of 36.6 months. Univariate and multivariate analyses and time‐dependent receiver operating characteristic (ROC) curves for markers associated with HBV recurrence were analysed. Results 48 patients (13.4%) had HBV recurrence after LT. HBcrAg, detectable HBV DNA, HCC and HCC recurrence were associated with HBV recurrence. In a multivariate analysis, HBcrAg level was independently associated with HBV recurrence, and the relationship between HBcrAg level and incident HBV recurrence was significant and graded (HR: 3.17 per unit; 95% CI: 1.97‐5.11; P for trend < .001). Additionally, HBcrAg level was superior to HBV DNA level in predicting HBV recurrence by time‐dependent ROC analysis. Patients with an HBcrAg ≥ 5.0 log U/mL had a significantly higher 5‐year cumulative recurrence rate than those with an HBcrAg < 5.0 log U/mL (37.6% vs 6%, P < .001); the adjusted hazard ratio was 5.27 (95% CI 2.47‐11.25, P < .001). Conclusion An elevated serum HBcrAg level was independently associated with the risk of HBV recurrence in patients with CHB after LT.

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Association of Hepatitis B Core-Related Antigen With Hepatitis B Virus Reactivation in Occult Viral Carriers Undergoing High-Risk Immunosuppressive Therapy

Cited by 66 publications

References 34 publications

A snapshot of virological presentation and outcome of immunosuppression‐driven HBV reactivation from real clinical practice: Evidence of a relevant risk of death and evolution from silent to chronic infection

A snapshot of virological presentation and outcome of immunosuppression‐driven HBV reactivation from real clinical practice: Evidence of a relevant risk of death and evolution from silent to chronic infection

Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application

The role of hepatitis B core‐related antigen in predicting hepatitis B virus recurrence after liver transplantation

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