Evidence map›Paper›PMID 39624922›Full record

Trial reportAlimentary pharmacology & therapeutics2025

Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials.

Edo J Dongelmans, Jordan J Feld, André Boonstra, Sylvia M Brakenhoff, David Wong, Colina Yim, Mark Claassen, Pieter Honkoop, Bettina E Hansen, Robert A de Man and 5 more

Registry-linked trialAbstract readClinical Trial, Phase IVRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alimentary pharmacology & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01911156 (Sustained Off-treatment Response After HBeAg Loss in HBeAg-Pos Chronic Hepatitis B Patients Treated With Nucleos), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01911156 phase4unknown statusnot on this map

Sustained Off-treatment Response After HBeAg Loss in HBeAg-Pos Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues

TypeinterventionalSponsorUniversity Health Network, TorontoRan2013 to 2016Enrolled66ConditionsChronic Hepatitis BArmsContinue NA treatment, Discontinue NA Treatment
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Edo J DongelmansDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0003-2746-1643
Jordan J FeldToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
André BoonstraDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Sylvia M BrakenhoffDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0001-7687-4036
David WongToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Colina YimToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Mark ClaassenDepartment of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands.
Pieter HonkoopDepartment of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
Bettina E HansenToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Robert A de ManDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Scott FungToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.ORCID https://orcid.org/0000-0003-0501-8800
Thomas BergDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
Florian van BömmelDivision of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.ORCID https://orcid.org/0000-0003-2679-0672
Harry L A JanssenDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Milan J SonneveldDepartment of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0002-9253-563X

Funding

Stichting voor Lever- en Maag-Darm Onderzoek
6 · The paper itself

Abstract

backgroundSevere flares (ALT ≥ 10×ULN) are a well-recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance.

methodsData were used from two prospective studies on NA cessation conducted in the Netherlands and Canada. Patients were eligible based on EASL criteria. HBcrAg and anti-HBc levels were measured at end of treatment (EOT) and week 6 (FUW6). Logistic regression was used to study the association with severe flares.

resultsSeventy-eight patients were analysed with a mean age of 49 years, 16 (21%) Caucasian and a majority (65%) were treated with Tenofovir. Overall, 22 patients (28%) developed a severe flare, and 29 (37%) patients were retreated. At EOT, higher HBcrAg levels (aOR: 1.97, p = 0.05; ≥ 4log: 47% severe flare vs. < 3log: 19%, p = 0.036), lower anti-HBc (aOR: 0.29, p = 0.036; < 2log: 50% vs. ≥ 3log: 11%, p = 0.029) and higher HBcrAg/anti-HBc-ratio (aOR: 3.17, p = 0.015; ≥ 2: 58% vs. < 1.5: 14%, p < 0.001) were associated with an increased risk of severe flares, adjusted for HBsAg. At FUW6, higher HBcrAg (aOR: 2.91, p = 0.035; ≥ 5log: 83%, < 3log: 4%, p < 0.001), lower anti-HBc (aOR: 0.46, p = 0.29; < 2log: 50% vs. ≥ 3log: 0%, p = 0.003) and higher HBcrAg/anti-HBc-ratio (aOR: 2.19, p = 0.048; ≥ 1.75: 52% vs. < 1.75: 8%, p < 0.001) were associated with an increased risk of severe flares, adjusted for HBV DNA and ALT.

conclusionHigher HBcrAg, lower anti-HBc and higher HBcrAg/anti-HBc ratio at EOT and during the first weeks of post-treatment follow-up are associated with an increased risk of hepatic flares after NA withdrawal and could therefore potentially be used to select patients eligible for therapy cessation and to identify patients requiring retreatment.

trial registrationThis study was a post hoc and follow-up study of two previously registered clinical trials (NCT01911156 & NTR7001). No new patients were prospectively included.

Indexed as

Antiviral AgentsHepatitis B Core AntigensAdultCanadaFemaleHepatitis B AntibodiesHepatitis B, ChronicHumansMaleMiddle AgedNetherlandsProspective StudiesRisk FactorsTenofovirAntiviral AgentsHepatitis B AntibodiesHepatitis B Core AntigensTenofoviranti‐HBcdiscontinuationflaresHBcrAgHBV

Identifiers

PMID39624922
PMCPMC11707647

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.