Evidence map›Paper›PMID 41239780›Full record

ArticleThe Journal of infectious diseases2026

Anti-HBs Immune Complex Levels: A Novel Marker of Hepatitis Flare Following Nucleos(t)ide Analog Withdrawal in HBeAg-negative Chronic Hepatitis B.

S J Hume, K Visvanathan, K Cheng, K Jackson, S Vogrin, S A L Hall, G S Burns, P V Desmond, D Ratnam, M T Levy and 13 more

Registry-linked trialAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02581033 (Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT02581033 naunknown statusnot on this map

Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients

TypeinterventionalSponsorSt Vincent's Hospital MelbourneRan2014 to 2018Enrolled200ConditionsChronic Hepatitis B.ArmsNucleoside Analogue therapy
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. 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

23 authors.

S J HumeSt Vincent's Hospital, Melbourne, Victoria, Australia.ORCID 0009-0002-0435-6138
K VisvanathanSt Vincent's Hospital, Melbourne, Victoria, Australia.ORCID 0000-0002-1176-5442
K ChengDepartment of Medicine, The University of Melbourne, Victoria, Australia.
K JacksonVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
S VogrinDepartment of Medicine, The University of Melbourne, Victoria, Australia.ORCID 0000-0002-1597-9421
S A L HallSt Vincent's Hospital, Melbourne, Victoria, Australia.ORCID 0000-0001-7158-585X
G S BurnsWestern Health, Melbourne, Victoria, Australia.
P V DesmondSt Vincent's Hospital, Melbourne, Victoria, Australia.
D RatnamDepartment of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia.
M T LevyLiverpool Hospital, Sydney, New South Wales, Australia.
R SawhneyEastern Health, Melbourne, Victoria, Australia.ORCID 0000-0002-8131-2182
S I StrasserRoyal Prince Alfred Hospital, Sydney, New South Wales, Australia.ORCID 0000-0001-6374-1525
M C NguConcord Hospital, Sydney, New South Wales, Australia.
M SinclairAustin Health, Melbourne, Victoria, Australia.
C MeredithBankstown-Lidcombe Hospital, Sydney, New South Wales, Australia.
G MatthewsSt Vincent's Hospital Sydney, Sydney, New South Wales, Australia.
Z ValaydonWestern Health, Melbourne, Victoria, Australia.
D WongAustin Health, Melbourne, Victoria, Australia.ORCID 0000-0003-1490-0547
M LittlejohnVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.ORCID 0000-0002-8206-2664
J A HolmesSt Vincent's Hospital, Melbourne, Victoria, Australia.
P A RevillVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
A J ThompsonSt Vincent's Hospital, Melbourne, Victoria, Australia.
N WarnerVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.ORCID 0000-0002-4252-086X

Funding

National Health and Medical Research Council of Australia 1066536National Health and Medical Research Council of Australia 1142976
6 · The paper itself

Abstract

BACKGROUND AND

aimsHumoral immunity is thought to play a key role in the immunopathogenesis of chronic hepatitis B (CHB). Peaks in anti-HBs immune complexes (HBsAg-ICs) have been associated with subsequent HBsAg seroclearance. Discontinuation of nucleos(t)ide analog (NA) therapy can promote HBsAg seroclearance but also carries a risk of hepatitis flare. We evaluated the relationship between serum HBsAg-IC levels and hepatitis flare following NA cessation in HBeAg-negative CHB.

methodsIn a multicentre prospective cohort of noncirrhotic HBeAg-negative CHB patients undergoing NA discontinuation, we conducted a nested case-control analysis (n = 38). Stored serum samples were tested for HBsAg-IC at end-of-treatment (EOT) and at serial timepoints off-treatment. Cases (n = 24) experienced a hepatitis flare (ALT >5× upper limit of normal); controls (n = 14) did not. Associations between HBsAg-IC levels and clinical outcomes were analyzed.

resultsSerum HBsAg-ICs were detectable in 97% of participants at EOT. High HBsAg-IC levels (≥40 IU/mL) at EOT were less frequent among those who developed hepatitis flare (8%) versus controls (57%, P = .002). Individuals treated with tenofovir (vs other NAs) had lower EOT HBsAg-IC levels. Longitudinal analysis revealed dynamic increases in HBsAg-IC levels during hepatitis flare, peaking with maximal ALT. Participants who experienced beneficial flares (≥1 log₁₀ HBsAg reduction) had higher peak off-treatment HBsAg-IC levels compared to those with nonbeneficial flares.

conclusionsSerum HBsAg-ICs are detectable in patients with CHB, and low levels at EOT are associated with the risk of hepatitis flare after NA cessation. These findings support the role of humoral immunity in CHB immunopathogenesis. CLINICAL TRIALS REGISTRATION: The study clinical trial ID is NCT02581033.

Indexed as

Antigen-Antibody ComplexAntiviral AgentsHepatitis B AntibodiesHepatitis B, ChronicHepatitis B Surface AntigensNucleosidesAdultBiomarkersCase-Control StudiesFemaleHepatitis B e AntigensHumansMaleMiddle AgedProspective StudiesAntigen-Antibody ComplexAntiviral AgentsBiomarkersHepatitis B AntibodiesHepatitis B e AntigensHepatitis B Surface AntigensNucleosidesbiomarkerchronic hepatitis Bhepatitis flareimmune complexesnucleos(t)ide analog withdrawal

Identifiers

PMID41239780
PMCPMC13017444

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.