Evidence dossier · candidate cand-hepatitis-b-hepatitis · VICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that Hepatitis B vaccine causes Hepatitis, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
supported
C2
Consistent temporal window
supported
C3
Epidemiologic excess risk
insufficient_data
missing: B1 B2
C4
Consistency / replication
insufficient_data
missing: B5 B6
C5
Specificity (product / dose)
insufficient_data
missing: C1n C2n
C6
Biological mechanism
insufficient_data
missing: E1
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: no established case definition (needs_human_review — not in spec §1's named-standard list) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportsno_data
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: Only one case report describes new hepatitis (MS-related neurological symptoms, not hepatitis) and no case reports describe new hepatitis attributed to Hepatitis B vaccine with onset in a risk window after vaccination and assessment of competing causes.
Case-certainty distribution (no established case definition): 3 Probable, 3 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Case reports pubmed · 66626 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
19 retrieved record(s)
supports_node 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
does_not_resolve 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
supports_node 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
does_not_resolve 30139924 · Journal of the Royal Army Medical Corps (2019) — Hepatitis B in a vaccinated soldier: a case report.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
ambiguous 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
A2 · Series with objective confirmationno_data
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: One case report describes acute hepatitis B in a hepatitis B vaccine non-responder, and another reports hepatitis B in a vaccinated soldier, but neither provides objective confirmation of new hepatitis attributed to the vaccine with onset within a pre-specified risk window after competing causes were assessed; the remaining retrieved evidence does not address this specific node.
Case-certainty distribution (no established case definition): 2 Probable, 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
supporting: Hepatitis B vaccine Hepatitis case report OR case series Series with objective confirmation pubmed · 6108 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
18 retrieved record(s)
does_not_resolve 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
ambiguous 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
does_not_resolve 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
does_not_resolve 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
supports_node 30139924 · Journal of the Royal Army Medical Corps (2019) — Hepatitis B in a vaccinated soldier: a case report.
supports_node 11784358 · European journal of neurology (2001) — Hepatitis B vaccine related-myelitis?
A3 · Onset histogramno_data
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: The retrieved evidence does not contain any reports of new Hepatitis attributed to Hepatitis B vaccine with onset within a pre-specified risk window. The relevant case reports describe acute hepatitis B in vaccine non‑responders and vaccine escape, which are not cases of vaccine-attributed hepatitis but rather vaccine failure; other reports describe different adverse events (e.g., multiple sclerosis, Bell’s palsy, lichenoid reaction, ocular complications) and are not about hepatitis after vaccination.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Onset histogram pubmed · 467 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
20 retrieved record(s)
ambiguous 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
does_not_resolve 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
ambiguous 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
supports_node 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
ambiguous 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
A4 · Temporal plausibilityno_data
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: The retrieved evidence includes only case reports and case series of autoimmune or neurological adverse events after hepatitis B vaccination (e.g., multiple sclerosis, Bell's palsy, lichenoid reaction) but no reports of hepatitis (liver inflammation attributed to the vaccine) with onset latency consistent with hepatitis pathophysiology. One case report describes acute hepatitis B in a vaccine non-responder, which is vaccine failure, not an adverse event.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Temporal plausibility pubmed · 495 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
18 retrieved record(s)
ambiguous 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
ambiguous 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
ambiguous 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
refutes_node 30139924 · Journal of the Royal Army Medical Corps (2019) — Hepatitis B in a vaccinated soldier: a case report.
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
supports_node 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
A5 · Onset-interval documentationno_data
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: Two case reports describe hepatitis B vaccine recipients developing hepatitis-like conditions with documented onset intervals: one patient developed acute hepatitis B after vaccination (onset interval not explicitly stated in abstract but vaccine non-response is noted), and another developed lichenoid reaction with liver involvement 5 weeks after the second dose; evidence is limited to case reports and does not directly address the specific node requirement of documented onset interval for new hepatitis attributed to the vaccine.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Onset-interval documentation pubmed · 465 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
20 retrieved record(s)
supports_node 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
supports_node 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
ambiguous 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
supports_node 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
does_not_resolve 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
A6 · Differential diagnosis excludedno_data
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: The retrieved evidence includes a case report of acute hepatitis B in a hepatitis B vaccine non-responder (PMID 38819810), but does not describe assessment or exclusion of competing causes for a new hepatitis event attributed to the vaccine. Other retrieved articles address adverse events from hepatitis B or other vaccines but none directly assess exclusion of competing diagnoses for hepatitis B vaccine-related hepatitis.
Case-certainty distribution (no established case definition): 2 Probable, 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Differential diagnosis excluded pubmed · 892 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
14 retrieved record(s)
ambiguous 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
does_not_resolve 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: One case series (PMID 15638050) reports positive re-challenge of symptoms following hepatitis B vaccination for conditions such as arthritis, myelitis, optic neuritis, and multiple sclerosis, but no retrieved evidence describes recurrence of hepatitis (the specific object) after a subsequent vaccine dose.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Rechallenge / re-exposure pubmed · 467 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
20 retrieved record(s)
supports_node 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
ambiguous 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
supports_node 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
ambiguous 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
A8 · Adjudicated by criteria (no established case definition)no_data
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: The retrieved evidence includes a case report of acute hepatitis B in a hepatitis B vaccine non-responder (PMID 38819810) and another case of hepatitis B in a vaccinated soldier (PMID 30139924), but neither case is adjudicated as 'definite' hepatitis attributed to the vaccine by a published criterion set, nor do they report onset within a pre-specified risk window after vaccination with competing causes assessed per the node's working definition. Other retrieved articles address unrelated adverse events or different vaccines.
Case-certainty distribution (no established case definition): 2 Probable, 2 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Adjudicated by criteria pubmed · 504 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
19 retrieved record(s)
does_not_resolve 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
supports_node 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
ambiguous 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
ambiguous 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
supports_node 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
ambiguous 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
A9 · Natural-history consistencyno_data
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: The retrieved evidence includes a single case report of a patient who developed acute hepatitis B after hepatitis B vaccination in a non-responder, but this describes failure of protection rather than vaccine-induced hepatitis, and no evidence describes a clinical course of new-onset hepatitis matching the natural history of hepatitis as an adverse event following vaccination.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series Natural-history consistency pubmed · 568 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
18 retrieved record(s)
supports_node 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
supports_node 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
supports_node 26411737 · Journal of medical case reports (2015) — Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.
supports_node 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
supports_node 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
does_not_resolve 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
A10 · No confounding objectno_data
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: None of the retrieved case reports describe new-onset hepatitis causally attributed to the hepatitis B vaccine. Reports of hepatitis B occurring after vaccination describe breakthrough infections in non-responders or vaccinated individuals, not vaccine-attributed hepatitis.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis case report OR case series No confounding object pubmed · 484 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis alternative diagnosis OR not vaccine-related pubmed · 4118 hits · run 2026-09-07
18 retrieved record(s)
does_not_resolve 38819810 · International journal of STD & AIDS (2024) — Acute hepatitis B in a hepatitis B vaccine non-responder.
ambiguous 36348919 · Cureus (2022) — Hepatitis B Vaccine and Multiple Sclerosis: Cause or Coincidence.
supports_node 39664732 · Clinical case reports (2024) — Lower Motor Neuron Facial Nerve Paralysis Following Recombinant Hepatitis B Vaccine Administration: A Case Report and Literature Review.
ambiguous 9293664 · The Australasian journal of dermatology (1997) — Lichenoid reaction to hepatitis B vaccination.
ambiguous 35198830 · American journal of ophthalmology case r (2022) — Paracentral acute middle maculopathy following hepatitis B vaccine.
ambiguous 34797375 · JAMA (2021) — Serologic Testing for Hepatitis B.
does_not_resolve 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
does_not_resolve 30139924 · Journal of the Royal Army Medical Corps (2019) — Hepatitis B in a vaccinated soldier: a case report.
D1 · Predicted site of injuryno_data
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
mirror: Hepatitis B vaccine Hepatitis Spared structures not consistent with mechanism pubmed · 2 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 29243216 · AAPS PharmSciTech (2018) — Lipid A adjuvanted Chylomicron Mimicking Solid Fat Nanoemulsions for Immunization Against Hepatitis B.
does_not_resolve 15884749 · Journal of health, population, and nutri (2005) — Introducing hepatitis B virus vaccine into the Expanded Programme on Immunization in Bangladesh: a proposed method to evaluate whether the existing infrastructu
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: The abstract discusses safety and immunogenicity of a combined DTaP/PRP-T vaccine versus separate injections, but does not mention hepatitis B vaccine, hepatitis adverse events, or any distribution (local vs systemic) of such events.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Local vs systemic distribution not consistent with mechanism pubmed · 1 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 9306481 · The Pediatric infectious disease journal (1997) — Vaccine antigen interactions after a combination diphtheria-tetanus toxoid-acellular pertussis/purified capsular polysaccharide of Haemophilus influenzae type b
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
Finding: The retrieved evidence describes the kinetics of anti-HBs antibody production and immune responses after hepatitis B vaccination, but does not address onset or offset kinetics of hepatitis disease attributed to the vaccine, nor provides data on a pre-specified risk window for hepatitis onset after vaccination.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis anatomic localization Kinetics class mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Kinetics class not consistent with mechanism pubmed · 5 hits · run 2026-09-07
5 retrieved record(s)
does_not_resolve 8950683 · Journal of medical virology (1996) — Nonresponse to hepatitis B vaccines and the kinetics of anti-HBs production.
does_not_resolve 6228457 · Developments in biological standardizati (1983) — Kinetics, subtype specificity and immunoglobulin class of anti-HBs induced by hepatitis B vaccine.
does_not_resolve 31687875 · Human vaccines & immunotherapeutics (2020) — A dendritic cell-targeted chimeric hepatitis B virus immunotherapeutic vaccine induces both cellular and humoral immune responses in vivo.
does_not_resolve 9831134 · Human immunology (1998) — Binding specificity of a class II-restricted hepatitis B epitope by DR molecules from responder and nonresponder vaccine recipients.
does_not_resolve 19031766 · Zhonghua liu xing bing xue za zhi = Zhon (2008) — [Cellular immune responses of recombinant hepatitis B (rHB) vaccine and HBsAG derived from Hansenula polymorpha cells].
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis anatomic localization Platform-mechanism match mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Targeted treatment reverses no effect intervention pubmed · 4 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 25034480 · Intervirology (2014) — Molecular virology of hepatitis B virus and targets for antiviral intervention.
does_not_resolve 26652035 · Expert review of vaccines (2016) — Prospects and progress of DNA vaccines for treating hepatitis B.
does_not_resolve 15885458 · International journal of pharmaceutics (2005) — Non-ionic surfactant based vesicles (niosomes) for non-invasive topical genetic immunization against hepatitis B.
I1 · No internal contradictionno_data
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis No internal contradiction coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis No internal contradiction inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: No evidence found.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Analogy to a known object coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Analogy to a known object inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
2 retrieved record(s)
ambiguous 15578364 · Clinical infectious diseases : an offici (2004) — Varicella vaccine for susceptible adults: do it today.
does_not_resolve 19477561 · Vaccine (2009) — Genetic polymorphisms in host response to meningococcal infection: the role of susceptibility and severity genes.
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Latency coherence coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Latency coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
J1 · Pre-specificationno_data
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: The retrieved evidence discusses the use of large language models to detect immune-related adverse events from immune checkpoint inhibitors and an AI system for adjudicating major adverse cardiovascular events in clinical trials, but neither study addresses the pre-specification of a risk window or hit rule for hepatitis attributable to hepatitis B vaccine.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Pre-specification pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Pre-specification post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J2 · Contrary-evidence logno_data
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Contrary-evidence log pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
J3 · No temporality-only claimno_data
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: The retrieved evidence describes a study using LLMs to identify immune-related adverse events from immune checkpoint inhibitors, not hepatitis B vaccine-related hepatitis.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis No temporality-only claim pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
J4 · Passive-surveillance roleno_data
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: No evidence found.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Passive-surveillance role pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
J5 · Dose mappingno_data
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Dose mapping pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Dose mapping post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselineno_data
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Excess vs baseline pubmed · 90904 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
does_not_resolve 34762265 · Journal of gastrointestinal cancer (2021) — Hepatitis B Before and After Hepatocellular Carcinoma.
B2 · SCCSno_data
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: No retrieved evidence from the provided list addresses a self-controlled case series (SCCS) risk ratio for hepatitis attributed to hepatitis B vaccination; the available PMIDs either do not use an SCCS design for this specific pair or do not report a risk ratio for hepatitis after hepatitis B vaccine.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis SCCS incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk SCCS pubmed · 91011 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
B3 · Cohort / risk-intervalno_data
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: The retrieved evidence includes an umbrella review of meta-analyses on hepatitis B vaccine efficacy and safety (PMID 38055218), but it does not report any incidence rate ratios (IRR) or cohort/risk-interval analyses for hepatitis (as a disease) following hepatitis B vaccination. No retrieved study provides an IRR > 1 with a CI excluding 1, stratified by age/sex, in a pre-specified risk window.
supporting: Hepatitis B vaccine Hepatitis Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Cohort / risk-interval pubmed · 90513 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
ambiguous 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: No retrieved evidence presents a pooled estimate with quantified heterogeneity (I²) for the association between hepatitis B vaccine and hepatitis. The only meta-analysis identified (PMID 38055218) is an umbrella review of efficacy and safety, but no pooled risk estimate >1 or <1 for hepatitis as an adverse event is reported.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 946 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Meta-analysis / pooling pubmed · 114346 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
B5 · Negative-control outcomesno_data
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: No retrieved evidence addresses the specific negative-control outcome of new hepatitis attributed to hepatitis B vaccine after competing causes are assessed; the available studies focus on vaccine efficacy, seroprotection, non-response, safety in pregnancy, musculoskeletal adverse events, and unrelated topics (antipsychotics, shingles vaccines).
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Negative-control outcomes pubmed · 90715 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
does_not_resolve 34762265 · Journal of gastrointestinal cancer (2021) — Hepatitis B Before and After Hepatocellular Carcinoma.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Other-antigen comparison pubmed · 90477 hits · run 2026-09-07
13 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
B7 · Absolute riskno_data
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: No retrieved evidence reports absolute risk per 100,000 for hepatitis attributed to hepatitis B vaccine within a pre-specified risk window; the retrieved literature focuses on vaccine efficacy, non-response, and non-hepatitis adverse events.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Absolute risk incidence risk cohort OR self-controlled case series pubmed · 947 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Absolute risk pubmed · 113747 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
B8 · Platform splitno_data
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: The retrieved evidence does not include any study that assesses the risk of hepatitis attributable to a specific Hepatitis B vaccine platform or product; it includes general safety reviews, immunogenicity studies, and one VAERS analysis of musculoskeletal events, none of which address a platform-specific risk for hepatitis.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Platform split incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Platform split pubmed · 90542 hits · run 2026-09-07
12 retrieved record(s)
refutes_node 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
B9 · Host-structure stratificationno_data
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: No retrieved evidence addresses risk of hepatitis attributed to hepatitis B vaccine concentrated in a defined host subgroup (e.g., by age, sex, or other host structure). The retrieved studies focus on other vaccines, other outcomes, or hepatitis B vaccine efficacy and non-response but not on incident hepatitis after vaccination stratified by host subgroup.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Host-structure stratification pubmed · 90475 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
ambiguous 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
B10 · Formulation / component changeno_data
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no association OR null OR no increased risk Formulation / component change pubmed · 90637 hits · run 2026-09-07
13 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 38055218 · Expert review of vaccines (2024) — Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.
does_not_resolve 38908915 · Best practice & research. Clinical obste (2024) — Screening for viral hepatitis carriage.
does_not_resolve 33358507 · Bulletin du cancer (2021) — [Hepatitis B vaccine and liver cancer].
does_not_resolve 10776195 · Journal of pediatric health care : offic (1999) — Hepatitis B vaccine.
H2 · Formulation natural experimentno_data
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Formulation natural experiment intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Formulation natural experiment no effect intervention pubmed · 1 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 19239919 · Journal of controlled release : official (2009) — Synthesis, characterization and evaluation of novel triblock copolymer based nanoparticles for vaccine delivery against hepatitis B.
H4 · Policy / pause signalno_data
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Policy / pause signal intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Infection coherence coherence OR latency OR susceptibility pubmed · 870070 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Infection coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 15578364 · Clinical infectious diseases : an offici (2004) — Varicella vaccine for susceptible adults: do it today.
does_not_resolve 19477561 · Vaccine (2009) — Genetic polymorphisms in host response to meningococcal infection: the role of susceptibility and severity genes.
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: No retrieved evidence examines a monotonic dose-response relationship between hepatitis B vaccine dose strength and the risk of new hepatitis attributed to the vaccine.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Dose strength gradient dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no dose effect OR no dose-response Dose strength gradient pubmed · 1676 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39616603 · JAMA (2025) — HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse: The BEe-HIVe Randomized Clinical Trial.
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 32186974 · Human vaccines & immunotherapeutics (2020) — Hepatitis B vaccine development and implementation.
does_not_resolve 28905444 · Reviews in medical virology (2017) — Response to hepatitis B vaccination in patients with liver cirrhosis.
does_not_resolve 39057781 · Pathogens (Basel, Switzerland) (2024) — Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.
does_not_resolve 33369439 · Asian Pacific journal of cancer preventi (2020) — Vaccination against Hepatitis B: A Scoping Review.
does_not_resolve 35906803 · The Annals of pharmacotherapy (2023) — PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: No retrieved evidence directly assesses the risk of hepatitis (as an adverse event) following hepatitis B vaccine across doses (1st vs 2nd vs 3rd). The only study examining dose number (PMID 36519244) evaluated vaccine dose (5 μg vs 10 μg) and protection against HBV infection, not adverse events. Other retrieved studies discuss vaccine efficacy, immunogenicity, or general adverse event reporting but do not stratify hepatitis risk by dose number.
supporting: Hepatitis B vaccine Hepatitis Dose number gradient dose-response OR dose effect pubmed · 1299194 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no dose effect OR no dose-response Dose number gradient pubmed · 2119 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 32186974 · Human vaccines & immunotherapeutics (2020) — Hepatitis B vaccine development and implementation.
does_not_resolve 28905444 · Reviews in medical virology (2017) — Response to hepatitis B vaccination in patients with liver cirrhosis.
does_not_resolve 39057781 · Pathogens (Basel, Switzerland) (2024) — Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.
does_not_resolve 33369439 · Asian Pacific journal of cancer preventi (2020) — Vaccination against Hepatitis B: A Scoping Review.
does_not_resolve 35906803 · The Annals of pharmacotherapy (2023) — PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.
does_not_resolve 16625613 · The Cochrane database of systematic revi (2006) — Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: No retrieved evidence examines the risk of new hepatitis (as an adverse event) according to measured-exposure tertiles of Hepatitis B vaccine dose. The available studies focus on vaccine effectiveness, immunogenicity, or safety surveillance, but none provide risk estimates stratified by measured exposure tertile.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Measured-exposure tertiles dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no dose effect OR no dose-response Measured-exposure tertiles pubmed · 1565 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39616603 · JAMA (2025) — HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse: The BEe-HIVe Randomized Clinical Trial.
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 32186974 · Human vaccines & immunotherapeutics (2020) — Hepatitis B vaccine development and implementation.
does_not_resolve 28905444 · Reviews in medical virology (2017) — Response to hepatitis B vaccination in patients with liver cirrhosis.
does_not_resolve 39057781 · Pathogens (Basel, Switzerland) (2024) — Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.
does_not_resolve 33369439 · Asian Pacific journal of cancer preventi (2020) — Vaccination against Hepatitis B: A Scoping Review.
does_not_resolve 35906803 · The Annals of pharmacotherapy (2023) — PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Organoid concentration curve dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no dose effect OR no dose-response Organoid concentration curve pubmed · 1576 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39616603 · JAMA (2025) — HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse: The BEe-HIVe Randomized Clinical Trial.
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 32186974 · Human vaccines & immunotherapeutics (2020) — Hepatitis B vaccine development and implementation.
does_not_resolve 28905444 · Reviews in medical virology (2017) — Response to hepatitis B vaccination in patients with liver cirrhosis.
does_not_resolve 39057781 · Pathogens (Basel, Switzerland) (2024) — Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.
does_not_resolve 33369439 · Asian Pacific journal of cancer preventi (2020) — Vaccination against Hepatitis B: A Scoping Review.
does_not_resolve 35906803 · The Annals of pharmacotherapy (2023) — PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.
C5n · EC50 vs Cmax coherenceno_data
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: No retrieved evidence addresses whether the achieved exposure (Cmax/tissue) of the hepatitis B vaccine plausibly reaches an in-vitro EC50 for hepatitis, or provides any pharmacokinetic or pharmacodynamic data relevant to this node.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 1565 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39616603 · JAMA (2025) — HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse: The BEe-HIVe Randomized Clinical Trial.
does_not_resolve 32186974 · Human vaccines & immunotherapeutics (2020) — Hepatitis B vaccine development and implementation.
does_not_resolve 28905444 · Reviews in medical virology (2017) — Response to hepatitis B vaccination in patients with liver cirrhosis.
does_not_resolve 39057781 · Pathogens (Basel, Switzerland) (2024) — Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.
does_not_resolve 33369439 · Asian Pacific journal of cancer preventi (2020) — Vaccination against Hepatitis B: A Scoping Review.
does_not_resolve 36519244 · Human vaccines & immunotherapeutics (2022) — Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.
does_not_resolve 35906803 · The Annals of pharmacotherapy (2023) — PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.
E1 · Mediator identified in casesno_data
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Mediator identified in cases not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E2 · Mediator in healthy vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Mediator in healthy vaccinees not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E3 · Infection contrastno_data
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: No evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Infection contrast in vitro OR patient-derived pubmed · 29246 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Infection contrast not associated mechanism pubmed · 188 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 40043858 · Gastroenterology (2025) — The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Hum
does_not_resolve 26854115 · Liver international : official journal o (2016) — New therapies for chronic hepatitis B.
does_not_resolve 26246574 · Journal of virology (2015) — Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection.
does_not_resolve 19100234 · Enfermedades infecciosas y microbiologia (2008) — [Hepatitis B in patients with HIV infection].
does_not_resolve 39945620 · International journal of cancer (2025) — Scientific approaches to defining HPV vaccine-induced protective immunity.
does_not_resolve 29097876 · World journal of gastroenterology (2017) — Testing for hepatitis B virus alone does not increase vaccine coverage in non-immunized persons.
does_not_resolve 23916846 · Gastroenterology (2013) — The hepatitis B vaccine protects re-exposed health care workers, but does not provide sterilizing immunity.
does_not_resolve 7647280 · Biomedicine & pharmacotherapy = Biomedec (1995) — Immunotherapy of chronic hepatitis B by anti HBV vaccine.
E4 · Transfer to recipientmixed
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: PMID 6235453 reports a placebo-controlled trial where hepatitis B vaccine did not reduce hepatitis B incidence in hemodialysis patients (6.4% vs 5.4%), but does not address transfer of hepatitis to naive recipients. PMID 8514268, 8050180, 11035369, 12558909, 17650294, and 26166767 describe adoptive transfer of hepatitis B immunity (anti-HBs or cellular responses) via bone marrow or liver transplantation from vaccinated donors to naive recipients, not transfer of hepatitis disease itself.
supporting: Hepatitis B vaccine Hepatitis mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Transfer to recipient not associated mechanism pubmed · 19 hits · run 2026-09-07
10 retrieved record(s)
refutes_node 6235453 · The New England journal of medicine (1984) — Hepatitis B vaccine in patients receiving hemodialysis. Immunogenicity and efficacy.
does_not_resolve 8514268 · Hepatology (Baltimore, Md.) (1993) — Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors.
does_not_resolve 17650294 · Journal of viral hepatitis (2007) — Cellular and humoral immune response to a third generation hepatitis B vaccine.
does_not_resolve 26166767 · Cellular & molecular immunology (2016) — Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV tr
does_not_resolve 18816503 · Reviews in medical virology (2009) — Hepatitis B and liver transplantation: 2008 update.
does_not_resolve 24103275 · Hepatobiliary & pancreatic diseases inte (2013) — Prevention of recurrent hepatitis B infection after liver transplantation.
does_not_resolve 11282206 · Vaccine (2001) — Unique immunogenicity of hepatitis B virus DNA vaccine presented by live-attenuated Salmonella typhimurium.
does_not_resolve 8050180 · Clinical and experimental immunology (1994) — Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from im
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: No retrieved evidence addresses the transfer of hepatitis attributed to hepatitis B vaccine via a specific mediator, nor describes a transfer experiment in which removal of the mediator abolishes the effect.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Transfer specificity in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Transfer specificity not associated mechanism pubmed · 46 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 31809638 · Human vaccines & immunotherapeutics (2020) — Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance.
does_not_resolve 28276802 · Infectious diseases (London, England) (2017) — No response to hepatitis B vaccine in infants born to HBsAg(+) mothers is associated to the transplacental transfer of HBsAg.
does_not_resolve 29540592 · Journal of virology (2018) — Domains of the Hepatitis B Virus Small Surface Protein S Mediating Oligomerization.
does_not_resolve 12660511 · Transplantation (2003) — Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation.
does_not_resolve 11282206 · Vaccine (2001) — Unique immunogenicity of hepatitis B virus DNA vaccine presented by live-attenuated Salmonella typhimurium.
does_not_resolve 31994701 · The Journal of infectious diseases (2021) — Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.
does_not_resolve 9382772 · Behring Institute Mitteilungen (1997) — Manipulation of immune responses via particle-mediated polynucleotide vaccines.
does_not_resolve 32001321 · Gastroenterology (2020) — Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-Titer Hepatitis B Virus Carrier Mice.
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Depletion / knockdown not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E7 · Add-back rescueno_data
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Add-back rescue in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Add-back rescue not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E8 · Neutralizationno_data
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: No retrieved evidence describes neutralization of a mediator (e.g., a specific immune or pathogenic mediator) that blocks a hepatitis phenotype attributed to the hepatitis B vaccine; the papers discuss vaccine-induced anti-HBs neutralization of HBV, not neutralization of a vaccine-elicited mediator that blocks an adverse event phenotype.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Neutralization in vitro OR patient-derived pubmed · 29247 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Neutralization not associated mechanism pubmed · 165 hits · run 2026-09-07
does_not_resolve 25483515 · Human vaccines & immunotherapeutics (2015) — Hepatitis B vaccination.
does_not_resolve 40043858 · Gastroenterology (2025) — The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Hum
does_not_resolve 36064848 · Nature communications (2022) — Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen.
does_not_resolve 41355797 · JCI insight (2025) — Anti-PD-L1-IFN-α-adjuvanted HBsAg vaccine overcomes HBV immune tolerance through targeting both DCs and macrophages.
does_not_resolve 28453967 · Current opinion in virology (2017) — Therapeutic vaccination for chronic hepatitis B.
does_not_resolve 38220203 · Uirusu (2023) — [Neutralization of hepatitis B virus with vaccine-escape mutations by novel hepatitis B vaccine with large-HBs antigen].
does_not_resolve 35676468 · Journal of medical virology (2022) — Longitudinal mapping of hepatitis B vaccine-induced B-cell linear epitopes in healthy individuals.
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: No evidence found in the retrieved abstracts that describes the use or failure of an isotype control in relation to Hepatitis B vaccine and hepatitis.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Isotype control in vitro OR patient-derived pubmed · 29246 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Isotype control not associated mechanism pubmed · 169 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 34516961 · American journal of obstetrics and gynec (2022) — Treatment and prevention of viral hepatitis in pregnancy.
does_not_resolve 36601747 · Sexually transmitted infections (2023) — Hepatitis A and B vaccine uptake and immunisation among men who have sex with men seeking PrEP: a substudy of the ANRS IPERGAY trial.
does_not_resolve 27156634 · Vaccine (2016) — Novel nanocarrier for oral Hepatitis B vaccine.
does_not_resolve 25738667 · The New England journal of medicine (2015) — Long-term efficacy of a hepatitis E vaccine.
does_not_resolve 28847980 · Pediatrics (2017) — Elimination of Perinatal Hepatitis B: Providing the First Vaccine Dose Within 24 Hours of Birth.
does_not_resolve 42124375 · Journal of viral hepatitis (2026) — Long-Term Persistence of Hepatitis A Virus Immunity in Healthcare Workers Upto 25 Years After Vaccination.
does_not_resolve 8158817 · JAMA (1994) — Protection against hepatitis A by an inactivated vaccine.
does_not_resolve 30208475 · JAMA pediatrics (2018) — Immunogenicity and Safety of Monovalent Acellular Pertussis Vaccine at Birth: A Randomized Clinical Trial.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Full product reproduces component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Empty vector / particle component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Empty vector / particle no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
does_not_resolve 42172979 · Virology (2026) — Towards the development of a mucosal vectored vaccine against enterovirus D68.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: No retrieved evidence discusses Hepatitis B vaccine causing hepatitis, nor does any study evaluate irrelevant cargo failing to reproduce the effect in that context.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Irrelevant cargo component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Irrelevant cargo no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Infection preparation component OR antigen OR vector pubmed · 2045314 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Infection preparation no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Cytokine / adjuvant mix no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Component combination component OR antigen OR vector pubmed · 2045367 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Component combination no effect component isolation pubmed · 1 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 8854010 · Developments in biological standardizati (1996) — Analysis of vaccine stability.
does_not_resolve 11864474 · Zhonghua yu fang yi xue za zhi [Chinese (1999) — [Component in diphtheria-pertussis-tetanus-hepatitis B vaccine].
does_not_resolve 27996332 · Expert review of vaccines (2017) — DTaP5-IPV-Hib-HepB, a hexavalent vaccine for infants and toddlers.
supports_node 32001321 · Gastroenterology (2020) — Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-Titer Hepatitis B Virus Carrier Mice.
G1 · 2D human cellsno_data
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: No evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis 2D human cells animal OR organoid OR cell model pubmed · 1818667 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis 2D human cells not reproduced model pubmed · 5 hits · run 2026-09-07
5 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
does_not_resolve 10223330 · Biological chemistry (1999) — Enhancing the immunogenicity of exogenous hepatitis B surface antigen-based vaccines for MHC-I-restricted T cells.
does_not_resolve 26479036 · Human vaccines & immunotherapeutics (2016) — Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation.
does_not_resolve 7666497 · Journal of virology (1995) — Nucleic acid vaccination primes hepatitis B virus surface antigen-specific cytotoxic T lymphocytes in nonresponder mice.
does_not_resolve 8957677 · Intervirology (1996) — Virus-like particles induce MHC class I-restricted T-cell responses. Lessons learned from the hepatitis B small surface antigen.
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: The study models steatohepatitis (fatty liver disease) with hepatitis-like inflammation and fibrosis using pluripotent stem cell-derived liver organoids, but does not investigate Hepatitis B vaccine as a trigger for Hepatitis or any vaccine-related adverse effect.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Organoid / chip animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
1 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
1 retrieved record(s)
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis mechanism Host-line dependence in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Host-line dependence not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G3 · Animal, clinical routeno_data
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: No retrieved evidence describes reproduction of hepatitis in an animal model via the clinical route of administration after hepatitis B vaccination.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Animal, clinical route animal OR organoid OR cell model pubmed · 1818669 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Animal, clinical route not reproduced model pubmed · 8 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
does_not_resolve 39540194 · Cureus (2024) — Awareness and Knowledge of Hepatitis B Vaccination Among Newly Enrolled First-Year Medical Undergraduates in South India: A Cross-Sectional Survey.
does_not_resolve 29510155 · Antiviral research (2018) — Nasal route favors the induction of CD4(+) T cell responses in the liver of HBV-carrier mice immunized with a recombinant hepatitis B surface- and core-based th
does_not_resolve 23924493 · Hepatobiliary & pancreatic diseases inte (2013) — HBsAg, HBcAg, and combined HBsAg/HBcAg-based therapeutic vaccines in treating chronic hepatitis B virus infection.
does_not_resolve 24911598 · International reviews of immunology (2016) — HBIG Remains Significant in the Era of New Potent Nucleoside Analogues for Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.
does_not_resolve 14505916 · Vaccine (2003) — Phase II safety and immunogenicity study of type F botulinum toxoid in adult volunteers.
does_not_resolve 20883166 · Viral immunology (2010) — The effect of the parenteral route of administration on the immune response to simultaneous nasal and parenteral immunizations using a new HBV therapeutic vacci
does_not_resolve 29454622 · Journal of pharmaceutical sciences (2018) — Development of Adjuvanted Solid Fat Nanoemulsions for Pulmonary Hepatitis B Vaccination.
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: No retrieved evidence describes an animal model in which administration of hepatitis B vaccine causes hepatitis; one paper discusses a chimpanzee model for hepatitis B virus infection, but not vaccine-induced disease.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Susceptible animal animal OR organoid OR cell model pubmed · 1818685 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Susceptible animal not reproduced model pubmed · 29 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
does_not_resolve 26033082 · Cold Spring Harbor perspectives in medic (2015) — The chimpanzee model for hepatitis B virus infection.
does_not_resolve 12782052 · International journal for parasitology (2003) — Hepatitis vaccines: recent advances.
does_not_resolve 25523197 · Medical microbiology and immunology (2015) — Mouse models for therapeutic vaccination against hepatitis B virus.
does_not_resolve 17634218 · Journal of virology (2007) — A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge.
refutes_node 12093985 · Pediatrics (2002) — No evidence of autoimmunity in 6-year-old children immunized at birth with recombinant hepatitis B vaccine.
does_not_resolve 1204971 · Developments in biological standardizati (1975) — Viral hepatitis type B: propects for active immunization.
does_not_resolve 34407383 · Human vaccines & immunotherapeutics (2021) — Hepatitis B virus infection seromarkers among college freshmen and their immune responses to different vaccination policies of hepatitis B vaccine.
G5 · Replication across labsno_data
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Replication across labs animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
1 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: No evidence found that addresses blinded assessment of primary outcomes for hepatitis attributed to Hepatitis B vaccine.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Blinded scoring animal OR organoid OR cell model pubmed · 1818664 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Blinded scoring not reproduced model pubmed · 10 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
does_not_resolve 10796693 · The Cochrane database of systematic revi (2000) — Vaccines for preventing hepatitis B in health-care workers.
does_not_resolve 12399191 · Vaccine (2002) — The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population.
does_not_resolve 12121601 · International journal of infectious dise (2002) — Immunogenicity and reactogenicity of a combined hepatitis A and B vaccine in healthy Chilean subjects.
refutes_node 12150176 · The Pediatric infectious disease journal (2002) — Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertu
does_not_resolve 33522927 · BMC pediatrics (2021) — The effect of inhaling mother's breast milk odor on the behavioral responses to pain caused by hepatitis B vaccine in preterm infants: a randomized clinical tri
does_not_resolve 37991714 · Indian journal of pediatrics (2024) — Comparison of Sucrose vs. Swaddling in Pain Management during Birth Dose of Hepatitis B Vaccine: A Randomized Control Trial.
does_not_resolve 21193975 · Indian journal of pediatrics (2011) — Pain response in newborns to the order of injecting BCG and Hepatitis-B vaccines: a randomized trial.
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: No retrieved evidence addresses the experimental time course of hepatitis onset following hepatitis B vaccination. The retrieved studies focus on vaccine immunogenicity, safety, and modeling of steatohepatitis, not on the temporal relationship between vaccination and new hepatitis cases.
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Experimental time course animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Experimental time course not reproduced model pubmed · 4 hits · run 2026-09-07
5 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
does_not_resolve 16964595 · Liver transplantation : official publica (2006) — Immunogenicity and safety of an experimental adjuvanted hepatitis B candidate vaccine in liver transplant patients.
does_not_resolve 32842315 · Zhonghua yu fang yi xue za zhi [Chinese (2020) — [Safety and immunogenicity analysis of recombinant （hansenula polymorpha) hepatitis B vaccine （CpG ODN adjuvant) among adults: the preliminary results of phase
does_not_resolve 21941089 · Human vaccines (2011) — Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults.
does_not_resolve 11312012 · Vaccine (2001) — Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine.
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Hepatitis Susceptibility trait coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Hepatitis Susceptibility trait inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 15578364 · Clinical infectious diseases : an offici (2004) — Varicella vaccine for susceptible adults: do it today.
does_not_resolve 19477561 · Vaccine (2009) — Genetic polymorphisms in host response to meningococcal infection: the role of susceptibility and severity genes.
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.