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COVID-19 vaccine → Hepatitis

Evidence dossier · candidate cand-covid-hepatitis · CICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that COVID-19 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)

ClaimLabelStatusMissing nodes
C1Coherent clinical object existssupported
C2Consistent temporal windowsupported
C3Epidemiologic excess riskinsufficient_datamissing: B1 B2 B3
C4Consistency / replicationinsufficient_datamissing: B5 B6
C5Specificity (product / dose)supported
C6Biological mechanismsupported

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.

ViewpointWhat it asksStatus (from evidence)
Temporality (necessary)cause precedes effect in a plausible window (necessary)met · via A3 A4 A5
Strengthsize/precision of the associationnot established
Consistencyreproduced across settings/designsnot established
Specificitytied to a specific product/dose/outcomenot established
Biological gradientdose-responsepartial / mixed · via C5n
Plausibilitya named biological mechanismmet · via E1
Coherencefits known biology/natural historymet · via A9 A10
Experimentintervention changes risknot established
Analogyprecedent for the patternnot established

NASEM weight-of-evidence synthesis (computed)

TrackWeightBasis
EpidemiologicINSUFFICIENTvia B1, B2, B3, B4, B5, B8
MechanisticWEAKvia A9, A10, C1n, C2n, C3n, C4n, C5n · missing: D1 D2 D3 D4 D5 E2 E3 E4 E5 E6 E7 E8 E9 E10 F1 F2 …
Synthesized conclusionInadequate to accept or reject

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 reportssupports
Measure: New definite object in risk window T
Comparator: Pre-vaccination baseline
Hit rule: Definite object present, onset in window, competing causes considered
Finding: Multiple case reports describe autoimmune hepatitis with onset within days after COVID-19 vaccination, with temporal association and consideration of competing causes in some reports.
Cited: PMID 36207131 PMID 35469403 PMID 35865787 PMID 37029249 PMID 35013724 PMID 35694999
supporting: COVID-19 vaccine Hepatitis case report OR case series Case reports
pubmed · 66244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
16 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 35013724 · Journal of translational autoimmunity (2022) — COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature.
ambiguous 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A2 · Series with objective confirmationsupports
Measure: Definite object plus objective test
Comparator: Reference range / diagnostic criteria
Hit rule: Objective confirmation in >=1 case per the working definition
Finding: Multiple case reports describe new-onset autoimmune hepatitis with objective laboratory confirmation (e.g., elevated liver enzymes, anti-smooth muscle antibodies, liver biopsy) occurring days to weeks after COVID-19 vaccination, including one case with 1-year follow-up, one with fulminant hepatitis after AstraZeneca vaccine, and one corticosteroid-refractory case after mRNA vaccine.
Cited: PMID 36207131 PMID 35865787 PMID 37029249
supporting: COVID-19 vaccine Hepatitis case report OR case series Series with objective confirmation
pubmed · 5719 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
13 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
A3 · Onset histogramsupports
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: Several case reports describe autoimmune hepatitis occurring within 7–10 days after COVID-19 vaccination, supporting clustering of onset within a pre-specified risk window.
Cited: PMID PMID 36207131 PMID PMID 35865787 PMID PMID 37029249 PMID PMID 34225251 PMID PMID 35694999
supporting: COVID-19 vaccine Hepatitis case report OR case series Onset histogram
pubmed · 78 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
17 retrieved record(s)
ambiguous 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
supports_node 34225251 · Journal of autoimmunity (2021) — Auto-immune hepatitis following COVID vaccination.
does_not_resolve 35702446 · Case reports in neurology (2022) — Acute Transient Encephalopathy after Moderna COVID-19 Vaccine.
A4 · Temporal plausibilitysupports
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 multiple case reports describing autoimmune hepatitis or fulminant hepatitis with onset 7–10 days after COVID-19 vaccination, which is consistent with a plausible latency period for immune-mediated hepatocyte injury following an antigenic trigger.
Cited: PMID 36207131 PMID 35469403 PMID 35865787 PMID 37029249 PMID 35694999 PMID 34225251
supporting: COVID-19 vaccine Hepatitis case report OR case series Temporal plausibility
pubmed · 107 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
16 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
does_not_resolve 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 34225251 · Journal of autoimmunity (2021) — Auto-immune hepatitis following COVID vaccination.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A5 · Onset-interval documentationsupports
Measure: Onset interval documented in source
Comparator: Dose date
Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: The retrieved evidence comprises only case reports of autoimmune hepatitis following COVID-19 vaccination, in which the onset interval (e.g., 8–10 days post-vaccination) is explicitly recorded in the primary source, though none of the reports formally documents a pre-specified risk window or systematic assessment of competing causes as defined in the working definition.
Cited: PMID 36207131 PMID 37029249 PMID 35469403 PMID 35865787 PMID 35694999 PMID 34225251
supporting: COVID-19 vaccine Hepatitis case report OR case series Onset-interval documentation
pubmed · 76 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
17 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
does_not_resolve 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 34225251 · Journal of autoimmunity (2021) — Auto-immune hepatitis following COVID vaccination.
does_not_resolve 35702446 · Case reports in neurology (2022) — Acute Transient Encephalopathy after Moderna COVID-19 Vaccine.
A6 · Differential diagnosis excludedsupports
Measure: Competing causes assessed and excluded
Comparator: Likely alternative diagnoses
Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: Two case reports describe autoimmune hepatitis following COVID-19 vaccination, with one reporting onset 10 days after the first dose and explicitly noting that competing causes were assessed (e.g., ruling out natural infection and drugs).
Cited: PMID 36207131 PMID 35469403
supporting: COVID-19 vaccine Hepatitis case report OR case series Differential diagnosis excluded
pubmed · 503 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
11 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
A7 · Rechallenge / re-exposureno_data
Measure: Object recurs on a further dose
Comparator: First-dose response
Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: The retrieved evidence includes several case reports of hepatitis or autoimmune hepatitis following COVID-19 vaccination, but none describe recurrence of hepatitis after a subsequent vaccine dose (rechallenge/re-exposure).
Cited: (none)
supporting: COVID-19 vaccine Hepatitis case report OR case series Rechallenge / re-exposure
pubmed · 78 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
16 retrieved record(s)
ambiguous 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
supports_node 34225251 · Journal of autoimmunity (2021) — Auto-immune hepatitis following COVID vaccination.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
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 consists solely of case reports and a correspondence letter describing instances of autoimmune hepatitis (AIH) or hepatitis following COVID-19 vaccination, with onset within 7–10 days after vaccination and after assessment of competing causes. No adjudication by a published criterion set (e.g., RUCAM or DSMB-defined criteria) is reported, and no study systematically applies a formal case-definition algorithm for 'definite' attribution.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis case report OR case series Adjudicated by criteria
pubmed · 115 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
17 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 34225251 · Journal of autoimmunity (2021) — Auto-immune hepatitis following COVID vaccination.
supports_node 35716255 · Clinical journal of gastroenterology (2022) — Autoimmune hepatitis with history of HCV treatment triggered by COVID-19 vaccination: case report and literature review.
A9 · Natural-history consistencysupports
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: Multiple case reports describe autoimmune hepatitis with onset within 7–10 days after COVID-19 vaccination, consistent with known natural history of drug/trigger-induced autoimmune hepatitis, though evidence is limited to isolated cases and does not establish population-level consistency.
Cited: PMID 36207131 PMID 35469403 PMID 35865787 PMID 37029249
supporting: COVID-19 vaccine Hepatitis case report OR case series Natural-history consistency
pubmed · 179 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
14 retrieved record(s)
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
does_not_resolve 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
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.
ambiguous 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A10 · No confounding objectsupports
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: Multiple case reports describe new-onset autoimmune hepatitis or fulminant hepatitis occurring days to weeks after COVID-19 vaccination, with competing causes (e.g., infection, drug-induced injury) assessed as unlikely in several reports, though all are single-case or small series with no controlled epidemiological data.
Cited: PMID 36207131 PMID 35469403 PMID 35865787 PMID 37029249 PMID 37591684 PMID 35694999 PMID 34225251
supporting: COVID-19 vaccine Hepatitis case report OR case series No confounding object
pubmed · 95 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis alternative diagnosis OR not vaccine-related
pubmed · 4056 hits · run 2026-09-07
16 retrieved record(s)
ambiguous 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 35469403 · Revista espanola de enfermedades digesti (2022) — COVID-19 vaccine and autoimmune hepatitis.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 37591684 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
supports_node 34225251 · Journal of autoimmunity (2021) — Auto-immune hepatitis following COVID vaccination.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
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: COVID-19 vaccine Hepatitis anatomic localization Predicted site of injury mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 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
Finding: No evidence was found in the retrieved PMID that directly addresses hepatitis as a spared structure for the COVID-19 vaccine; the paper discusses pemphigus foliaceus, an autoimmune blistering disease that spares mucosal surfaces, not the liver or hepatitis.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis anatomic localization Spared structures mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Spared structures not consistent with mechanism
pubmed · 1 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39203983 · Vaccines (2024) — A Comprehensive Review on the Intricate Interplay between COVID-19 Immunization and the New Onset of Pemphigus Foliaceus.
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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis anatomic localization Local vs systemic distribution mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Local vs systemic distribution not consistent with mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis anatomic localization Kinetics class mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Kinetics class not consistent with mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
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: COVID-19 vaccine Hepatitis anatomic localization Platform-mechanism match mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 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: COVID-19 vaccine Hepatitis Targeted treatment reverses intervention OR treatment OR reversal
pubmed · 15142392 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Targeted treatment reverses no effect intervention
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
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: COVID-19 vaccine Hepatitis No internal contradiction coherence OR latency OR susceptibility
pubmed · 870068 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis No internal contradiction inconsistent OR contradicts
pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 32718125 · Turkish journal of medical sciences (2021) — Hepatitis A susceptibility parallels high COVID-19 mortality.
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: The retrieved evidence shows an ecological correlation between hepatitis A virus susceptibility and COVID-19 mortality, but does not address new hepatitis attributed to COVID-19 vaccination, nor does it provide any data on hepatitis as an adverse event following COVID-19 vaccine.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Analogy to a known object coherence OR latency OR susceptibility
pubmed · 870068 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Analogy to a known object inconsistent OR contradicts
pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 32718125 · Turkish journal of medical sciences (2021) — Hepatitis A susceptibility parallels high COVID-19 mortality.
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: The retrieved evidence discusses a possible protective association between hepatitis A immunity and COVID-19 mortality, but provides no information on latency coherence for a putative adverse event of hepatitis following COVID-19 vaccination.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Latency coherence coherence OR latency OR susceptibility
pubmed · 870068 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Latency coherence inconsistent OR contradicts
pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 32718125 · Turkish journal of medical sciences (2021) — Hepatitis A susceptibility parallels high COVID-19 mortality.
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 does not address hepatitis as an adverse event following COVID-19 vaccination; it focuses on AI adjudication of cardiovascular events and immune-related adverse events from immune checkpoint inhibitors, respectively.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Pre-specification pre-specified OR adjudicated
pubmed · 13550 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Pre-specification post-hoc OR hypothesis-generating only
pubmed · 1700 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
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
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: COVID-19 vaccine Hepatitis Contrary-evidence log pre-specified OR adjudicated
pubmed · 13550 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Contrary-evidence log post-hoc OR hypothesis-generating only
pubmed · 1700 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis No temporality-only claim pre-specified OR adjudicated
pubmed · 13550 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis No temporality-only claim post-hoc OR hypothesis-generating only
pubmed · 1700 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
ambiguous 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: COVID-19 vaccine Hepatitis Passive-surveillance role pre-specified OR adjudicated
pubmed · 13550 hits · run 2026-09-07
mirror: COVID-19 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: COVID-19 vaccine Hepatitis Dose mapping pre-specified OR adjudicated
pubmed · 13550 hits · run 2026-09-07
mirror: COVID-19 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 retrieved evidence directly investigates the risk of hepatitis following COVID-19 vaccination; the retrieved studies address shingles, Guillain-Barré syndrome, arrhythmias, RSV, ocular events, NAFLD, and hepatitis prevalence models, none of which involve COVID-19 vaccine and hepatitis as an outcome.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Excess vs baseline incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Excess vs baseline
pubmed · 88799 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
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 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 39969879 · JAMA network open (2025) — Respiratory Syncytial Virus Vaccine and Nirsevimab Uptake Among Pregnant People and Their Neonates.
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 directly addresses an SCCS risk ratio for hepatitis following COVID-19 vaccination; the only SCCS studies retrieved concern shingles after Shingrix vaccination, Guillain-Barré syndrome after COVID-19 vaccination, and arrhythmias after COVID-19 infection, none of which report on hepatitis as an outcome.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis SCCS incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk SCCS
pubmed · 88906 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 39969879 · JAMA network open (2025) — Respiratory Syncytial Virus Vaccine and Nirsevimab Uptake Among Pregnant People and Their Neonates.
does_not_resolve 41347672 · Journal of medical virology (2025) — Systematic Review of Postvaccination Ocular Adverse Events: A Comprehensive Analysis of Published Reports.
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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Cohort / risk-interval incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Cohort / risk-interval
pubmed · 88408 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 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 39426837 · Lancet (London, England) (2024) — Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years a
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
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 addresses a pooled estimate or meta-analysis of hepatitis risk following COVID-19 vaccination. The retrieved studies concern shingles, Guillain-Barré syndrome, arrhythmias, HCV prevalence, COVID-19 vaccine effectiveness, and ocular adverse events; none provide a meta-analytic pooled effect for hepatitis after COVID-19 vaccines.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Meta-analysis / pooling incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Meta-analysis / pooling
pubmed · 112244 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
does_not_resolve 40014628 · MMWR. Morbidity and mortality weekly rep (2025) — Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.
ambiguous 41347672 · Journal of medical virology (2025) — Systematic Review of Postvaccination Ocular Adverse Events: A Comprehensive Analysis of Published Reports.
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 risk of new hepatitis attributed to COVID-19 vaccination. The only retrieved study mentioning hepatitis B vaccine is a systematic review of ocular adverse events after non-COVID antiviral vaccines, not COVID-19 vaccines.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Negative-control outcomes incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Negative-control outcomes
pubmed · 88610 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort 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 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 39426837 · Lancet (London, England) (2024) — Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years a
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
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 retrieved evidence addresses the risk of hepatitis following COVID-19 vaccination compared with a different-antigen comparator.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Other-antigen comparison incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Other-antigen comparison
pubmed · 88372 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
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 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 39426837 · Lancet (London, England) (2024) — Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years a
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
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 new hepatitis attributed to COVID-19 vaccination within a pre-specified risk window; the only mention of hepatitis in the retrieved PMIDs (PMID 41347672) is in the context of hepatitis B vaccine ocular adverse events, not COVID-19 vaccine-related hepatitis.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Absolute risk incidence risk cohort OR self-controlled case series
pubmed · 946 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Absolute risk
pubmed · 111646 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
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 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
refutes_node 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 29211679 · The New England journal of medicine (2017) — Contemporary Hormonal Contraception and the Risk of Breast Cancer.
does_not_resolve 23484825 · The New England journal of medicine (2013) — Risk of ischemic heart disease in women after radiotherapy for breast cancer.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
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 includes a systematic review of ocular adverse events after non-COVID vaccines (PMID 41347672) but does not address hepatitis as an adverse event following COVID-19 vaccination, nor does any retrieved study examine risk of hepatitis by vaccine platform or product.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Platform split incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Platform split
pubmed · 88437 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
refutes_node 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37806668 · Human vaccines & immunotherapeutics (2023) — Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-a
does_not_resolve 39426837 · Lancet (London, England) (2024) — Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years a
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Host-structure stratification incidence risk cohort OR self-controlled case series
pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Host-structure stratification
pubmed · 88370 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 39426837 · Lancet (London, England) (2024) — Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years a
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 39969879 · JAMA network open (2025) — Respiratory Syncytial Virus Vaccine and Nirsevimab Uptake Among Pregnant People and Their Neonates.
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: COVID-19 vaccine Hepatitis Formulation / component change incidence risk cohort OR self-controlled case series
pubmed · 946 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no association OR null OR no increased risk Formulation / component change
pubmed · 88531 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 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 37806668 · Human vaccines & immunotherapeutics (2023) — Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-a
does_not_resolve 39426837 · Lancet (London, England) (2024) — Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years a
does_not_resolve 35180382 · The lancet. Gastroenterology & hepatolog (2022) — Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
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: COVID-19 vaccine Hepatitis Formulation natural experiment intervention OR treatment OR reversal
pubmed · 15142392 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Formulation natural experiment no effect intervention
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
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: COVID-19 vaccine Hepatitis Policy / pause signal intervention OR treatment OR reversal
pubmed · 15142392 hits · run 2026-09-07
mirror: COVID-19 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: The retrieved evidence shows an ecological correlation between hepatitis A susceptibility and COVID-19 mortality, but does not address post-vaccine hepatitis patterns or their coherence with natural infection.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Infection coherence coherence OR latency OR susceptibility
pubmed · 870070 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Infection coherence inconsistent OR contradicts
pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 32718125 · Turkish journal of medical sciences (2021) — Hepatitis A susceptibility parallels high COVID-19 mortality.

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: The retrieved evidence includes only case reports and a systematic review of autoimmune hepatitis following COVID-19 vaccination, but none of these studies examine a monotonic dose-response gradient in dose strength (larger dose → higher risk). No study compares different dose sizes or strengths to assess risk of hepatitis.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Dose strength gradient dose-response OR dose effect
pubmed · 1299193 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no dose effect OR no dose-response Dose strength gradient
pubmed · 250 hits · run 2026-09-07
9 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 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
ambiguous 40014628 · MMWR. Morbidity and mortality weekly rep (2025) — Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
supports_node 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
ambiguous 37366868 · Diseases (Basel, Switzerland) (2023) — Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review.
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: The retrieved evidence includes case reports of hepatitis following COVID-19 vaccination, but none of the retrieved studies systematically compare risk across dose numbers (1st vs 2nd vs 3rd) or provide epidemiological data on a dose-number gradient. One case report (PMID 37029249) describes hepatitis after the third dose, but this does not constitute a pattern across doses.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Dose number gradient dose-response OR dose effect
pubmed · 1299193 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no dose effect OR no dose-response Dose number gradient
pubmed · 694 hits · run 2026-09-07
9 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 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 40014628 · MMWR. Morbidity and mortality weekly rep (2025) — Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 35694999 · Immunotherapy (2022) — Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report.
supports_node 37366868 · Diseases (Basel, Switzerland) (2023) — Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review.
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
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: The retrieved evidence includes multiple case reports and a systematic review of 39 cases describing autoimmune hepatitis following COVID-19 vaccination, but no study directly examines risk ordered by measured-exposure tertile (high > mid > low). The evidence is limited to uncontrolled case series and does not provide quantitative exposure-tertile comparisons.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Measured-exposure tertiles dose-response OR dose effect
pubmed · 1299193 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no dose effect OR no dose-response Measured-exposure tertiles
pubmed · 139 hits · run 2026-09-07
9 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 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 40014628 · MMWR. Morbidity and mortality weekly rep (2025) — Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.
ambiguous 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
supports_node 37366868 · Diseases (Basel, Switzerland) (2023) — Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review.
does_not_resolve 36969905 · Journal of clinical and translational he (2023) — Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases.
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: The retrieved evidence includes several case reports and a systematic review describing instances of autoimmune hepatitis (AIH) occurring after COVID-19 vaccination, with onset typically within days of vaccination. However, none of the retrieved studies provide data from an organoid concentration curve testing dose-dependent effects of COVID-19 vaccine antigen on hepatitis outcomes in an organoid model.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Organoid concentration curve dose-response OR dose effect
pubmed · 1299193 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no dose effect OR no dose-response Organoid concentration curve
pubmed · 150 hits · run 2026-09-07
10 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 28000606 · Diseases of aquatic organisms (2016) — Development of Streptococcus agalactiae vaccines for tilapia.
does_not_resolve 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 40014628 · MMWR. Morbidity and mortality weekly rep (2025) — Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
supports_node 37366868 · Diseases (Basel, Switzerland) (2023) — Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review.
C5n · EC50 vs Cmax coherencemixed
Measure: Measured exposure reaches effect threshold
Comparator: Pharmacokinetic Cmax vs EC50
Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: Case reports and a systematic review describe instances of autoimmune hepatitis and fulminant hepatitis following COVID-19 vaccination, with onset days after vaccination, suggesting vaccine-triggered immune-mediated liver injury; however, the retrieved evidence does not provide pharmacokinetic or pharmacodynamic data linking measured Cmax/tissue concentrations to in-vitro EC50 values for hepatitis.
Cited: PMID 35865787 PMID 37029249 PMID 37366868 PMID 36207131 PMID 35694999
supporting: COVID-19 vaccine Hepatitis EC50 vs Cmax coherence dose-response OR dose effect
pubmed · 1299193 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis no dose effect OR no dose-response EC50 vs Cmax coherence
pubmed · 139 hits · run 2026-09-07
9 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 37517414 · The lancet. Gastroenterology & hepatolog (2023) — Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.
does_not_resolve 40014628 · MMWR. Morbidity and mortality weekly rep (2025) — Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.
supports_node 35865787 · Clinical case reports (2022) — Fulminant hepatitis following COVID-19 vaccination: A case report.
supports_node 37029249 · Clinical journal of gastroenterology (2023) — Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.
ambiguous 37366868 · Diseases (Basel, Switzerland) (2023) — Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review.
supports_node 36207131 · European journal of hospital pharmacy : (2023) — COVID-19 vaccine triggered autoimmune hepatitis: case report.
ambiguous 36969905 · Journal of clinical and translational he (2023) — Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases.
E1 · Mediator identified in casessupports
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: PMID 37715471 reports altered liver function tests after COVID-19 vaccination compared to influenza vaccine controls, indicating possible liver injury; PMID 35567545 describes immune-mediated hepatitis features and corticosteroid response in a case series of liver injury after SARS-CoV-2 vaccination.
Cited: PMID 37715471 PMID 35567545
supporting: COVID-19 vaccine Hepatitis mechanism Mediator identified in cases in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Mediator identified in cases not associated mechanism
pubmed · 3 hits · run 2026-09-07
3 retrieved record(s)
ambiguous 37715471 · Pharmacoepidemiology and drug safety (2024) — Altered liver function test after Covid-19 vaccines: A retrospective control group study.
supports_node 37242502 · Pharmaceuticals (Basel, Switzerland) (2023) — Immune-Mediated Organ-Specific Reactions to COVID-19 Vaccines: A Retrospective Descriptive Study.
supports_node 35567545 · Hepatology (Baltimore, Md.) (2022) — Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome.
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: COVID-19 vaccine Hepatitis mechanism Mediator in healthy vaccinees in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 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: COVID-19 vaccine Hepatitis mechanism Infection contrast in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Infection contrast not associated mechanism
pubmed · 23 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 38304200 · Infection prevention in practice (2024) — Two versus three doses of COVID-19 vaccine and post-vaccination COVID-19 infection in hemodialysis patients.
does_not_resolve 34352133 · Journal of viral hepatitis (2022) — COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST, A Year Later.
does_not_resolve 36136332 · JAMA network open (2022) — Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes.
does_not_resolve 40963305 · Human vaccines & immunotherapeutics (2025) — Documented vaccination as proof of immunity compared to serology in medical students.
does_not_resolve 33559128 · Immunological reviews (2021) — Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID-19.
does_not_resolve 40260163 · Frontiers in public health (2025) — Chrono-optimizing vaccine administration: a systematic review and meta-analysis.
does_not_resolve 39608249 · Vaccine (2025) — COVID-19 vaccine responses are influenced by distinct risk factors in naive and SARS-CoV-2 experienced hemodialysis recipients.
does_not_resolve 40219638 · Human reproduction (Oxford, England) (2025) — COVID-19 vaccination and pregnancy-induced hypertension risk in women undergoing assisted reproduction.
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system
Comparator: Control transfer
Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis mechanism Transfer to recipient in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Transfer to recipient not associated mechanism
pubmed · 2 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 41237791 · The Lancet. Infectious diseases (2026) — Safety, tolerability, and immunogenicity of the ChAdOx1 RVF vaccine against Rift Valley fever among healthy adults in Uganda: a single-centre, single-blind, ran
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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis mechanism Transfer specificity in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Transfer specificity not associated mechanism
pubmed · 5 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 36462102 · Molecular biotechnology (2023) — Lipid-Based Delivery Systems in Development of Genetic and Subunit Vaccines.
does_not_resolve 39077045 · Science in One Health (2023) — Human health implications of emerging diseases and the current situation in India's vaccine industry.
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: COVID-19 vaccine Hepatitis mechanism Depletion / knockdown in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 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: COVID-19 vaccine Hepatitis mechanism Add-back rescue in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 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 directly tests whether neutralizing the mediator (e.g., an antibody or immune factor) blocks vaccine-associated hepatitis in humans or animals.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis mechanism Neutralization in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Neutralization not associated mechanism
pubmed · 119 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 41136606 · Nature biomedical engineering (2026) — Nanobody-based combination vaccine using licensed protein nanoparticles protects animals against respiratory and viral infections.
does_not_resolve 36263669 · Clinical and molecular hepatology (2022) — COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis.
does_not_resolve 41785011 · The Journal of general virology (2026) — Immunogenicity of SARS-CoV-2 vaccine prototype based on virus-like particles of hepatitis B core antigen from genotype G and interleukin 12 expressing Semliki F
does_not_resolve 34699647 · Reviews in medical virology (2022) — Safety and potency of BIV1-CovIran inactivated vaccine candidate for SARS-CoV-2: A preclinical study.
does_not_resolve 36742314 · Frontiers in immunology (2023) — Analysis of neutralizing antibodies to COVID-19 inactivated or subunit recombinant vaccines in hospitalized patients with liver dysfunction.
does_not_resolve 38005976 · Vaccines (2023) — Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection.
does_not_resolve 42079457 · Clinical kidney journal (2026) — Vaccine efficacy in CKD patients not on dialysis: a systematic review and meta-analysis.
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: The retrieved evidence does not address isotype control experiments or their failure to reproduce a block/activation effect in the context of COVID-19 vaccine and hepatitis.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis mechanism Isotype control in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Isotype control not associated mechanism
pubmed · 43 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 38757595 · Bratislavske lekarske listy (2024) — Investigation of SARS-CoV-2 antibody levels after COVID-19 vaccine in chronic hepatitis B patients.
does_not_resolve 39432992 · Vaccine (2024) — Anti-RBD IgG dynamics following infection or vaccination.
does_not_resolve 35344281 · Hepatology communications (2022) — Antibody response to the messenger RNA-1273 vaccine (Moderna) in liver transplant recipients.
does_not_resolve 35107848 · Liver international : official journal o (2022) — Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection.
does_not_resolve 37213672 · International journal of medical science (2023) — Immune responses to inactivated COVID-19 vaccine were decreased in Chinese patients with chronic respiratory diseases.
does_not_resolve 37457966 · Frontiers in cellular and infection micr (2023) — Humoral immune responses to inactivated COVID-19 vaccine up to 1 year in children with chronic hepatitis B infection.
does_not_resolve 36849838 · European journal of clinical microbiolog (2023) — The safety and immunogenicity of inactivated COVID-19 vaccine in old pulmonary tuberculosis patients.
does_not_resolve 36620297 · Frontiers in public health (2022) — Safety and immunogenicity of inactivated COVID-19 vaccine in patients with metabolic syndrome: A cross-sectional observational study.
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: COVID-19 vaccine Hepatitis Full product reproduces component OR antigen OR vector
pubmed · 2045311 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Full product reproduces no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
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 retrieved evidence addresses the relationship between an empty vaccine vector/particle backbone alone and hepatitis as an adverse event following COVID-19 vaccination; the retrieved articles discuss live bacterial or viral vector platforms for antigen delivery, not safety outcomes such as hepatitis.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Empty vector / particle component OR antigen OR vector
pubmed · 2045311 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Empty vector / particle no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
6 retrieved record(s)
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
F3 · Antigen alone reproducesno_data
Measure: Isolated antigen reproduces the effect
Comparator: Vehicle
Hit rule: The isolated antigen (not the full product) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Antigen alone reproduces component OR antigen OR vector
pubmed · 2045311 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Antigen alone reproduces no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
6 retrieved record(s)
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Irrelevant cargo component OR antigen OR vector
pubmed · 2045311 hits · run 2026-09-07
mirror: COVID-19 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 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer 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: COVID-19 vaccine Hepatitis Infection preparation component OR antigen OR vector
pubmed · 2045314 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Infection preparation no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
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 retrieved evidence addresses whether a cytokine/adjuvant mix alone reproduces hepatitis following COVID-19 vaccination.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Cytokine / adjuvant mix component OR antigen OR vector
pubmed · 2045311 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Cytokine / adjuvant mix no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
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: COVID-19 vaccine Hepatitis Component combination component OR antigen OR vector
pubmed · 2045313 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Component combination no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-07
6 retrieved record(s)
does_not_resolve 41136606 · Nature biomedical engineering (2026) — Nanobody-based combination vaccine using licensed protein nanoparticles protects animals against respiratory and viral infections.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 25105278 · Viruses (2014) — Virus-vectored influenza virus vaccines.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
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: COVID-19 vaccine Hepatitis 2D human cells animal OR organoid OR cell model
pubmed · 1818663 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis 2D human cells 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.
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: This study developed human liver organoids that recapitulate steatohepatitis features, but does not test or report any effect of COVID-19 vaccine on hepatitis in an organoid or organ-on-chip system.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Organoid / chip animal OR organoid OR cell model
pubmed · 1818663 hits · run 2026-09-07
mirror: COVID-19 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 retrieved evidence addresses whether blocking a mediator or mechanism for COVID-19 vaccine-associated hepatitis prevents or reverses the effect.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Block in vitro / in vivo intervention OR treatment OR reversal
pubmed · 15142392 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Block in vitro / in vivo no effect intervention
pubmed · 0 hits (0 hits — negative) · run 2026-09-07

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: COVID-19 vaccine Hepatitis mechanism Host-line dependence in vitro OR patient-derived
pubmed · 29244 hits · run 2026-09-07
mirror: COVID-19 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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Animal, clinical route animal OR organoid OR cell model
pubmed · 1818665 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Animal, clinical route not reproduced model
pubmed · 2 hits · 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.
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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Susceptible animal animal OR organoid OR cell model
pubmed · 1818669 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Susceptible animal not reproduced model
pubmed · 7 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 31155493 · Cell metabolism (2019) — Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
does_not_resolve 39048693 · Scientific reports (2024) — An inactivated SARS-CoV-2 vaccine based on a Vero cell culture-adapted high-titer virus confers cross-protection in small animals.
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: The study in PMID 31155493 develops a human liver organoid model to study steatohepatitis, but does not address replication of hepatitis following COVID-19 vaccination in an independent laboratory.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Replication across labs animal OR organoid OR cell model
pubmed · 1818663 hits · run 2026-09-07
mirror: COVID-19 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
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Blinded scoring animal OR organoid OR cell model
pubmed · 1818663 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Blinded scoring not reproduced model
pubmed · 1 hits · 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.
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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Experimental time course animal OR organoid OR cell model
pubmed · 1818663 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Experimental time course not reproduced model
pubmed · 1 hits · 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.
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: The retrieved evidence examines the relationship between hepatitis A virus (HAV) susceptibility and COVID-19 mortality, not new hepatitis attributed to COVID-19 vaccination.
Cited: (none)
supporting: COVID-19 vaccine Hepatitis Susceptibility trait coherence OR latency OR susceptibility
pubmed · 870068 hits · run 2026-09-07
mirror: COVID-19 vaccine Hepatitis Susceptibility trait inconsistent OR contradicts
pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 32718125 · Turkish journal of medical sciences (2021) — Hepatitis A susceptibility parallels high COVID-19 mortality.

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.