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Hepatobiliary involvement in Kawasaki disease: from cholestatic hepatitis to the hepatic vascular-biliary unit hypothesis—a state-of-the-art review
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DOI：10.3389/fimmu.2026.1852636.png)
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Abstract
En 中文
BackgroundThis review provides a comprehensive synthesis of hepatobiliary involvement in Kawasaki disease (KD); with emphasis on cholestatic hepatitis as a clinical sentinel of hyperinflammation. We critically evaluate current evidence; propose an integrated pathogenic framework—the hepatic vascular-biliary unit injury hypothesis—and identify priority research areas.Data sourcesNarrative review of high-quality literature (2015–2025) with inclusion of seminal historical studies; using Oxford Centre for Evidence-Based Medicine (OCEBM) evidence-level grading.ResultsCholestatic hepatitis occurs in 5.2%–17.8% of acute KD cases; rising to 22%–35% among intravenous immunoglobulin (IVIG)-resistant patients. Large retrospective cohort studies (OCEBM Level 3b) have identified a clinical “risk triangle” comprising IVIG resistance; coronary artery lesions (CALs); and cholestasis as interdependent factors. We propose the hepatic vascular-biliary unit injury hypothesis as an integrated pathogenic framework; supported by correlative pathological and molecular evidence (OCEBM Level 3–4); though causality remains unproven and requires validation in conditional endothelial-specific animal models. Current therapeutic evidence for moderate-to-severe cholestasis derives exclusively from retrospective cohorts and case series (OCEBM Level 3–4). Emerging evidence from Phase I/IIa trials supports the use of interleukin-1 blockade (anakinra) in refractory cases; predominantly derived from studies of coronary artery aneurysms rather than cholestasis-specific populations.ConclusionsKD-associated cholestatic hepatitis is a critical marker of disease severity with prognostic significance. The hepatic vascular-biliary unit hypothesis provides a mechanistic framework linking systemic vasculitis to cholestasis; pending experimental validation. Definitive evidence for optimal therapeutic strategies is lacking; well-designed randomized controlled trials specifically targeting the cholestasis subpopulation are urgently needed. Given the highest incidence in East Asian populations; clinicians in this region should maintain a particularly high index of suspicion for KD-associated cholestasis; particularly in infants presenting with unexplained jaundice.
Keywords:
risk stratification
Kawasaki disease
anakinra
IVIG resistance
cholestatic hepatitis
hepatic vascular-biliary unit
multi-system inflammation
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