Sage open pathology · 2026
Autoimmune Biliary Diseases: From Fragmented Pathways to Precision Diagnosis.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Bedran Anthony, Hoyek Karim, Houcheimy Doha, Kreidi Joanna, Chami Angelo, Nabhan Serena, Karam Karam, Bedran Khalil
Аннотация
BACKGROUND AND SIGNIFICANCE: Autoimmune biliary diseases, such as primary sclerosing cholangitis (PSC), Primary biliary cholangitis (PBC) and IgG4-related sclerosing cholangitis (IgG4-SC) are recognized as contributors to chronic cholestatic liver disease. Time-to-diagnosis remains prolonged, despite the presence of high resolution MRCP, expanded autoantibody panels and improved endoscopic tissue acquisition. This is due to the fragmented disease-specific pathways, variable marker sensitivity, overlap syndromes, malignant mimickers and in some cases early/small-duct imaging limitations.
OBJECTIVES: Critically evaluate and synthesize current diagnostic modalities and propose an integrated, precision-layered, phenotype-defined, and tissue-informed diagnostic pathway that standardizes evaluation across autoimmune and immune-mediated cholangiopathies.
METHODS: Major society guidelines such as AASLD/EASL, key reviews and pivotal studies were used in order to extract evidence regarding autoimmune serologies, MRCP and advanced MRCP techniques, elastography/MRE for fibrosis staging and targeted endoscopic-tissue diagnostics, emphasizing on overlap phenotypes, intermediate strictures and malignancy exclusion.
RESULTS: Seronegative/atypical PBC, limited sensitivity of MRCP in early or small-duct PSC, as well as frequent misclassification of IgG4-SC as PSC; are remarkable contributors of diagnostic delay. Iterative resolution, achieved through sequential escalation from serology to non-invasive ductal mapping, selective tissue clarification and investigational molecular and AI-assisted tools such as radiomics-enhanced MRCP, molecular cytology and liquid biopsy when conventional modalities fail, all aimed to improve discrimination of overlaps and support risk-stratified surveillance.
CONCLUSION: Diagnostic uncertainty and disease misclassification may be reduced by implementing a precision-layered, phenotype-defined, and tissue-informed diagnostic pathway. This will standardize evaluation across autoimmune biliary diseases. It is important to note that these emerging tools remain investigational and require prospective validation prior to routine clinical integration.
OBJECTIVES: Critically evaluate and synthesize current diagnostic modalities and propose an integrated, precision-layered, phenotype-defined, and tissue-informed diagnostic pathway that standardizes evaluation across autoimmune and immune-mediated cholangiopathies.
METHODS: Major society guidelines such as AASLD/EASL, key reviews and pivotal studies were used in order to extract evidence regarding autoimmune serologies, MRCP and advanced MRCP techniques, elastography/MRE for fibrosis staging and targeted endoscopic-tissue diagnostics, emphasizing on overlap phenotypes, intermediate strictures and malignancy exclusion.
RESULTS: Seronegative/atypical PBC, limited sensitivity of MRCP in early or small-duct PSC, as well as frequent misclassification of IgG4-SC as PSC; are remarkable contributors of diagnostic delay. Iterative resolution, achieved through sequential escalation from serology to non-invasive ductal mapping, selective tissue clarification and investigational molecular and AI-assisted tools such as radiomics-enhanced MRCP, molecular cytology and liquid biopsy when conventional modalities fail, all aimed to improve discrimination of overlaps and support risk-stratified surveillance.
CONCLUSION: Diagnostic uncertainty and disease misclassification may be reduced by implementing a precision-layered, phenotype-defined, and tissue-informed diagnostic pathway. This will standardize evaluation across autoimmune biliary diseases. It is important to note that these emerging tools remain investigational and require prospective validation prior to routine clinical integration.