Ductular Reaction, Late-Onset Bile Duct Deficiency, and Cirrhosis: A Case Report Highlighting Misleading Histological Morphology in Alagille Syndrome

Aim: to highlight the diagnostic challenges of Alagille syndrome (AGS), which can mimic other cholestatic diseases like biliary atresia. We aim to emphasize the importance of integrative diagnostic approaches, including genetic testing, to avoid misdiagnosis and unnecessary surgical procedures in cases where histological findings, such as ductular proliferation, do not follow typical patterns of AGS.

Key points. Diagnosing Alagille syndrome AGS is quite complex as it shares symptoms similar to those of other cholestatic diseases, especially biliary atresia. Bile duct paucity is the major pattern of AGS. Infants more than six months of age usually already show a visible bile duct paucity. However, in this case, our patient, who was more than six months old, didn’t show bile duct paucity and ductular reaction was the major pattern. A four-year-old girl presented with chronic cholestasis, congenital heart disease, skeletal anomalies, ocular abnormalities, and facial deformity. Her liver biopsy at the age of one year predominantly showed ductular proliferation. Initially, we diagnosed her with biliary atresia. However, subsequent examination of a total hepatectomy sample at the age of four revealed bile ducts were difficult to identify in most portal tracts. Genetic testing in 2022 identified a heterozygous likely pathogenic variant in the JAG1 gene, confirming AGS. The patient underwent liver transplantation.

Conclusion. We report the histology findings in AGS that can potentially be mistaken for other cholestatic diseases. We also highlight the importance of integrative diagnostic approaches to avoid misdiagnosis and unwarranted surgical procedures.

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