Navigating Prognostic Factors and Long-Term Outcomes in Caroli’s Disease and Syndrome - A Prospective Observational Cohort Study

Abstract

<title>Abstract</title> Background Caroli’s disease (CD) and Caroli’s syndrome (CS) are rare congenital disorders of the intrahepatic bile ducts associated with significant morbidity and risk of malignant transformation. Differentiating the clinical course between CD and CS remains critical for tailoring surveillance and management. Aim To compare the clinical characteristics, complications, and outcomes of patients with CD and CS and identify potential predictors of biliary malignancy. Methods This cross-sectional observational study included 19 patients diagnosed with CD (n = 7) or CS (n = 12) at Zagazig University Hospitals between November 2015 and December 2022. Diagnosis was confirmed via MRCP. Clinical, biochemical, endoscopic, and imaging assessments were performed. Patients were followed longitudinally for 85 months. Outcomes included incidence of cholangitis, liver decompensation, variceal bleeding, malignancy, and mortality. Statistical comparisons were conducted using nonparametric tests, and correlations were assessed using Spearman’s rank. Results Patients with CS exhibited significantly higher bilirubin (p = 0.018), INR (p = 0.014), and CA 19 − 9 (p &lt; 0.001), and lower albumin and platelet counts (p = 0.028, 0.016) compared to CD. Portal hypertension and esophageal varices were observed exclusively in CS. Three CS patients developed cholangiocarcinoma after a mean of 28.3 ± 5.7 months and died within 3.3 ± 2.3 months of diagnosis. Correlation analysis revealed strong associations between malignancy and AST (ρ = 0.642), number of cholangitis episodes (ρ = 0.735), platelet count (ρ=–0.753), and CA 19 − 9 (ρ = 0.754). Kaplan–Meier analysis demonstrated significantly reduced survival in CS vs. CD (median survival 45.0 vs. 59.0 months, p = 0.020). Conclusion Caroli’s syndrome is associated with a more severe clinical phenotype, higher complication rate, and increased risk of malignancy compared to Caroli’s disease. Identifying predictors of poor outcomes may guide individualized surveillance and management. Regular monitoring, even in asymptomatic patients, is essential for early detection of complications and malignancy.