Clinical, laboratory, and genetic evaluation of infants with cholestasis

ABSTRACT CLINICAL, LABORATORY, AND GENETIC EVALUATION OF INFANTS WITH CHOLESTASIS Introduction: In this study, infants with cholestasis were retrospectively evaluated. These cases were comprehensively analyzed in terms of their medical history, physical examinations, family history, laboratory findings, imaging studies, and genetic tests. We believe that this study will provide valuable insights for clinicians in approaching infants with cholestasis. Additionally, we anticipate that our extensive case series will contribute to the literature by improving the differential diagnosis of cholestasis in infants. Materials and Methods: This study was designed to retrospectively investigate the clinical, laboratory, and genetic aspects of infants with cholestasis followed at the Pediatric Gastroenterology and Pediatric Metabolism Departments of Çukurova University Faculty of Medicine. Ethical approval for the study was obtained from the Non-Interventional Clinical Research Ethics Committee of Çukurova University on September 1, 2023 (Meeting No. 136, Decision No. 13). Results: Among 137 cases, 36.4% (n=50) were diagnosed with biliary atresia (BA), 24.8% (n=34) with neonatal hepatitis, and 8.0% (n=11) with total parenteral nutrition (TPN)-associated cholestasis. For the PFIC subgroups, PFIC3 accounted for 5.1% (n=7), PFIC2 for 4.4% (n=6), PFIC4 for 2.9% (n=4), PFIC1 for 0.7% (n=1), and PFIC7 for 0.7% (n=1). Tyrosinemia was identified in 5.1% (n=7), bile acid synthesis defect in 1.5% (n=2), Alagille syndrome in 1.5% (n=2), and other conditions, including choledochal cyst, portosystemic shunt, ARC syndrome, glycogen storage disease, fatty acid oxidation defect, Niemann-Pick disease type C, galactosemia, congenital hypothyroidism, cystic fibrosis, CMV infection, congenital toxoplasmosis, and DGUOK deficiency, each accounted for 0.7% (n=1).The study included 137 cases, of which 72 were female (52.5%) and 65 were male (47.5%). The mean age of symptom onset was 13.6 ± 11.1 days in the biliary atresia group, compared to 72.5 ± 129.6 days in the other cholestasis group (p<0.001). In the biliary atresia group, the median interval between the onset of symptoms and Kasai portoenterostomy was 52.5 days (range: 12–119 days). Jaundice was detected in all cases (100%), with hepatomegaly observed in 68.6% and splenomegaly in 36.4% of the cases . Liver biopsy was performed in all 50 cases in the biliary atresia group, confirming the diagnosis in 46 cases (92%). Our findings support previously reported key diagnostic parameters for biliary atresia, including acholic stools, elevated GGT levels, and ultrasound findings of the gallbladder. Among the 50 cases diagnosed with biliary atresia, the families of 33 were contacted, and it was learned that 15 patients had undergone liver transplantation. A ten-year survival analysis revealed that 33% (n=5) of these transplanted patients had died, while 67% (n=10) were alive. Conclusion: In our study, 137 cases of cholestasis were analyzed. Despite significant differences in the etiological causes, symptoms, clinical findings, and laboratory results showed similarities. It was observed that there is no single diagnostic method or laboratory parameter with sufficiently high sensitivity and specificity to establish a definitive diagnosis. Therefore, a comprehensive and systematic approach should be applied in patients with cholestasis, and the obtained data should be integrated with biopsy findings. Keywords: infants, cholestasis, biliary atresia, acholic stool, jaundice