Genetic and clinical factors influencing CF-associated liver disease: the impact of variants and genotypes in Romanian pediatric cystic fibrosis patients.
Elena-Simona Moiceanu, Iustina Violeta Stan, Simona Elena Moşescu, Adina Chiş, Romana Vulturar, Daniel-Corneliu Leucuţa, Gabriela Viorela Niţescu, Maria Iacobescu, Elena Mădălina Petran, Dan Lucian Dumitraşcu
Author Information
Elena-Simona Moiceanu: Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Romania.
Iustina Violeta Stan: Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Simona Elena Moşescu: Department of Pediatrics, Grigore Alexandrescu Clinical Emergency Hospital for Children, Bucharest, Romania.
Adina Chiş: Discipline of Cell and Molecular Medicine, Department of Molecular Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Romana Vulturar: Discipline of Cell and Molecular Medicine, Department of Molecular Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Daniel-Corneliu Leucuţa: Medical Informatics and Biostatistics Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Gabriela Viorela Niţescu: Pediatric Poison Centre, Grigore Alexandrescu Clinical Emergency Hospital for Children, Bucharest, Romania.
Maria Iacobescu: Institute of Medical Research and Life Sciences - MEDFUTURE, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Elena Mădălina Petran: Pediatric Poison Centre, Grigore Alexandrescu Clinical Emergency Hospital for Children, Bucharest, Romania.
Dan Lucian Dumitraşcu: 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Background: Hepatic disease represents a significant complication in children with cystic fibrosis (CF), yet its relationship with specific genetic factors, including CFTR (Cystic fibrosis transmembrane conductance regulator) mutations and SERPINA1 alleles, is not well understood. This study aims to clarify these associations within a Romanian pediatric CF population. Methods: In this cross-sectional, prospective study, we examined 71 children with CF, comparing those with hepatic disease (n=25) to those without (n=46). We collected comprehensive clinical, biochemical, and genetic data, focusing on CFTR genotypes and SERPINA1 alleles. Key outcomes included the prevalence of hepatic disease in relation to specific genotypes, fibrosis markers, and liver function tests. Results: The DF508/DF508 genotype was the most prevalent, occurring in 49% of the cohort. No significant associations were found between hepatic disease and specific CFTR genotypes or SERPINA1 alleles. However, children with hepatic disease exhibited significantly higher fibrosis scores (APRI and FIB-4), suggesting more advanced liver involvement. Additionally, a slight delay in CF diagnosis was observed in those with hepatic disease, though this difference did not reach statistical significance. Conclusion: This pioneering study in Romania underscores the complexity of hepatic disease in CF. While specific CFTR genotypes and SERPINA1 alleles were not significantly associated with hepatic complications, the findings emphasize the importance of early diagnosis and monitoring using fibrosis markers to identify children at risk for liver involvement.
