Liver transplantation is currently the most treatment for fulminant hepatitis, end-stage liver failure, hepatocellular carcinoma, and liver-originated metabolic diseases in children. With technological advances, improvements in surgical techniques and immunosuppressive therapy protocols have increased 1-year survival rates to 80%-90%. Our center successfully performs both living donor and cadaveric liver transplants in children. This study retrospectively analyzed the preoperative and postoperative data of 72 pediatric patients who underwent liver transplantation between July 2022 and July 2024. We included 72 patients who underwent liver transplantation between July 1, 2022, and July 1, 2024. Cases were evaluated based on demographic data, liver failure etiology, and postoperative complications. Of the cases, 37 were female (58%) and 35 male (42%), with a mean age of 6.6 years (ranging from 5 months to 17 years and 11 months). Indications included biliary atresia (25), autoimmune hepatitis (9), cryptogenic cirrhosis (7), PFIC (7), congenital hepatic fibrosis (1), Caroli disease (2), Wilson's disease (4), Alagille syndrome (3), hepatocellular carcinoma (2), primary hyperoxaluria type 1 (2), Crigler Najjar syndrome type 1 (3), Budd-Chiari syndrome (1), glycogen storage disease type 3 (1), portal vein thrombosis (1), and acute fulminant hepatitis (4). Mean PELD score for patients under 12 years was 18 (range 0-37), and MELD score for patients over 12 years was 19.3 (range 11-40). A total of 69 patients received orthotopic liver transplantation from living donors. Two patients received combined liver and kidney transplants, and 1 received a cadaveric liver transplant. Donors included 40 females and 32 males. Left lobe transplants were performed in 58 patients, and right lobe in 14. Immunosuppression included Tacrolimus + MMF in 70 patients and Cyclosporine in 2. Postoperative complications included biliary anastomosis stenosis (3), bile leakage (2), hepatic vein thrombosis (1), portal vein thrombosis (4), intestinal perforation secondary to Bogota syndrome (5), PRES syndrome due to Tacrolimus toxicity (1), primary graft dysfunction (1), and postoperative bleeding (2). Within the first month, 12 patients (16.6%) died, and 3 (4%) died between 1 month and 1 year postoperatively. The most common early cause of death was sepsis and multiorgan failure. One patient developed chronic rejection but recovered with steroid immunosuppression without the need for re-transplantation. Liver transplantation is a high-risk procedure requiring lifelong medication and follow-up. It is, however, the most effective treatment method for several severe pediatric liver conditions.

Bile acids in the ileum act as a feedback regulator of their own synthesis by inducing the release of ileal fibroblast growth factor 19 (FGF19), which inhibits the cholesterol-7-alpha hydroxylase enzyme. In cholestasis, this feedback mechanism is dysregulated. FGF19 is not expressed in the healthy liver. We aimed to assess the hepatic expression of FGF19 in neonatal cholestasis (NC) and its relation to serum bile acids. The study included 41 patients with NC. FGF19 immunohistochemical staining in liver tissue (hepatocytes, endothelial cells, bile ducts, and bile canaliculi) was evaluated as negative, weak, moderate, and strong staining. FGF19 staining in 6 liver samples from explants of children with Crigler-Najjar syndrome type-1 served as controls. Hepatocyte, endothelial, and canalicular FGF19 expression was significantly higher in cholestasis group compared to controls (P = .039, .006, and .028 respectively). Serum bile acids had significant correlation with hepatocyte FGF19, endothelial, and bile duct FGF19 expressions (P = .002, .003, and .01, respectively) but not with canalicular FGF19 expression. Hepatocyte FGF19 expression significantly associated with cholestasis severity in terms of serum total bilirubin, direct bilirubin, and aspartate transaminase levels (P = .01, .02, and .02, respectively). Hepatic FGF19 expression significantly upregulated in NC and correlated with cholestasis severity. Crigler-Najjar syndrome is a rare autosomal recessive disorder causing hyperbilirubinemia in newborns. Bilirubin metabolism involves the uptake of bilirubin from circulation, intracellular storage, conjugation with glucuronic acid, and excretion into bile. Abnormalities in any of these processes lead to hyperbilirubinemia. Crigler-Najjar syndrome is characterized by the absence or decreased activity of UDP-glucuronosyltransferase (UGT), an enzyme required for glucuronidation of unconjugated bilirubin in the liver. This deficiency is a significant cause of congenital nonhemolytic jaundice. The syndrome is classified into 2 types based on the level of UGT activity: Type 1: Characterized by severe symptoms due to minimal or a complete absence of enzyme activity, individuals with Crigler-Najjar syndrome type 1 (CN1) experience life-threatening and severe jaundice, requiring regular phototherapy for treatment. Patients with this form of the disease are at very high risk of developing neurological complications, including permanent damage such as kernicterus. The only cure for CN1 syndrome is a liver transplant. Type 2: This form of Crigler-Najjar syndrome is characterized by milder symptoms resulting from reduced enzyme activity. Individuals with Crigler-Najjar syndrome type 2 (CN2) experience intermittent jaundice triggered by stress and typically manage the condition through conservative measures. Permanent neurological damage is rare in CN2, and the need for a liver transplant is infrequent.

The aim of the study was to assess the health-related quality of life (HRQOL) and cognitive function in patients with Crigler-Najjar syndrome (CNS) type I and its impact on their lives. Twenty-one patients diagnosed with CNS type I aged 1 month to 18 years in the Paediatric Hepatology Unit of Cairo University Children's Hospital were enrolled in this cross-sectional observational study. The patients' health-related quality of life (HRQOL) was assessed using the World Health Organization Quality Of Life BREF questionnaire (WHOQOL-BREF) and the Short Form 36 Health Survey Questionnaire (SF-36). Cognitive function was assessed using the Stanford-Binet Intelligence Scale: Fifth Edition (SB5). All patients had a history of admission to a neonatal intensive care unit, 17 were managed by phototherapy only and 5 also underwent exchange transfusion. According to the WHOQOL questionnaire, 11 cases (52.4%) had a low QOL score, and 7 of 13 patients had an average score for their total IQ test. Cases with poor compliance to phototherapy had statistically significantly lower QOL scores (p=0.001), while, according to the SF36 survey, cases who received exchange transfusion had statistically significantly higher cognitive function (p=0.03). There was a positive correlation between the neurological effect as a complication of the disease and poor physical QOL. Paediatric patients with CNS have significantly lower HRQOL, especially physically, psychologically and environmentally. It is recommended that assessment of HRQOL should be a routine part of follow-up in CNS patients. Patients whose HRQOL is affected receive regular psychiatric counselling, social support and rehabilitation.Abbreviations: CNS: Crigler-Najjar syndrome; HRQOL: health-related quality of life; IQ: intelligence quotient; NICU: neonatal intensive care unit; QOL: quality of life; SB5: Stanford-Binet intelligence scale: 5th edition; SF-36: Short Form 36 Health Survey Questionnaire; UDGT: uridine diphosphate glucuronosyl transferase; UGT1A1: uridine 5'-diphosphate glucuronosyltransferase; WHOQOL-BREF: World Health Organization Quality of Life Brief Version.

Crigler-Najjar syndrome (CNS) is an exceedingly rare autosomal recessive disease with an estimated incidence of 1 in a million live births. CNS type 1 (CNS1) is the most severe form, characterized by severe unconjugated hyperbilirubinemia since birth due to the absence of hepatic uridine 5'-diphosphate glucuronyltransferase (UGT1A1) activity. Daily phototherapy (PT) and liver transplant (LT) are the mainstays of therapy. Here, we present a higher-than-expected incidence of CNS1 in Croatia (6,1 in a million). In the last 31 years, we treated eight CNS1 patients from five families with no reported consanguinity. Four patients are descendants of an isolated enclave in Kosovo with a small gene pool and a high potential for inbreeding. Severe unconjugated hyperbilirubinemia was verified in a neonatal period and PT was initiated. Four patients underwent LT from living-related donors. One of them had unsuccessful hepatocyte transplantation earlier. LT was successful in three patients, and one patient died due to primary graft dysfunction. Four patients are currently treated with 9-12 h daily PT with inconsistent disease control, and gradually increasing bilirubin. One patient developed kernicterus before LT, while others have normal psychomotor development and no neurologic impairment. Genetic testing of the UGT1A1 gene in six patients from three families revealed three different homozygous mutations (c.722_723 delAG, c.717_718 delAG, and c.1021 C >T), all previously described in other populations. There is a possibility of the founder effect as an explanation for the higher incidence of CNS1 in at least a subgroup of Croatians.

This is the first report of the concurrent development of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and Crigler-Najjar syndrome type 1 (CNs1) inherited via uniparental disomy of chromosome 2, which are both autosomal recessive pathologies. Through an expanded newborn metabolic panel, a male infant was identified as having an acylcarnitine pattern typical for LCHADD, later confirmed to be caused by a well-characterized pathogenic variant in the HADHA gene located at 2p23. Prolonged non-hematologic jaundice requiring repetitive phototherapy prompted further genetic analysis, leading to the identification of another genetic abnormality consistent with CNs1, which was caused by a novel pathogenic variant in the UGT1A1 gene located at 2q37. The two identified point mutations in chromosome 2 were homozygous and present on separate arms, which indicated potential uniparental disomy. Microarray analysis of the genetic material from the patient and his parents confirmed paternal isodisomy of chromosome 2. Further studies are needed to identify other possible pathogenic variants located on the same defective chromosome, evaluate the combined effect of the two metabolic abnormalities, and plan the best possible treatment and care.