Outcome of liver transplantation and prevalence of liver fibrosis in Crigler-Najjar syndrome.

INTRODUCTION: Crigler-Najjar syndrome (CNS) is a rare inherited disorder that is characterized by high levels of non-hemolytic, unconjugated hyperbilirubinemia leading to brain damage and even death. Liver transplantation (LT) can correct the metabolic defect, but there are little data regarding LT in this patient cohort. The liver parenchyma has been considered to be structurally normal in CNS, but there is growing evidence of clinically silent but histologically significant fibrosis in CNS patients. PATIENTS AND METHODS: We included 13 patients in our retrospective study who underwent LT at our center. Patient survival, graft function, and long-term complications were evaluated over a median follow-up period of 10 years (range: 1-16 years). In addition, the prevalence of histologically relevant fibrosis was characterized. RESULTS: The overall survival among our LT patients was 100%. The graft survival was only 61.5%. During the follow-up period, 5 LT patients had to undergo retransplantation. More than 45% of our patients showed histological signs of fibrosis. CONCLUSION: LT remains the only definite therapeutic option for severe CNS but needs to be considered thoroughly regarding the clinical risk-benefit-ratio and impact on quality of life. Furthermore, hepatic parenchymal injury needs to be considered while evaluating future therapeutic options for CNS.

[The first case of Crigler-Najjar syndrome in the Czech Republic]. / První prípad Criglerova-Najjarova syndromu v Ceské republice.

BACKGROUND: Crigler-Najjar syndrome is a rare disease due to a congenital deficiency of bilirubin UDP glucuronosyl transferase in the liver tissue. It is characterised by high levels of unconjugated bilirubin in plasma through the whole life. The aim of the study was to confirm the clinical diagnosis of the first Crigler-Najjar syndrome case in our country. METHODS AND RESULTS: 34 years old Gypsy women was admitted to our GI clinic for clinical examination before scheduled cholecystectomy. The high plasmatic level of unconjugated bilirubin was found and therefore the diagnosis of Crigler-Najjar syndrome was anticipated. The diagnosis was based on the chromatographic analysis of biliary bile pigments. The amount of diconjugates was considerable decreased. In addition, the molecular analysis of DNA isolated from peripheral blood leukocyte was performed to confirm our conclusions. Our patients was found to be homozygous for a nucleotide shift in the unique exon of bilirubin UDP glucuronosyl transferase 1, substituting guanine into an adenine at position 211.

Hereditary hyperbilirubinemias.

Inherited disorders of bilirubin metabolism involve four autosomal recessive syndromes: Gilbert, CriglerNajjar, Dubin-Johnson and Rotor, among which the first two are characterized by unconjugated and the second two by conjugated hyperbilirubinemia. Gilbert syndrome occurs in 2%-10% of general population, while others are rare. Except for Crigler-Najjar syndrome, hereditary hyperbilirubinemias belong to benign disorders and thus no treatment is required.