Liver transplantation in children

Muiesan, Paolo; Vergani, Diego; Mieli‐Vergani, Giorgina

doi:10.1016/j.jhep.2006.11.006

Cited by 72 publications

(60 citation statements)

References 68 publications

(60 reference statements)

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“…A large group of patients with this condition was expected, as this is the main cause for orthotopic liver transplantation in children (Muiesan et al, 2007;Sokal et al, 2008; Adam and Hoti, Fig. 2.…”

Section: Discussionmentioning

confidence: 98%

“…In adults, the main indications for liver transplantation are noncholestatic liver cirrhosis (6 60%) resulting from alcoholism or hepatitis C, liver cancers (6 10%), cholestatic diseases (6 10%), acute hepatic failure, and metabolic disorders (Adam and Hoti, 2009). In children, however, biliary atresia is the main indication for liver transplantation, followed by fulminant liver failure; other cholestatic diseases, such as progressive familial intrahepatic cholestatis (PFIC) and Alagille syndrome; and other metabolic diseases (Muiesan et al, 2007;Sokal et al, 2008;Adam and Hoti, 2009).…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

et al. 2012

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To improve the modeling and simulation of pharmacokinetics in pediatric patients, research into developmental and disease-specific determinants is needed. This article describes the evaluation of the activity of in vitro cytochrome P450 (P450), an important enzyme family in drug metabolism, in children with hepatic dysfunction. The activity of six P450 isoforms (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) was evaluated in 31 patients with different pathologies, predominantly biliary atresia (n = 23). Hypervariable activity was observed for all the isoforms. Compared with average adult activity, low activity levels were seen for CYP1A2, 2C19, 2E1, and 3A4. For CYP2E1 and 3A4, a positive correlation between activity and abundance was observed. Age, comedication, and genotype could not be used as predictors for P450 activity in this patient population. In contrast, the pediatric end-stage liver disease score was negatively correlated with the ln(activity). This finding suggests a decrease in P450 activity with deteriorating hepatic function. Moreover, the activity of all isoforms was correlated, demonstrating a concomitant decrease of all isoforms in young patients with liver disease. To our knowledge, this is the first study to evaluate P450 activity in children with hepatic impairment. The presented data may provide support in the further optimization of a diseasespecific model in this patient population.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

et al. 2012

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“…colestase, prurido e/ou ascite intratáveis do ponto de vista clínico; hipertensão porta com sangramento de varizes sem resposta ao tratamento; episódios múltiplos de colangite ou episódios de peritonite bacteriana espontânea; síntese hepá-tica progressivamente deficiente; repercussão no crescimento pondo-estatural e encefalopatia hepática 3,4 . A atresia biliar é a principal indicação na faixa etária pediátrica 3,4,5 .…”

Section: Introductionunclassified

Pediatric liver transplantation: 10 years of experience at a single center in Brazil

Mesquita

Ferreira

Veloso³

et al. 2008

J Pediatr (Rio J)

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“…UGT1A1 function is fully restored after liver transplantation and serum bilirubin levels return to normal. However, due to the risk of complications, a mortality up to 10 % in the first year [70], the burden of lifelong immunosuppressive therapy and the lack of sufficient liver donors, the development of new alternative curative therapies is warranted. Since only about 10 % of normal UGT1A1 activity is sufficient to reduce serum bilirubin levels to levels below those causing brain damage, several patients have been treated with transplantation of donor hepatocytes [71][72][73].…”

Section: Current Treatment For Crigler-najjar Syndromementioning

confidence: 99%

Gene Replacement Therapy for Genetic Hepatocellular Jaundice

Dijk

Beuers

Bosma

2014

Clinic Rev Allerg Immunol

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Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.

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Liver transplantation in children

Cited by 72 publications

References 68 publications

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

In Vitro Cytochrome P450 Activity Decreases in Children with High Pediatric End-Stage Liver Disease Scores

Pediatric liver transplantation: 10 years of experience at a single center in Brazil

Gene Replacement Therapy for Genetic Hepatocellular Jaundice

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