Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management

Oishi, Kimihiko; Arnon, Ronen; Wasserstein, Melissa P.; Diaz, George A.

doi:10.1111/petr.12741

Cited by 49 publications

(48 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liver transplantation is considered a curative treatment for various liver diseases [ 111 ]. However, for PFIC2 patients, the recurrence of the BSEP defect has been reported due to circulating BSEP antibodies [ 112 , 113 ].…”

Section: Main Textmentioning

confidence: 99%

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

et al. 2018

View full text Add to dashboard Cite

BackgroundJaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis.Main bodyThe major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 (ATP8B1), BSEP (ABCB11), or MDR3 (ABCB4). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway.Short conclusionUnderstanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.

show abstract

Section: Main Textmentioning

confidence: 99%

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Liver transplant can be used to cure some IMDs (which are similar in adults and children). Since this is the subject of several recent reviews (Moini et al 2010;McKiernan 2013;Oishi et al 2016), it will not be the focus here. It is worth noting though that some patients, such as those with methylmalonic acidemia (Kasahara et al 2006)or maple syrup urine disease (Al-Shamsi et al 2016), treated with OLTX with curative intent may still be at risk of metabolic decompensation although this risk is dramatically reduced.…”

Section: Spectrum Of Imds Treated With Oltx In Adults and Childrenmentioning

confidence: 99%

Transplantation as disease modifying therapy in adults with inherited metabolic disorders

Sirrs

Hannah‐Shmouni

Nantel

et al. 2018

J of Inher Metab Disea

View full text Add to dashboard Cite

Transplantation is an established disease modifying therapy in selected children with certain inherited metabolic diseases (IMDs). Transplantation of hematopoietic stem cells or solid organs can be used to partially correct the underlying metabolic defect, address life threatening disease manifestations (such as neutropenia) or correct organ failure caused by the disease process. Much less information is available on the use of transplantation in adults with IMDs. Transplantation is indicated for the same IMDs in adults as in children. Despite similar disease specific indications, the actual spectrum of diseases for which transplantation is used differs between these age groups and this is partly related to the natural history of disease. There are diseases (such as urea cycle defects and X-linked adrenoleukodystrophy) for which transplantation is recommended for selected symptomatic patients as a treatment strategy in both adults and children. In those diseases, the frequency with which transplantation is used in adults is lower than in children and this may be related in part to a reduced awareness of transplantation as a treatment strategy amongst adult clinicians as well as limited donor availability and allocation policies which may disadvantage adult patients with IMDs. Risks of transplantation and disease-specific prognostic factors influencing outcomes also differ with age. We review the use of transplantation as a disease modifying strategy in adults focusing on how this differs from use in children to highlight areas for future research.

show abstract

“…These disorders are typically a result of mutations that affect amino acid, metal, lipid metabolism or mitochondrial function. Some metabolic diseases such as Wilson's disease, tyrosinemia, α1-antitrypsin deficiency, urea cycle defects and Maple syrupurine disease [15]. Hepatoblastoma is the most common pediatric primary liver tumor and is the most prevalent indication for liver transplantation for malignant disease [16].…”

Section: Discussionmentioning

confidence: 99%

Pediatric living donor liver transplantation: A single center experiences

Ertuğrul¹,

Hizarci²

2019

Journal of Surgery and Medicine

View full text Add to dashboard Cite

Aim: The only definitive treatment of chronic liver disease (cholestatic, metabolic, autoimmune), acute liver failure and liver tumors are liver transplantation in pediatric patients. The aim of this study was to present the experience of our center on pediatric living donor liver transplantation and review of the literature. Methods: This is retrospective cohort study. Pediatric patients who receive living donor liver transplantation between December 2014 and December 2017 included in the study. Demographic features, complications after transplantation, and mortality rates were recorded. Results: A total 29 patients were included in the study. Mean age of cases were 3.1 (1-13) years, 18 (62.1%) of the patients were male. Mean Pediatric End-Stage Liver Disease (PELD) scores were 15.6 (-6-37). Mean follow-up period was 60 months. Complication was detected in 11 patients (37.9%) and 5 patients died (mortality rate: 17.9%). In our study, the causes of death were disseminated intravascular coagulation in three patients and sepsis due to biliary leakage in two patients. Conclusion: Complications and mortality rates related to pediatric patients with donor liver transplantation in our center are consistent with the literature.

show abstract

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management

Cited by 49 publications

References 142 publications

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

Transplantation as disease modifying therapy in adults with inherited metabolic disorders

Pediatric living donor liver transplantation: A single center experiences

Contact Info

Product

Resources

About