Successful Plasmapheresis for Acute and Severe Unconjugated Hyperbilirubinemia in a Child with Crigler Najjar Type I Syndrome

Sellier, A.; Labrune, Philippe; Kwon, Thérèsa; Boudjemline, Alix Mollet; Deschênes, Georges; Gajdos, Vincent

doi:10.1007/8904_2011_40

Cited by 9 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, these results may be important for CNS patients that do not undergo liver transplantation early in age. Because phototherapy treatment is less efficacious after growth and pubertal development, adult CNS patients may have very high levels of plasma bilirubin with sporadic spikes of even higher levels of plasma bilirubin [65], putting them at risk of DNA damage. In fact, the accumulation of DNA lesions in other scenarios contributes to neuronal cell death [66], a phenomenon observed in specific regions of the brain both in hyperbilirubinemic patients and rodent animal models [15, 27, 67, 68].…”

Section: Discussionmentioning

confidence: 99%

Bilirubin‐Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double‐Strand Break Repair Pathways in Human Cells

Rawat

Bortolussi

Gazzin

et al. 2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Unconjugated bilirubin is considered a potent antioxidant when present at moderate levels. However, at high concentrations, it produces severe neurological damage and death associated with kernicterus due to oxidative stress and other mechanisms. While it is widely recognized that oxidative stress by different toxic insults results in severe damage to cellular macromolecules, especially to DNA, no data are available either on DNA damage in the brain triggered by hyperbilirubinemia during the neonatal period or on the activation of DNA repair mechanisms. Here, using a mouse model of neonatal hyperbilirubinemia, we demonstrated that DNA damage occurs in vivo in the cerebellum, the brain region most affected by bilirubin toxicity. We studied the mechanisms associated with potential toxic action of bilirubin on DNA in in vitro models, which showed significant increases in DNA damage when neuronal and nonneuronal cells were treated with 140 nM of free bilirubin (Bf), as determined by γH2AX Western blot and immunofluorescence analyses. Cotreatment of cells with N-acetyl-cysteine, a potent oxidative-stress inhibitor, prevented DNA damage by bilirubin, supporting the concept that DNA damage was caused by bilirubin-induced oxidative stress. Bilirubin treatment also activated the main DNA repair pathways through homologous recombination (HR) and nonhomologous end joining (NHEJ), which may be adaptive responses to repair bilirubin-induced DNA damage. Since DNA damage may be another important factor contributing to neuronal death and bilirubin encephalopathy, these results contribute to the understanding of the mechanisms associated with bilirubin toxicity and may be of relevance in neonates affected with severe hyperbilirubinemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Bilirubin‐Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double‐Strand Break Repair Pathways in Human Cells

Rawat

Bortolussi

Gazzin

et al. 2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Ursodiol therapy is often prescribed and phenobarbital can be effective in patients with less severe enzyme defects. Additional therapeutic avenues include plasmapheresis, albumin infusions, prophylactic cholecystectomy, and the avoidance of medication-induced bilirubin displacement (7,(9)(10)(11).…”

Section: What Is Newmentioning

confidence: 99%

Hepatic Parenchymal Injury in Crigler‐Najjar Type I

Mitchell¹,

Ranganathan

McKiernan³

et al. 2018

J. pediatr. gastroenterol. nutr.

View full text Add to dashboard Cite

show abstract

“…But as age progresses, phototherapy becomes less effective due to a larger body surface area and thickening of the skin, and bilirubin can rise dangerously during intercurrent illness[ 72 ]. Plasmapheresis has also been reported to be a useful tool in CNS when a rapid decrease in bilirubin serum concentration is required[ 73 ]. Plasmapheresis has been recommended as a useful treatment for extreme acute unconjugated hyperbilirubinemia in children with CNS when phototherapy is transiently impaired for any adverse complication or during nonavailability of heme oxygenase inhibitors[ 74 ].…”

Section: Group Bmentioning

confidence: 99%

Pediatric metabolic liver diseases: Evolving role of liver transplantation

Menon¹,

Vij²,

Sachan³

et al. 2021

WJT

View full text Add to dashboard Cite

Metabolic liver diseases (MLD) are the second most common indication for liver transplantation (LT) in children. This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation. LT is also performed in metabolic disorders for end-stage liver disease, its sequelae including hepatocellular cancer. It is also performed for preventing metabolic crisis’, arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia. Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis, cholestasis, inflammation, variable amount of fibrosis, and cirrhosis. The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT. A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters. Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver. The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.

show abstract

Successful Plasmapheresis for Acute and Severe Unconjugated Hyperbilirubinemia in a Child with Crigler Najjar Type I Syndrome

Cited by 9 publications

References 13 publications

Bilirubin‐Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double‐Strand Break Repair Pathways in Human Cells

Bilirubin‐Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double‐Strand Break Repair Pathways in Human Cells

Hepatic Parenchymal Injury in Crigler‐Najjar Type I

Pediatric metabolic liver diseases: Evolving role of liver transplantation

Contact Info

Product

Resources

About