588 results match your criteria Crigler-Najjar Syndrome


Ultrasound-guided in utero transplantation of placental stem cells into the liver of Crigler-Najjar Syndrome (CNS) model rat.

Transplantation 2019 Apr 8. Epub 2019 Apr 8.

Department of Surgery, Keck School of Medicine, University of Southern California.

Background: Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over post-natal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small animal models exist for preclinical testing. Read More

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http://dx.doi.org/10.1097/TP.0000000000002735DOI Listing

Phase I/II Trial of Liver Derived Mesenchymal Stem Cells in Pediatric Liver Based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-Derived Progenitor Cells (HepaStem®) in Urea Cycle Disorders and Crigler-Najjar Syndrome patients.

Transplantation 2019 Feb 18. Epub 2019 Feb 18.

Department of Paediatrics, Paediatric Gastroenterology and Hepatology unit, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.

Background: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.

Aim: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months post-transplantation. The secondary objective included the assessment of safety up to 12 months post-infusion, and of preliminary efficacy. Read More

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http://dx.doi.org/10.1097/TP.0000000000002605DOI Listing
February 2019
12 Reads

Preclinical Development of an AAV8-hUGT1A1 Vector for the Treatment of Crigler-Najjar Syndrome.

Mol Ther Methods Clin Dev 2019 Mar 31;12:157-174. Epub 2018 Dec 31.

INTEGRARE, Genethon, INSERM, Univ. Evry, Université Paris-Saclay, 91002 Evry, France.

Adeno-associated viruses (AAVs) are among the most efficient vectors for liver gene therapy. Results obtained in the first hemophilia clinical trials demonstrated the long-term efficacy of this approach in humans, showing efficient targeting of hepatocytes with both self-complementary (sc) and single-stranded (ss) AAV vectors. However, to support clinical development of AAV-based gene therapies, efficient and scalable production processes are needed. Read More

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http://dx.doi.org/10.1016/j.omtm.2018.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348934PMC
March 2019
5 Reads

[Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia].

Zhonghua Gan Zang Bing Za Zhi 2018 Dec;26(12):898-902

Liver Disease Department, Nanjing Second Hospital, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, China.

To compare and analyze patient's general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients' demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by (2) test. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2018.12.005DOI Listing
December 2018
9 Reads

[Clinical and pathological features of inherited metabolic liver disease in adults].

Authors:
Z Y He H You X Y Zhao

Zhonghua Gan Zang Bing Za Zhi 2018 Dec;26(12):889-893

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Inherited metabolic liver disease is a kind of metabolic disorders caused by the interactions between host and environmental factors because of genetic defects. The incidence of inherited metabolic liver disease is low and its clinical manifestations are complex and diverse, which initiates difficulties in clinical diagnosis. In addition, hereditary hemochromatosis and Wilson's disease are common types of metabolic abnormalities, often seem in clinical practice, and early diagnosis and treatment can improve the prognosis. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2018.12.003DOI Listing
December 2018
2 Reads

Genes and Pathways Promoting Long-Term Liver Repopulation by hYAP-ERT2 Transduced Hepatocytes and Treatment of Jaundice in Gunn Rats.

Hepatol Commun 2019 Jan 20;3(1):129-146. Epub 2018 Nov 20.

Department of Medicine Marion Bessin Liver Research Center, Albert Einstein College of Medicine Bronx NY.

Hepatocyte transplantation is an attractive alternative to liver transplantation. Thus far, however, extensive liver repopulation by adult hepatocytes has required ongoing genetic, physical, or chemical injury to host liver. We hypothesized that providing a regulated proliferative and/or survival advantage to transplanted hepatocytes should enable repopulation in a normal liver microenvironment. Read More

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http://dx.doi.org/10.1002/hep4.1278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312667PMC
January 2019
4 Reads

AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.

Mol Ther Methods Clin Dev 2018 Dec 5;11:191-201. Epub 2018 Dec 5.

Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administered wild-type rhesus macaques with 1. Read More

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http://dx.doi.org/10.1016/j.omtm.2018.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282099PMC
December 2018
2 Reads

UGT1A1 genotypes and unconjugated hyperbilirubinemia phenotypes in post-neonatal Chinese children: A retrospective analysis and quantitative correlation.

Medicine (Baltimore) 2018 Dec;97(49):e13576

Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China.

To retrospectively analyze and quantitatively correlate UGT1A1 (bilirubin UDP- glucuronosyltransferase gene) genotypes and unconjugated hyperbilirubinemia (UCH) phenotypes among Chinese children.We retrospectively reviewed UCH patients, quantitatively analyzed genotype-phenotype correlation by comparing with healthy controls. Pfam database, SWISS-model, and Pymol were used for UGT1A1 protein domain analysis and protein modeling for assessing the effect of novel missense variants on protein structure. Read More

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http://dx.doi.org/10.1097/MD.0000000000013576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310575PMC
December 2018
2 Reads

A Novel Pathogenic Variant in a Sudanese Child with Type 1 Crigler-Najjar Syndrome.

Drug Metab Dispos 2019 01 1;47(1):45-48. Epub 2018 Nov 1.

Department of Pediatrics, Milton S. Hershey Penn State Medical Center, Hershey, Pennsylvania (W.E.); Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Helsinki, Finland (E.J., J.M., M.F.); Pediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut (W.J., A.G.S., M.K., S.A.L.); Departments of Pathology and Cell Biology (A.C.I.) and Surgery (S.J.L.), Columbia University Medical Center, New York, New York; and Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (A.C.)

Uridine diphosphate glucuronosyltransferases (UGTs) are key enzymes responsible for the body's ability to process a variety of endogenous and exogenous compounds. Significant gains in understanding UGT function have come from the analysis of variants seen in patients. We cared for a Sudanese child who showed clinical features of type 1 Crigler-Najjar syndrome (CN-1), namely severe unconjugated hyperbilirubinemia leading to liver transplantation. Read More

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http://dmd.aspetjournals.org/lookup/doi/10.1124/dmd.118.0843
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http://dx.doi.org/10.1124/dmd.118.084368DOI Listing
January 2019
5 Reads

Auxiliary Partial Orthotopic Liver Transplantation for Monogenic Metabolic Liver Diseases: Single-Centre Experience.

JIMD Rep 2019 12;45:29-36. Epub 2018 Oct 12.

Institute of Liver Disease and Transplantation, Gleneagles Global Health City, Chennai, India.

Purpose: Auxiliary partial orthotopic liver transplantation (APOLT) in metabolic liver disease (MLD) has the advantage of correcting the metabolic defect, preserving the native liver for gene therapy in the future with the possibility of withdrawal of immunosuppression.

Methods: Retrospective analysis of safety and efficacy of APOLT in correcting the underlying defect and its impact on neurological status of children with MLD.

Results: A total of 13 APOLT procedures were performed for MLD during the study period. Read More

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http://link.springer.com/10.1007/8904_2018_137
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http://dx.doi.org/10.1007/8904_2018_137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336549PMC
October 2018
36 Reads

Case report: multiple UGT1A1 gene variants in a patient with Crigler-Najjar syndrome.

BMC Pediatr 2018 Oct 3;18(1):317. Epub 2018 Oct 3.

Scientific Laboratory of Molecular Genetics, Riga Stradiņš University, Dzirciema Street 16, Riga, LV 1007, Latvia.

Background: Inherited unconjugated hyperbilirubinemia is caused by variants in the gene UGT1A1 leading to Gilbert's syndrome and Crigler-Najjar syndrome types I and II. These syndromes are differentiated on the basis of UGT1A1 residual enzymatic activity and its affected bilirubin levels and responsiveness to phenobarbital treatment.

Case Presentation: In this report, we present a boy with Crigler-Najjar syndrome type II with high unconjugated bilirubin levels that decreased after phenobarbital treatment but increased in adolescence. Read More

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https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887
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http://dx.doi.org/10.1186/s12887-018-1285-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169020PMC
October 2018
4 Reads

Transplanted Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Support Liver Regeneration in Gunn Rats.

Stem Cells Dev 2018 Nov 20. Epub 2018 Nov 20.

1 Institute for Stem Cell Research and Regenerative Medicine, Neonatolgy and Pediatric Cardiology, Heinrich Heine University , Düsseldorf, Germany .

Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1a1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In this study, the Gunn rat was used as an animal model for heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. Read More

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https://www.liebertpub.com/doi/10.1089/scd.2018.0010
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http://dx.doi.org/10.1089/scd.2018.0010DOI Listing
November 2018
18 Reads

Crigler-Najjar Syndrome Type II Diagnosed in a Patient with Jaundice Since Birth.

J Coll Physicians Surg Pak 2018 Oct;28(10):806-808

Department of Medicine, King Edward Medical University, Lahore, Pakistan.

Crigler-Najjar syndrome type II is caused by mutations in the UGT1A1 gene resulting in severely reduced hepatic activity of UDP-glucoronyltransferase - an enzyme required to convert bilirubin into a more soluble form that can then be removed from the body. Absence or severe deficiency of this enzyme can lead to bilirubin accumulation in the body resulting in yellow skin and eyes (jaundice). The earliest signs of this disease can be apparent in the neonatal period. Read More

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http://dx.doi.org/3028DOI Listing
October 2018
6 Reads
0.318 Impact Factor

Liver Cirrhosis in a Patient with Crigler Najjar Syndrome.

Fetal Pediatr Pathol 2018 Aug 27;37(4):301-306. Epub 2018 Sep 27.

c Department of Pathology , Baskent University Faculty of Medicine , Ankara , Turkey.

Introduction: Crigler Najjar (CN) disease is a genetic disorder which results in increased unconjugated bilirubin level. Liver parenchyma was previously considered structurally normal. Recent reports describe significant fibrosis in the liver parenchyma of patients with CN syndrome. Read More

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http://dx.doi.org/10.1080/15513815.2018.1492053DOI Listing
August 2018
4 Reads

Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a Mouse Model of Crigler-Najjar Syndrome.

Mol Ther Methods Clin Dev 2018 Sep 21;10:237-244. Epub 2018 Jul 21.

Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) activity. This syndrome is characterized by hyperbilirubinemia and jaundice. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23290501183007
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http://dx.doi.org/10.1016/j.omtm.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090885PMC
September 2018
20 Reads

Neuro-inflammatory effects of photodegradative products of bilirubin.

Sci Rep 2018 May 10;8(1):7444. Epub 2018 May 10.

Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

Phototherapy was introduced in the early 1950's, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown. This is very relevant in light of recent clinical observations demonstrating that the use of aggressive phototherapy can increase morbidity or even mortality, in extremely low birthweight (ELBW) infants. Read More

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http://dx.doi.org/10.1038/s41598-018-25684-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945592PMC
May 2018
3 Reads

Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand.

J Pediatr Genet 2018 Jun 16;7(2):67-73. Epub 2018 Feb 16.

Pediatric Surgery Unit, Department of Surgery, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. Read More

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http://dx.doi.org/10.1055/s-0038-1632395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916803PMC
June 2018
6 Reads

Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1.

CPT Pharmacometrics Syst Pharmacol 2018 Jun 26;7(6):404-412. Epub 2018 Apr 26.

Alexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.

Crigler-Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by a marked decrease in uridine-diphosphate-glucuronosyltransferase (UGT1A1) enzyme activity. Delivery of hUGT1A1-modRNA (a modified messenger RNA encoding for UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients. To support translation from preclinical to clinical studies, and first-in-human studies, a quantitative systems pharmacology (QSP) model was developed. Read More

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http://doi.wiley.com/10.1002/psp4.12301
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http://dx.doi.org/10.1002/psp4.12301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391595PMC
June 2018
19 Reads

AAV8 Gene Therapy Rescues the Newborn Phenotype of a Mouse Model of Crigler-Najjar.

Hum Gene Ther 2018 07;29(7):763-770

Gene Therapy Program, Department of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.

Adeno-associated viral (AAV) vectors can target the liver, making them an attractive platform for gene therapy approaches that require the correction of hepatocytes. Crigler-Najjar syndrome is an autosomal recessive disorder of bilirubin metabolism that occurs when the liver's uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) enzyme activity is partially or completely absent. This syndrome is characterized by elevated bilirubin levels in the blood. Read More

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http://dx.doi.org/10.1089/hum.2017.185DOI Listing
July 2018
4 Reads

Severe Neonatal Hyperbilirubinemia in Crigler-Najjar Syndrome Model Mice Can Be Reversed With Zinc Protoporphyrin.

Hepatol Commun 2017 Oct 10;1(8):792-802. Epub 2017 Aug 10.

Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, CA.

Neurotoxic bilirubin is solely conjugated by UDP-glucuronosyltransferase (UGT) 1A1. Due to an inadequate function of UGT1A1, human neonates develop mild to severe physiological hyperbilirubinemia. Accumulation of bilirubin in the brain leads to the onset of irreversible brain damage called kernicterus. Read More

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http://doi.wiley.com/10.1002/hep4.1082
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http://dx.doi.org/10.1002/hep4.1082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678921PMC
October 2017
7 Reads

Diagnostic criteria and contributors to Gilbert's syndrome.

Crit Rev Clin Lab Sci 2018 03 1;55(2):129-139. Epub 2018 Feb 1.

b School of Medical Science and Menzies Health Institute Queensland , Griffith University , Gold Coast , Australia.

Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert's, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Read More

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http://dx.doi.org/10.1080/10408363.2018.1428526DOI Listing
March 2018
11 Reads

Crigler-Najjar Syndrome: Current Perspectives and the Application of Clinical Genetics.

Endocr Metab Immune Disord Drug Targets 2018 ;18(3):201-211

Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Crigler-Najjar syndrome (CNS, OMIM: 218800) is the paradigm of an inborn error of metabolism and a rare genetic disease with an estimated incidence of 0.6-1.0 per million live births. Read More

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http://dx.doi.org/10.2174/1871530318666171213153130DOI Listing
September 2018
2 Reads

Hepatic Parenchymal Injury in Crigler-Najjar Type I.

J Pediatr Gastroenterol Nutr 2018 04;66(4):588-594

Division of Gastroenterology, Hepatology and Nutrition.

Background: Crigler-Najjar syndrome type I (CNI) arises from biallelic variants of UGT1A1 that abrogate uridine diphosphate glucuronosyltransferase (UGT1A1) activity resulting in unconjugated hyperbilirubinemia. Historically, liver parenchyma in CNI was considered structurally and histologically normal. Recent review of CNI liver explants revealed fibrosis. Read More

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http://dx.doi.org/10.1097/MPG.0000000000001843DOI Listing
April 2018
7 Reads

Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II.

Medicine (Baltimore) 2017 Nov;96(45):e8620

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.

Diagnosis of Crigler-Najjar syndrome type II (CNS-II) and Gilbert syndrome (GS) based on the serum bilirubin concentration is difficult, because this parameter can fluctuate under certain conditions. The aim of this study was to explore differences in UGT1A1 gene mutations, which cause both CNS and GS, and pathological changes between CNS-II and GS.Ninety-five Chinese patients with hereditary unconjugated hyperbilirubinemia were enrolled in this study. Read More

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http://dx.doi.org/10.1097/MD.0000000000008620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690788PMC
November 2017
23 Reads

UGT1A1 gene linkage analysis: application of polymorphic markers rs4148326/rs4124874 in the Iranian population.

Iran J Basic Med Sci 2017 Aug;20(8):880-885

Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Objectives: Mutations in the UGT1A1 gene are responsible for hyperbilirubinemia syndromes including Crigler-Najjar type 1 and 2 and Gilbert syndrome. In view of the genetic heterogeneity and involvement of large numbers of the disease causing mutations, the application of polymorphic markers in the UGTA1 gene could be useful in molecular diagnosis of the disease.

Materials And Methods: In the present study, two polymorphic markers including rs4148326 and rs4124874 in the UGT1A1 gene region were characterized. Read More

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http://dx.doi.org/10.22038/IJBMS.2017.9109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651473PMC
August 2017
4 Reads

Crigler Najjar Syndrome Type 2 (CNS Type 2): An Unwonted Cause of Jaundice in Adults.

J Clin Diagn Res 2017 Jul 1;11(7):OD05-OD06. Epub 2017 Jul 1.

Consultant, Department of Genetic Medicine, Sir Ganga Ram Hospital, New Delhi, India.

Crigler Najjar Syndrome (CNS) Type 2 is an uncommon genetic disorder characterised by non-haemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase- 1, required for the conjugation and further excretion of bilirubin from the body. Affected individuals are usually asymptomatic apart from the jaundice and investigations reveal isolated indirect hyperbilirubinemia. Read More

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http://jcdr.net/article_fulltext.asp?issn=0973-709x&year
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http://dx.doi.org/10.7860/JCDR/2017/28195.10221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583863PMC
July 2017
16 Reads

Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler-Najjar Syndrome Type I.

Gene Ther 2017 10 14;24(10):649-660. Epub 2017 Aug 14.

Mouse Molecular Genetics, Molecular Medicine and Cellular Immunology Groups, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

Adeno-associated virus (AAV) -mediated gene therapy is a promising strategy to treat liver-based monogenic diseases. However, two major obstacles limit its success: first, vector dilution in actively dividing cells, such as hepatocytes in neonates/children, due to the non-integrating nature of the vector; second, development of an immune response against the transgene and/or viral vector. Crigler-Najjar Syndrome Type I is a rare monogenic disease with neonatal onset, caused by mutations in the liver-specific UGT1 gene, with toxic accumulation of unconjugated bilirubin in plasma, tissues and brain. Read More

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http://www.nature.com/doifinder/10.1038/gt.2017.75
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http://dx.doi.org/10.1038/gt.2017.75DOI Listing
October 2017
43 Reads

Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model.

EMBO Mol Med 2017 10;9(10):1346-1355

International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

Crigler-Najjar syndrome type I (CNSI) is a rare monogenic disease characterized by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of neurological damage and death. Liver transplantation is the only curative option, which has several limitations and risks. We applied an gene targeting approach based on the insertion, without the use of nucleases, of a promoterless therapeutic cDNA into the albumin locus of a mouse model reproducing all major features of CNSI Neonatal transduction with the donor vector resulted in the complete rescue from neonatal lethality, with a therapeutic reduction in plasma bilirubin lasting for at least 12 months, the latest time point analyzed. Read More

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http://dx.doi.org/10.15252/emmm.201707601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623861PMC
October 2017
40 Reads

Liver Fibrosis Associated With Crigler-Najjar Syndrome in a Compound Heterozygote: A Case Report.

Pediatr Dev Pathol 2017 Nov-Dec;20(6):522-525. Epub 2017 Mar 14.

1 Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Crigler-Najjar syndrome is a hereditary unconjugated hyperbilirubinemia. Two forms of the disease are recognized. Type I is more severe and results in kernicterus if left untreated, and Type II is less severe and responds to phenobarbital. Read More

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http://dx.doi.org/10.1177/1093526617697059DOI Listing
March 2017
31 Reads

Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1 mouse model.

J Neuroinflammation 2017 03 24;14(1):64. Epub 2017 Mar 24.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149, Trieste, Italy.

Background: Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced neurological damage and eventually death by kernicterus. Bilirubin neurotoxicity is characterized by a wide array of neurological deficits, including irreversible abnormalities in motor, sensitive and cognitive functions, due to bilirubin accumulation in the brain. Read More

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http://dx.doi.org/10.1186/s12974-017-0838-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366125PMC
March 2017
18 Reads

UGT1A1 polymorphisms in cancer: impact on irinotecan treatment.

Pharmgenomics Pers Med 2017 28;10:61-68. Epub 2017 Feb 28.

Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, Japan.

Mutations in the gene have been implicated in Gilbert syndrome, which shows mild hyperbilirubinemia, and a more aggressive childhood subtype, Crigler-Najjar syndrome. To date, more than 100 variants have been found in the gene. Among them, and have been reported to be associated with severe toxicities in patients treated with irinotecan-based chemotherapy by increasing the dose of SN-38 (7-ethyl-10-hydroxycamptothecin), an active form of irinotecan. Read More

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http://dx.doi.org/10.2147/PGPM.S108656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338934PMC
February 2017
10 Reads

Unusual Indications for a Liver Transplant: A Single-Center Experience.

Exp Clin Transplant 2017 Feb;15(Suppl 1):128-132

Department of General Surgery, Baskent University, Ankara, Turkey.

Objectives: This study sought to evaluate the efficacy of liver transplant for unusual liver diseases.

Materials And Methods: The results of 476 patients who underwent liver transplant from 1988 to January 2015 were retrospectively analyzed. Two hundred forty-five of them were adult patients and 231 of them were pediatric. Read More

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http://dx.doi.org/10.6002/ect.mesot2016.P11DOI Listing
February 2017
5 Reads

Intense blue light therapy during the night-time does not suppress the rhythmic melatonin biosynthesis in a young boy.

Endocr Regul 2017 Jan;51(1):31-34

Objective: Melatonin is a hormone predominantly synthesized and secreted during the night by the pineal gland. Artificial light at night, especially its blue part, acutely suppresses the melatonin production. Th e aim of the present study was to find out, whether an intense blue light phototherapy of severe hyperbilirubinemia, may suppress the melatonin production during the night when the eyes will be properly protected by a sleep mask. Read More

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http://dx.doi.org/10.1515/enr-2017-0004DOI Listing
January 2017
7 Reads

Clinical UGT1A1 Genetic Analysis in Pediatric Patients: Experience of a Reference Laboratory.

Mol Diagn Ther 2017 06;21(3):327-335

Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Neonatal hyperbilirubinemia can be severe or prolonged and warrant exploration into the underlying etiology, which may include genetic assessment of UGT1A1 for inherited disorders (i.e. Crigler-Najjar syndrome or Gilbert syndrome). Read More

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http://dx.doi.org/10.1007/s40291-017-0265-0DOI Listing
June 2017
50 Reads

Death from pulmonary embolism of cyanoacrylate glue following gastric varix endoscopic injection.

Forensic Sci Med Pathol 2017 Mar 14;13(1):82-85. Epub 2017 Jan 14.

Victorian Institute of Forensic Medicine, 65 Kavanagh Street, Southbank, Victoria, 3006, Australia.

We present the case of a 25 year old woman with a complex past medical history including Crigler-Najjar syndrome (Type 1) with a liver transplant in 1993 and subsequent development of cirrhosis with portal hypertension in the transplanted liver. The deceased presented to hospital with hematemesis and investigations showed a large gastric varix. The varix was injected with cyanoacrylate glue. Read More

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http://dx.doi.org/10.1007/s12024-016-9835-4DOI Listing
March 2017
7 Reads

[The analysis of UGT1A1 gene mutations in hereditary unconjugated hyperbilirubinemia].

Zhonghua Gan Zang Bing Za Zhi 2016 Nov;24(11):863-866

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.

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http://doi.med.wanfangdata.com.cn/10.3760/cma.j.issn.1007-34
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2016.11.013DOI Listing
November 2016
5 Reads

Gunn Rats as a Surrogate Model for Evaluation of Hepatocyte Transplantation-Based Therapies of Crigler-Najjar Syndrome Type 1.

Methods Mol Biol 2017 ;1506:131-147

Division of Gastroenterology and Liver Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

Liver transplantation has been established as a curative therapy for acute and chronic liver failure, as well as liver-based inherited metabolic diseases. Because of the complexity of organ transplantation and the worldwide shortage of donor organs, hepatocyte transplantation is being developed as a bridging therapy until donor organs become available, or for amelioration of inherited liver-based diseases. The Gunn rat is a molecular and metabolic model of Crigler-Najjar syndrome type 1, which is characterized by lifelong unconjugated hyperbilirubinemia due to the lack of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-mediated bilirubin glucuronidation. Read More

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http://link.springer.com/10.1007/978-1-4939-6506-9_9
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http://dx.doi.org/10.1007/978-1-4939-6506-9_9DOI Listing
January 2018
10 Reads

Rigler Sign in a Child With Posttransplant Lymphoproliferative Disease: A Sign That Should Not Be Missed.

Exp Clin Transplant 2018 Jun 20;16(3):352-354. Epub 2016 Oct 20.

>From the Department of Pediatric Hematology and Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.

Rigler sign is a double wall sign suggesting pneumoperitoneum and intestinal perforation, and it needs emergency surgical treatment. Early diagnosis of intestinal perforation by clinical symptoms, presence of Rigler sign in abdominal radiography, and then early surgical treatment can reduce mortality. Here, we report a patient with Crigler-Najjar syndrome who underwent liver transplant and then developed posttransplant lymphoproliferative disease and received chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Read More

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http://dx.doi.org/10.6002/ect.2016.0006DOI Listing
June 2018
6 Reads
0.800 Impact Factor

A translationally optimized AAV-UGT1A1 vector drives safe and long-lasting correction of Crigler-Najjar syndrome.

Mol Ther Methods Clin Dev 2016 20;3:16049. Epub 2016 Jul 20.

Genethon, Evry, France; Universite' Pierre et Marie Curie - Paris 6, Paris, France; INSERM U951, Evry, France.

Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimized a vector expressing the UGT1A1 transgene. For this purpose, we designed and tested and multiple codon-optimized UGT1A1 transgene cDNAs. Read More

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http://dx.doi.org/10.1038/mtm.2016.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052023PMC
July 2016
24 Reads

[Genetic analysis of a child affected with Crigler-Najjar syndrome type II].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2016 Jun;33(3):328-31

Neonatal Department, Hunan Children's Hospital, Changsha, Hunan 410007, China.

Objective: To detect potential mutation of the UGT1A1 gene in a child affected with Crigler-Najjar syndrome type II.

Methods: Blood samples were collected from the patient and his parents for the extraction of genomic DNA. Potential mutation of the UGT1A1 gene was detected with polymerase chain reaction (PCR) and direct sequencing. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2016.03.011DOI Listing
June 2016
4 Reads

[Phenobarbital in Crigler-Najjar syndrome type 1: A therapeutic option].

An Pediatr (Barc) 2016 Aug 28;85(2):115-116. Epub 2016 Apr 28.

Servicio de Pediatría, Hospital de Poniente, El Ejido, Almería, España.

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http://dx.doi.org/10.1016/j.anpedi.2016.03.017DOI Listing
August 2016
3 Reads

Management of pregnancy in Crigler Najjar syndrome type 2.

World J Hepatol 2016 Apr;8(11):530-2

Alisha Nitin Chaubal, Ruchir Patel, Dhaval Choksi, Kaivan Shah, Meghraj Ingle, Prabha Sawant, Department of Gastroenterology, LTMG Hospital, Mumbai 400022, India.

Crigler Najjar syndrome is associated with indirect hyperbilirubinemia due to a deficiency of enzyme Uridine Di Phospho Glucoronosyl Transferase (UDPGT). Presented here is a case of a female in the first trimester of pregnancy, who was diagnosed to have type 2 Crigler Najjar syndrome. We also discuss the management of this rare disease especially in pregnancy. Read More

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http://dx.doi.org/10.4254/wjh.v8.i11.530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832095PMC
April 2016
7 Reads

Acute cholangitis in an old patient with Crigler-Najjar syndrome type II - a case report.

BMC Gastroenterol 2016 Mar 11;16:33. Epub 2016 Mar 11.

Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Avenida Professor Egas Moniz, Lisboa, 1649-035, Portugal.

Background: Crigler-Najjar syndrome (CN) is a very rare genetic disorder characterized by an inability to conjugate bilirubin. Contrary to CN type I, patients with CN II exhibit residual capacity to conjugate bilirubin and may present a normal life expectancy.

Case Presentation: We report an unusual late diagnosis of CN type II in an 80-year-old female admitted with severe acute cholangitis. Read More

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http://dx.doi.org/10.1186/s12876-016-0449-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788912PMC
March 2016
12 Reads

Two Different UGT1A1 Mutations causing Crigler-Najjar Syndrome types I and II in an Iranian Family.

J Gastrointestin Liver Dis 2015 Dec;24(4):523-6

Division of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Crigler-Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Read More

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http://www.jgld.ro/wp/y2015/n4/a19.pdf
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http://dx.doi.org/10.15403/jgld.2014.1121.244.ugtDOI Listing
December 2015
7 Reads

Reduction of hyperbilirubinemia with hypericum extract (St. John's Wort) in a patient with Crigler-Najjar syndrome type II.

Br J Clin Pharmacol 2016 May 7;81(5):1002-4. Epub 2016 Mar 7.

Division of Clinical Pharmacology & Toxicology, University Hospital Basel and Department of Biomedicine, University of Basel, Switzerland.

Aims: Crigler-Najjar syndrome (CN) type II is a congenital disease with unconjugated hyperbilirubinemia due to a deficiency of uridine 5'-diphospho-glucuronosyltransferase 1A1. Since the currently proposed treatment with phenobarbital is associated with adverse reactions, we investigated the effect of hypericum extract.

Methods: Repetitive determination of total serum bilirubin in a female with CN type II before, during and after daily treatment with 900 mg hypericum extract on two occasions for 8 weeks. Read More

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http://dx.doi.org/10.1111/bcp.12869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834607PMC
May 2016
24 Reads

X-linked ichthyosis and Crigler-Najjar syndrome I: Coexistence in a male patient with two copy number variable regions of 2q37.1 and Xp22.3.

Mol Med Rep 2016 Feb 10;13(2):1135-40. Epub 2015 Dec 10.

Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.

X-linked ichthyosis (XLI) is an X-linked recessive skin disorder generally restricted to males, which arises from mutations in the steroid sulfatase (STS) gene located on Xp22.3. Crigler-Najjar syndrome (CN-I) is a rare autosomal recessive disease caused by the homozygous or compound heterozygous mutations in the UPD‑glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene on chromosome 2q37. Read More

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http://dx.doi.org/10.3892/mmr.2015.4674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732863PMC
February 2016
11 Reads

[A 14-day-old boy with jaundice and apnoea].

Tidsskr Nor Laegeforen 2015 Dec 15;135(23-24):2167-70. Epub 2015 Dec 15.

Barne- og ungdomsklinikken Akershus universitetssykehus.

We describe an infant who was readmitted from home at 14 days of age with jaundice and a history of apnoea and episodes of retrocollis/opisthotonos. He had been only mildly jaundiced on discharge from the maternity clinic at 2 days of age. The total serum bilirubin (TSB) on admission was 542 µmol/L, and the infant was treated intensively with triple phototherapy and exchange transfusion. Read More

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http://dx.doi.org/10.4045/tidsskr.15.0519DOI Listing
December 2015
3 Reads

Inherited disorders of bilirubin clearance.

Pediatr Res 2016 Mar 23;79(3):378-86. Epub 2015 Nov 23.

Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey.

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g. Read More

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http://dx.doi.org/10.1038/pr.2015.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821713PMC
March 2016
9 Reads

De Novo Donor-Specific HLA Antibody Formation in Two Patients With Crigler-Najjar Syndrome Type I Following Human Hepatocyte Transplantation With Partial Hepatectomy Preconditioning.

Am J Transplant 2016 Mar 2;16(3):1021-30. Epub 2015 Nov 2.

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Clinical hepatocyte transplantation is hampered by low engraftment rates and gradual loss of function resulting in incomplete correction of the underlying disease. Preconditioning with partial hepatectomy improves engraftment in animal studies. Our aim was to study safety and efficacy of partial hepatectomy preconditioning in clinical hepatocyte transplantation. Read More

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http://dx.doi.org/10.1111/ajt.13487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061095PMC
March 2016
2 Reads
10 Citations
5.683 Impact Factor

Coronary Artery Disease in Patients With Disorders of Bilirubin Excretion.

Am J Ther 2017 Nov/Dec;24(6):e653-e658

1Department of Internal Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY; 2Department of Medicine, Sinai Hospital of Baltimore, Johns Hopkins University, Baltimore, MD; 3Department of Medicine, Englewood Hospital and Medical Center, Mount Sinai School of Medicine, Englewood, NJ; 4Government Medical College, Amritsar, India; and 5Department of Medicine, Division of Gastroenterology and Hepatobiliary Disease, New York Medical College, Westchester Medical Center, Valhalla, NY.

We aimed to determine the predictors of coronary artery disease (CAD) in patients with abnormal bilirubin excretion, that is, Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and Rotor syndrome. We analyzed data from the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality, Rockville, MD for the period 2009 to 2010. All patients ≥18 years of age with a primary diagnosis of "disorders of bilirubin excretion" [International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9CM) code 277. Read More

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http://Insights.ovid.com/crossref?an=00045391-201711000-0000
Publisher Site
http://dx.doi.org/10.1097/MJT.0000000000000343DOI Listing
June 2018
22 Reads