Significant Hyperbilirubinemia and Acute Hepatocellular Jaundice in a Pediatric Patient Receiving Deferasirox: A Case Report

Feldman, Elizabeth A.; Miller, Christopher D.; Wojnowicz, Sarabeth; Seabury, Robert W.

doi:10.5863/1551-6776-23.1.64

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…Unlike previous findings, among the 13 pediatric patients, the levels of both direct bilirubin and unconjugated bilirubin were elevated (Table 2), which was the same as hepatocellular jaundice. [12] A direct/total bilirubin ratio of >15% to 20% or a DB level above 1.0 mg/dL is collectively defined as direct hyperbilirubinemia. [11] Twelve of the patients (92.3%) in our study were defined as direct hyperbilirubinemia according to the diagnostic criteria.…”

Section: Discussionmentioning

confidence: 99%

Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients

et al. 2019

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Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.

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Section: Discussionmentioning

confidence: 99%

Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients

et al. 2019

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“…With the wide and continuous consumption of DFS in clinical practice, adverse reactions caused by DFS exposure, i.e., gastrointestinal reactions, rashes, diarrhea, headache, fever, kidney injury, , and liver injury, , have been accumulating. DSF-consuming patients presented acute hepatitis accompanied with elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities .…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Metabolic Activation of Deferasirox In Vitro and In Vivo

Zhao

et al. 2023

Chem. Res. Toxicol.

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Deferasirox (DFS) is used for the treatment of iron accumulation caused by the need for long-term blood transfusions, such as thalassemia or other rare anemia. Liver injury due to exposure to DFS has been documented, and the toxic mechanisms of DFS are unknown. The present study aimed to investigate the reactive metabolites of DFS in vitro and in vivo to help us understand the mechanisms of DFS hepatotoxicity. Two hydroxylated metabolites (5-OH and 5'-OH) were identified during incubation of DFS-supplemented rat liver microsomes. Such microsomal incubations fortified with glutathione (GSH) or N-acetylcysteine (NAC) as capture agents offered two GSH conjugates and two NAC conjugates. These GSH conjugates and NAC conjugates were also detected in bile and urine of rats given DFS. CYP1A2 and CYP3A4 were found to dominate the metabolic activation of DFS. Administration of DFS induced decreased cell survival in cultured primary hepatocytes. Pretreatment with ketoconazole and 1-aminobenzotrizole made hepatocytes less susceptible to the cytotoxicity of DFS.

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“…DFX long-term administration is known to be associated with various adverse events and mild to severe alterations of hepatic and kidney functions are the most relevant among them. Reports of drug-induced liver injury, including hepatic failure, have been reported during post-approval use of this compound, showing a hepatocellular pattern of injury with marked elevations in serum aminotransferase in the most severe cases 17 , 18 . A reversible, mild increase in serum creatinine (sCr) has been reported since the core registration trials 19 ; successively, acute nephrotoxicity related to DFX was reported in cases of proximal tubulopathy and Fanconi syndrome or acute interstitial nephritis.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

Piolatto

Berchialla

Allegra

et al. 2021

Sci Rep

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Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose–response correlation [Spearman r (dose-serum ferritin variation): − 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.

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Significant Hyperbilirubinemia and Acute Hepatocellular Jaundice in a Pediatric Patient Receiving Deferasirox: A Case Report

Cited by 3 publications

References 11 publications

Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients

Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients

Evidence for the Metabolic Activation of Deferasirox In Vitro and In Vivo

Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring

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