Acute Hepatic Failure in a Child Treated With Lamotrigine

Arnon, Ronen; DeVivo, Darryl C.; DeFelice, Amy R.; Kazlow, Philip

doi:10.1016/s0887-8994(97)00196-3

Cited by 34 publications

(12 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drugrelated hepatotoxicity is relatively common in children, particularly those taking neuroleptic medications, yet ALF is rare. (25,26) The mechanism of injury leading to ALF is thought to be an idiosyncratic reaction in most cases; however, children with ALF related to valproic acid should be evaluated for an underlying mitochondrial disorder. (27)In addition, polymorphisms of genes associated with drug detoxification or cytokine expressions may enhance a patient's susceptibility to liver injury.…”

Section: Discussionmentioning

confidence: 99%

Acute liver failure in children: The first 348 patients in the pediatric acute liver failure study group

Squires

Shneider

Bucuvalas

et al. 2006

The Journal of Pediatrics

740

734

View full text Add to dashboard Cite

Objectives-To determine short-term outcome for children with acute liver failure (ALF) as it relates to etiology, clinical status, patient demographics and to determine prognostic factors.Study design-A prospective, multi-center case study collecting demographic, clinical, laboratory and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and INR remained ≥ 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures three weeks after study entry were death, death after transplant, alive with native liver, alive with transplanted organ.Results-The etiology of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-APAP drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never developed clinical encephalopathy.Conclusions-Etiologies of ALF in children differ from adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.Corresponding Address: Robert H. Squires, Jr., M.D., Professor of Pediatrics, University of Pittsburgh, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, Phone: 412-692-8181, Fax: 412-692-7355, Email: Robert.squires@chp.edu. edited by WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (11), development of a reliable prognostic score will be useful in allocating organs to the most needy patients. NIH Public AccessThe Pediatric Acute Liver Failure (PALF) study group was formed in 1999 to develop a database that would facilitate an improved understanding of the etiopathogenesis, treatment and outcome of ALF in children. These data will also serve to identify factors that will help to predict the likelihood of death or need for liver transplant. Methods OrganizationThe PALF study group began as an adjunct to the Data CollectionFollowing informed consent from a parent or legal guardian, demographic, clinical and laboratory information were recorded daily for seven days. In most patients, an additional aliquot of serum or plasma was collected on each of the seven study days, frozen at −70° C and then shipped to the Data Coordinating Center (DCC) located at the University of Texas Southwestern Medical Center in Dallas, Texas. Diagnostic evaluation and medical management were consistent with the...

show abstract

Section: Discussionmentioning

confidence: 99%

Acute liver failure in children: The first 348 patients in the pediatric acute liver failure study group

Squires

Shneider

Bucuvalas

et al. 2006

The Journal of Pediatrics

740

734

View full text Add to dashboard Cite

show abstract

“…Her only symptoms were nausea and a diffuse erythematous macular rash. Previous case reports [3][4][5][6][7][8] of lamotrigine-induced AHS with severe hepatotoxicity have described fever and some signs of encephalopathy or hepatic decompensation. Our patient did not have any fever and was mentally and neurologically normal, which was unlike most previously reported patients with severe hepatic involvement.…”

Section: Discussionmentioning

confidence: 99%

“…In such an event, the immediate discontinuation of the medication should be accompanied by vigorous resuscitation and supportive care to prevent further morbidity or mortality [6].…”

Section: Discussionmentioning

confidence: 99%

“…Mucosal and skin involvement feature prominently with lamotrigine use [2]. There are very few reports associating lamotrigine with severe hepatotoxicity [3][4][5][6][7][8]. We believe this to be the first case reported of a patient with extremely high liver enzymes (AST/ALT Ͼ1000 IU/L) when lamotrigine was added to oxcarbazepine treatment, with eventual complete resolution of symptoms and enzyme levels after termination of the medication and supportive management.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Lamotrigine-associated reversible severe hepatitis: A case report

2008

View full text Add to dashboard Cite

A 43-year-old woman with a history of depression, which was being treated with oxcarbazepine twice a day (300 mg/morning and 450 mg/evening), was started on lamotrigine 2 weeks prior to her presentation, with the dose increased to 50 mg/day just prior to admission.Two weeks after starting the lamotrigine, she developed nausea and a generalized pruritic macular rash. She sought treatment in ABSTRACTIntroduction: Anticonvulsant hypersensitivity syndrome is a severe idiosyncratic reaction to antiepileptic drugs. We report a case of a woman with lamotrigine-associated hepatitis who recovered spontaneously with supportive treatment.Case Report: A 43-year-old woman was being treated with oxcarbazepine for depression and was started on lamotrigine 2 weeks prior to her presentation. The patient then developed nausea and a generalized pruritic macular rash, and was found to have elevated liver enzymes, which peaked at AST, 6079 IU/L; ALT, 6900 IU/L; total bilirubin, 3.9 mg/dL(66.7 mol/L); alkaline phosphatase, 149 IU/L; international normalized ration (INR), 1.9. The patient showed no signs of encephalopathy and her clinical examination was essentially normal except for very mild jaundice and a diffuse erythematous pruritic macular rash. The patient was hydrated and managed with supportive care. On the third day of hospitalization, her liver enzymes had improved substantially and she was discharged. At follow-up 1 month later the patient's liver enzymes were within the normal range.Discussion: We hypothesize that lamotrigine was directly responsible for the patient's rash and liver impairment given the time sequence of drug introduction and resolution of symptoms and liver enzyme abnormality once the drug was withdrawn. The patient suffered severe transaminitis when lamotrigine was added to oxcarbazepine, which resolved after termination of the medication and supportive management. We recommend monitoring the hepatic function in patients who have just been initiated on lamotrigine, especially if they develop jaundice.

show abstract

“…A significant increase in both ALT & AST liver enzymes, a decrease in TBARS content with an increase in the activities of both catalase and glutathione reductase enzymes was also reported in rats with induced convulsion, treated by LTG [11]. Hepatic failure and multi-organ failure has been reported in children as well as in adults by the use of LTG [12,13,14].…”

Section: Introductionmentioning

confidence: 92%