Effect of
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            -carnitine treatment for valproate-induced hepatotoxicity

Bohan, Timothy P.; Helton, Edward D.; McDonald, I. R.; König, S. A.; Gazitt, S.; Sugimoto, Takeshi; Scheffner, D.; Cusmano, L.; Li, S.; Koch, Gary G.

doi:10.1212/wnl.56.10.1405

Cited by 174 publications

(90 citation statements)

References 13 publications

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“…Decreased CPS I levels cause decreased hepatic urea formation and resultant hyperammonemia. Administration of L-carnitine in VHE will reduce serum ammonia levels, and recently has been shown to boost survival from 10 to 48% in patients with VPA hepatotoxicity (12). Carnitine was given to one patient (case 7) in our series, even before low total and free carnitine levels were reported by the laboratory.…”

Section: Discussionmentioning

confidence: 85%

Serum and CSF Glutamine Levels in Valproate‐related Hyperammonemic Encephalopathy

et al. 2002

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Summary:Purpose: To investigate ammonia and glutamine levels in valproate (VPA)-related hyperammonemic encephalopathy (VHE).Methods: We reviewed the medical records and EEG recordings of seven adults diagnosed with VHE.Results: Venous ammonia levels were elevated in five (71%) of the seven patients. Elevated serum or cerebrospinal fluid (CSF) glutamine levels were found in four (80%) of five cases tested, including two who had normal ammonia levels. Initial behavioral signs included violent outbursts in three patients, paranoid ideation severe enough to require restraint in two cases, and milder abnormalities in two instances. The severity of encephalopathy was not related to any particular serum VPA level. In four patients serum VPA levels did not exceed 100 g/ml, and in one case, VHE developed after taking only one 250-mg dose. Symptoms eventually cleared after reducing the dose of, or discontinuing, VPA. Liver-function tests were normal. Each of six patients tested had EEG findings that supported the diagnosis of VHE and excluded nonconvulsive status epilepticus. The rate of normalization of one patient's serum glutamine level and the EEGs of two cases correlated better with the timing of their delayed clinical recovery than did the more rapid rate of decline of the serum ammonia levels. Conclusions: Serum or CSF glutamine levels are initially elevated in a majority of patients with suspected VHE, sometimes in the absence of hyperammonemia. Glutamine levels may be useful adjunctive laboratory tests for the diagnosis of VHE.

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Section: Discussionmentioning

confidence: 85%

Serum and CSF Glutamine Levels in Valproate‐related Hyperammonemic Encephalopathy

et al. 2002

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“…5,6 Data from prospective DILI registries suggest that antibiotics remain the most common cause of idiosyncratic DILI. The American DILI Network (DILIN) reported antibiotics to be implicated in 45.4% of cases. 7 Other common drug classes reported by the American DILIN were herbal and dietary supplements (HDS; 16.1% -a significant increase over the last 10 years), cardiovascular agents (9.8%), central nervous system agents (9.1%), anti-neoplastic agents (5.5%) and analgesics (3.7%).…”

Section: Epidemiologymentioning

confidence: 99%

“…There are also therapies for specific causes of DILI; for example, N-acetylcysteine (NAC) for paracetamol overdose 44 and L-carnitine for valproic acid overdose. 45 Corticosteroid therapy in DILI has a limited role and is reserved for those with immune-mediated DILI or 'druginduced' AIH. The former may only need a short course of steroids, whereas the latter, which is often indistinguishable from idiopathic AIH, often requires prolonged courses of steroids and/or additional immunosuppression.…”

Section: Management Of Dilimentioning

confidence: 99%

Drug-induced liver injury

2016

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Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature because affected individuals represent only a small proportion of those treated with such drugs. In many cases, the mechanism for idiosyncrasy is immune-mediation and is often identifi ed by genetic risk determined by human leukocyte antigen variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, although recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued, especially in the presence of elevated transaminases (aspartate aminotransferase/alanine aminotransferase ratio ≥5 times the upper limit of normal) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefi t of N-acetylcysteine in the early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory. KEYWORDS : Autoimmune hepatitis , cholestasis , drug-induced acute liver failure , herbal and dietary supplements , hepatocellular DILI , hepatotoxicity IntroductionAt a regulatory level, drug-induced liver injury (DILI) is the commonest reason for withdrawing drugs from the market and/or issuing warnings and modification of use.1 DILI is classified as either predictable or unpredictable (idiosyncratic). 2The former tends to be dose-related, has a short latency (days), is due to direct toxicity of the drug or its metabolite, and is ABSTRACT Drug-induced liver injuryreproducible in animal models (eg paracetamol overdose). 3The vast majority of DILI, however, is idiosyncratic or unpredictable -it is unexpected based on the pharmacological actions of the drug and in most cases routine animal toxicology fails to identify the risk of subsequent clinical toxicity. 4 This review shall largely focus on idiosyncratic DILI .

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“…52 In a case controlled study of 92 patients with valproateinduced hepatotoxicity, 42% of the 42 patients treated with L-carnitine survived compared to 10% of the other 50 patients treated with supportive care (p < 0.001); intravenous rather than oral administration was associated with greatest survival. 103 In those with valproate DILI, steroids generally are not useful in DILI unless features of drug-induced hypersensitivity features are present.…”

Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 99%