Suspected Carbamazepine‐Induced Hepatotoxicity

Morales-Diaz, Marta; Pinilla-Roa, Elizabeth; Ruiz, Inés

doi:10.1592/phco.19.3.252.30918

Cited by 16 publications

(3 citation statements)

References 13 publications

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“…[24][25][26] In the list of potential etiologic factors, drug-induced liver injury must be considered. In this respect, valproateand carbamazepine-induced liver injury [27][28][29][30][31] have been described previously in children. However, the age of our patients (49.5 Ϯ 12.1 years [range, [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]) and the delayed onset of the hepatitis with respect to the introduction of valproate (48 and 122 months), and carbamazepine (120 and 41 months) argue against a direct druginduced effect.…”

Section: Discussionmentioning

confidence: 99%

Fulminant Hepatitis After Grand Mal Seizures: Mechanisms and Role of Liver Transplantation

et al. 2003

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Fulminant liver failure is a rare complication of grand mal seizures with a high mortality, the prognosis being largely determined by the combination of the hepatic and neurologic insults. The mechanisms of acute liver failure secondary to grand mal epilepsy and the place of liver transplantation in this context are poorly defined and are the subject of this report. A series of 6 such patients is presented. All had a history of chronic primary or post-traumatic epilepsy and presented with acute liver failure shortly after a grand mal fit. Detailed accounts of background, presentation, and management are given and integrated with blood, radiologic, and histologic investigations. Two of the 6 patients survived, 1 making a full recovery and the other with neurologic sequelae. Two patients underwent liver transplantation but died with severe neurologic sequelae despite improving liver function. The remaining 2 patients were considered too unwell to undergo liver transplantation and died in multiple organ failure. Liver histology from needle biopsy and/or native liver explants identified lesions compatible with a combination of steatosis and necrosis. Factor V and transaminase levels may allow early identification of patients in whom liver function is likely to improve spontaneously. In conclusion, the mechanisms of liver failure occurring after grand mal seizures appear multifactorial, including hypoxia, steatosis, and drug-induced components. The neurological prognosis and overall survival of these patients remains poor. F ulminant liver failure is a rare complication of status epilepticus and is associated with a high mortality. The grim prognosis in this condition appears determined by the combination of the hepatic and neurological insults, although the mechanism of the hepatic injury remains unclear. To date, there are no reports of patients offered liver transplantation for this particular cause of fulminant liver failure. We describe a series of 6 patients presenting with fulminant liver failure secondary to status epilepticus, 2 of whom survived, and report the first 2 cases of liver transplantation for this indication.The article reviews the background, medications, presentation, and clinical evolution of these patients, with a particular emphasis on hepatic and neurologic status. These data are correlated with histologic findings to bring to light possible mechanisms of the hepatic injury as well as factors that may predict its prognosis. Finally, we discuss management issues of these patients including the place of liver transplantation. Patients and MethodsPatient Recruitment. From 1994 to 2001, 251 patients with fulminant hepatitis or acute liver failure were admitted to our center. Of these, 6 patients (2 women, 4 men), mean age of 39.7 years (range, 29-58 years), were referred to our center with acute liver failure following grand mal seizures.

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Section: Discussionmentioning

confidence: 99%

Fulminant Hepatitis After Grand Mal Seizures: Mechanisms and Role of Liver Transplantation

et al. 2003

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“…It is known that carbamazepine, a potent anticonvulsant used to treat partial and tonic-clonic seizures, can induce granuloma formation and cholestatic and hepatocellular damage in the liver [11][12][13][14][15][16][17][18][19]. In addition, the FDA approved the AMPA antagonist antiepileptic drug perampanel in 2012 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Even though it undergoes hepatic biotransformation, few studies assess its hepatotoxicity [21].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of in vitro hepatotoxicity of perampanel in comparison with carbamazepine: old versus new

Farmanlı,

Ilgın,

Ergun

et al. 2023

Eur J Life Sci

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Since the liver metabolizes many drugs, including antiepileptics, this organ is the main target of drug-induced damage. There is very little data on hepatotoxicity due to carbamazepine and perampanel metabolized in the liver. The available data are based solely on published case reports. For this reason, this study aims to evaluate the hepatotoxicity of carbamazepine and perampanel, which are frequently used in treating epilepsy and which do not have a detailed investigation, although they are suspected of hepatotoxicity. Hepatotoxicity in the HepG2 cell line, IC50 values were calculated by MTT cytotoxicity test, followed by determination of apoptosis/necrosis, various biochemical analyzes (ALT, AST, urea), which is currently a biomarker for liver injury, and hepatotoxicity by ROS and GSH determination. Both drugs increased liver biomarkers, oxidative stress, and cytotoxicity in HepG2 cells. The investigation found that the drugs triggered liver apoptosis, not necrosis. In conclusion, Perampanel may have hepatotoxicity similar to carbamazepine.

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“…CBZ causes many adverse reactions within the liver, and there have been reports of CBZ‐induced hepatitis, vanishing bile duct syndrome (14) and granulomatous hepatitis (15), but liver failure secondary to CBZ is very rare and mostly reported in children (16,17). The mechanism of idiosyncratic hepatic reactions to CBZ is poorly understood, although bio‐activation of the drug to its toxic arene oxide metabolites is thought to be important (18).…”

Section: Discussionmentioning

confidence: 99%

Carbamazepine-induced acute liver failure as part of the DRESS syndrome

Naisbitt

et al. 2005

International Journal of Clinical Practice

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Carbamazepine is a widely used drug. It is commonly associated with hepatic abnormalities, ranging from an asymptomatic rise in liver function tests to acute liver failure. The most severe reaction occurs as part of a generalised hypersensitivity reaction, also known as drug reaction, eosinophilia and systemic symptoms (DRESS). We describe a case of a young adult who presented with non-specific symptoms, which progressed to fulminant hepatic failure, displaying the hallmarks of DRESS. We highlight the need for awareness of such an association.

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Suspected Carbamazepine‐Induced Hepatotoxicity

Cited by 16 publications

References 13 publications

Fulminant Hepatitis After Grand Mal Seizures: Mechanisms and Role of Liver Transplantation

Fulminant Hepatitis After Grand Mal Seizures: Mechanisms and Role of Liver Transplantation

Evaluation of in vitro hepatotoxicity of perampanel in comparison with carbamazepine: old versus new

Carbamazepine-induced acute liver failure as part of the DRESS syndrome

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