valproic acid and Chemical and Drug Induced Liver Injury studies

Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.
valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.

Chemical and Drug Induced Liver Injury: A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment.

Research Excerpts

Excerpt	Relevance	Reference
"Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity."	9.01	Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update. ( Chen, F; Guo, HL; Hu, YH; Jing, X; Lu, XP; Ni, MM; Qiu, JC; Sun, JY; Wang, T; Xu, ZJ, 2019)
"This study was aimed at identifying genetic and non-genetic risk factors for valproic acid (VPA)-induced hyperammonaemia in Chinese paediatric patients with epilepsy."	7.88	Risk Factors for Valproic Acid-induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy. ( Li, X; Zhang, T; Zhao, L; Zhu, X, 2018)
"We describe four children with Dravet syndrome treated with the combination of valproic acid (VPA) and topiramate (TPM) who developed transient liver toxicity."	7.74	Acute hepatic injury in four children with Dravet syndrome: valproic acid, topiramate or acetaminophen? ( Ceulemans, B; Gunning, B; Leroy, PL; Nicolai, J; Vles, JS, 2008)
"Glioblastoma patients undergoing treatment with surgery followed by radiation and temozolomide chemotherapy often develop a state of immunosuppression and are at risk for opportunistic infections and reactivation of hepatitis and herpes viruses."	7.74	Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide. ( Hoorens, A; Neyns, B; Stupp, R, 2008)
"We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy."	7.74	Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS. ( Gerstner, T; Koenig, SA; Kohlmueller, D; Longin, E; Mehlem, P; Schulze, A; Teich, M; Treiss, I; Werner, T, 2007)
"Use of valproic acid may be possible for some patients with hepatitis C."	7.72	The safety of valproic acid use for patients with hepatitis C infection. ( Barnes, RF; Dominitz, JA; Felker, BL; Sloan, KL, 2003)
"In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L-carnitine supplementation in childhood epilepsy."	7.70	L-carnitine supplementation in childhood epilepsy: current perspectives. ( Bohan, TP; Coulter, DL; De Vivo, DC; Dreifuss, FE; Greenwood, RS; Nordli, DR; Shields, WD; Stafstrom, CE; Tein, I, 1998)
" In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML."	6.73	Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes. ( Hallman, H; Honkanen, T; Juvonen, E; Kauppila, M; Koistinen, P; Kutila, A; Mikkola, M; Nyländen, P; Poikonen, E; Rauhala, A; Savolainen, ER; Siitonen, T; Sinisalo, M; Suominen, M; Terävä, V; Timonen, T, 2007)
"Valproic acid (VPA) has been widely used more frequently as its approved indications have been expanded."	5.62	Rhabdomyolysis and Hepatotoxicity From Valproic Acid: Case Reports. ( Deb, S; Walker, CP, 2021)
"Valproic acid (VPA) is an antiepileptic drug (AED) used for generalized and absence seizures."	5.32	Effects of age and polytherapy, risk factors of valproic acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)-2,4-diene VPA in people with epilepsy taking VPA. ( Abbott, F; Farrell, K; Gopaul, S, 2003)
"Side effects of carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) are rare during long-term use but rather common and usually transient during the early phases of treatment."	5.27	Side effects of carbamazepine, valproate and clonazepam during long-term treatment of epilepsy. ( Keränen, T; Sivenius, J, 1983)
"Valproate therapy shows no benefit over short-term phenytoin therapy for prevention of early seizures and neither treatment prevents late seizures."	5.09	Valproate therapy for prevention of posttraumatic seizures: a randomized trial. ( Anderson, GD; Awan, A; Cohen, W; Dikmen, SS; Holmes, MD; Nelson, P; Newell, DW; Temkin, NR; Wilensky, AJ; Winn, HR, 1999)
"Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity."	5.01	Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update. ( Chen, F; Guo, HL; Hu, YH; Jing, X; Lu, XP; Ni, MM; Qiu, JC; Sun, JY; Wang, T; Xu, ZJ, 2019)
"Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world."	4.90	Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity. ( Felker, D; Johnson, DE; Lynn, A; Wang, S, 2014)
"Valproic acid is an effective first line drug for the treatment of epilepsy."	4.90	Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. ( Choonara, I; Edwards, IR; Star, K, 2014)
"This review analyses the concept of extended-release (ER) formulations in epilepsy and evaluates ER formulations of carbamazepine, valproic acid and a modified-release (MR) formulation of oxcarbazepine."	4.84	Extended-release formulations for the treatment of epilepsy. ( Bialer, M, 2007)
"We report a case of pancreatitis with fatal liver failure, in a 21-year-old, mentally retarded patient, taking valproic acid (VPA) therapy, together with a review of the literature of this rare side effect."	4.78	Valproic-acid-induced pancreatitis. Case report and review of the literature. ( Binek, J; Hany, A; Heer, M, 1991)
"This study was aimed at identifying genetic and non-genetic risk factors for valproic acid (VPA)-induced hyperammonaemia in Chinese paediatric patients with epilepsy."	3.88	Risk Factors for Valproic Acid-induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy. ( Li, X; Zhang, T; Zhao, L; Zhu, X, 2018)
" We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment."	3.83	Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study. ( Geddes, JR; Hayes, JF; King, M; Marston, L; Osborn, DP; Walters, K, 2016)
"Children with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied."	3.78	[Valproic acid-induced idiosyncratic liver injury in 4 cases]. ( Bao, XH; Jiang, YW; Liu, CT; Qin, J; Wu, XP; Xiong, H; Zhang, YH; Zhao, H, 2012)
"Valproic acid monotherapy is associated with NAFLD in a high percentage of adolescents with epilepsy who have typical VPA-related metabolic disturbances."	3.77	Nonalcoholic fatty liver disease in adolescents receiving valproic acid. ( Agostinelli, S; Chiarelli, F; Coppola, G; Parisi, P; Verrotti, A, 2011)
"We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy."	3.74	Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS. ( Gerstner, T; Koenig, SA; Kohlmueller, D; Longin, E; Mehlem, P; Schulze, A; Teich, M; Treiss, I; Werner, T, 2007)
"We describe four children with Dravet syndrome treated with the combination of valproic acid (VPA) and topiramate (TPM) who developed transient liver toxicity."	3.74	Acute hepatic injury in four children with Dravet syndrome: valproic acid, topiramate or acetaminophen? ( Ceulemans, B; Gunning, B; Leroy, PL; Nicolai, J; Vles, JS, 2008)
"Glioblastoma patients undergoing treatment with surgery followed by radiation and temozolomide chemotherapy often develop a state of immunosuppression and are at risk for opportunistic infections and reactivation of hepatitis and herpes viruses."	3.74	Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide. ( Hoorens, A; Neyns, B; Stupp, R, 2008)
"We report the case of a 4-year-old boy with long-term sodium valproate (valproic acid; VPA) therapy who suddenly developed clinically relevant thrombocytopenia and signs of hepatotoxicity."	3.72	Valproic-acid-induced thrombocytopenia and hepatotoxicity: discontinuation of treatment? ( Lackmann, GM, 2004)
"Use of valproic acid may be possible for some patients with hepatitis C."	3.72	The safety of valproic acid use for patients with hepatitis C infection. ( Barnes, RF; Dominitz, JA; Felker, BL; Sloan, KL, 2003)
"We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM)."	3.71	Topiramate enhances the risk of valproate-associated side effects in three children. ( Koelfen, W; König, S; Longin, E; Teich, M, 2002)
"In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L-carnitine supplementation in childhood epilepsy."	3.70	L-carnitine supplementation in childhood epilepsy: current perspectives. ( Bohan, TP; Coulter, DL; De Vivo, DC; Dreifuss, FE; Greenwood, RS; Nordli, DR; Shields, WD; Stafstrom, CE; Tein, I, 1998)
"The authors report a case of fatal hepatic failure in a 19-year old young man suffering from absence seizures and treated for two months with valproic acid (VPA)."	3.69	[Fatal hepatic necrosis during treatment with sodium valproate]. ( Benaguida, M; Chlihi, A; Miguil, M; Mjahed, K; Moutawakkil, S; Sarf, I, 1995)
"Valproic acid (VPA) is an anti-seizure drug that causes idiosyncratic liver injury."	2.82	Valproic acid induced liver injury: An insight into molecular toxicological mechanism. ( Ezhilarasan, D; Mani, U, 2022)
" In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML."	2.73	Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes. ( Hallman, H; Honkanen, T; Juvonen, E; Kauppila, M; Koistinen, P; Kutila, A; Mikkola, M; Nyländen, P; Poikonen, E; Rauhala, A; Savolainen, ER; Siitonen, T; Sinisalo, M; Suominen, M; Terävä, V; Timonen, T, 2007)
"Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds."	2.52	Mechanistic review of drug-induced steatohepatitis. ( Guo, GL; Schumacher, JD, 2015)
"Valproic acid (VPA) is an anti-epileptic and mood-stabilizing compound successfully used in the clinics since many decades."	2.50	Cardio-hepatic metabolic derangements and valproic acid. ( Longhitano, C; Mazzoccoli, G; Vinciguerra, M, 2014)
" It is postulated that carnitine supplementation may increase the beta-oxidation of VPA, thereby limiting cytosolic omega-oxidation and the production of toxic metabolites that are involved in liver toxicity and ammonia accumulation."	2.45	Carnitine in the treatment of valproic acid-induced toxicity. ( Hantson, P; Lheureux, PE, 2009)
" VPA is a relatively safe drug, but its use is associated with idiosyncratic hepatotoxicity, which in some cases may lead to fatality."	2.43	Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity. ( Abbott, FS; Chang, TK, 2006)
" However, these issues deserve further investigation in controlled, randomized and probably multicentre trials to evaluate the clinical value and the appropriate dosage of L-carnitine in each of these conditions."	2.43	Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? ( Gris, M; Lheureux, PE; Penaloza, A; Zahir, S, 2005)
"Carnitine was strongly recommended for children at risk of developing a carnitine deficiency."	2.41	The role of carnitine supplementation during valproic acid therapy. ( El-Chaar, GM; Raskind, JY, 2000)
"Starting from Valproat dosage recommendations and serum levels and patient risk from acute hepatic failure, the results of our therapeutic service are set forth."	2.38	[Valproate dosage]. ( Meyer, FP; Walther, H, 1989)
"Rare, serious adverse effects of antiepileptic drugs (AEDs) include hepatotoxicity and bone marrow suppression."	2.38	Routine laboratory monitoring for serious adverse effects of antiepileptic medications: the controversy. ( Wyllie, E; Wyllie, R, 1991)
"Carnitine is an important nutrient that is present in the diet (particularly in meat and dairy products) and is synthesized from dietary amino acids."	2.38	Carnitine, valproate, and toxicity. ( Coulter, DL, 1991)
" These deal mainly with biochemical systems that are known to be affected by VPA, or with the possible idiosyncratic production of toxic VPA metabolites, especially delta 4-VPA."	2.38	Valproate hepatotoxicity syndrome: hypotheses of pathogenesis. ( Levy, RH; Stephens, JR, 1992)
" These findings were confirmed with histopathological changes where Ac was capable of reversing the toxic effects of valproic acid on liver cells CONCLUSION: It is concluded that Ac showed significant hepatoprotective effects at different doses in the animal model used in this study."	1.72	Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats. ( Ahmed, MM; Andleeb, S; Arshad, S; Aslam, A; Iqbal, MO; Javaid, U; Khan, IA; Manzoor, M; Manzoor, Z; Mumtaz, A; Munawar, SH; Riaz, R, 2022)
" VPA has been reported to be associated with many adverse effects, including hepatotoxicity."	1.62	Protective effects of naringin on valproic acid-induced hepatotoxicity in rats. ( Ates, B; Colak, C; Gunata, M; Koroglu, OF; Parlakpinar, H; Tanriverdi, LH; Vardi, N; Yildiz, A, 2021)
"Valproic acid (VPA) has been widely used more frequently as its approved indications have been expanded."	1.62	Rhabdomyolysis and Hepatotoxicity From Valproic Acid: Case Reports. ( Deb, S; Walker, CP, 2021)
"Valproic acid is a medication most commonly used in the treatment of emotional and neurological depression, psychological imbalances, epilepsy, and bipolar disorder."	1.62	Protective Effect of Thyme Honey against Valproic Acid Hepatotoxicity in Wistar Rats. ( Boroujeni, MB; Omidipour, R; Rajabzadeh, A; Zarei, L, 2021)
"Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages."	1.56	Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats. ( Buyuk, B; Coskun, O; Ovali, MA; Oztopuz, O; Sehitoglu, MH; Turkon, H; Uzun, M, 2020)
"Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy."	1.56	Ellagic acid attenuates liver toxicity induced by valproic acid in rats. ( Abdelkader, NF; Assaf, N; Elesawy, WH; Elyamany, M; Fawzy, HM; Gad, AM, 2020)
"Valproic acid (VPA) is a clinical medicine primarily prescribed to control epileptic symptoms."	1.51	Potential biomarker of fibroblast growth factor 21 in valproic acid-treated livers. ( Chen, J; Guo, C; Li, R; Liang, X; Xu, X, 2019)
"While the serious adverse effects of VPA noted were all reversible with the discontinuation of the treatment, the occurrence of encephalopathies with hyperammoniemia is a serious complication that is potentially lethal and calls for close clinical monitoring of newborns treated with valproate."	1.51	Adverse Effects of Treatment with Valproic Acid during the Neonatal Period. ( Baudou, E; Benevent, J; Hachon LeCamus, C; Montastruc, JL; Touati, G, 2019)
" Clinical data on epilepsy, characteristics of VPA treatment, risk factors for VHT, laboratory data on liver and pancreas functions, and adverse effects were collected."	1.48	Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate-induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy. ( Ansakorpi, H; Eriksson, K; Haapala, P; Haataja, L; Hinttala, R; Hynynen, J; Jyrkilä, A; Kälviäinen, R; Kärppä, M; Komulainen-Ebrahim, J; Lähdetie, J; Majamaa, K; Mäkitalo, A; Myllynen, P; Pokka, T; Pylvänen, L; Rantala, H; Sokka, A; Uusimaa, J; Vieira, P; Ylikotila, P, 2018)
"Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies."	1.46	Sulforaphane protects against sodium valproate-induced acute liver injury. ( Atef, H; El-Khouly, OA; Nazmy, EA; Said, E, 2017)
"Using pentylenetetrazole (PTZ)-induced seizures model in mice, the effect of DATS on the anticonvulsant activity of VP was found to be positive, meaning that combination of DATS with VP can confer protection against VP-induced hepatic injurious effects through its antioxidant, antiinflammatory, and antiapoptotic properties without affecting VP antiepileptic activity."	1.46	Cytoprotective effects of diallyl trisulfide against valproate-induced hepatotoxicity: new anticonvulsant strategy. ( El-Agamy, DS; Shaaban, AA, 2017)
" We also investigated the changes in the central carbon metabolism of HepaRG cells exposed to orally bioavailable concentrations of both drugs."	1.43	In Silico Modeling for the Prediction of Dose and Pathway-Related Adverse Effects in Humans From In Vitro Repeated-Dose Studies. ( Bucher, J; Heinzle, E; Klein, S; Maggioni, S; Mauch, K; Mueller, D; Niklas, J; Noor, F; Shevchenko, V, 2016)
"The human hepatoma cell line HepaRG has been used for human relevant toxicity assessment."	1.40	Long-term maintenance of HepaRG cells in serum-free conditions and application in a repeated dose study. ( Klein, S; Mueller, D; Noor, F; Schevchenko, V, 2014)
"The activity of these compounds on seizure control is independent of histone deacetylase inhibitory activity (associated with the teratogenicity of VPA), and does not correlate with liver cell toxicity."	1.39	Seizure control by ketogenic diet-associated medium chain fatty acids. ( Chang, P; Chen, PE; Plant, N; Terbach, N; Walker, MC; Williams, RS, 2013)
" We finally concluded that VPA hepatotoxicity is a result of metabolic activation by CYP2E1 and ROS formation, leading to lysosomal labialization, mitochondrial/lysosomal toxic cross-talk and finally general cellular proteolysis in the rat hepatocytes."	1.38	A new approach on valproic acid induced hepatotoxicity: involvement of lysosomal membrane leakiness and cellular proteolysis. ( Eskandari, MR; Fard, JK; Kaghazi, A; Pourahmad, J; Shahraki, J; Shaki, F, 2012)
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."	1.37	FDA-approved drug labeling for the study of drug-induced liver injury. ( Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)
"On VPA 1000 mg/d, the seizure frequency decreased significantly."	1.37	Valproate treatment after liver transplant in a patient with Lennox-Gastaut syndrome. ( Crespel, A; Gelisse, P; Genton, P; Pageaux, GP; Velizarova, R, 2011)
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."	1.36	Developing structure-activity relationships for the prediction of hepatotoxicity. ( Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010)
"The aim of this study was to investigate the relationship between hepatotoxicity, levels of glucuronide conjugates of valproic acid (VPA), and the toxic metabolites of VPA (4-ene VPA and 2,4-diene VPA)."	1.35	The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid. ( Baek, DJ; Chung, BC; Jung, BH; Kim, BJ; Lee, MS; Lee, YJ; Shin, KJ, 2009)
"Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies."	1.33	Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003. ( Borusiak, P; Boxtermann, W; Brückner, R; Buesing, D; Degen, I; Degenhardt, V; Fitzek, S; Gerstner, T; Haensch, CA; Hanusch, R; Hartmann, M; Häussermann, P; Hoppen, T; Jungck, A; Kasper, JM; Kluger, G; Knapp, R; Koenig, SA; Korenke, GC; Kuhn, H; Lindmayer, F; Longin, E; Müller-Deile, A; Oehring, R; Richard, HH; Samii, K; Seitz, R; Specht, U; Weber, Y; Weidner, B, 2006)
"Valproic acid (VPA) is an antiepileptic drug (AED) used for generalized and absence seizures."	1.32	Effects of age and polytherapy, risk factors of valproic acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)-2,4-diene VPA in people with epilepsy taking VPA. ( Abbott, F; Farrell, K; Gopaul, S, 2003)
"A 6-month-old girl developed West syndrome and it remitted in association with valproate-induced hepatic dysfunction."	1.31	Remission of West syndrome associated with valproate hepatotoxicity. ( Go, T, 2002)
"A 29-year-old female patient with Friedreich's ataxia and partial seizures with acute liver failure during VPA treatment is reported."	1.30	Fatal liver failure associated with valproate therapy in a patient with Friedreich's disease: review of valproate hepatotoxicity in adults. ( Hehlmann, R; Heubner, C; Holm, E; König, I; König, SA; Schenk, M; Sick, C; Weiss, A, 1999)
"Valproic acid is a useful antiepileptic drug, with occasional gastrointestinal side effects."	1.29	[Hepatotoxicity induced by valproic acid in adults. Report of 3 cases]. ( Aguilera, L; Chesta, J; Galdames, D; Silva, C, 1993)
" The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation."	1.28	The high incidence of valproate hepatotoxicity in infants may relate to familial metabolic defects. ( Applegarth, DA; Appleton, RE; Davidson, AG; Dimmick, JE; Farrell, K; Wong, LT, 1990)
" By analogy with certain spontaneous and acquired human disorders of branched chain amino acid metabolism, it is suggested that valproate-associated hepatotoxicity may represent the consequences of a valproate overload on a limited mitochondrial beta-oxidation capacity, causing accumulation of a toxic product of endogenous branched chain amino acid metabolism."	1.28	Valproate metabolism during hepatotoxicity associated with the drug. ( Dickinson, RG; Dunstan, PR; Eadie, MJ; MacLaughlin, D; McKinnon, GE, 1990)
" However, whereas toxic reactions following phenytoin and carbamazepine are characterised by a rather short duration of exposure before symptoms occur with accompanying clinical features of hypersensitivity, valproate-induced hepatic toxicity exhibits no signs of hypersensitivity and often occurs following prolonged exposure, speaking in favor of a metabolic aberration as the underlying cause."	1.27	Hepatic toxicity of antiepileptic drugs: a review. ( Bentsen, KD; Gram, L, 1983)
"Side effects of carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) are rare during long-term use but rather common and usually transient during the early phases of treatment."	1.27	Side effects of carbamazepine, valproate and clonazepam during long-term treatment of epilepsy. ( Keränen, T; Sivenius, J, 1983)
"Thirty children with simple febrile convulsions were treated with sodium valproate following their second convulsion."	1.26	Sodium valproate in the prophylaxis of simple febrile convulsions. ( Evans-Jones, LG; Groom, PJ; Kindley, AD; Williams, AJ, 1979)

Research

Studies (236)

Authors

Clinical Trials (7)

Trial Overview

Trial Outcomes

Mean Change From Baseline in Best Corrected Visual Acuity

Timeframe	Studies, this research(%)	All Research%
pre-1990	72 (30.51)	18.7374
1990's	44 (18.64)	18.2507
2000's	41 (17.37)	29.6817
2010's	58 (24.58)	24.3611
2020's	21 (8.90)	2.80

Authors	Studies
Yogeeswari, P	1
Sriram, D	1
Thirumurugan, R	1
Raghavendran, JV	1
Sudhan, K	1
Pavana, RK	1
Stables, J	1
Fourches, D	1
Barnes, JC	1
Day, NC	1
Bradley, P	1
Reed, JZ	1
Tropsha, A	1
Greene, N	1
Fisk, L	1
Naven, RT	1
Note, RR	1
Patel, ML	1
Pelletier, DJ	1
Ekins, S	1
Williams, AJ	2
Xu, JJ	1
Chen, M	3
Vijay, V	1
Shi, Q	2
Liu, Z	2
Fang, H	2
Tong, W	3
Dawson, S	1
Stahl, S	2
Paul, N	1
Barber, J	1
Kenna, JG	2
Ding, D	1
Kelly, R	1
Sakatis, MZ	1
Reese, MJ	2
Harrell, AW	1
Taylor, MA	1
Baines, IA	1
Chen, L	3
Bloomer, JC	1
Yang, EY	1
Ellens, HM	1
Ambroso, JL	1
Lovatt, CA	1
Ayrton, AD	1
Clarke, SE	1
Warner, DJ	1
Chen, H	1
Cantin, LD	1
Walker, CL	1
Noeske, T	1
Suzuki, A	3
Thakkar, S	1
Yu, K	1
Hu, C	1
Moreno-Torres, M	1
García-Llorens, G	1
Moro, E	1
Méndez, R	1
Quintás, G	1
Castell, JV	1
Wang, L	1
Li, H	1
Zeng, G	1
Shi, L	1
Zhu, M	1
Luo, J	1
Zhang, Z	1
Wartman, C	1
VandenBerg, A	1
Iqbal, MO	1
Manzoor, M	1
Mumtaz, A	1
Riaz, R	1
Arshad, S	1
Khan, IA	1
Javaid, U	1
Manzoor, Z	1
Munawar, SH	1
Andleeb, S	1
Ahmed, MM	1
Aslam, A	1
Gheena, S	1
Ezhilarasan, D	2
Shree Harini, K	1
Rajeshkumar, S	1
Gao, Y	1
Jiang, D	1
Wang, C	1
An, G	1
Zhu, L	1
Cui, C	1
Mani, U	1
Harju, T	1
Hurme-Niiranen, A	1
Suo-Palosaari, M	1
Nygaard Nielsen, S	1
Hinttala, R	3
Schmiegelow, K	1
Uusimaa, J	3
Harila, A	1
Niinimäki, R	1
Hofmeister, B	2
von Stülpnagel, C	2
Berweck, S	2
Abicht, A	1
Kluger, G	3
Weber, P	2
Oztopuz, O	1
Turkon, H	1
Buyuk, B	1
Coskun, O	1
Sehitoglu, MH	1
Ovali, MA	1
Uzun, M	1
Walker, CP	1
Deb, S	1
Zhou, L	2
Zeng, X	2
Liao, J	1
Ouyang, D	2
Finsterer, J	1
Pirozzi, C	1
Lama, A	1
Annunziata, C	1
Cavaliere, G	1
De Caro, C	1
Citraro, R	1
Russo, E	1
Tallarico, M	1
Iannone, M	1
Ferrante, MC	1
Mollica, MP	1
Mattace Raso, G	1
De Sarro, G	1
Calignano, A	1
Meli, R	1
Fasbender, F	1
Obholzer, M	1
Metzler, S	1
Stöber, R	1
Hengstler, JG	1
Watzl, C	1
Abdelkader, NF	1
Elyamany, M	1
Gad, AM	1
Assaf, N	1
Fawzy, HM	1
Elesawy, WH	1
Omidipour, R	1
Zarei, L	1
Boroujeni, MB	1
Rajabzadeh, A	1
Koroglu, OF	1
Gunata, M	1
Vardi, N	1
Yildiz, A	1
Ates, B	1
Colak, C	1
Tanriverdi, LH	1
Parlakpinar, H	1
Rao, T	1
Tan, Z	1
Zhou, G	1
Khodayar, MJ	1
Kalantari, H	1
Khorsandi, L	1
Ahangar, N	1
Samimi, A	1
Alidadi, H	1
Shaaban, AA	1
El-Agamy, DS	3
Cuykx, M	1
Claes, L	1
Rodrigues, RM	2
Vanhaecke, T	2
Covaci, A	1
Zhu, X	1
Li, X	1
Zhang, T	2
Zhao, L	3
Hynynen, J	1
Pokka, T	1
Komulainen-Ebrahim, J	1
Myllynen, P	1
Kärppä, M	1
Pylvänen, L	1
Kälviäinen, R	1
Sokka, A	1
Jyrkilä, A	1
Lähdetie, J	1
Haataja, L	1
Mäkitalo, A	1
Ylikotila, P	1
Eriksson, K	1
Haapala, P	1
Ansakorpi, H	1
Vieira, P	1
Majamaa, K	1
Rantala, H	1
Ahmed, N	1
Aljuhani, N	1
Al-Hujaili, HS	1
Al-Hujaili, MA	1
Elkablawy, MA	1
Noah, MM	1
Abo-Haded, H	1
Ma, L	1
Pan, Y	1
Sun, M	1
Shen, H	1
Guo, Y	1
Baudou, E	1
Benevent, J	1
Montastruc, JL	1
Touati, G	1
Hachon LeCamus, C	1
Guo, HL	1
Jing, X	1
Sun, JY	1
Hu, YH	1
Xu, ZJ	1
Ni, MM	1
Chen, F	1
Lu, XP	1
Qiu, JC	1
Wang, T	1
Calitz, C	1
Hamman, JH	1
Fey, SJ	1
Viljoen, AM	1
Gouws, C	1
Wrzesinski, K	1
Xu, X	1
Guo, C	2
Liang, X	1
Li, R	1
Chen, J	1
Amathieu, R	1
Levesque, E	1
Merle, JC	1
Chemit, M	1
Costentin, C	1
Compagnon, P	1
Dhonneur, G	1
Klein, S	2
Mueller, D	2
Schevchenko, V	1
Noor, F	2
Lopez, AM	1
Hendrickson, RG	1
Zhang, LF	1
Liu, LS	1
Chu, XM	1
Xie, H	1
Cao, LJ	1
A, JY	1
Cao, B	1
Li, MJ	1
Wang, GJ	1
Hao, HP	1
Felker, D	1
Lynn, A	1
Wang, S	1
Johnson, DE	1
Vitins, AP	1
Kienhuis, AS	1
Speksnijder, EN	1
Roodbergen, M	1
Luijten, M	1
van der Ven, LT	1
Abdel-Dayem, MA	1
Elmarakby, AA	1
Abdel-Aziz, AA	1
Pye, C	1
Said, SA	2
El-Mowafy, AM	1
Mattes, W	1
Davis, K	1
Fabian, E	1
Greenhaw, J	1
Herold, M	1
Looser, R	1
Mellert, W	1
Groeters, S	1
Marxfeld, H	1
Moeller, N	1
Montoya-Parra, G	1
Prokoudine, A	1
van Ravenzwaay, B	1
Strauss, V	1
Walk, T	1
Kamp, H	1
Huo, T	1
Chen, X	1
Lu, X	1
Qu, L	1
Liu, Y	1
Cai, S	1
Star, K	1
Edwards, IR	1
Choonara, I	1
Li, S	2
Guo, J	1
Ying, Z	1
Chen, S	1
Yang, L	2
Chen, K	1
Long, Q	1
Qin, D	1
Pei, D	1
Liu, X	1
Branson, S	1
De Boe, V	1
Sachinidis, A	1
Rogiers, V	1
De Kock, J	1
Komulainen, T	1
Lodge, T	1
Bolszak, M	1
Pietilä, M	1
Koivunen, P	1
Hakkola, J	1
Poulton, J	1
Morten, KJ	1
Yuen, NA	1
Ilic, K	1
Miller, RT	1
Brown, HR	1
Ambroso, JI	1
Falls, JG	1
Hunt, CM	1
Vinken, M	1
Schumacher, JD	1
Guo, GL	1
Maggioni, S	1
Bucher, J	1
Niklas, J	1
Shevchenko, V	1
Mauch, K	1
Heinzle, E	1
Hayes, JF	1
Marston, L	1
Walters, K	1
Geddes, JR	1
King, M	1
Osborn, DP	1
Nazmy, EA	1
El-Khouly, OA	1
Atef, H	1
Said, E	1
Almario, EE	1
Borlak, J	1
Zhao, M	1
Li, G	1
Qiu, F	1
Sun, Y	1
Mata Zubillaga, D	1
Prieto Espuñes, S	1
Ferrero de la Mano, L	1
Herrero Mendoza, B	1
Neyns, B	1
Hoorens, A	1
Stupp, R	1
Franciotta, D	2
Kwan, P	1
Perucca, E	2
Lheureux, PE	2
Hantson, P	1
Lee, MS	1
Lee, YJ	1
Kim, BJ	1
Shin, KJ	1
Chung, BC	1
Baek, DJ	1
Jung, BH	1
Podymova, SD	1
Sadovnikova, IV	2
Ikura, Y	1
Iwasa, Y	1
Ueda, M	1
Amini-Shirazi, N	1
Ghahremani, MH	1
Ahmadkhaniha, R	1
Mandegary, A	1
Dadgar, A	1
Abdollahi, M	1
Shadnia, S	1
Pakdaman, H	1
Kebriaeezadeh, A	1
Shang, Y	1
Jiang, YX	1
Ding, ZJ	1
Shen, AL	1
Xu, SP	1
Yuan, SY	1
Yao, SL	1
Chaudrey, KH	1
Naser, TB	1
Steinberg, A	1
Avashia, KD	1
Nouri-Kolouri, M	1
Asadi, S	1
Irshad Khan, SI	1
Ihsan, M	1
Verrotti, A	1
Agostinelli, S	1
Parisi, P	1
Chiarelli, F	1
Coppola, G	1
Rupasinghe, J	1
Jasinarachchi, M	1
Velizarova, R	1
Gelisse, P	1
Pageaux, GP	1
Genton, P	2
Crespel, A	1
Kiang, TK	1
Teng, XW	1
Surendradoss, J	1
Karagiozov, S	1
Abbott, FS	2
Chang, TK	2
Lin, YH	1
Chien, YL	1
Pourahmad, J	1
Eskandari, MR	1
Kaghazi, A	1
Shaki, F	1
Shahraki, J	1
Fard, JK	1
van Zoelen, MA	1
de Graaf, M	1
van Dijk, MR	1
Bogte, A	1
van Erpecum, KJ	1
Rockmann, H	1
Maarschalk-Ellerbroek, LJ	1
Wang, W	1
Lin, R	1
Zhang, J	1
Mao, Y	1
Bu, X	1
Ji, Q	1
Zhai, X	1
Lin, Q	1
Zhang, K	1
Sokmen, BB	1
Tunali, S	1
Yanardag, R	1
Schmid, MM	1
Freudenmann, RW	1
Keller, F	1
Connemann, BJ	1
Hiemke, C	1
Gahr, M	1
Kratzer, W	1
Fuchs, M	1
Schönfeldt-Lecuona, C	1
Chang, P	1
Terbach, N	1
Plant, N	1
Chen, PE	1
Walker, MC	1
Williams, RS	1
Mazzoccoli, G	1
Longhitano, C	1
Vinciguerra, M	1
Xiong, H	1
Liu, CT	1
Zhang, YH	1
Bao, XH	1
Jiang, YW	1
Zhao, H	1
Wu, XP	1
Qin, J	1
Kreher, U	1
Darius, J	1
Wien, F	1
Felker, BL	1
Sloan, KL	1
Dominitz, JA	1
Barnes, RF	1
Tein, I	3
Gopaul, S	1
Farrell, K	2
Abbott, F	1
Bumb, A	1
Diederich, N	1
Beyenburg, S	1
Lackmann, GM	1
Peterson, GM	1
Naunton, M	1
Penaloza, A	1
Zahir, S	1
Gris, M	1
Baran, OP	1
Kervancioglu, P	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Effect of Adding Lamotrigine to Sodium Valproate in Childhood Epilepsy: Clinicolabratory Study[NCT05881928]	Phase 4	50 participants (Anticipated)	Interventional	2023-07-25	Not yet recruiting
A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Autosomal Dominant Retinitis Pigmentosa[NCT01233609]	Phase 2	90 participants (Actual)	Interventional	2010-11-30	Completed
Bioequivalence Study of Sodium Valproate and Valproic Acid Extended Release Tablets in Healthy Human Volunteers[NCT05641649]	Phase 4	16 participants (Anticipated)	Interventional	2023-08-06	Active, not recruiting
Estudio clínico Fase III Para Evaluar la Eficacia terapéutica en Pacientes Mexicanos Con Dislipidemia Mediante el Uso vía Oral de L-Carnitina + Atorvastatina Comparado Con Atorvastatina[NCT03696940]	Phase 3	120 participants (Actual)	Interventional	2018-05-28	Active, not recruiting
In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy[NCT00374075]	Phase 1	42 participants	Interventional	2003-09-30	Completed
Phase I/II Trial of Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy Type I (CARNI-VAL Type I)[NCT00661453]	Phase 1/Phase 2	40 participants (Actual)	Interventional	2008-04-30	Completed
Multi-center Phase II Trial of Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy (SMA CARNI-VAL Trial)[NCT00227266]	Phase 2	94 participants (Actual)	Interventional	2005-09-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Mean change in best corrected visual acuity as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) method from baseline to week 52 (NCT01233609)
Timeframe: baseline to week 52

Mean Change in Visual Field Area From Baseline to 52 Weeks--I4e Isopter

Intervention	letters read correctly (Mean)
Valproic Acid -- Right Eye	-1.4
Valproic Acid--Left Eye	0.0
Placebo --Right Eye	0.2
Placebo --Left Eye	1.3

Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the I4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model (NCT01233609)
Timeframe: baseline to week 52

Mean Change in Visual Field Area From Baseline to 52 Weeks--III4e Isopter

Intervention	Visual field area (degrees squared) (Mean)
Placebo--Right Eye	80.9
Placebo--Left Eye	115.7
Valproic Acid--Right Eye	5.3
Valproic Acid--Left Eye	19.5

Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the III4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model (NCT01233609)
Timeframe: baseline to week 52

Static Perimetry by Treatment Arm--Full Field Hill of Vision

Intervention	Visual field area (degrees squared) (Mean)
Placebo--Right Eye	-122.9
Placebo--Left Eye	-112.0
Valproic Acid--Right Eye	-293.7
Valproic Acid--Left Eye	-237.1

Mean change from baseline at week 52 for Full field Hill of Vision (Static perimetry) (NCT01233609)
Timeframe: baseline to week 52

Static Perimetry Volume--30 Degree Hill of Vision

Intervention	db-steridians (Mean)
Placebo--Right Eye	-0.3
Placebo--Left Eye	-1.4
Valproic Acid--Right Eye	-0.2
Valproic Acid--Left Eye	-0.6

Mean Change from baseline to week 52 for Static Perimetry Volume --30 Degree Hill of Vision. Full field static perimetry protocol was followed using the Octopus 900 (Haag-Streit) for a single session for each eye. (NCT01233609)
Timeframe: baseline to week 52

Anthropometric Measures of Nutritional Status (Body Mass Index [BMI] Z-scores, Weight for Length Ratios, Lean/Fat Mass Via DEXA, Growth Parameters, and Triceps Skinfold Measures)

Max CMAP Amplitude (Mean)

Intervention	db-steridans (Mean)
Placebo--Right Eye	-0.3
Placebo--Left Eye	-0.3
Valproic Acid--Right Eye	-0.2
Valproic Acid--Left Eye	-0.2

Intervention	g (Mean)
	Lean Mass Baseline	Lean Mass 3 months	Lean Mass 6 months	Fat Mass Baseline	Fat Mass 3 months	Fat Mass 6 months
SMA Type 1	4317.15	4993.92	5133.83	3011.37	3618.25	4316.08

The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed. (NCT00227266)
Timeframe: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)

Max CMAP Amplitude Median

Intervention	mV (Mean)
	Baseline	6 months
Cohort 1a Sitters Placebo Then Treatment	2.28	2.32
Cohort 1b Sitters Treatment	2.93	2.37
Cohort 2 Standers and Walkers - Treatment	5.52	6.56

Max CMAP Area (Mean)

Intervention	mV (Median)
	Baseline	6 months
Cohort 1a Sitters Placebo Then Treatment	1.91	1.44
Cohort 1b Sitters Treatment	2.2	1.8
Cohort 2 Standers and Walkers - Treatment	5.3	5.85

The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve. (NCT00227266)
Timeframe: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)

Max CMAP Area (Median)

Intervention	mVms (Mean)
	Baseline	6 months
Cohort 1a Sitters Placebo Then Treatment	5.46	5.28
Cohort 1b Sitters Treatment	5.45	5.26
Cohort 2 Standers and Walkers - Treatment	14.85	16.26

Modified Hammersmith Change From Baseline to 6 Months

Intervention	mVms (Median)
	Baseline	6 months
Cohort 1a Sitters Placebo Then Treatment	3.6	3.74
Cohort 1b Sitters Treatment	4.6	3.4
Cohort 2 Standers and Walkers - Treatment	13.65	16.85

Comparison of Modified Hammersmith Change from baseline to 6 months. Scores range from 0 to 40. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of non-ambulant children with SMA in multiple research trials as well as in clinical settings. (NCT00227266)
Timeframe: 0 months, 6 months

Modified Hammersmith Extend Baseline

Intervention	Score (Mean)
	Baseline visit (0 weeks)	6 Month visit (V2)	Change from Baseline
Cohort 1a Sitters Placebo Then Treatment	20.0	20.6	0.6
Cohort 1b Sitters Treatment	16.6	16.8	0.2

"Baseline Modified Hammersmith Extend testing. The baseline test is the score they receive during their screening visits. This scale ranges from 0 to 56. A higher score indicates a better outcome.~This scale is used to assess gross motor abilities of children with SMA in multiple research trials as well as in clinical settings." (NCT00227266)
Timeframe: 1 month prior to enrollment, at enrollment (0 months)

Reviews

39 reviews available for valproic acid and Chemical and Drug Induced Liver Injury

Trials

Other Studies

191 other studies available for valproic acid and Chemical and Drug Induced Liver Injury

Intervention	Score (Mean)
	Modified Hammersmith Extend at S1 (-4 weeks)	Modified Hammersmith Extend at S2 (0 weeks)
Cohort 2 Experimental	47.0	48.3

Article	Year
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug discovery today, 2016, Volume: 21, Issue:4 Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Drug Labeling; Humans; Pharmaceutical Pr	2016
Valproate: Not All Boxed Warnings Are Created Equal. The Annals of pharmacotherapy, 2022, Volume: 56, Issue:12 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Labeling; Drug-Related Side Effects an	2022
Valproic acid induced liver injury: An insight into molecular toxicological mechanism. Environmental toxicology and pharmacology, 2022, Volume: 95 Topics: Adenosine Triphosphate; Ammonia; Anticonvulsants; Carnitine O-Palmitoyltransferase; Chemical and Dru	2022
Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update. Current pharmaceutical design, 2019, Volume: 25, Issue:3 Topics: Anticonvulsants; Antioxidants; Carnitine; Chemical and Drug Induced Liver Injury; Epilepsy; Humans;	2019
[Severe toxic acute liver failure: etiology and treatment]. Annales francaises d'anesthesie et de reanimation, 2013, Volume: 32, Issue:6 Topics: Acetaminophen; Acetylcysteine; Acute Kidney Injury; Anti-Infective Agents; Blood Coagulation Disorde	2013
Toxin-induced hepatic injury. Emergency medicine clinics of North America, 2014, Volume: 32, Issue:1 Topics: Acetaminophen; Alcohols; Amanita; Analgesics, Non-Narcotic; Anticonvulsants; Chemical and Drug Induc	2014
Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity. Expert review of clinical pharmacology, 2014, Volume: 7, Issue:2 Topics: Animals; Anticonvulsants; Bipolar Disorder; Carnitine; Chemical and Drug Induced Liver Injury; Child	2014
Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. PloS one, 2014, Volume: 9, Issue:10 Topics: Adverse Drug Reaction Reporting Systems; Anticonvulsants; Chemical and Drug Induced Liver Injury; Ch	2014
Adverse Outcome Pathways and Drug-Induced Liver Injury Testing. Chemical research in toxicology, 2015, Jul-20, Volume: 28, Issue:7 Topics: Bosentan; Chemical and Drug Induced Liver Injury; Cholestasis; Fatty Liver; Humans; Liver Cirrhosis;	2015
Mechanistic review of drug-induced steatohepatitis. Toxicology and applied pharmacology, 2015, Nov-15, Volume: 289, Issue:1 Topics: Amiodarone; Animals; Camptothecin; Chemical and Drug Induced Liver Injury; Disease Models, Animal; F	2015
Genetic basis for idiosyncratic reactions to antiepileptic drugs. Current opinion in neurology, 2009, Volume: 22, Issue:2 Topics: Anticonvulsants; Carbamazepine; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Epile	2009
Carnitine in the treatment of valproic acid-induced toxicity. Clinical toxicology (Philadelphia, Pa.), 2009, Volume: 47, Issue:2 Topics: Animals; Anticonvulsants; Antidotes; Carnitine; Chemical and Drug Induced Liver Injury; Energy Metab	2009
Cardio-hepatic metabolic derangements and valproic acid. Current clinical pharmacology, 2014, Volume: 9, Issue:2 Topics: Animals; Anticonvulsants; Antimanic Agents; Chemical and Drug Induced Liver Injury; Epigenesis, Gene	2014
Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy. Journal of child neurology, 2002, Volume: 17 Suppl 3 Topics: Acyl-CoA Dehydrogenase; Anticonvulsants; Carnitine; Carrier Proteins; Chemical and Drug Induced Live	2002
Carnitine transport: pathophysiology and metabolism of known molecular defects. Journal of inherited metabolic disease, 2003, Volume: 26, Issue:2-3 Topics: Animals; Biological Transport; Carnitine; Carrier Proteins; Chemical and Drug Induced Liver Injury;	2003
Valproate: a simple chemical with so much to offer. Journal of clinical pharmacy and therapeutics, 2005, Volume: 30, Issue:5 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Epilepsy; Female; History, 20th Century; Hu	2005
Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Critical care (London, England), 2005, Oct-05, Volume: 9, Issue:5 Topics: Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury; Drug Overdose; Hepatic Encephalo	2005
Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity. Drug metabolism reviews, 2006, Volume: 38, Issue:4 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; DNA; Humans; Lipid Peroxidation; O	2006
Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia, 2007, Volume: 48, Issue:7 Topics: Age Factors; Anemia, Aplastic; Anticonvulsants; B-Lymphocytes; Central Nervous System Diseases; Chem	2007
Extended-release formulations for the treatment of epilepsy. CNS drugs, 2007, Volume: 21, Issue:9 Topics: Animals; Anticonvulsants; Carbamazepine; Chemical and Drug Induced Liver Injury; Delayed-Action Prep	2007
Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review. Journal of inherited metabolic disease, 2008, Volume: 31, Issue:2 Topics: Animals; Anticonvulsants; Biotransformation; Chemical and Drug Induced Liver Injury; Fatty Acids; Fa	2008
[Mechanisms of action and biochemical toxicology of valproic acid]. L'Encephale, 1984, Volume: 10, Issue:4 Topics: 4-Aminobutyrate Transaminase; Aldehyde Oxidoreductases; Ammonia; Animals; Anticonvulsants; Aspartic	1984
Hepatotoxicity to sodium valproate: a review. Gut, 1984, Volume: 25, Issue:6 Topics: Adolescent; Adult; Ammonia; Animals; Chemical and Drug Induced Liver Injury; Child; Child, Preschool	1984
Drug therapy: Valproic acid. The New England journal of medicine, 1980, Mar-20, Volume: 302, Issue:12 Topics: Adult; Alopecia; Behavior; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Chil	1980
The role of cytochrome P450 enzymes in hepatic and extrahepatic human drug toxicity. Pharmacology & therapeutics, 1995, Volume: 68, Issue:3 Topics: Abnormalities, Drug-Induced; Acetaminophen; Chemical and Drug Induced Liver Injury; Cytochrome P-450	1995
[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin]. Der Nervenarzt, 1998, Volume: 69, Issue:10 Topics: Adolescent; Adult; Anticonvulsants; Blood Coagulation Tests; Chemical and Drug Induced Liver Injury;	1998
The role of carnitine supplementation during valproic acid therapy. The Annals of pharmacotherapy, 2000, Volume: 34, Issue:5 Topics: Adolescent; Adult; Aged; Ammonia; Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury	2000
Children versus adults: pharmacokinetic and adverse-effect differences. Epilepsia, 2002, Volume: 43 Suppl 3 Topics: Adolescent; Age Factors; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Child, Pres	2002
Valproate hepatotoxicity syndrome: hypotheses of pathogenesis. Pharmaceutisch weekblad. Scientific edition, 1992, Jun-19, Volume: 14, Issue:3A Topics: Ammonia; Animals; Carnitine; Chemical and Drug Induced Liver Injury; Humans; Liver; Liver Diseases;	1992
Routine laboratory monitoring for serious adverse effects of antiepileptic medications: the controversy. Epilepsia, 1991, Volume: 32 Suppl 5 Topics: Anemia, Aplastic; Anticonvulsants; Carbamazepine; Chemical and Drug Induced Liver Injury; Drug Monit	1991
Valproic-acid-induced pancreatitis. Case report and review of the literature. Journal of clinical gastroenterology, 1991, Volume: 13, Issue:6 Topics: Adult; Chemical and Drug Induced Liver Injury; Humans; Male; Pancreatitis; Valproic Acid	1991
Valproate toxicity: risk-screening strategies. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Enzymes; Epilepsy; Hepatic Encephalopathy;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
Carnitine, valproate, and toxicity. Journal of child neurology, 1991, Volume: 6, Issue:1 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Hepatic Encephalopathy; Humans;	1991
[Acute fatal liver insufficiency due to valproic acid therapy]. Schweizerische medizinische Wochenschrift, 1991, Feb-16, Volume: 121, Issue:7 Topics: Adult; Chemical and Drug Induced Liver Injury; Epilepsy; Hepatic Encephalopathy; Humans; Liver; Male	1991
[Valproate dosage]. Psychiatrie, Neurologie, und medizinische Psychologie, 1989, Volume: 41, Issue:3 Topics: Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Epilepsy; Humans; Valproic	1989
Valproate: an updated review. Acta neurologica Scandinavica, 1985, Volume: 72, Issue:2 Topics: Abnormalities, Drug-Induced; Brain Diseases; Chemical and Drug Induced Liver Injury; Coma; Dyskinesi	1985
Valproic acid and the liver. Clinical chemistry, 1988, Volume: 34, Issue:5 Topics: Amino Acids; Carnitine; Chemical and Drug Induced Liver Injury; Drug Interactions; Fatty Acids; Huma	1988
[Hepatitis due to antiepileptic agents]. Gastroenterologie clinique et biologique, 1985, Volume: 9, Issue:2 Topics: Acute Disease; Anticonvulsants; Barbiturates; Benzodiazepines; Carbamazepine; Chemical and Drug Indu	1985
[Drug damage to the liver: role of reactive metabolites and pharmacokinetics]. Schweizerische medizinische Wochenschrift, 1985, Sep-21, Volume: 115, Issue:38 Topics: Acetaminophen; Amiodarone; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adv	1985

Article	Year
Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes. Haematologica, 2007, Volume: 92, Issue:8 Topics: Acetylation; Aged; Aged, 80 and over; Calcitriol; Cheilitis; Chemical and Drug Induced Liver Injury;	2007
Potential relationships between transaminase abnormality and valproic acid clearance or serum carnitine concentrations in Japanese epileptic patients. The Journal of pharmacy and pharmacology, 2008, Volume: 60, Issue:2 Topics: Adolescent; Adult; Ammonia; Anticonvulsants; Body Weight; Carnitine; Chemical and Drug Induced Liver	2008
Drug therapy: Valproic acid. The New England journal of medicine, 1980, Mar-20, Volume: 302, Issue:12 Topics: Adult; Alopecia; Behavior; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Chil	1980
Individualized patient assessment in the treatment of epilepsy with sodium valproate. Epilepsia, 1980, Volume: 21, Issue:4 Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Child; Clinical Trials as Topic; Epilepsy	1980
The effect of carnitine supplementation in valproate-induced hyperammonaemia. Acta paediatrica (Oslo, Norway : 1992), 1996, Volume: 85, Issue:4 Topics: Adolescent; Adult; Ammonia; Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury; Chil	1996
Valproate therapy for prevention of posttraumatic seizures: a randomized trial. Journal of neurosurgery, 1999, Volume: 91, Issue:4 Topics: Adult; Anticonvulsants; Blood Coagulation Disorders; Brain Injuries; Chemical and Drug Induced Liver	1999
A comparative study of progabide, valproate, and placebo as add-on therapy in patients with refractory epilepsy. Journal of neurology, neurosurgery, and psychiatry, 1986, Volume: 49, Issue:11 Topics: Adolescent; Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug	1986

Article	Year
Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore-based design. Journal of medicinal chemistry, 2005, Oct-06, Volume: 48, Issue:20 Topics: 4-Aminobutyrate Transaminase; Animals; Anticonvulsants; Benzamides; Chemical and Drug Induced Liver	2005
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species. Chemical research in toxicology, 2010, Volume: 23, Issue:1 Topics: Animals; Chemical and Drug Induced Liver Injury; Cluster Analysis; Databases, Factual; Humans; MEDLI	2010
Developing structure-activity relationships for the prediction of hepatotoxicity. Chemical research in toxicology, 2010, Jul-19, Volume: 23, Issue:7 Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Humans; Structure-Activity Relationship;	2010
A predictive ligand-based Bayesian model for human drug-induced liver injury. Drug metabolism and disposition: the biological fate of chemicals, 2010, Volume: 38, Issue:12 Topics: Bayes Theorem; Chemical and Drug Induced Liver Injury; Humans; Ligands	2010
FDA-approved drug labeling for the study of drug-induced liver injury. Drug discovery today, 2011, Volume: 16, Issue:15-16 Topics: Animals; Benchmarking; Biomarkers, Pharmacological; Chemical and Drug Induced Liver Injury; Drug Des	2011
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug metabolism and disposition: the biological fate of chemicals, 2012, Volume: 40, Issue:1 Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters	2012
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). PLoS computational biology, 2011, Volume: 7, Issue:12 Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Da	2011
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds. Chemical research in toxicology, 2012, Oct-15, Volume: 25, Issue:10 Topics: Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme	2012
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification. Drug metabolism and disposition: the biological fate of chemicals, 2012, Volume: 40, Issue:12 Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters	2012
Factors that influence the quality of metabolomics data in in vitro cell toxicity studies: a systematic survey. Scientific reports, 2021, 11-11, Volume: 11, Issue:1 Topics: Acetaminophen; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Citric Acid; Hep G2 Cells;	2021
Correlation of GSTP1 rs1695 and CAT rs769217 with elevated AST induced by valproate sodium in Chinese children with epilepsy. Pakistan journal of pharmaceutical sciences, 2021, Volume: 34, Issue:5 Topics: Adolescent; Anticonvulsants; Aspartate Aminotransferases; Catalase; Chemical and Drug Induced Liver	2021
Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2022, Volume: 150 Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Fabaceae; Liver; Male; Phytochemicals	2022
Syringic acid and silymarin concurrent administration inhibits sodium valproate-induced liver injury in rats. Environmental toxicology, 2022, Volume: 37, Issue:9 Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chemical and Drug Induced Liver Injury; Chemical an	2022
Comprehensive Analysis of Metabolic Changes in Male Mice Exposed to Sodium Valproate Based on GC-MS Analysis. Drug design, development and therapy, 2022, Volume: 16 Topics: Amino Acids; Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Gas Chromatography-Ma	2022
DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship? The pharmacogenomics journal, 2023, Volume: 23, Issue:5 Topics: Chemical and Drug Induced Liver Injury; DNA Polymerase gamma; Humans; Mercaptopurine; Precursor Cell	2023
Cooccurrence of Two Different Genetic Diseases: A Case of Valproic Acid Hepatotoxicity in Nicolaides-Baraitser Syndrome (SMARCA2 Mutation)-Due to a POLG1-Related Effect? Neuropediatrics, 2020, Volume: 51, Issue:1 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; DNA Polymerase gamma; Facies; Female	2020
Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats. Molecular biology reports, 2020, Volume: 47, Issue:1 Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Glutathione; Glutathione Peroxidase;	2020
Rhabdomyolysis and Hepatotoxicity From Valproic Acid: Case Reports. Journal of pharmacy practice, 2021, Volume: 34, Issue:4 Topics: Adult; Anticonvulsants; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Female;	2021
Ginsenoside compound K alleviates sodium valproate-induced hepatotoxicity in rats via antioxidant effect, regulation of peroxisome pathway and iron homeostasis. Toxicology and applied pharmacology, 2020, 01-01, Volume: 386 Topics: Animals; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury; Ginsenosides; Homeostasis	2020
Overlapping Phenotype from Double Trouble SMARCA2 and POLG1 Variants c.2556A > C and c.3708G > T, Respectively. Neuropediatrics, 2020, Volume: 51, Issue:3 Topics: Chemical and Drug Induced Liver Injury; Facies; Foot Deformities, Congenital; Humans; Hypotrichosis;	2020
Butyrate prevents valproate-induced liver injury: In vitro and in vivo evidence. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020, Volume: 34, Issue:1 Topics: Anticonvulsants; Butyric Acid; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liv	2020
Enhanced activation of human NK cells by drug-exposed hepatocytes. Archives of toxicology, 2020, Volume: 94, Issue:2 Topics: Antibodies, Neutralizing; Aspirin; Chemical and Drug Induced Liver Injury; Coculture Techniques; Cyt	2020
Ellagic acid attenuates liver toxicity induced by valproic acid in rats. Journal of pharmacological sciences, 2020, Volume: 143, Issue:1 Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Chemical and Drug	2020
Response To: Overlapping Phenotype from Double Trouble SMARCA2 and POLG1 Variants c.2556A > C and c.3708G > T, Respectively. Neuropediatrics, 2020, Volume: 51, Issue:5 Topics: Chemical and Drug Induced Liver Injury; Facies; Foot Deformities, Congenital; Humans; Hypotrichosis;	2020
Protective Effect of Thyme Honey against Valproic Acid Hepatotoxicity in Wistar Rats. BioMed research international, 2021, Volume: 2021 Topics: Animals; Chemical and Drug Induced Liver Injury; Honey; Male; Rats; Rats, Wistar; Thymus Plant; Valp	2021
Protective effects of naringin on valproic acid-induced hepatotoxicity in rats. Tissue & cell, 2021, Volume: 72 Topics: Animals; Body Weight; Catalase; Chemical and Drug Induced Liver Injury; Flavanones; Glutathione; Liv	2021
Evaluating the protective effects of individual or combined ginsenoside compound K and the downregulation of soluble epoxide hydrolase expression against sodium valproate-induced liver cell damage. Toxicology and applied pharmacology, 2021, 07-01, Volume: 422 Topics: Antioxidants; Cell Line; Chemical and Drug Induced Liver Injury; Down-Regulation; Epoxide Hydrolases	2021
Taurine attenuates valproic acid-induced hepatotoxicity via modulation of RIPK1/RIPK3/MLKL-mediated necroptosis signaling in mice. Molecular biology reports, 2021, Volume: 48, Issue:5 Topics: Animals; Apoptosis; Chemical and Drug Induced Liver Injury; Imidazoles; Indoles; Male; Mice; Necropt	2021
Cytoprotective effects of diallyl trisulfide against valproate-induced hepatotoxicity: new anticonvulsant strategy. Naunyn-Schmiedeberg's archives of pharmacology, 2017, Volume: 390, Issue:9 Topics: Allyl Compounds; Animals; Anti-Inflammatory Agents; Anticonvulsants; Antioxidants; Apoptosis; Chemic	2017
Metabolomics profiling of steatosis progression in HepaRG Toxicology letters, 2018, Volume: 286 Topics: Biomarkers; Chemical and Drug Induced Liver Injury; Chromatography, Liquid; Disease Progression; Hep	2018
Risk Factors for Valproic Acid-induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy. Basic & clinical pharmacology & toxicology, 2018, Volume: 123, Issue:5 Topics: Age Factors; Ammonia; Anticonvulsants; Aspartate Aminotransferases; Chemical and Drug Induced Liver	2018
Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate-induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy. Epilepsia, 2018, Volume: 59, Issue:11 Topics: Adolescent; Adult; Alanine Transaminase; Anticonvulsants; Aspartate Aminotransferases; Chemical and	2018
Agmatine protects against sodium valproate-induced hepatic injury in mice via modulation of nuclear factor-κB/inducible nitric oxide synthetase pathway. Journal of biochemical and molecular toxicology, 2018, Volume: 32, Issue:12 Topics: Agmatine; Alanine Transaminase; Alkaline Phosphatase; Animals; Anticonvulsants; Antioxidants; Aspart	2018
Catalase C-262T Polymorphism Is a Risk Factor for Valproic Acid-Induced Abnormal Liver Function in Chinese Patients With Epilepsy. Therapeutic drug monitoring, 2019, Volume: 41, Issue:1 Topics: Adolescent; Anticonvulsants; Asian People; Catalase; Chemical and Drug Induced Liver Injury; Child;	2019
Adverse Effects of Treatment with Valproic Acid during the Neonatal Period. Neuropediatrics, 2019, Volume: 50, Issue:1 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Consciousness Disorders; Female; Hematologi	2019
A sub-chronic Xysmalobium undulatum hepatotoxicity investigation in HepG2/C3A spheroid cultures compared to an in vivo model. Journal of ethnopharmacology, 2019, Jul-15, Volume: 239 Topics: Adenosine Triphosphate; Alanine Transaminase; Animals; Apocynaceae; Aspartate Aminotransferases; Che	2019
Potential biomarker of fibroblast growth factor 21 in valproic acid-treated livers. BioFactors (Oxford, England), 2019, Volume: 45, Issue:5 Topics: Adult; Animals; Anticonvulsants; Biomarkers; Case-Control Studies; Chemical and Drug Induced Liver I	2019
Long-term maintenance of HepaRG cells in serum-free conditions and application in a repeated dose study. Journal of applied toxicology : JAT, 2014, Volume: 34, Issue:10 Topics: Animal Testing Alternatives; Anticonvulsants; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Surv	2014
Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats. Acta pharmacologica Sinica, 2014, Volume: 35, Issue:3 Topics: Animals; Bile; Biomarkers; Chemical and Drug Induced Liver Injury; Citric Acid Cycle; Diet, High-Fat	2014
Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models. Archives of toxicology, 2014, Volume: 88, Issue:8 Topics: Amiodarone; Animals; Binding Sites; Cell Line; Chemical and Drug Induced Liver Injury; Disease Model	2014
Valproate-induced liver injury: modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen. Drugs in R&D, 2014, Volume: 14, Issue:2 Topics: Administration, Oral; Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Docosahexaen	2014
Detection of hepatotoxicity potential with metabolite profiling (metabolomics) of rat plasma. Toxicology letters, 2014, Nov-04, Volume: 230, Issue:3 Topics: Animals; Atropine; Captopril; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Dr	2014
An effective assessment of valproate sodium-induced hepatotoxicity with UPLC-MS and (1)HNMR-based metabonomics approach. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2014, Oct-15, Volume: 969 Topics: Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid	2014
Valproic acid-induced hepatotoxicity in Alpers syndrome is associated with mitochondrial permeability transition pore opening-dependent apoptotic sensitivity in an induced pluripotent stem cell model. Hepatology (Baltimore, Md.), 2015, Volume: 61, Issue:5 Topics: Anticonvulsants; Apoptosis; Cells, Cultured; Chemical and Drug Induced Liver Injury; Diffuse Cerebra	2015
In vitro assessment of drug-induced liver steatosis based on human dermal stem cell-derived hepatic cells. Archives of toxicology, 2016, Volume: 90, Issue:3 Topics: Cells, Cultured; Chemical and Drug Induced Liver Injury; Flow Cytometry; Gene Expression Regulation;	2016
Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model. Toxicology, 2015, May-04, Volume: 331 Topics: Adenosine Triphosphate; Anticonvulsants; Cell Death; Cell Proliferation; Cell Respiration; Chemical	2015
Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase™. Regulatory toxicology and pharmacology : RTP, 2015, Volume: 72, Issue:3 Topics: Acetaminophen; Adverse Drug Reaction Reporting Systems; Amoxicillin-Potassium Clavulanate Combinatio	2015
In Silico Modeling for the Prediction of Dose and Pathway-Related Adverse Effects in Humans From In Vitro Repeated-Dose Studies. Toxicological sciences : an official journal of the Society of Toxicology, 2016, Volume: 149, Issue:1 Topics: Bosentan; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Computer Simulation; Dose-Respon	2016
Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study. PLoS medicine, 2016, Volume: 13, Issue:8 Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cardiovascular Diseases; Chemical an	2016
Sulforaphane protects against sodium valproate-induced acute liver injury. Canadian journal of physiology and pharmacology, 2017, Volume: 95, Issue:4 Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Anticonvulsants; A	2017
Drug-Induced Liver Injury. BioMed research international, 2017, Volume: 2017 Topics: Animals; Chemical and Drug Induced Liver Injury; Cyclosporine; Disease Models, Animal; Humans; Medic	2017
Associations of CYP2C9 and CYP2A6 Polymorphisms with the Concentrations of Valproate and its Hepatotoxin Metabolites and Valproate-Induced Hepatotoxicity. Basic & clinical pharmacology & toxicology, 2017, Volume: 121, Issue:2 Topics: Adolescent; Adult; Alleles; Anticonvulsants; Biotransformation; Chemical and Drug Induced Liver Inju	2017
[Valproic acid induced-idiosyncratic hepatotoxicity]. Anales de pediatria (Barcelona, Spain : 2003), 2008, Volume: 69, Issue:5 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Female; Humans; Valproic Acid	2008
Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide. Acta neurologica Belgica, 2008, Volume: 108, Issue:4 Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemical and Drug Induced Liver Injury; Chemothe	2008
The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid. Archives of pharmacal research, 2009, Volume: 32, Issue:7 Topics: Administration, Oral; Alanine Transaminase; Animals; Anticonvulsants; Aspartate Aminotransferases; B	2009
[Pathogenetic basis of pharmaceutical hepatitis induced by depakine in children]. Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology, 2009, Issue:8 Topics: Anticonvulsants; Biliary Dyskinesia; Case-Control Studies; Chemical and Drug Induced Liver Injury; C	2009
Valproic acid administration for hepatic fibrosis: a balance between antifibrotic efficacy and hepatotoxicity. Hepatology (Baltimore, Md.), 2010, Volume: 51, Issue:6 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Hepatic Stellate Cells; Humans; Li	2010
Influence of CYP2C9 polymorphism on metabolism of valproate and its hepatotoxin metabolite in Iranian patients. Toxicology mechanisms and methods, 2010, Volume: 20, Issue:8 Topics: Adolescent; Adult; Aryl Hydrocarbon Hydroxylases; Chemical and Drug Induced Liver Injury; Cytochrome	2010
Valproic acid attenuates the multiple-organ dysfunction in a rat model of septic shock. Chinese medical journal, 2010, Volume: 123, Issue:19 Topics: Acute Kidney Injury; Animals; Blotting, Western; Chemical and Drug Induced Liver Injury; Lung Injury	2010
Prevention of sodium valproate-induced hepatotoxicity by curcumin, rosiglitazone and N-acetylcysteine in rats. Arzneimittel-Forschung, 2010, Volume: 60, Issue:11 Topics: Acetylcysteine; Animals; Anticonvulsants; Body Weight; Chemical and Drug Induced Liver Injury; Convu	2010
Thinking beyond the obvious: hepatotoxicity secondary to idiosyncratic depakote toxicity. American journal of therapeutics, 2012, Volume: 19, Issue:6 Topics: Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Monitoring; Epilepsy; Female; H	2012
Nonalcoholic fatty liver disease in adolescents receiving valproic acid. Epilepsy & behavior : E&B, 2011, Volume: 20, Issue:2 Topics: Adolescent; Alanine Transaminase; Anticonvulsants; Blood Pressure; Body Weight; Chemical and Drug In	2011
Progressive encephalopathy with cerebral oedema and infarctions associated with valproate and diazepam overdose. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2011, Volume: 18, Issue:5 Topics: Adult; Antimanic Agents; Brain Edema; Brain Infarction; Chemical and Drug Induced Liver Injury; Coma	2011
Valproate treatment after liver transplant in a patient with Lennox-Gastaut syndrome. Seizure, 2011, Volume: 20, Issue:6 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Electroencephalography; Female; Fructose; H	2011
Glutathione depletion by valproic acid in sandwich-cultured rat hepatocytes: Role of biotransformation and temporal relationship with onset of toxicity. Toxicology and applied pharmacology, 2011, May-01, Volume: 252, Issue:3 Topics: Animals; Biotransformation; Cell Survival; Chemical and Drug Induced Liver Injury; Cytochrome P-450	2011
Valproic Acid-related anticonvulsant hypersensitivity syndrome and subsequent olanzapine-related neutropenia and thrombocytopenia: a case report. Journal of clinical psychopharmacology, 2012, Volume: 32, Issue:1 Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; C	2012
A new approach on valproic acid induced hepatotoxicity: involvement of lysosomal membrane leakiness and cellular proteolysis. Toxicology in vitro : an international journal published in association with BIBRA, 2012, Volume: 26, Issue:4 Topics: Animals; Anticonvulsants; Antioxidants; Cells, Cultured; Chemical and Drug Induced Liver Injury; Cyt	2012
Valproic acid-induced DRESS syndrome with acute liver failure. The Netherlands journal of medicine, 2012, Volume: 70, Issue:3 Topics: Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Eosinophilia;	2012
Involvement of fatty acid metabolism in the hepatotoxicity induced by divalproex sodium. Human & experimental toxicology, 2012, Volume: 31, Issue:11 Topics: Acetyltransferases; Alanine Transaminase; Animals; Anticonvulsants; Aspartate Aminotransferases; Cel	2012
Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2012, Volume: 50, Issue:10 Topics: Animals; Chemical and Drug Induced Liver Injury; Female; Liver; Random Allocation; Rats; Rats, Sprag	2012
Non-fatal and fatal liver failure associated with valproic acid. Pharmacopsychiatry, 2013, Volume: 46, Issue:2 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Chemical and Drug Indu	2013
Seizure control by ketogenic diet-associated medium chain fatty acids. Neuropharmacology, 2013, Volume: 69 Topics: Animals; Anticonvulsants; Caprylates; Cell Line; Chemical and Drug Induced Liver Injury; Convulsants	2013
[Valproic acid-induced idiosyncratic liver injury in 4 cases]. Zhonghua er ke za zhi = Chinese journal of pediatrics, 2012, Volume: 50, Issue:12 Topics: Anticonvulsants; Biomarkers; Carnitine; Chemical and Drug Induced Liver Injury; Child; Child, Presch	2012
Abnormal alterations in the metabolic patterns of patients on valproate therapy. The Journal of pharmacy and pharmacology, 2002, Volume: 54, Issue:7 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Humans; Infant; Liver Diseases; Male; Metab	2002
The safety of valproic acid use for patients with hepatitis C infection. The American journal of psychiatry, 2003, Volume: 160, Issue:1 Topics: Adult; Alanine Transaminase; Chemical and Drug Induced Liver Injury; Female; Follow-Up Studies; Hepa	2003
Effects of age and polytherapy, risk factors of valproic acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)-2,4-diene VPA in people with epilepsy taking VPA. Epilepsia, 2003, Volume: 44, Issue:3 Topics: Acetylcysteine; Adolescent; Adult; Age Factors; Anticonvulsants; Chemical and Drug Induced Liver Inj	2003
[Experimental validation of regeneration therapy in hepatitis caused by toxic medication]. Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology, 2003, Issue:4 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Hepatocytes; Liver Regeneration; N	2003
Adding topiramate to valproate therapy may cause reversible hepatic failure. Epileptic disorders : international epilepsy journal with videotape, 2003, Volume: 5, Issue:3 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Epilepsies, Part	2003
Valproic-acid-induced thrombocytopenia and hepatotoxicity: discontinuation of treatment? Pharmacology, 2004, Volume: 70, Issue:2 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Child, Preschool; Epilepsy, Generalized; Hu	2004
Ultrastructural investigation of the protective role of folic acid and vitamin E against toxic effects of valproic acid on maternal liver tissue during period of gestation. Saudi medical journal, 2006, Volume: 27, Issue:3 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Female; Folic Acid; Injections, Su	2006
Hepatotoxicity and valproate therapy. Internal medicine journal, 2006, Volume: 36, Issue:11 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Female; Humans; Middle Aged; Seizures; Trea	2006
Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003. Epilepsia, 2006, Volume: 47, Issue:12 Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Chil	2006
Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS. Epilepsia, 2007, Volume: 48, Issue:1 Topics: Adolescent; Anticonvulsants; Carbamazepine; Carnitine; Chemical and Drug Induced Liver Injury; Child	2007
Reversible hepatotoxicity, pancreatitis, coagulation disorder and simultaneous bone marrow suppression with valproate in a 2-year-old girl. Seizure, 2007, Volume: 16, Issue:6 Topics: Blood Coagulation Disorders; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Child, Pr	2007
Searching for a needle in a haystack: use of ICD-9-CM codes in drug-induced liver injury. The American journal of gastroenterology, 2007, Volume: 102, Issue:11 Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Li	2007
Acute hepatic injury in four children with Dravet syndrome: valproic acid, topiramate or acetaminophen? Seizure, 2008, Volume: 17, Issue:1 Topics: Acetaminophen; Analgesics, Non-Narcotic; Anticonvulsants; Chemical and Drug Induced Liver Injury; De	2008
Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver. Toxicology and applied pharmacology, 2008, Feb-01, Volume: 226, Issue:3 Topics: Administration, Oral; Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Dose-Respons	2008
Simultaneous toxicities in a child on multiple anticonvulsants. Journal of child neurology, 2008, Volume: 23, Issue:9 Topics: Anticonvulsants; Bone Marrow; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Child, P	2008
Drugs and the liver. Comprehensive therapy, 1984, Volume: 10, Issue:12 Topics: Acetaminophen; Adult; Aspirin; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liv	1984
Fatal hepatotoxicity in child on phenobarbitone and sodium valproate. Lancet (London, England), 1980, Mar-29, Volume: 1, Issue:8170 Topics: Chemical and Drug Induced Liver Injury; Child; Epilepsy, Tonic-Clonic; Humans; Male; Phenobarbital;	1980
Acute liver disease associated with sodium valproate. Lancet (London, England), 1980, Nov-22, Volume: 2, Issue:8204 Topics: Acute Disease; Adult; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Epilepsy; Fat	1980
Sodium valproate and the liver. Lancet (London, England), 1980, Nov-22, Volume: 2, Issue:8204 Topics: Chemical and Drug Induced Liver Injury; Child; Epilepsy; Humans; Liver; Liver Diseases; Valproic Aci	1980
Hepatotoxicity of sodium valproate. Clinical and experimental neurology, 1983, Volume: 19 Topics: Adolescent; Adult; Aged; Carbamazepine; Chemical and Drug Induced Liver Injury; Child; Fibrinogen; g	1983
Valproic acid and metabolites: pharmacological and toxicological studies. Epilepsia, 1984, Volume: 25 Suppl 1 Topics: Abnormalities, Drug-Induced; Animals; Brain; Chemical and Drug Induced Liver Injury; Chemical Phenom	1984
Abnormal metabolism of valproic acid in fatal hepatic failure. European journal of pediatrics, 1983, Volume: 141, Issue:1 Topics: Chemical and Drug Induced Liver Injury; Child; Epilepsy, Tonic-Clonic; Humans; Liver Diseases; Male;	1983
Side effects of carbamazepine, valproate and clonazepam during long-term treatment of epilepsy. Acta neurologica Scandinavica. Supplementum, 1983, Volume: 97 Topics: Abnormalities, Drug-Induced; Arousal; Benzodiazepinones; Carbamazepine; Chemical and Drug Induced Li	1983
Hepatic toxicity of antiepileptic drugs: a review. Acta neurologica Scandinavica. Supplementum, 1983, Volume: 97 Topics: Anticonvulsants; Carbamazepine; Chemical and Drug Induced Liver Injury; Energy Metabolism; Epilepsy;	1983
Sodium valproate and the development of acute hepatic failure. Pediatric research, 1984, Volume: 18, Issue:4 Topics: Chemical and Drug Induced Liver Injury; Humans; Infant; Male; Ornithine Carbamoyltransferase Deficie	1984
Protection against sodium valproate injury in isolated hepatocytes by alpha-tocopherol and N,N'-diphenyl-p-phenylenediamine. Journal of clinical pharmacology, 1984, Volume: 24, Issue:4 Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Glucuronates; Lipid Peroxides; Liver;	1984
Phenytoin intoxication as the first symptom of fatal liver damage induced by sodium valproate. British journal of clinical pharmacology, 1984, Volume: 17, Issue:5 Topics: Adult; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Epilepsies, Partial; Femal	1984
On the toxicity of valproic acid. American journal of diseases of children (1960), 1984, Volume: 138, Issue:10 Topics: Adolescent; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Humans; Infant;	1984
Sodium valproate and routine liver function tests. Archives of disease in childhood, 1984, Volume: 59, Issue:9 Topics: Chemical and Drug Induced Liver Injury; Child; Epilepsy; Humans; Liver Diseases; Liver Function Test	1984
Prophylaxis against febrile convulsions. British medical journal, 1980, Mar-22, Volume: 280, Issue:6217 Topics: Chemical and Drug Induced Liver Injury; Child; Humans; Seizures; Seizures, Febrile; Valproic Acid	1980
Sodium valproate and acute hepatic failure. Developmental medicine and child neurology, 1980, Volume: 22, Issue:4 Topics: Chemical and Drug Induced Liver Injury; Child; Drug Therapy, Combination; Epilepsy; Humans; Valproic	1980
[Severe liver damage following administration of valproic acid (Depakine)]. Nederlands tijdschrift voor geneeskunde, 1980, Aug-23, Volume: 124, Issue:34 Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Epilepsy; Female; Humans; Liver; Val	1980
Side effects of sodium valproate. The Medical journal of Australia, 1981, Mar-07, Volume: 1, Issue:5 Topics: Chemical and Drug Induced Liver Injury; Humans; Valproic Acid	1981
Toxic reactions with valproic acid therapy. Neurology, 1981, Volume: 31, Issue:5 Topics: Chemical and Drug Induced Liver Injury; Child; Female; Humans; Valproic Acid	1981
Hepatotoxicity from Depakene. FDA drug bulletin, 1981, Volume: 11, Issue:2 Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Humans; Infant;	1981
[Complications of valproic acid therapy: an overview (author's transl)]. Der Nervenarzt, 1981, Volume: 52, Issue:10 Topics: Adult; Alcohol Withdrawal Delirium; Chemical and Drug Induced Liver Injury; Child; Coma; Electroence	1981
A case of fatal toxic hepatitis: recommendations for the administration of sodium valproate. Epilepsia, 1981, Volume: 22, Issue:6 Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Humans; Male; Valproic Acid	1981
[Liver involvement and encephalopathy in a child during sodium valproate therapy]. Ugeskrift for laeger, 1982, Jan-11, Volume: 144, Issue:2 Topics: Brain Diseases; Chemical and Drug Induced Liver Injury; Child, Preschool; Female; Humans; Valproic A	1982
[Fatal hepatic failure and sodium valproate (author's transl)]. Gastroenterologie clinique et biologique, 1982, Volume: 6, Issue:5 Topics: Acute Disease; Adolescent; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Valproic A	1982
Adverse Drug Reactions Advisory Committee: ADRAC report for 1980. The Medical journal of Australia, 1982, May-15, Volume: 1, Issue:10 Topics: Adolescent; Adult; Aged; Agranulocytosis; Australia; Bronchial Spasm; Chemical and Drug Induced Live	1982
[Hepatic toxicity of sodium valproate]. Archives francaises de pediatrie, 1982, Volume: 39, Issue:4 Topics: Adolescent; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Humans; Infant;	1982
2 cases of reversible liver lesion induced by valproate. Acta neurologica Scandinavica, 1982, Volume: 66, Issue:3 Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Liver Diseases; Valproic	1982
Sodium valproate-induced liver injury. The American journal of gastroenterology, 1982, Volume: 77, Issue:11 Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Diseases; Valproic Acid	1982
[Liver damage caused by valproic acid]. Nederlands tijdschrift voor geneeskunde, 1982, Nov-13, Volume: 126, Issue:46 Topics: Chemical and Drug Induced Liver Injury; Child; Humans; Liver; Valproic Acid	1982
Valproic acid producing a Reye-like syndrome. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1982, Volume: 9, Issue:4 Topics: Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry;	1982
Fatal hepatic failure in a child treated with phenytoin and valproic acid. Developmental medicine and child neurology, 1982, Volume: 24, Issue:6 Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Drug Interactions; Drug Therapy, Combinati	1982
Several hematic parameters in children treated with sodium valproate. Acta neurologica, 1982, Volume: 4, Issue:6 Topics: Blood Platelet Disorders; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; H	1982
[Fatal liver disorder during treatment with sodium valproate and carbamazepine]. Archives francaises de pediatrie, 1982, Volume: 39, Issue:9 Topics: Carbamazepine; Chemical and Drug Induced Liver Injury; Child; Drug Therapy, Combination; Epilepsies,	1982
[Fatal hepatic necrosis during treatment with sodium valproate]. Cahiers d'anesthesiologie, 1995, Volume: 43, Issue:3 Topics: Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Fatal Outcome; Hepatic Encephalopath	1995
Isolated increase in serum alkaline phosphatase with sodium valproate therapy. The Annals of pharmacotherapy, 1995, Volume: 29, Issue:5 Topics: Alkaline Phosphatase; Chemical and Drug Induced Liver Injury; Epilepsy, Tonic-Clonic; Female; Humans	1995
Plasma and hepatic carnitine and coenzyme A pools in a patient with fatal, valproate induced hepatotoxicity. Gut, 1995, Volume: 37, Issue:1 Topics: Adult; Carnitine; Chemical and Drug Induced Liver Injury; Coenzyme A; Fatal Outcome; Female; Humans;	1995
Effect of chronic administration of sodium valproate on the morphology of the rat brain hemispheres. Neuropatologia polska, 1993, Volume: 31, Issue:3-4 Topics: Animals; Brain; Capillary Permeability; Chemical and Drug Induced Liver Injury; Culture Techniques;	1993
A comparative study of serum F protein and other liver function tests as an index of hepatocellular damage in epileptic patients. Acta neurologica Scandinavica, 1994, Volume: 89, Issue:4 Topics: Adult; Alkaline Phosphatase; Anticonvulsants; Aspartate Aminotransferases; Carbamazepine; Chemical a	1994
A reversible parkinsonian syndrome and hepatotoxcity following addition of carbamazepine to sodium valproate. Australian and New Zealand journal of medicine, 1994, Volume: 24, Issue:4 Topics: Aged; Carbamazepine; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Interactions; Drug Th	1994
[Hepatotoxicity induced by valproic acid in adults. Report of 3 cases]. Revista medica de Chile, 1993, Volume: 121, Issue:12 Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Epilepsy; Female; Humans; Male; Valproic	1993
Effects of valproate and E-2-en-valproate on functional and morphological parameters of rat liver. III. Influence of fasting. Epilepsy research, 1993, Volume: 16, Issue:3 Topics: Animals; Chemical and Drug Induced Liver Injury; Fasting; Liver Diseases; Male; Random Allocation; R	1993
The rapid change to monotherapy with valproic acid in children. Journal of child neurology, 1993, Volume: 8, Issue:4 Topics: Adolescent; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Epilep	1993
Hepatic toxic effects associated with valproate therapy. The Journal of pediatrics, 1994, Volume: 124, Issue:2 Topics: Chemical and Drug Induced Liver Injury; Humans; Valproic Acid	1994
Hepatotoxic effects in a child receiving valproate and carnitine. The Journal of pediatrics, 1993, Volume: 123, Issue:2 Topics: Carnitine; Chemical and Drug Induced Liver Injury; Humans; Infant; Male; Treatment Failure; Valproic	1993
Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology, 1996, Volume: 46, Issue:2 Topics: Adolescent; Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Child, Preschool;	1996
The mitochondrial permeability transition: a new pathophysiological mechanism for Reye's syndrome and toxic liver injury. The Journal of pharmacology and experimental therapeutics, 1996, Volume: 278, Issue:3 Topics: Animals; Aspirin; Carboxylic Acids; Chemical and Drug Induced Liver Injury; Cyclosporine; Male; Memb	1996
Valproate metabolites in high-dose valproate plus phenytoin therapy. Epilepsia, 1996, Volume: 37, Issue:12 Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injur	1996
Valproic-acid-associated pancreatitis and hepatic toxicity in children with endstage renal disease. Pediatric radiology, 1997, Volume: 27, Issue:2 Topics: Adolescent; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Fatal Outcome; Fatty Liv	1997
Biochemical basis of sodium valproate hepatotoxicity and renal tubular disorder: time dependence of peroxidative injury. Pharmacological research, 1997, Volume: 35, Issue:2 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Glutathione; Kidney; Kidney Diseas	1997
Effects of long-term administration of the antiepileptic drug--sodium valproate upon the ultrastructure of hepatocytes in rats. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, 1997, Volume: 49, Issue:3-4 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Liver; Liver Diseases; Male; Micro	1997
[A case of anticonvulsive drug-induced liver injury accompanied by a transient appearance of antimitochondrial antibody, M2]. Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 1998, Volume: 95, Issue:3 Topics: Aged; Anticonvulsants; Autoantibodies; Chemical and Drug Induced Liver Injury; Female; Humans; Liver	1998
L-carnitine supplementation in childhood epilepsy: current perspectives. Epilepsia, 1998, Volume: 39, Issue:11 Topics: Age Factors; Ammonia; Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury; Child; Chi	1998
Influence of valproic acid on the expression of various acyl-CoA dehydrogenases in rats. Pediatrics international : official journal of the Japan Pediatric Society, 1999, Volume: 41, Issue:1 Topics: Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenase, Long-Chain; Animals; Anticonvulsants; Carnitine; Che	1999
Fatal liver failure associated with valproate therapy in a patient with Friedreich's disease: review of valproate hepatotoxicity in adults. Epilepsia, 1999, Volume: 40, Issue:7 Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Comorbidity; Epilepsy; Fatal Outcome; Fem	1999
Pathomorphological changes in mouse liver and kidney during prolonged valproate administration. International journal of tissue reactions, 2000, Volume: 22, Issue:1 Topics: Animals; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Epilepsy; Kidney; Kid	2000
Valproate metabolism during valproate-associated hepatotoxicity in a surviving adult patient. Epilepsy research, 2000, Volume: 41, Issue:3 Topics: Adult; Anticonvulsants; Biotransformation; Chemical and Drug Induced Liver Injury; Electroencephalog	2000
Effect of L-carnitine treatment for valproate-induced hepatotoxicity. Neurology, 2001, May-22, Volume: 56, Issue:10 Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury;	2001
Retrospective evaluation of the effect of valproate therapy on transaminase elevations in patients with hepatitis C. Pharmacotherapy, 2001, Volume: 21, Issue:11 Topics: Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Chi-Squar	2001
Effect of L-carnitine treatment for valproate-induced hepatotoxicity. Neurology, 2002, Feb-12, Volume: 58, Issue:3 Topics: Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury; Epilepsy; Humans; Liver Diseases	2002
Topiramate enhances the risk of valproate-associated side effects in three children. Epilepsia, 2002, Volume: 43, Issue:4 Topics: Affective Symptoms; Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Therapy, Combinati	2002
Remission of West syndrome associated with valproate hepatotoxicity. Brain & development, 2002, Volume: 24, Issue:4 Topics: Anticonvulsants; beta-Alanine; Chemical and Drug Induced Liver Injury; Electroencephalography; Femal	2002
Sodium valproate and hepatotoxicity in epileptics. The Medical journal of Australia, 1979, Dec-01, Volume: 2, Issue:11 Topics: Adolescent; Adult; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Drug Therapy, Com	1979
Acute hepatic failure associated with the use of sodium valproate. The New England journal of medicine, 1979, Apr-26, Volume: 300, Issue:17 Topics: Acute Disease; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Epilepsy; Humans; Li	1979
Valproic acid and fatal hepatitis. Neurology, 1979, Volume: 29, Issue:2 Topics: Chemical and Drug Induced Liver Injury; Humans; Infant; Valproic Acid	1979
Sodium valproate in the prophylaxis of simple febrile convulsions. Clinical pediatrics, 1979, Volume: 18, Issue:7 Topics: Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Evaluation; Fever; Gastrointes	1979
Hepatic failure from valproic acid. The New England journal of medicine, 1979, Aug-23, Volume: 301, Issue:8 Topics: Biopsy; Chemical and Drug Induced Liver Injury; Humans; Liver; Organoids; Valproic Acid	1979
Hepatic failure from valproic acid. The New England journal of medicine, 1979, Aug-23, Volume: 301, Issue:8 Topics: Chemical and Drug Induced Liver Injury; Child; Humans; Liver; Mitochondria, Liver; Organoids; Valpro	1979
Reye-like syndrome associated with valproic acid therapy. The Journal of pediatrics, 1979, Volume: 95, Issue:1 Topics: Chemical and Drug Induced Liver Injury; Child; Epilepsy; Female; Humans; Reye Syndrome; Valproic Aci	1979
Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity. Annals of neurology, 1992, Volume: 32, Issue:6 Topics: Brain; Chemical and Drug Induced Liver Injury; Diagnostic Errors; Diffuse Cerebral Sclerosis of Schi	1992
Effects of valproate and E-2-en-valproate on functional and morphological parameters of rat liver. I. Biochemical, histopathological and pharmacokinetic studies. Epilepsy research, 1992, Volume: 13, Issue:3 Topics: Animals; Anticonvulsants; Chemical and Drug Induced Liver Injury; Fatty Acids, Monounsaturated; Live	1992
Liver damage in long-term anticonvulsant therapy: a serological and histological study. The Quarterly journal of medicine, 1991, Volume: 79, Issue:288 Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Chemical and Drug Induced Liver Injury; Drug Combinatio	1991
Valproic acid hepatotoxicity in adults and older children. Clinical pharmacy, 1991, Volume: 10, Issue:9 Topics: Adult; Age Factors; Chemical and Drug Induced Liver Injury; Child; Humans; Liver Diseases; Valproic	1991
Sodium valporate formulations. The Journal of the Association of Physicians of India, 1991, Volume: 39, Issue:6 Topics: Chemical and Drug Induced Liver Injury; Chemistry, Pharmaceutical; Humans; Valproic Acid	1991
Use of antiepileptic drugs in childhood epilepsy. Archives of disease in childhood, 1991, Volume: 66, Issue:10 Topics: Adult; Aminocaproates; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child; Child, Presch	1991
[Incidence of pathologic ammonia concentrations in the plasma in children with seizure disorders treated with Convulsofin/Convulex and other anticonvulsants in comparison with children with brain damage and healthy children]. Kinderarztliche Praxis, 1990, Volume: 58, Issue:1 Topics: Adolescent; Ammonia; Anticonvulsants; Brain Damage, Chronic; Chemical and Drug Induced Liver Injury;	1990
The high incidence of valproate hepatotoxicity in infants may relate to familial metabolic defects. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1990, Volume: 17, Issue:2 Topics: Chemical and Drug Induced Liver Injury; Humans; Infant; Liver Diseases; Male; Metabolism, Inborn Err	1990
Valproate-induced hepatoxicity: protective effect of L-carnitine supplementation. The Japanese journal of psychiatry and neurology, 1990, Volume: 44, Issue:2 Topics: Anticonvulsants; Carnitine; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Dose-Re	1990
Acute liver failure in a patient with hepatitis A infection on sodium valproate therapy. The Ceylon medical journal, 1990, Volume: 35, Issue:2 Topics: Acute Disease; Adolescent; Chemical and Drug Induced Liver Injury; Hepatitis A; Hepatovirus; Humans;	1990
[Valproic acid: association of a fatal acute hepatitis and pancreatitis]. Annales de medecine interne, 1990, Volume: 141, Issue:5 Topics: Adult; Chemical and Drug Induced Liver Injury; Humans; Male; Pancreatitis; Valproic Acid	1990
Carnitine metabolism and morphometric change of liver mitochondria in valproate-treated rats. Neuropediatrics, 1990, Volume: 21, Issue:4 Topics: Animals; Carnitine; Chemical and Drug Induced Liver Injury; Male; Mitochondria, Liver; Muscles; Rats	1990
Valproate metabolism during hepatotoxicity associated with the drug. The Quarterly journal of medicine, 1990, Volume: 77, Issue:284 Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Half-Life; Humans; Liver Diseases; Male; Midd	1990
Side-effects of sodium valproate, mainly related to its hepatic and pancreatic toxicity. International journal of clinical pharmacology research, 1986, Volume: 6, Issue:3 Topics: Adolescent; Adult; Aged; Amylases; Body Weight; Chemical and Drug Induced Liver Injury; Child; Child	1986
Valproic acid hepatic fatalities. II. US experience since 1984. Neurology, 1989, Volume: 39, Issue:2 Pt 1 Topics: Adolescent; Adult; Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Live	1989
The occurrence of intramitochondrial Ca2+ granules in valproate-induced liver injury. Journal of pediatric gastroenterology and nutrition, 1989, Volume: 8, Issue:1 Topics: Calcium; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Humans; Mitochondr	1989
Valproic acid therapy and mitochondrial alterations. Journal of pediatric gastroenterology and nutrition, 1989, Volume: 8, Issue:1 Topics: Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Humans; Infant; Mitochondria, Liver	1989
Valproate for epilepsy in renal transplant recipients receiving cyclosporine. Transplantation, 1989, Volume: 48, Issue:3 Topics: Adult; Chemical and Drug Induced Liver Injury; Cyclosporins; Epilepsy; Female; Humans; Kidney Transp	1989
Valproic acid hepatic fatalities: revised table. Neurology, 1989, Volume: 39, Issue:11 Topics: Chemical and Drug Induced Liver Injury; Humans; Liver Diseases; Valproic Acid	1989
Fatal liver failure in children on valproate. Lancet (London, England), 1986, Aug-30, Volume: 2, Issue:8505 Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Epilepsy; German	1986
Valproate or infective hepatitis? Lancet (London, England), 1986, Nov-08, Volume: 2, Issue:8515 Topics: Adolescent; Chemical and Drug Induced Liver Injury; Female; Humans; Valproic Acid	1986
Fatal liver failure in children on valproate. Lancet (London, England), 1987, Jan-03, Volume: 1, Issue:8523 Topics: Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Humans; Valproic Acid	1987
Valproate hepatotoxicity. Lancet (London, England), 1987, Feb-14, Volume: 1, Issue:8529 Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Humans; Valproic Acid	1987
Sodium valproate, pregnancy, and infantile fatal liver failure. Lancet (London, England), 1987, Dec-26, Volume: 2, Issue:8574 Topics: Acute Disease; Chemical and Drug Induced Liver Injury; Epilepsy; Female; Humans; Infant; Infant, New	1987
[Incidence of hypofibrinogenemia under valproate. Could it allow the detection of hepatotoxicity of this drug?]. Presse medicale (Paris, France : 1983), 1986, Oct-11, Volume: 15, Issue:34 Topics: Afibrinogenemia; Chemical and Drug Induced Liver Injury; Humans; Valproic Acid	1986
Valproate causes metabolic disturbance in normal man. Journal of neurology, neurosurgery, and psychiatry, 1986, Volume: 49, Issue:4 Topics: Acetoacetates; Administration, Oral; Blood Glucose; Chemical and Drug Induced Liver Injury; Humans;	1986
[Severe liver involvement during use of sodium valproate]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 1986, Apr-30, Volume: 106, Issue:11 Topics: Adult; Chemical and Drug Induced Liver Injury; Humans; Liver; Male; Valproic Acid	1986
Cytochrome P-450--catalyzed formation of delta 4-VPA, a toxic metabolite of valproic acid. Science (New York, N.Y.), 1987, Feb-20, Volume: 235, Issue:4791 Topics: Animals; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Fatty Acids, Monoun	1987
Valproic acid hepatic fatalities: a retrospective review. Neurology, 1987, Volume: 37, Issue:3 Topics: Adolescent; Adult; Age Factors; Aged; Anticonvulsants; Chemical and Drug Induced Liver Injury; Child	1987
Biochemical and morphological changes induced by sodium valproate in rat liver. Pharmacology & toxicology, 1987, Volume: 60, Issue:3 Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury;	1987
[Fatal hepatic failure in a normally developed 5-year-old boy caused by VPA monotherapy]. Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde, 1987, Volume: 135, Issue:6 Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Epilepsies, Partial; Epilepsy, Absence; He	1987
[Reye-like syndrome following valproate therapy in an adult]. Psychiatrie, Neurologie, und medizinische Psychologie, 1988, Volume: 40, Issue:6 Topics: Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Epilepsies, Partial; Humans; Male	1988
Valproic acid toxicity. American journal of diseases of children (1960), 1985, Volume: 139, Issue:7 Topics: Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Epilepsy; Humans; Infant; Pancreati	1985
Valproic acid and liver damage. Acta paediatrica Scandinavica, 1985, Volume: 74, Issue:5 Topics: Chemical and Drug Induced Liver Injury; Female; Humans; Infant; Pregnancy; Prenatal Exposure Delayed	1985
Valproate hepatotoxicity: a review and report of two instances in adults. Clinical and experimental neurology, 1985, Volume: 21 Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Electroencephalography; Epilepsy; Humans;	1985