Abstract
Background. Patients treated with valproic acid (VPA) present a high incidence of non-alcoholic fatty liver disease (NAFLD) (around 61%). Several recent studies suggest that low copper stores could be associated with NAFLD, and a significant decrease of copper availability in VPA-treated patients has been described.Design and methods. In 101 adult epileptic patients treated with valproic acid in monotherapy (n = 75) and polytherapy (n = 26) the copper availability was evaluated using the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) and the copper/ceruloplasmin ratio. Copper deficiency was supposed in the cases in which this biochemical variable was smaller than the lower reference limit (333 U/g).Results. The differences between the groups of patients with ceruloplasmin oxidase activity smaller or greater than 333 U/g for the serum levels of aminotransferases, gamma-glutamyltransferase, butyrylcholinesterase, cholesterol, triglycerides, and C-reactive protein, and the APRI and FIB-4 liver fibrosis scores were not statistically significant. Most patients (93%) had low APRI and FIB-4 scores, suggesting absence of significant liver fibrosis.Conclusions. The results obtained do not confirm the hypothesis of an association between diminished copper availability and NAFLD in patients treated with valproic acid.
Highlights
Valproic acid (VPA) has been widely used since the late 1960s for the treatment of generalized and partial seizures, and it is still the antiepileptic drug with the broadest spectrum [1]
Treated with valproic acid (VPA) [6,7], and around 38% of these patients may have a diminished copper availability [11], a particular condition that would be involved in the development of liver steatosis [12,13,14]
A relevant proportion of non-alcoholic fatty liver disease patients had low copper stores [12,13], which is associated with more pronounced insulin resistance and other clinical features of the metabolic syndrome, and might be a typical feature of pathophysiological relevance to its hepatic manifestation as non-alcoholic fatty liver disease [12,13]
Summary
Valproic acid (VPA) has been widely used since the late 1960s for the treatment of generalized and partial seizures, and it is still the antiepileptic drug with the broadest spectrum [1]. New roles for this old drug were later confirmed, due to its beneficial effects in bipolar disorders, schizophrenia, depression, neurological pain, migraine headaches, and a number of neurodegenerative diseases [2,3]. Patients treated with valproic acid (VPA) present a high incidence of non-alcoholic fatty liver disease (NAFLD) (around 61%). The results obtained do not confirm the hypothesis of an association between diminished copper availability and NAFLD in patients treated with valproic acid
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