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World J Hepatol. May 28, 2015; 7(9): 1251-1257
Published online May 28, 2015. doi: 10.4254/wjh.v7.i9.1251
Valproic acid and nonalcoholic fatty liver disease: A possible association?
Edoardo Farinelli, David Giampaoli, Anja Cenciarini, Ephraim Cercado, Alberto Verrotti
Edoardo Farinelli, David Giampaoli, Anja Cenciarini, Alberto Verrotti, Department of Pediatrics, University of Perugia, 06100 Perugia, Italy
Ephraim Cercado, General Surgery Department, Lung Center of the Philippines, Quezon Avenue, Diliman, Quezon City, 1101 Metro Manila, Philippines
Author contributions: All authors contributed equally to this work.
Conflict-of-interest: The researchers involved in this study have no financial interests and are not affiliated in any company involved with the medications mentioned in this research.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alberto Verrotti, MD, PhD, Department of Pediatrics, University of Perugia, Via G. Dottori 1, 06100 Perugia, Italy. averrott@unich.it
Telephone: +39-075-5782491 Fax: +39-075-5782492
Received: November 19, 2014
Peer-review started: November 22, 2014
First decision: December 26, 2014
Revised: January 21, 2015
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: May 28, 2015
Processing time: 182 Days and 8.5 Hours
Abstract

Valproic acid (VPA) is one of the most prescribed drugs in children with newly diagnosed epilepsy. Weight gain and obesity have been observed as side effects of VPA. These are often linked with other metabolic disturbances such as development of insulin resistance, dyslipidemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD). NAFLD refers to a group of liver disorders with marked hepatic steatosis. It is associated with an increased incidence of cardiovascular diseases and overall reduced life expectancy. NAFLD occurs in 20%-25% of the general population and it is known to be the most common cause of chronic liver disease. NAFLD therefore represents a major public health issue worldwide. This study reviews and summarizes relevant literature that supports the existence of an association between VPA therapy and the development of NAFLD in children. Long-term VPA-therapy appears to be associated with an increased risk of developing NAFLD. Further studies are needed to clarify the pathogenic mechanisms that lie behind this association and to standardize the options for the use of this drug in overweight patients and in those with risks for developing MetS and NAFLD.

Keywords: Nonalcoholic fatty liver disease; Valproic acid; Obesity; Insulin resistance

Core tip: Nonalcoholic fatty liver disease (NAFLD) is a major medical issue worldwide. It affects 20%-25% of the general population including children. The term NAFLD covers a wide spectrum of hepatic diseases. These diseases include simple hepatic steatosis, inflammation, cirrhosis and the development of hepatocellular carcinoma. Valproic acid (VPA), one of the most used anti-epileptic drugs, has been investigated as a contributing factor for the development of NAFLD. This association seems stronger with long term VPA therapy. Further studies are required to determine the mechanism of this association.