Effect of treatment with polyunsaturated fatty acids on HCV- or diet-induced fatty liver
Authors: Donatella Comparcola, Valerio Nobili, Anna Alisi, Clara Balsano
Journal: Journal of Hepatology (2011)

Pathogenesis of lipid metabolism disorder in hepatitis C: Polyunsaturated fatty acids counteract lipid alterations induced by the core proteinJournal of HepatologyVol. 54Issue 3PreviewDisturbance in lipid metabolism is one of the features of chronic hepatitis C, being a crucial determinant of the progression of liver fibrosis. Experimental studies have revealed that the core protein of hepatitis C virus (HCV) induces steatosis. Full-Text PDF Reply to the Letter to the Editor ‘Effect of treatment with polyunsatured fatty acids on HCV- or diet-induced fatty liver’Journal of HepatologyVol. 54Issue 6PreviewThis is a reply to the Letter to the Editor by Comparcola et al. Full-Text PDF Open Access We read with great interest an article recently published in the Journal of Hepatology [[1]Miyoshi H. Moriya K. Tsutsumi T. Shinzawa S. Fujie H. Shintani Y. et al.Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein.J Hepatol. 2011; 54: 432-438Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar]. In this study Miyoshi et al. demonstrate that hepatic over-expression of the hepatitis C virus (HCV) core protein is able to induce lipid metabolism dysfunction and fatty liver accumulation in HepG2 cells. In this context, HCV core protein might directly or indirectly interfere with the cellular components of hepatocytes, which ultimately contribute to the onset of steatosis. The authors discuss that one hypothesis of the direct steatogenic effect of HCV core protein could be ascribed to the ability of the viral protein to interfere with mitochondrial function resulting in the accumulation of NADH. Interestingly, Vial et al., in another recent article published in this Journal, demonstrate that the impairment of NADH oxidation to NAD, with consequent NADH accumulation, is a characteristic figure of mitochondrial dysfunction occurring in fatty liver due to high fat diet (HFD) in rats [[2]Vial G. Dubouchaud H. Couturier K. Cottet-Rousselle C. Taleux N. Athias A. et al.Effects of a high-fat diet on energy metabolism and ROS production in rat liver.J Hepatol. 2010; ([Epub ahead of print])PubMed Google Scholar]. Furthermore, Miyoshi et al. [[1]Miyoshi H. Moriya K. Tsutsumi T. Shinzawa S. Fujie H. Shintani Y. et al.Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein.J Hepatol. 2011; 54: 432-438Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] demonstrate that, in HepG2 cells, HCV core protein expression influences the nature of fatty acids rather than their quantity. These same effects on fatty acid composition are seen in hepatocytes from HFD rats [[2]Vial G. Dubouchaud H. Couturier K. Cottet-Rousselle C. Taleux N. Athias A. et al.Effects of a high-fat diet on energy metabolism and ROS production in rat liver.J Hepatol. 2010; ([Epub ahead of print])PubMed Google Scholar]. Data from these two studies represent another relevant demonstration of numerous similarities between fatty liver by HCV, and non-alcoholic fatty liver disease. Besides fatty liver, chronic hepatitis C resembles NAFLD in numerous aspects, such as insulin resistance, and oxidative stress in the liver. Therefore, HCV infection needs to be viewed not only as a chronic liver disease but also as a metabolic disease, opening up a novel way to the molecular understanding of the pathogenesis of chronic hepatitis C, as a virus-associated fatty liver [[3]Balsano C. Alisi A. Nobili V. Liver fibrosis and therapeutic strategies: the goal for improving metabolism.Curr Drug Targets. 2009; 10: 505-512Crossref PubMed Scopus (27) Google Scholar]. Finally, Miyoshi et al. [[1]Miyoshi H. Moriya K. Tsutsumi T. Shinzawa S. Fujie H. Shintani Y. et al.Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty acids counteract lipid alterations induced by the core protein.J Hepatol. 2011; 54: 432-438Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] demonstrate that the treatment with exogenous polyunsaturated fatty acids (PUFAs) reverts the HCV core protein-associated changes in fatty acid metabolism. Dietary PUFAs, which are well established negative regulators of hepatic lipogenesis, are able to alleviate liver inflammation and reduce fat content in steatotic livers [[4]Ishii H. Horie Y. Ohshima S. Anezaki Y. Kinoshita N. Dohmen T. et al.Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice.J Hepatol. 2009; 50: 562-571Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar]. Recently, we demonstrate that docosahexaenoic acid (DHA) treatment in children with NAFLD reduces the levels of plasma triglycerides, and improves insulin resistance and ultrasonographic features of fatty liver [[5]Nobili V, Bedogni G, Alisi A, Pietrobattista A, Risé P, Galli C, et al. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child, doi:10.1136/adc.2010.192401.Google Scholar]. DHA might downregulate hepatic triglyceride accumulation by decreasing transcriptional activity of sterol regulatory element binding protein-1 (SREBP-1), and inducing fatty acid catabolism by activating the peroxisome proliferator-activated receptors (PPARs) [[6]Jump D.B. N-3 polyunsaturated fatty acid regulation of hepatic gene transcription.Curr Opin Lipidol. 2008; 19: 242-247Crossref PubMed Scopus (342) Google Scholar]. Since Miyoshi et al. suggest that HCV core protein may induce hepatic triglyceride accumulation by SREBP-1 activation and consequent desaturase activation, it is probable that DHA supplementation may be an efficient therapy also to prevent/treat fatty liver associated with HCV infection. Finally, since insulin resistance is a common metabolic risk of NAFLD and chronic hepatitis C, we believe DHA might significantly reduce hepatic triglyceride content, ameliorating insulin sensitivity and other metabolic features that associate NAFLD to HCV infection. These types of treatments, for their almost complete absence of adverse effects, might be suitable for both adults and children. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.