- Email: [email protected]
Omega-3 polyunsaturated fatty acids: A specific liver drug for non-alcoholic fatty liver disease (NAFLD)
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[3]
[4]
[5]
[6]
[7] [8]
[9]
Correspondence including reducing the risk of age and atherosclerosis. Med Hypotheses 2007;68:415–33. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New Engl J Med 2005;352: 1092–102. White WB, West CR, Borer JS, et al. Risk of cardiovascular events in patients receiving Celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol 2007;99:91–8. Solomon SD, Wittes J, Finn PV, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008;117:2104–13. Antman EM, Bennett JS, Daugherty A, et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians. A scientific statement from the American Heart Association. Circulation 2007;115:1634–42. Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation 2005;112:759–70. Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet 2007;370:2138–51. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. New Engl J Med 2005;352: 1071–80.
[10] Arber N, Eagle CJ, Spicak J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. New Engl J Med 2006;355:885–95. [11] Singh G, Graham D, Wang H, Mithal A, Triadafilopoulos G. Concommitant aspirin use reduces the risk of acute myocardial infarction in users of cyclooxygenase-2 selective and some non-selective nonsteroidal anti-inflammatory drugs. Ann Rheum Dis 2006;65(Suppl 11):II61.. Abstract. [12] Le ´vesque LE, Brophy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Ann Int Med 2005;142:481–9.
H. Richard Hellstrom * Department of Pathology, Anatomical Pathology, College of Medicine, SUNY Upstate Medical University, Room 2106 Weiskotten Hall, 750 East Adams Street, Syracuse, NY 13210, United States *Tel.: +1 315 446 4380; fax: +1 315 464 7130 E-mail address: [email protected]
doi:10.1016/j.mehy.2008.07.009
Omega-3 polyunsaturated fatty acids: A specific liver drug for non-alcoholic fatty liver disease (NAFLD) Non-alcoholic fatty liver disease (NAFLD) has emerged as a serious obesity-related disorder. NAFLD encompasses a wide spectrum of hepatic derangements ranging from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis(NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma [1]. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. In our opinion, liver steatosis is present in young patients, it could be a predictive factor of death from cardio-vascular diseases other than hepatocellular carcinoma, as well as of the onset of type 2 diabetes. These considerations strongly indicate the necessity to treat each stage of NAFLD. Currently, there are no effective drugs for NASH, as NASH’s natural history and prognosis are not well understood. Consequently, therapy of patients with non-alcoholic fatty liver has typically been focused on the management of associated conditions
such as obesity, diabetes mellitus, and hyperlipidemia. No specific drug is actually present to treat liver steatosis or NASH. The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercisemay be considered a basal universal approach. Specific liver drugs for NAFLD are needed in the future research [2]. Omega-3 polyunsaturated fatty acids(PUFA), cannot be synthesized by the human body and thus must be derived from exogenous sources. It has been demonstrated that omega-3 polyunsaturated fatty acids are negative regulators of hepatic lipogenesis and that they can also modulate the inflammatory response in mice. Furthermore, they may attenuate hepatic steatosis even in leptin-deficient ob/ob mice [3]. A study by Alwayn et al. [4] indicates that omega-3 polyunsaturated fatty acid supplementation may protect the liver against hepatic steatosis in a murine model of parenteral nutrition in which all animals develop steatosis and liver enzyme disturbances.
Correspondence More recent study by Allard et al. [5] demonstrated that NASH patients have more metabolic abnormalities, and this is associated with higher oxidative stress and lower omega-3 PUFA in the liver in the absence of any differences in dietary fatty acid composition. TNF-a also has direct effects on insulin receptor substrate(IRS) phosphorylation and stimulates suppressor-of-cytokine-signalling-3 (SOCS3) formation via interleukin 6 (IL-6) and inhibitory kB-kinase (IKK), thereby worsening insulin resistance (IR) and steatosis. TNF-a is responsible for the progression from simple fatty liver to NASH [6]. Another study showed that in subjects with NAFLD, PUFA treatment added to diet reduced liver fat content and alanine aminotransferase levels, decreased TNF-a serum levels, and improved insulin resistance [7]. With mentioned above, we propose that omega3 polyunsaturated fatty acids is a specific liver drug for NAFLD in the future. Omega-3 polyunsaturated fatty acid supplementation offers an attractive alternative to other therapies, because it possesses both nutritional and therapeutic benefits. Large, long-term, biopsy-controlled prospective studies are necessary to validate this hypothesis.
References [1] Evert M, Dombrowski F. Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe 2008;29:47–52. [2] Federico A, Niosi M, Vecchio Blanco CD, Loguercio C. Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drug 2008;13:145–58. [3] Alwayn IP, Andersson C, Zauscher B, Gura K, Nose V, Puder M. Omega-3 fatty acids improve hepatic steatosis in a murine model: potential implications for the marginal steatotic liver donor. Transplantation 2005;79: 606–8. [4] Alwayn IP, Gura K, Nose V, et al. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res 2005;57:445–52. [5] Allard JP, Aghdassi E, Mohammed S, et al. Nutritional assessment and hepatic fatty acid composition in nonalcoholic fatty liver disease (NAFLD): a cross-sectional study. J Hepatol 2008;48:300–7.
821 [6] Schreuder TC, Verwer BJ, van Nieuwkerk CM, Mulder CJ. Nonalcoholic fatty liver disease: an overview of current insights in pathogenesis, diagnosis and treatment. World J Gastroenterol 2008;14:2474–86. [7] Lee S, Gura KM, Puder M. Omega-3 fatty acids and liver disease. Hepatology 2007;45:841–5.
Yong-Ning Xin Qingdao Municipal Hospital, Qingdao, 266021 Shandong Province, China Shi-Ying Xuan * Qingdao Municipal Hospital, Qingdao, 266021 Shandong Province, China College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China * Tel.: +86 532 88905508; fax: +86 532 82031522 E-mail address: [email protected] Jian-Hua Zhang Qingdao Municipal Hospital, Qingdao, 266021 Shandong Province, China School of Medicine, Qingdao University, Qingdao, 266021 Shandong Province, China Ming-Hua Zheng Department of Infection and Liver Disease, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000 Zhejiang Province, China Hua-Shi Guan College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
doi:10.1016/j.mehy.2008.07.008
The etiology of optic neuritis in Asian population Optic neuritis (ON) is an acute demyelinating disease of optic nerve, characterized by an acute onset with a relatively high incidence in young person [1]. The patients with ON have a risk of developing
multiple sclerosis and neuromyelitis optica. The famous optic neuritis treatment trial (ONTT) has showed that almost half of the patients with ON developed multiple sclerosis during 10-years follow
[3]
[4]
[5]
[6]
[7] [8]
[9]
Correspondence including reducing the risk of age and atherosclerosis. Med Hypotheses 2007;68:415–33. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New Engl J Med 2005;352: 1092–102. White WB, West CR, Borer JS, et al. Risk of cardiovascular events in patients receiving Celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol 2007;99:91–8. Solomon SD, Wittes J, Finn PV, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008;117:2104–13. Antman EM, Bennett JS, Daugherty A, et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians. A scientific statement from the American Heart Association. Circulation 2007;115:1634–42. Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation 2005;112:759–70. Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet 2007;370:2138–51. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. New Engl J Med 2005;352: 1071–80.
[10] Arber N, Eagle CJ, Spicak J, et al. Celecoxib for the prevention of colorectal adenomatous polyps. New Engl J Med 2006;355:885–95. [11] Singh G, Graham D, Wang H, Mithal A, Triadafilopoulos G. Concommitant aspirin use reduces the risk of acute myocardial infarction in users of cyclooxygenase-2 selective and some non-selective nonsteroidal anti-inflammatory drugs. Ann Rheum Dis 2006;65(Suppl 11):II61.. Abstract. [12] Le ´vesque LE, Brophy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Ann Int Med 2005;142:481–9.
H. Richard Hellstrom * Department of Pathology, Anatomical Pathology, College of Medicine, SUNY Upstate Medical University, Room 2106 Weiskotten Hall, 750 East Adams Street, Syracuse, NY 13210, United States *Tel.: +1 315 446 4380; fax: +1 315 464 7130 E-mail address: [email protected]
doi:10.1016/j.mehy.2008.07.009
Omega-3 polyunsaturated fatty acids: A specific liver drug for non-alcoholic fatty liver disease (NAFLD) Non-alcoholic fatty liver disease (NAFLD) has emerged as a serious obesity-related disorder. NAFLD encompasses a wide spectrum of hepatic derangements ranging from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis(NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma [1]. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. In our opinion, liver steatosis is present in young patients, it could be a predictive factor of death from cardio-vascular diseases other than hepatocellular carcinoma, as well as of the onset of type 2 diabetes. These considerations strongly indicate the necessity to treat each stage of NAFLD. Currently, there are no effective drugs for NASH, as NASH’s natural history and prognosis are not well understood. Consequently, therapy of patients with non-alcoholic fatty liver has typically been focused on the management of associated conditions
such as obesity, diabetes mellitus, and hyperlipidemia. No specific drug is actually present to treat liver steatosis or NASH. The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercisemay be considered a basal universal approach. Specific liver drugs for NAFLD are needed in the future research [2]. Omega-3 polyunsaturated fatty acids(PUFA), cannot be synthesized by the human body and thus must be derived from exogenous sources. It has been demonstrated that omega-3 polyunsaturated fatty acids are negative regulators of hepatic lipogenesis and that they can also modulate the inflammatory response in mice. Furthermore, they may attenuate hepatic steatosis even in leptin-deficient ob/ob mice [3]. A study by Alwayn et al. [4] indicates that omega-3 polyunsaturated fatty acid supplementation may protect the liver against hepatic steatosis in a murine model of parenteral nutrition in which all animals develop steatosis and liver enzyme disturbances.
Correspondence More recent study by Allard et al. [5] demonstrated that NASH patients have more metabolic abnormalities, and this is associated with higher oxidative stress and lower omega-3 PUFA in the liver in the absence of any differences in dietary fatty acid composition. TNF-a also has direct effects on insulin receptor substrate(IRS) phosphorylation and stimulates suppressor-of-cytokine-signalling-3 (SOCS3) formation via interleukin 6 (IL-6) and inhibitory kB-kinase (IKK), thereby worsening insulin resistance (IR) and steatosis. TNF-a is responsible for the progression from simple fatty liver to NASH [6]. Another study showed that in subjects with NAFLD, PUFA treatment added to diet reduced liver fat content and alanine aminotransferase levels, decreased TNF-a serum levels, and improved insulin resistance [7]. With mentioned above, we propose that omega3 polyunsaturated fatty acids is a specific liver drug for NAFLD in the future. Omega-3 polyunsaturated fatty acid supplementation offers an attractive alternative to other therapies, because it possesses both nutritional and therapeutic benefits. Large, long-term, biopsy-controlled prospective studies are necessary to validate this hypothesis.
References [1] Evert M, Dombrowski F. Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe 2008;29:47–52. [2] Federico A, Niosi M, Vecchio Blanco CD, Loguercio C. Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drug 2008;13:145–58. [3] Alwayn IP, Andersson C, Zauscher B, Gura K, Nose V, Puder M. Omega-3 fatty acids improve hepatic steatosis in a murine model: potential implications for the marginal steatotic liver donor. Transplantation 2005;79: 606–8. [4] Alwayn IP, Gura K, Nose V, et al. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res 2005;57:445–52. [5] Allard JP, Aghdassi E, Mohammed S, et al. Nutritional assessment and hepatic fatty acid composition in nonalcoholic fatty liver disease (NAFLD): a cross-sectional study. J Hepatol 2008;48:300–7.
821 [6] Schreuder TC, Verwer BJ, van Nieuwkerk CM, Mulder CJ. Nonalcoholic fatty liver disease: an overview of current insights in pathogenesis, diagnosis and treatment. World J Gastroenterol 2008;14:2474–86. [7] Lee S, Gura KM, Puder M. Omega-3 fatty acids and liver disease. Hepatology 2007;45:841–5.
Yong-Ning Xin Qingdao Municipal Hospital, Qingdao, 266021 Shandong Province, China Shi-Ying Xuan * Qingdao Municipal Hospital, Qingdao, 266021 Shandong Province, China College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China * Tel.: +86 532 88905508; fax: +86 532 82031522 E-mail address: [email protected] Jian-Hua Zhang Qingdao Municipal Hospital, Qingdao, 266021 Shandong Province, China School of Medicine, Qingdao University, Qingdao, 266021 Shandong Province, China Ming-Hua Zheng Department of Infection and Liver Disease, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000 Zhejiang Province, China Hua-Shi Guan College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
doi:10.1016/j.mehy.2008.07.008
The etiology of optic neuritis in Asian population Optic neuritis (ON) is an acute demyelinating disease of optic nerve, characterized by an acute onset with a relatively high incidence in young person [1]. The patients with ON have a risk of developing
multiple sclerosis and neuromyelitis optica. The famous optic neuritis treatment trial (ONTT) has showed that almost half of the patients with ON developed multiple sclerosis during 10-years follow