Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

XU Yancheng; FANG Yijie; YAN Lan; JIANG Yuanying; CAO Yongbing

doi:10.3969/j.issn.1006-0111.2014.06.004

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2014 > 32(6): 412-415,464

XU Yancheng, FANG Yijie, YAN Lan, JIANG Yuanying, CAO Yongbing. Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(6): 412-415,464. doi: 10.3969/j.issn.1006-0111.2014.06.004

Citation:

XU Yancheng, FANG Yijie, YAN Lan, JIANG Yuanying, CAO Yongbing. Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(6): 412-415,464. doi: 10.3969/j.issn.1006-0111.2014.06.004

Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

doi: 10.3969/j.issn.1006-0111.2014.06.004

1.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China;School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang 110016, China
3.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2013-10-29
Rev Recd Date: 2014-06-11

Abstract

Hepatotoxicity is one of the most common adverse reactions during anti-hyperlipidemia treatment. Mechanisms of anti-hyperlipidemia drug-induced hepatotoxicity are not clear yet, but most of the toxic reactions are dose-related hypersensitivity and could be released after drug withdrawal. It is accepted that clinical risk factors for the development of hepatotoxicity during anti-hyperlipidemia treatment are high age and chronic illnesses. Treatment of anti-hyperlipidemia drug-induced hepatotoxicity has not been unified and most of the treatments are non-specific and symptomatic. Researching hypotoxicity and hepatoprotection antihyperlipidemia drug, especially TCM and pharmaceutics will become a promising direction.
- hyperlipidemia,
- drug,
- hepatotoxicity

References

[1]	Grundy SM, Cleeman JI, Merz CN,et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines[J]. J Am Coll Cardiol,2004,44(3):720-732.
[2]	Argo CK, Loria P, Caldwell SH, et al. Statins in liver disease: a molehill, an iceberg, or neither?[J]. Hepatology, 2008,48(2):662-669.
[3]	Talbert RL. Safety issues with statin therapy[J]. J Am Pharm Assoc,2006;46(4):479-488.
[4]	Vuppalanchi R, Chalasani N. Statins for hyperlipidemia in patients with chronic liver disease: are they safe?[J]. Clin Gastroenterol Hepatol,2006,4(7):838-839.
[5]	李光明, 范建高. 慢性肝病患者应用他汀的安全性及疗效[J]. 中华肝脏病杂志,2010,18(5):328-330.
[6]	Cash J, Callender ME, McDougall NI, et al. Statin safety and chronic liver disease[J]. Int J Clin Pract,2008,62(12): 1831-1835.
[7]	Gupta NK, Lewis JH. Review article: the use of potentially hepatotoxic drugs in patients with liver disease[J]. Aliment Pharmacol Ther,2008,28(9): 1021-1041.
[8]	Jimenez-Alonso J, Osorio JM, Guierrez-Cabello F, et al. Atorvastatin-induced cholestatic hepatitis in a young woman with systemic lupus erythematosus[J]. A Arch Intern Med,1999,159(15):1811-1812.
[9]	de Castro ML, Hermo JA, Baz A, et al. Acute cholestatic hepatitis afteratorvastatin reintroduction[J]. Gastroenterol Hepatol,2006,29(1):21-24.
[10]	Nakad A, Bataille L, Hamoir V, et al. Atorvastatin-induced acute hepatitis with absence of cross-toxicity with simvastatin[J]. Lancet,1999,353(9166):1763-1764.
[11]	Gershovich OE, Lyman AE. Liver function test abnormalities and pruritis in a patient treated with atorvastatin: case report and review of the literature[J]. Pharmacotherapy,2004,24(1):150-154.
[12]	Grimbert S, Pessayre D, Degott C, et al. Acute hepatitis induced by HMG-CoA reductase inhibitor, lovastatin[J]. Dig Dis Sci,1994,39(9):2032-2033.
[13]	Vuppalanchi R, Teal E. Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes[J]. Am J Med Sci,2005,329(2):62-65.
[14]	Ricaurte B, Guirguis A, Taylor HC, et al. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity[J]. Ann Pharmacother,2006,40(4):753-757.
[15]	Kanathur N, Mathai MG, Byrd RP Jr, et al. Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis[J]. Tenn Med,2001,94(9):339-341.
[16]	Caldwell SH, Hespenheide EE, von Borstel RW. Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin[J]. Dig Dis Sci,2001,46(2):376-378.
[17]	Ashar U, Desai D, Bhaduri A. Flutamide-induced hepatotoxicity with possible potentiation by simvastatin[J]. J Assoc Physicians India,2003,51(1):75-77.
[18]	Cornwell PD, De Souza AT, Ulrich RG. Profiling of hepatic gene expression in rats treated with fibric acid analogs[J]. Mutat Res,2004,549(12):131-145.
[19]	Alsheikh-Ali AA, Kuvin JT, Karas RH. Risk of adverse events with fibrates[J]. Am J Cardiol,2004,94(7):935-938.
[20]	Grubisic-Cabo F, Vrdoljak E. Drug-induced hepatitis in a patient with malignant melanoma treated with interferon alfa 2b adjuvantly who had been administered gemfibrozil in therapy[J]. Med Oncol,2006,23(1):121-124.
[21]	Vogt A, Kassner U, Hostalek U, et al. NAUTILUS Study Group. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study[J]. Curr Med Res Opin,2006,22(2):417-425.
[22]	Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin[J]. JAMA,1990,264(2):241-243.
[23]	Moon YS, Kashyap ML. Niacin extended-release/lovastatin: combination therapy for lipid disorders[J]. Expert Opin Pharmacother,2002,3(12):1763-1771.
[24]	Coppola A, Brady PG, Nord HJ. Niacin-induced hepatotoxicity: unusual presentations[J]. South Med J,1994,87(1):30-32.
[25]	McKenney J. Niacin for dyslipidemia: considerations in product selection[J]. Am J Health Syst Pharm,2003,60(10):995-1005.
[26]	Stolk MF, Becx MC, Kuypers KC, et al. Severe hepatic side effects of ezetimibe[J]. Clin Gastroenterol Hepatol,2006,4(7):908-911.
[27]	Cruz-Fernandez JM, Bedarida GV, Adgey J, et al. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease[J]. Int J Clin Pract,2005,59(6):619-627.
[28]	Armani A, Toth PP. Colesevelam hydrochloride in the management of dyslipidemia[J]. Expert Rev Cardiovasc Ther,2006,4(3):283-291.
[29]	Sirmans SM, Beck JK, Banh HL, et al. Colestipol-induced hepatotoxicity[J]. Pharmacotherapy,2001,21(4):513-516.
[30]	Graf D, Kohlmann C, Haselow K, et al. Bile acids inhibit interleukin-6 signaling via gp130 receptor-dependent and independent pathways in rat liver[J]. Hepatology,2006,44(5):1206-1217.
[31]	Brewer HB Jr. High-density lipoprotein: a new potential therapeutic target for the prevention of cardiovascular disease[J]. Arterioscler Thromb Vasc Biol,2004,24:387-391.
[32]	FDA Statement: Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety[R].2006.
[33]	彭颂兴, 黎玉容. 药物性肝损伤的病因与临床分析[J]. 临床医药实践,2012,21(8):586-587.
[34]	Kar kiner A,Temir G,Utku M,et al.The efficacy of nonoperative management in childhood blunt hepatic trauma[J]. Ulus Travma Derg,2005,11(2):128-133.
[35]	王慧铭, 夏道宗, 夏明,等. 香菇多糖降血脂作用及其机制的研究[J]. 浙江中西医结合杂志,2005,15(10):599-602.
[36]	狄建彬,顾振纶,赵笑东,等. 姜黄素防治大鼠高脂性脂肪肝的研究[J]. 中草药,2010,41(8):1322-1326.
[37]	段玉梅,单松波. 降血脂药物开发应用新进展[J]. 黑龙江医药,2004,17(6):449-451.

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通讯作者: 陈斌, [email protected]

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China;School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang 110016, China

3. School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2013-10-29

Rev Recd Date: 2014-06-11

Key words:

hyperlipidemia /
drug /
hepatotoxicity

Abstract: Hepatotoxicity is one of the most common adverse reactions during anti-hyperlipidemia treatment. Mechanisms of anti-hyperlipidemia drug-induced hepatotoxicity are not clear yet, but most of the toxic reactions are dose-related hypersensitivity and could be released after drug withdrawal. It is accepted that clinical risk factors for the development of hepatotoxicity during anti-hyperlipidemia treatment are high age and chronic illnesses. Treatment of anti-hyperlipidemia drug-induced hepatotoxicity has not been unified and most of the treatments are non-specific and symptomatic. Researching hypotoxicity and hepatoprotection antihyperlipidemia drug, especially TCM and pharmaceutics will become a promising direction.

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Reference (37)

[1]	Grundy SM, Cleeman JI, Merz CN,et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines[J]. J Am Coll Cardiol,2004,44(3):720-732.
[2]	Argo CK, Loria P, Caldwell SH, et al. Statins in liver disease: a molehill, an iceberg, or neither?[J]. Hepatology, 2008,48(2):662-669.
[3]	Talbert RL. Safety issues with statin therapy[J]. J Am Pharm Assoc,2006;46(4):479-488.
[4]	Vuppalanchi R, Chalasani N. Statins for hyperlipidemia in patients with chronic liver disease: are they safe?[J]. Clin Gastroenterol Hepatol,2006,4(7):838-839.
[5]	李光明, 范建高. 慢性肝病患者应用他汀的安全性及疗效[J]. 中华肝脏病杂志,2010,18(5):328-330.
[6]	Cash J, Callender ME, McDougall NI, et al. Statin safety and chronic liver disease[J]. Int J Clin Pract,2008,62(12): 1831-1835.
[7]	Gupta NK, Lewis JH. Review article: the use of potentially hepatotoxic drugs in patients with liver disease[J]. Aliment Pharmacol Ther,2008,28(9): 1021-1041.
[8]	Jimenez-Alonso J, Osorio JM, Guierrez-Cabello F, et al. Atorvastatin-induced cholestatic hepatitis in a young woman with systemic lupus erythematosus[J]. A Arch Intern Med,1999,159(15):1811-1812.
[9]	de Castro ML, Hermo JA, Baz A, et al. Acute cholestatic hepatitis afteratorvastatin reintroduction[J]. Gastroenterol Hepatol,2006,29(1):21-24.
[10]	Nakad A, Bataille L, Hamoir V, et al. Atorvastatin-induced acute hepatitis with absence of cross-toxicity with simvastatin[J]. Lancet,1999,353(9166):1763-1764.
[11]	Gershovich OE, Lyman AE. Liver function test abnormalities and pruritis in a patient treated with atorvastatin: case report and review of the literature[J]. Pharmacotherapy,2004,24(1):150-154.
[12]	Grimbert S, Pessayre D, Degott C, et al. Acute hepatitis induced by HMG-CoA reductase inhibitor, lovastatin[J]. Dig Dis Sci,1994,39(9):2032-2033.
[13]	Vuppalanchi R, Teal E. Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes[J]. Am J Med Sci,2005,329(2):62-65.
[14]	Ricaurte B, Guirguis A, Taylor HC, et al. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity[J]. Ann Pharmacother,2006,40(4):753-757.
[15]	Kanathur N, Mathai MG, Byrd RP Jr, et al. Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis[J]. Tenn Med,2001,94(9):339-341.
[16]	Caldwell SH, Hespenheide EE, von Borstel RW. Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin[J]. Dig Dis Sci,2001,46(2):376-378.
[17]	Ashar U, Desai D, Bhaduri A. Flutamide-induced hepatotoxicity with possible potentiation by simvastatin[J]. J Assoc Physicians India,2003,51(1):75-77.
[18]	Cornwell PD, De Souza AT, Ulrich RG. Profiling of hepatic gene expression in rats treated with fibric acid analogs[J]. Mutat Res,2004,549(12):131-145.
[19]	Alsheikh-Ali AA, Kuvin JT, Karas RH. Risk of adverse events with fibrates[J]. Am J Cardiol,2004,94(7):935-938.
[20]	Grubisic-Cabo F, Vrdoljak E. Drug-induced hepatitis in a patient with malignant melanoma treated with interferon alfa 2b adjuvantly who had been administered gemfibrozil in therapy[J]. Med Oncol,2006,23(1):121-124.
[21]	Vogt A, Kassner U, Hostalek U, et al. NAUTILUS Study Group. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study[J]. Curr Med Res Opin,2006,22(2):417-425.
[22]	Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin[J]. JAMA,1990,264(2):241-243.
[23]	Moon YS, Kashyap ML. Niacin extended-release/lovastatin: combination therapy for lipid disorders[J]. Expert Opin Pharmacother,2002,3(12):1763-1771.
[24]	Coppola A, Brady PG, Nord HJ. Niacin-induced hepatotoxicity: unusual presentations[J]. South Med J,1994,87(1):30-32.
[25]	McKenney J. Niacin for dyslipidemia: considerations in product selection[J]. Am J Health Syst Pharm,2003,60(10):995-1005.
[26]	Stolk MF, Becx MC, Kuypers KC, et al. Severe hepatic side effects of ezetimibe[J]. Clin Gastroenterol Hepatol,2006,4(7):908-911.
[27]	Cruz-Fernandez JM, Bedarida GV, Adgey J, et al. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease[J]. Int J Clin Pract,2005,59(6):619-627.
[28]	Armani A, Toth PP. Colesevelam hydrochloride in the management of dyslipidemia[J]. Expert Rev Cardiovasc Ther,2006,4(3):283-291.
[29]	Sirmans SM, Beck JK, Banh HL, et al. Colestipol-induced hepatotoxicity[J]. Pharmacotherapy,2001,21(4):513-516.
[30]	Graf D, Kohlmann C, Haselow K, et al. Bile acids inhibit interleukin-6 signaling via gp130 receptor-dependent and independent pathways in rat liver[J]. Hepatology,2006,44(5):1206-1217.
[31]	Brewer HB Jr. High-density lipoprotein: a new potential therapeutic target for the prevention of cardiovascular disease[J]. Arterioscler Thromb Vasc Biol,2004,24:387-391.
[32]	FDA Statement: Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety[R].2006.
[33]	彭颂兴, 黎玉容. 药物性肝损伤的病因与临床分析[J]. 临床医药实践,2012,21(8):586-587.
[34]	Kar kiner A,Temir G,Utku M,et al.The efficacy of nonoperative management in childhood blunt hepatic trauma[J]. Ulus Travma Derg,2005,11(2):128-133.
[35]	王慧铭, 夏道宗, 夏明,等. 香菇多糖降血脂作用及其机制的研究[J]. 浙江中西医结合杂志,2005,15(10):599-602.
[36]	狄建彬,顾振纶,赵笑东,等. 姜黄素防治大鼠高脂性脂肪肝的研究[J]. 中草药,2010,41(8):1322-1326.
[37]	段玉梅,单松波. 降血脂药物开发应用新进展[J]. 黑龙江医药,2004,17(6):449-451.

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Progress on the hepatotoxicity of lipid-lowering drugs and its prevention strategies

doi: 10.3969/j.issn.1006-0111.2014.06.004

Abstract

References

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通讯作者: 陈斌, [email protected]

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