甲巯咪唑致肝损害的研究进展
|
摘要
甲巯咪唑作为抗甲状腺药物因其良好的药效被广泛应用,其主要的副作用是恶心、呕吐、皮疹、皮肤瘙痒等,严重副作用有粒细胞缺乏、再生障碍性贫血、抗中性粒细胞胞质抗体相关性血管炎、肝损害等,其中肝损害比较少见。甲巯咪唑引起肝损害的类型可为肝细胞型、胆汁淤积型、混合型。目前甲巯咪唑引起肝损害的发病机制不明,既往认为机体变态反应是其主要的发病机制,现认为免疫反应和其代谢产物可能是引起肝损害的主要原因,而且有研究发现在饮酒、其他药物的联用以及存在其他疾病时服用甲巯咪唑将会增加肝损害的发生率。发生肝损害后,最关键的治疗措施是停药,其次是换用其他药物治疗甲亢、保肝、糖皮质激素、人工肝支持技术等。
Methimazole is widely used as an antithyroid drug because of its good efficacy. The main side effects of it are nausea, vomiting, rash, and itchy skin, and serious side effects include neutropenia, aplastic anemia, antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV), and liver damage. Among them, liver damage is relatively rare. The types of liver damage caused by methimazole are mainly hepatocellular type, cholestatic type, and mixed type. At present, the pathogenesis of liver damage caused by methimazole is unknown. In the past, allergic reaction was considered to be its main pathogenesis. Nowadays, immune response and its metabolites are considered to be the main causes of liver damage. And studies have found that taking methimazole in alcohol, combined use of other drugs, and other diseases will increase the incidence of liver damage. After liver damage, the most important treatment is to discontinue using methimazole, followed by anti-hyperthyroidism treatment, hepatoprotective drugs, and glucocorticoids, artificial liver support technology.
Methimazole is widely used as an antithyroid drug because of its good efficacy. The main side effects of it are nausea, vomiting, rash, and itchy skin, and serious side effects include neutropenia, aplastic anemia, antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV), and liver damage. Among them, liver damage is relatively rare. The types of liver damage caused by methimazole are mainly hepatocellular type, cholestatic type, and mixed type. At present, the pathogenesis of liver damage caused by methimazole is unknown. In the past, allergic reaction was considered to be its main pathogenesis. Nowadays, immune response and its metabolites are considered to be the main causes of liver damage. And studies have found that taking methimazole in alcohol, combined use of other drugs, and other diseases will increase the incidence of liver damage. After liver damage, the most important treatment is to discontinue using methimazole, followed by anti-hyperthyroidism treatment, hepatoprotective drugs, and glucocorticoids, artificial liver support technology.
引文
[1] Franklyn J. Thyrotoxicosis[J]. Clin Med(Lond), 2003, 3(1):11-15.
[2] Akmal A, Kung J. Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity[J]. Expert Opin Drug Saf, 2014, 13(10):1397-1406.
[3] Arab DM, Malatjalian DA, Rittmaster RS. Severe cholestatic jaundice in uncomplicated hyperthyroidism treated with methimazole[J].J Clin Endocrinol Metab, 1995, 80(4):1083-1085.
[4] Chalasani NP, Hayashi PH, Bonkovsky HL. ACG Clinical Guideline:the diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2014, 109(7):950-966.
[5] Wang MT, Lee WJ, Huang TY, et al. Antithyroid d rug-related hepatotoxicity in hyperthyroidism patients:a population-based cohort study[J]. Br J Clin Pharmacol, 2014, 78(3):619-629.
[6] Yang J, Li LF, Xu Q, et al. Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China[J]. Thyroid,2015. 25(3):278-283.
[7]陶娌娜,曲晓宇,张四喜,等.甲巯咪唑致肝细胞损伤型肝损害1例[J].药物流行病学杂志, 2017, 26(12):850-851.
[8] Zou H, Jin L, Wang LR, et al. Methimazole-induced cholestatic hepatitis:two cases report and literature review[J]. Oncotarget, 2016, 7(4):5088-5091.
[9] Hung YT, Yu WK, Chow E. Delayed cholestatic hepatitis due to methimazole[J]. Hong Kong Med J, 1999, 5(2):200-201.
[10] Heidari R, Niknahad H, Jamshidzadeh A, et al. Factors affecting drug-induced liver injury:antithyroid drugs as instances[J]. Clin Mol Hepatol, 2014, 20(3):237-248.
[11]李瑞珺,钱方,陆瑜,等. 1例甲巯咪唑致混合型药物性肝损伤患者的药学监护[J].中国药物应用与监测, 2016, 13(4):227-230.
[12]陈陶,汤杰,李娟,等.甲巯咪唑致混合性肝损伤1例[J].医药导报,2014, 33(10):1393-1394.
[13] Shen C, Zhao CY, Liu F, et al. Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot:case report[J]. BMC Gastroenterol, 2010, 10:93-93.
[14] Smathers RL, Galligan JJ, Shearn CT, et al. Susceptibility of L-FABP-/-mice to oxidative stress in early-stage alcoholic liver[J]. J Lipid Res, 2013, 54(5):1335-1345.
[15] Heidari R, Babaei H, Eghbal M. Mechanisms of me-thimazole cytotoxicity in isolated rat hepatocytes[J]. Drug Chem Toxicol, 2013, 36(4):403-411.
[16] Heidari R, Babaei H, Roshangar L. Effects of enzyme induction and/or glutathione depletion on methimazole-induced hepatotoxicity in mice and the protective role of N-Acetylcysteine[J]. Adv Pharm Bull, 2014, 4(1):21-28.
[17]李文红,王芳,付莹,等.肺结核药物性肝损害的相关因素分析[J].临床肺科杂志, 2016, 21(11):2097-2100.
[18]陆人杰,朱珊梅,唐风雷,等. 424例药物性肝损伤临床特征及相关危险因素分析[J].肝脏, 2017, 22(3):235-239.
[19] Kang H, Choi JD, Jung IG, et al. A case of methima-zole-induced acute hepatic failure in a patient with chronic hepatitis B carrier[J].Korean J Intern Med, 1990, 5(1):69-73.
[20] Kulaksizoglu M, Gonen MS, Kebapcilar L, et al. Multiorgan dysfunction accompanied with metimazole and thyroid storm[J]. Transfus Apher Sci, 2012, 46(2):149-152.
[21] Zhang M, Zhou HW, He RH, et al. Steroids for the treatment of methimazole-induced severe cholestatic jaundice in a 74-year-old woman with type 2 diabetes[J]. Endocrine, 2010, 37(2):241-243.
[22]王玉霞,都健.抗甲状腺药物肝损伤临床诊治进展[J].实用肝脏病杂志, 2017, 20(02):135-138.
[23]陈富琴,陈章,张俊然,等.药物性肝损害临床流行病学研究进展[J].药物流行病学杂志, 2016, 25(12):810-813, 818.
[24] Bray TM, Taylor CG. Tissue glutathione, nutrition, and oxidative stress[J]. Can J Physiol Pharmacol, 1993, 71(9):746-751.
[25] Niknahad H, Jamshidzadeh A, Heidari R, et al. Paradoxical effect of methimazole on liver mitochondria:In vitro and in vivo[J]. Toxicol Lett, 2016, 259:108-115.
[26] Kobayashi M, Hiquchi S, Ide M, et al. Th2 cytokine-mediated methimazole-induced acute liver injury in mice[J]. J Appl Toxicol,2012, 32(10):823-833.
[27]于乐成,茅益民,陈成伟,等.药物性肝损伤诊治指南[S].实用肝脏病杂志, 2017, 20(2):257-274.
[28] Lin TY, Shekar AO, Li N, et al. Incidence of abnormal liver biochemical tests in hyperthyroidism[J]. Clin Endocrinol(Oxf), 2017, 86(5):755-759.
[29] EASL Clinical Practice Guidelines:management of cholestatic liver diseases[J]. J Hepatol, 2009, 51(2):237-67.
[30]江杰,李丽,王利红.熊去氧胆酸联合糖皮质激素治疗药物性淤胆型肝炎疗效观察[J].湖北中医药大学学报, 2014, 16(1):78-80.
[31]苏婷婷,张波,周颜.腺苷蛋氨酸联合糖皮质激素治疗药物性胆汁淤积性肝病疗效[J].胃肠病学和肝病学杂志, 2011, 20(8):767-768.
[32] Qin G, Shao JG, Wang B, et al. Artificial liver support system improves short-and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure:a single-center experience[J]. Medicine(Baltimore), 2014, 93(28):e338.
[33] Ling Q, Xu X, Wei Q, et al. Downgrading MELD improves the outcomes after liver transplantation in patients with acute-on-chronic hepatitis B liver failure[J]. PLoS One, 2012, 7(1):e30322.
[2] Akmal A, Kung J. Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity[J]. Expert Opin Drug Saf, 2014, 13(10):1397-1406.
[3] Arab DM, Malatjalian DA, Rittmaster RS. Severe cholestatic jaundice in uncomplicated hyperthyroidism treated with methimazole[J].J Clin Endocrinol Metab, 1995, 80(4):1083-1085.
[4] Chalasani NP, Hayashi PH, Bonkovsky HL. ACG Clinical Guideline:the diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2014, 109(7):950-966.
[5] Wang MT, Lee WJ, Huang TY, et al. Antithyroid d rug-related hepatotoxicity in hyperthyroidism patients:a population-based cohort study[J]. Br J Clin Pharmacol, 2014, 78(3):619-629.
[6] Yang J, Li LF, Xu Q, et al. Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China[J]. Thyroid,2015. 25(3):278-283.
[7]陶娌娜,曲晓宇,张四喜,等.甲巯咪唑致肝细胞损伤型肝损害1例[J].药物流行病学杂志, 2017, 26(12):850-851.
[8] Zou H, Jin L, Wang LR, et al. Methimazole-induced cholestatic hepatitis:two cases report and literature review[J]. Oncotarget, 2016, 7(4):5088-5091.
[9] Hung YT, Yu WK, Chow E. Delayed cholestatic hepatitis due to methimazole[J]. Hong Kong Med J, 1999, 5(2):200-201.
[10] Heidari R, Niknahad H, Jamshidzadeh A, et al. Factors affecting drug-induced liver injury:antithyroid drugs as instances[J]. Clin Mol Hepatol, 2014, 20(3):237-248.
[11]李瑞珺,钱方,陆瑜,等. 1例甲巯咪唑致混合型药物性肝损伤患者的药学监护[J].中国药物应用与监测, 2016, 13(4):227-230.
[12]陈陶,汤杰,李娟,等.甲巯咪唑致混合性肝损伤1例[J].医药导报,2014, 33(10):1393-1394.
[13] Shen C, Zhao CY, Liu F, et al. Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot:case report[J]. BMC Gastroenterol, 2010, 10:93-93.
[14] Smathers RL, Galligan JJ, Shearn CT, et al. Susceptibility of L-FABP-/-mice to oxidative stress in early-stage alcoholic liver[J]. J Lipid Res, 2013, 54(5):1335-1345.
[15] Heidari R, Babaei H, Eghbal M. Mechanisms of me-thimazole cytotoxicity in isolated rat hepatocytes[J]. Drug Chem Toxicol, 2013, 36(4):403-411.
[16] Heidari R, Babaei H, Roshangar L. Effects of enzyme induction and/or glutathione depletion on methimazole-induced hepatotoxicity in mice and the protective role of N-Acetylcysteine[J]. Adv Pharm Bull, 2014, 4(1):21-28.
[17]李文红,王芳,付莹,等.肺结核药物性肝损害的相关因素分析[J].临床肺科杂志, 2016, 21(11):2097-2100.
[18]陆人杰,朱珊梅,唐风雷,等. 424例药物性肝损伤临床特征及相关危险因素分析[J].肝脏, 2017, 22(3):235-239.
[19] Kang H, Choi JD, Jung IG, et al. A case of methima-zole-induced acute hepatic failure in a patient with chronic hepatitis B carrier[J].Korean J Intern Med, 1990, 5(1):69-73.
[20] Kulaksizoglu M, Gonen MS, Kebapcilar L, et al. Multiorgan dysfunction accompanied with metimazole and thyroid storm[J]. Transfus Apher Sci, 2012, 46(2):149-152.
[21] Zhang M, Zhou HW, He RH, et al. Steroids for the treatment of methimazole-induced severe cholestatic jaundice in a 74-year-old woman with type 2 diabetes[J]. Endocrine, 2010, 37(2):241-243.
[22]王玉霞,都健.抗甲状腺药物肝损伤临床诊治进展[J].实用肝脏病杂志, 2017, 20(02):135-138.
[23]陈富琴,陈章,张俊然,等.药物性肝损害临床流行病学研究进展[J].药物流行病学杂志, 2016, 25(12):810-813, 818.
[24] Bray TM, Taylor CG. Tissue glutathione, nutrition, and oxidative stress[J]. Can J Physiol Pharmacol, 1993, 71(9):746-751.
[25] Niknahad H, Jamshidzadeh A, Heidari R, et al. Paradoxical effect of methimazole on liver mitochondria:In vitro and in vivo[J]. Toxicol Lett, 2016, 259:108-115.
[26] Kobayashi M, Hiquchi S, Ide M, et al. Th2 cytokine-mediated methimazole-induced acute liver injury in mice[J]. J Appl Toxicol,2012, 32(10):823-833.
[27]于乐成,茅益民,陈成伟,等.药物性肝损伤诊治指南[S].实用肝脏病杂志, 2017, 20(2):257-274.
[28] Lin TY, Shekar AO, Li N, et al. Incidence of abnormal liver biochemical tests in hyperthyroidism[J]. Clin Endocrinol(Oxf), 2017, 86(5):755-759.
[29] EASL Clinical Practice Guidelines:management of cholestatic liver diseases[J]. J Hepatol, 2009, 51(2):237-67.
[30]江杰,李丽,王利红.熊去氧胆酸联合糖皮质激素治疗药物性淤胆型肝炎疗效观察[J].湖北中医药大学学报, 2014, 16(1):78-80.
[31]苏婷婷,张波,周颜.腺苷蛋氨酸联合糖皮质激素治疗药物性胆汁淤积性肝病疗效[J].胃肠病学和肝病学杂志, 2011, 20(8):767-768.
[32] Qin G, Shao JG, Wang B, et al. Artificial liver support system improves short-and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure:a single-center experience[J]. Medicine(Baltimore), 2014, 93(28):e338.
[33] Ling Q, Xu X, Wei Q, et al. Downgrading MELD improves the outcomes after liver transplantation in patients with acute-on-chronic hepatitis B liver failure[J]. PLoS One, 2012, 7(1):e30322.