水飞蓟制剂预防性治疗抗结核药物性肝损伤效果的Meta分析

陶娌娜; 曲晓宇; 张越; 宋燕青; 张四喜

doi:10.3969/j.issn.1001-5256.2019.08.025

水飞蓟制剂预防性治疗抗结核药物性肝损伤效果的Meta分析

DOI: 10.3969/j.issn.1001-5256.2019.08.025

吉林大学第一医院药学部

基金项目:

国家自然科学基金项目(81803608)；

详细信息

中图分类号: R575;R52
计量
- 文章访问数: 1833
- HTML全文浏览量: 81
- PDF下载量: 271
- 被引次数: 0
出版历程
- 收稿日期: 2019-06-19
- 出版日期: 2019-08-20

Clinical effect of Silybum marianum preparation in the prophylactic treatment of antitubercular agent-induced liver injury: A Meta-analysis of randomized controlled trials

Department of Pharmacy, The First Hospital of Jilin University

Research funding:

摘要

摘要:
目的评估水飞蓟制剂在预防抗结核药物性肝损伤（ATB-DILI）中的作用。方法检索MEDLINE、PubMed、Embase和Cochrane对照试验中心注册库（CENTRAL）截至2018年11月30日,水飞蓟制剂与安慰剂相比预防ATB-DILI的随机对照试验研究。所有统计分析均使用STATA12. 0软件进行。使用具有95%可信区间（95%CI）的标准化均值差（SMD）和相对危险度（RR）来评估水飞蓟制剂的作用。纳入研究的质量根据Cochrane手册进行评估。使用漏斗图和Egger’s测试评估发生偏倚。采用敏感性分析以评估每项研究对整体效应大小的影响。结果共纳入5项随机对照试验的1198例患者（585例使用水飞蓟制剂,613例使用安慰剂）。水飞蓟制剂在第4周显著降低了ATB-DILI的发生风险（RR=0. 33,95%CI:0. 15～0. 75,P=0. 008）。此外,水飞蓟制剂对接受抗结核药物治疗的患者肝功能有保护作用（ALT:SMD=-0. 15,95%CI:-0. 24～-0. 07,P <0. 001; AST:SMD=-0. 14,95%CI:-0. 23～-0....
- 化学性与药物性肝损伤 /
- 抗结核药 /
- 水飞蓟素 /
- Meta分析(主题)
Abstract:
Objective To evaluate the clinical effect of Silybum marianum preparation in the prophylactic treatment of antitubercular agent-induced liver injury (ATB-DILI) , since there have always been controversies over the development of Silybum marianum preparation for the prophylactic treatment of ATB-DILI. Methods MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) on Silybum marianum preparation versus placebo in preventing ATB-DILI published up to November 30, 2018. STATA 12. 0 software was used for statistical analyses. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CI) were used to evaluate the effect of Silybum marianum preparation. The Cochrane handbook was used to assess the quality of RCTs, and funnel plots and Egger's tests were used to evaluate publication bias. A sensitivity analysis was conducted to assess the influence of each RCT on overall effect. Results A total of five RCTs with 1198 patients were included, and among these patients, 585 received Silybum marianum preparation and 613 received placebo. Silybum marianum preparation significantly reduced the risk of the onset of ATB-DILI at week 4 (RR = 0. 33, 95% CI: 0. 15-0. 75, P = 0. 008) . In addition, Silybum marianum preparation had a protective effect on liver function in patients receiving antitubercular agents (alanine aminotransferase: SMD =-0. 15, 95% CI:-0. 24 to-0. 07, P < 0. 001; aspartate aminotransferase: SMD =-0. 14, 95% CI:-0. 23 to-0. 06, P = 0. 001; alkaline phosphatase: SMD =-0. 12, 95% CI:-0. 20 to-0. 03, P = 0. 008) . Silybum marianum preparation had a similar risk of adverse events as placebo (RR = 1. 09, 95%CI: 0. 86-1. 39, P = 0. 47) . Conclusion In patients with tuberculosis, prophylactic treatment with Silybum marianum preparation can significantly reduce the risk of the onset of ATB-DILI after 4 weeks of treatment. In addition, Silybum marianum preparation can also improve the liver function of patients treated with antitubercular agents.
- chemical and drug induced liver injury /
- antitubercular agents /
- silymarin /
- Meta-analysis as topic

HTML全文

参考文献(51)

[1] World Health Organization. Global tuberculosis report 2017[EB/OL]. Geneva:WHO, 2017.

[2] HORSBURGH CR Jr, BARRY CE 3rd, LANGE C. Treatment of tuberculosis[J]. N Engl J Med, 2015, 373 (22) :2149-2160.

[3] WU S, XIA Y, LV X, et al. Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti-tuberculosis agents in a large cohort of Chinese patients[J]. J Gastroenterol Hepatol, 2015, 30 (3) :540-545.

[4] TOSTMANN A, BOEREE MJ, AARNOUTSE RE, et al. Antituberculosis drug-induced hepatotoxicity:Concise up-to-date review[J]. J Gastroenterol Hepatol, 2008, 23 (2) :192-202.

[5] SAUKKONEN JJ, COHN DL, JASMER RM, et al. An official ATS statement:Hepatotoxicity of antituberculosis therapy[J].Am J Respir Crit Care Med, 2006, 174 (8) :935-952.

[6] METUSHI I, UETRECHT J, PHILLIPS E. Mechanism of isoniazid-induced hepatotoxicity:Then and now[J]. Br J Clin Pharmacol, 2016, 81 (6) :1030-1036.

[7] BASKARAN UL, SABINA EP. Clinical and experimental research in antituberculosis drug-induced hepatotoxicity:A review[J]. J Integr Med, 2017, 15 (1) :27-36.

[8] HACKETT ES, TWEDT DC, GUSTAFSON DL. Milk thistle and its derivative compounds:A review of opportunities for treatment of liver disease[J]. J Vet Intern Med, 2013, 27 (1) :10-16.

[9] KIDD PM. Bioavailability and activity of phytosome complexes from botanical polyphenols:The silymarin, curcumin, green tea, and grape seed extracts[J]. Altern Med Rev, 2009, 14 (3) :226-246.

[10] LEE JI, NARAYAN M, BARRETT JS. Analysis and comparison of active constituents in commercial standardized silymarin extracts by liquid chromatography-electrospray ionization mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2007, 845 (1) :95-103.

[11] SHERIF IO, AL-GAYYAR MM. Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite[J]. Eur Cytokine Netw, 2013, 24 (3) :114-121.

[12] KARIMI G, VAHABZADEH M, LARI P, et al. Silymarin, a promising pharmacological agent for treatment of diseases[J]. Iran J Basic Med Sci, 2011, 14 (4) :308-317.

[13] AU AY, HASENWINKEL JM, FRONDOZA CG. Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro[J]. J Anim Physiol Anim Nutr (Berl) , 2013, 97 (2) :331-341.

[14] SINGH M, SASI P, GUPTA VH, et al. Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model[J]. Hum Exp Toxicol, 2012, 31 (8) :788-797.

[15] EMINZADE S, URAZ F, IZZETTIN FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals[J]. Nutr Metab (Lond) , 2008, 5 (1) :18.

[16] MANN A, PELZ T, RENNERT K, et al. Evaluation of HepaRG cells for the assessment of indirect drug-induced hepatotoxicity using INH as a model substance[J]. Hum Cell, 2017, 30 (4) :267-278.

[17] ABENAVOLI L, CAPASSO R, MILIC N, et al. Milk thistle in liver diseases:Past, present, future[J]. Phytother Res, 2010, 24 (10) :1423-1432.

[18] LIU Q, GARNER P, WANG Y, et al. Drugs and herbs given to prevent hepatotoxicity of tuberculosis therapy:Systematic review of ingredients and evaluation studies[J]. BMC Public Health, 2008, 8:365-372.

[19] LUANGCHOSIRI C, THAKKINSTIAN A, CHITPHUK S, et al. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury[J].BMC Complement Altern Med, 2015, 15 (1) :334.

[20] MARJANI M, BAGHAEI P, KAZEMPOUR DIZAJI M, et al.Evaluation of hepatoprotective effect of silymarin among under treatment tuberculosis patients:A randomized clinical trial[J]. Iran J Pharm Res, 2016, 15 (1) :247-252.

[21] ZHANG S, PAN H, PENG X, et al. Preventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury:A randomized controlled trial[J]. J Gastroenterol Hepatol, 2016, 31 (2) :409-416.

[22] KNOBLOCH K, YOON U, VOGT PM, et al. Preferred reporting items for systematic reviews and Meta-analyses (PRISMA) statement and publication bias[J]. J Craniomaxillofac Surg, 2011, 39 (2) :91-92.

[23] HIGGINS J. Cochrane handbook for systematic reviews of interventions version 5. 1. 0[EB/OL]. (2011-03) . The Cochrane Collaboration, 2011. http://handbook. cochrane.org/.

[24] WAN X, WANG WQ, LIU JM, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range[J]. BMC Med Res Methodol, 2014, 14 (1) :135.

[25] RAMANATHAN R, SIVANESAN K. Evaluation of ameliorative ability of Silibinin against zidovudine and isoniazid-induced hepatotoxicity and hyperlipidaemia in rats:Role of Silibinin in Phase I and II drug metabolism[J]. Chem Biol Interact, 2017, 273:142-153.

[26] GHOSH K, INDRA N, JAGADEESAN G. The ameliorating effect of centella asiatica ethanolic extract on albino rats treated with isoniazid[J]. J Basic Clin Physiol Pharmacol, 2017, 28 (1) :67-77.

[27] MARTIN SJ, SABINA EP. Amelioration of anti-tuberculosis drug induced oxidative stress in kidneys by spirulina fusiformis in a rat model[J]. Ren Fail, 2016, 38 (7) :1115-1121.

[28] EVAN PRINCE S, UDHAYA LB, SUNITHA PS, et al. Reparation of isoniazid and rifampicin combinatorial therapy-induced hepatotoxic effects by bacopa monnieri[J]. Pharmacology, 2016, 98 (1-2) :29-34.

[29] MARTIN SJ, BASKARAN UL, VEDI M, et al. Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina fusiformis, a candidate food supplement[J]. Toxicol Mech Methods, 2014, 24 (8) :584-592.

[30] SRIVASTAVA RK, SHARMA S, VERMA S, et al. Influence of diabetes on liver injury induced by antitubercular drugs and on silymarin hepatoprotection in rats[J]. Methods Find Exp Clin Pharmacol, 2008, 30 (10) :731-737.

[31] WU JW, TSAI TH. Effect of silibinin on the pharmacokinetics of pyrazinamide and pyrazinoic acid in rats[J]. Drug Metab Dispos, 2007, 35 (9) :1603-1610.

[32] TASDUQ SA, PEERZADA K, KOUL S, et al. Biochemical manifestations of anti-tuberculosis drugs induced hepatotoxicity and the effect of silymarin[J]. Hepatol Res, 2005, 31 (3) :132-135.

[33] OOSTHUIZEN C, ARBACH M, MEYER D, et al. Diallyl polysulfides from allium sativum as immunomodulators, hepatoprotectors, and antimycobacterial agents[J]. J Med Food, 2017, 20 (7) :685-690.

[34] CRONJL, EDMONDSON N, EISENACH KD, et al. Iron and iron chelating agents modulate Mycobacterium tuberculosis growth and monocyte-macrophage viability and effector functions[J].FEMS Immunol Med Microbiol, 2005, 45 (2) :103-112.

[35] CHAN MK, CHAN PC, WONG KK, et al. Hepatitis B infection and renal transplantation:The absence of anti-delta antibodies and the possible beneficial effect of silymarin during acute episodes of hepatic dysfunction[J]. Nephrol Dial Transplant, 1989, 4 (4) :297-301.

[36] KATAOKA K, KONO Y, SUGIMOTO M, et al. Hepatocyteprotective and anti-oxidant effects of rifampicin on human chronic hepatitis C and murine acute hepatocyte disorder[J].Exp Ther Med, 2010, 1 (6) :1041-1047.

[37] CHENG S. To research the antiviral treatment of low grade chronic hepatitis B associated with tuberculosis patients (82 cases contrast analysis) [C]. Hepatology international conference:26th annual conference of the Asian Pacific Association for the Study of the Liver, China, 2017.

[38] BEDI S, GOEL A, CHAND N, et al. A prospective study for evaluating the effect of silymarin on hepatic functions in tubercular patients receiving dots[J]. Chest, 2009, 136:74S.

[39] CHENG S. The efficacy of silymarin on the prevention of hepatotoxicity from antituberculosis drugs[J]. Gastroenterology, 144 (5 Suppl 1) :s993.

[40] Clinicaltrials. gov. Effect of prophylactic use of silymarin on hepatotoxicity induced by anti-tuberculosis drugs (PESOHHERZ) [EB/OL].[2017-11-30]. https://clinicaltrials.gov/ct2/show/NCT01436929? term=silymarin&cond=tuberculosis&rank=1.

[41] LI J, LIN WF, PAN YY, et al. Protective effect of silibinin on liver injury induced by antituberculosis drugs[J]. Chin J Hepatol, 2010, 18 (5) :385-386.

[42] HU Z, YANG X, HO PC, et al. Herb-drug interactions:A literature review[J]. Drugs, 2005, 65 (9) :1239-1282.

[43] GU J, TANG SJ, TAN SY, et al. An open-label, randomized and multi-center clinical trial to evaluate the efficacy of Silibinin in preventing drug-induced liver injury[J]. Int J Clin Exp Med, 2015, 8 (3) :4320-4327.

[44] HEO E, KIM DK, OH SH, et al. Effect of prophylactic use of silymarin on anti-tuberculosis drugs induced hepatotoxicity[J]. Tuberc Respir Dis (Seoul) , 2017, 80 (3) :265-269.

[45] RAMAPPA V, AITHAL GP. Hepatotoxicity related to anti-tuberculosis drugs:Mechanisms and management[J]. J Clin Exp Hepatol, 2013, 3 (1) :37-49.

[46] LEE CM, LEE SS, LEE JM, et al. Early monitoring for detection of antituberculous drug-induced hepatotoxicity[J]. Korean J Intern Med, 2016, 31 (1) :65-72.

[47] METUSHI IG, ZHU X, CHEN X, et al. Mild isoniazid-induced liver injury in humans is associated with an increase in Th17cells and T cells producing IL-10[J]. Chem Res Toxicol, 2014, 27 (4) :683-689.

[48] METUSHIIG, CAI P, ZHU X, et al. A fresh look at the mechanism of isoniazid-induced hepatotoxicity[J]. Clin Pharmacol Ther, 2011, 89 (6) :911-914.

[49] SU M, CHEN H, WEI C, et al. Potential protection of vitamin C against liver-lesioned mice[J]. Int Immunopharmacol, 2014, 22 (2) :492-497.

[50] ABENAVOLI L, IZZO AA, MILIC'N, et al. Milk thistle (Silybum marianum) :A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases[J]. Phytother Res, 2018, 32 (11) :2202-2213.

[51] ABOUZID SF, AHMED HS, ABD EL, et al. Linear regression analysis of silychristin A, silybin A and silybin B contents in Silybum marianum[J]. Nat Prod Res, 2018.[Epub ahead of print]

施引文献

资源附件(0)

访问统计