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Polukhova Sh.M., Musayeva E.M., Huseinova G.A., Kasymova S.V., Jafarova R.A.
Drug-induced hepatopathies
Azerbaijan Medical University, Baku, Azerbaijan

Vestnik VGMU. 2018;17(4):29-36.

The review of the available literature shows that the prevalence of hepatopathies is increasing year after year in the whole world. Practically all drugs that are metabolized in the liver are hepatotoxic. The probability of the liver failure depends both on physical and chemical properties of drugs and patient’s individual characteristics, including the genetic ones. Hepatotoxicity of drugs increases in case of repeated administration and when a combination of several drugs is taken. Hepatotoxicity of various medications develops according to different scenarios of pathogenetic mechanisms and may possess morphologically individual features. Depending on individual characteristics of the human body one and the same drug can trigger distinct pathology development mechanisms with different morphological features, for all this hepatotoxicity of the medications representing totally different groups can develop in the same way.
Key words: liver, drugs, toxicity, ethiopathogenetical mechanisms.


1. Shirokova EN. Drug-induced liver injury [Elektronnyi resurs]. Internist. Natsional’noe Internet Obshchestvo spetsialistov po vnutrennim bolezniam: [sait]. Rezhim dostupa: Data dostupa: 10.08.2018. (In Russ.)
2. Bunchorntavakul C, Reddy KR. Drug Hepatotoxicity: Newer Agents. Clin Liver Dis. 2017 Feb;21(1):115-134. doi:
3. Ushkalova E. Drug-induced liver injury. Vrach. 2007;(3):22-6. (In Russ.)
4. Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, et al. Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology. 2002 Aug;36(2):451-5. doi:
5. Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, et al. Drug-Induced Liver Injury: An Analysis of 461 Incidences Submitted to the Spanish Registry Over a 10-Year Period. Gastroenterology. 2005 Aug;129(2):512-21. doi:
6. Bjоrnsson E, Olsson R. Outcome and Prognostic Markers in Severe Drug-Induced Liver Disease. Hepatology. 2005 Aug;42(2):481-9. doi:
7. Khomeriki SG. Pathogenetic mechanisms and morphological manifestations of medicinal liver lesions. Eksperim Klin Gastroenterologiia. 2011;(6):11-21. (In Russ.)
8. Dzhafarova RE. Balance of interests of manufacturers and consumers of medicines: bioethical aspects of relations. Dostizheniia Med Nauki Prakt zdravookhraneniia. (In Russ.)
9. Zvyagintseva TD, Chernobay AI. Medicinal hepatitis: from pathogenesis to treatment. Novosti Meditsiny Farmatsii Gastroenterologiia. 2011;(375). (In Russ.)
10. Ho H, Bartlett A, Hunte P. Virtual liver models in pre-surgical planning, intra-surgical navigation and prognosis analysis. Drug Discovery Today: Disease Models. 2016;22:51-6.
11. Novik EI, Dwyer J, Morelli JK, Parekh A, Cho C, Pludwinski E, et al. Long-enduring primary hepatocyte-based co-cultures improve prediction of hepatotoxicity. Toxicol Appl Pharmacol. 2017 Dec;336:20-30. doi:
12. Adukauskiene D, Dockiene I, Naginiene R, Kevelaitis E, Pundzius J, Kupcinskas L. Acute liver failure in Lithuania. Medicina (Kaunas). 2008;44(7):536-40.
13. Eremina EYu. Drug-induced hepatitis in pregnant women. Problemy Zhen Zdorov’ia. 2011;6(4):46-55. (In Russ.)
14. Eremina EYu. Drug-induced hepatitis in pregnant women. Vrach. 2015;(8):11-3. (In Russ.)
15. Patel V, Sanyal AJ. Drug-Induced Steatohepatitis. Clin Liver Dis. 2013 Nov;17(4):533-46, vii. doi:
16. Ramappa V, Aithal GP. Hepatotoxicity Related to Antituberculosis Drugs: Mechanisms and Management. J Clin Exp Hepatol. 2013 Mar;3(1):37-49. doi:
17. Luyendyk JP, Ganey PE, Fullerton A, Roth RA. Inflammation and Hepatotoxicity. Comprehensive Toxicology. 2018;2:324-45. doi:
18. LeCluyse EL, Norona LM, Akingbasote JA, Howell LS, Woodhead JL, Cross MJ, et al. Leading-Edge Approaches for In Vitro Hepatotoxicity Evaluation. Comprehensive Toxicology. 2018;2:651-712. doi:
19. Bueverova AO, Maevskaya MV, Ivashkina VT. Alcoholic liver disease. Ros Med Zhurn Bolezni Organov Pishchevareniia. 2001;(2):61. (In Russ.)
20. Neuberger J, Williams R. Halotane hepatitis. Dig Dis. 1988;6(1):52-64. doi:
21. Shetty A, Cho W, Alazawi W, Syn WK. Methotrexate Hepatotoxicity and the Impact of Nonalcoholic Fatty Liver Disease. Am J Med Sci. 2017 Aug;354(2):172-181. doi:
22. Guo HL, Hassan HM, Ding PP, Wang SJ, Chen X, Wang T, et al. Pyrazinamide-induced hepatotoxicity is alleviated by 4-PBA via inhibition of the PERK-eIF2α-ATF4-CHOP pathway. Toxicology. 2017 Mar;378:65-75. doi:
23. Shehu AI, Ma X, Venkataramanan R. Mechanisms of Drug-Induced Hepatotoxicity. Clin Liver Dis. 2017 Feb;21(1):35-54. doi:
24. Chazoilleres O, Housset C. Intahepatic cholestasis. In: Rodés J, Benhamou J-P, Blei A, Reichen J, Rizzetto M, Friedman SL. Textbook of Hepatology: From Basik Science to Clinical Practice. 3rd ed. Blakwell; 2007. Р. 1481-500.   
25. Lu J, Zhang Y, Sun M, Liu M, Wang X. Comprehensive assessment of Cucurbitacin E related hepatotoxicity and drug-drug interactions involving CYP3A and P-glycoprotein. Phytomedicine. 2017 Mar;26:1-10. doi:
26. Liu C, Sekine S, Ito K. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes. Toxicol Appl Pharmacol. 2016 Jul;302:23-30. doi:
27. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21(1):3-16.
28. Song Q, Guo R, Wei W, Lv L, Song Z, Feng R, et al. Histidine-alleviated hepatocellular death in response to 4-hydroxynonenal contributes to the protection against high-fat diet-induced liver injury. J Functional Foods. 2017 Dec;39:74-83. doi:
29. Lee WM. Acetaminophen (APAP) hepatotoxicity-Isn’t it time for APAP to go away? J Hepatol. 2017 Dec;67(6):1324-1331. doi:
30. McEneny-King A, Osman W, Edginton AN, Rao PPN. Cytochrome P450 binding studies of novel tacrine derivatives: Predicting the risk of hepatotoxicity. Bioorg Med Chem Lett. 2017 Jun;27(11):2443-9. doi:
31. Ngouleun W, Cabral P, Nya B, Pieme AC, Telefo PB. Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/AIDS-coinfected patients under tuberculosis treatment. Int J Mycobacteriol. 2016 Dec;5(4):482-8. doi:
32. Goering PL, Liu J. Hepatotoxicity of Copper, Iron, Cadmium, and Arsenic. Comprehensive Toxicology. 2018;2:575-96. doi:
33. Mohammed NE, Messiha BA, Abo-Saif AA. Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats. Saudi Pharm J. 2016 Nov;24(6):635-644.
34. Silva AM, Barbosa IA, Seabra C, Beltrão N, Santos R, Vega-Naredo I, et al. Involvement of mitochondrial dysfunction in nefazodone-induced hepatotoxicity. Food Chem Toxicol. 2016 Aug;94:148-58. doi:
35. Zhao DS, Jiang LL, Fan YX, Dong LC, Ma J, Dong X, et al. Identification of urine tauro-β-muricholic acid as a promising biomarker in Polygoni Multiflori Radix-induced hepatotoxicity by targeted metabolomics of bile acids. Food Chem Toxicol. 2017 Oct;108(Pt B):532-542. doi:
36. Zhou L, Zhou C, Feng Z, Liu Z, Zhu H, Zhou X. Triptolide-induced hepatotoxicity can be alleviated when combined with Panax notoginseng saponins and Catapol. J Ethnopharmacol. 2018 Mar;214:232-239. doi:
37. Shibata Y, Hagihara M, Kato H, Kawasumi N, Hirai J, Nishiyama N, et al. Caspofungin versus micafungin in the incidence of hepatotoxicity in patients with normal to moderate liver failure. J Infect Chemother. 2017 Jun;23(6):349-353. doi:
38. Maes M, Vinken M, Jaeschke H. Experimental models of hepatotoxicity related to acute liver failure. Toxicol Appl Pharmacol. 2016 Jan;290:86-97. doi:
39. van der Velden WJFM, de Weerd-de Jong EC, de Haan AFJ, Blijlevens NMA. Busulfan-Dependent Hepatotoxicity of Antithymocyte Globulin Formulations During Conditioning for Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018 Feb;24(2):410-412. doi:
40. Lazebnik LB, Zvenigorodskaya LA, Khomeriki SG, Efremov LI, Cherkashova EA. Medicinal (statin) hepatitis. Eksperim Klin Gastroenterologiia. 2009;(3):110-6. (In Russ.)
41. Kamola PJ, Maratou K, Wilson PA, Rush K, Mullaney T, McKevitt T, et al. Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs. Mol Ther Nucleic Acids. 2017 Sep;8:383-394. doi:

Information about authors:
Polukhova Sh.M. – Candidate of Biological Sciences, senior research officer of the Chair of Pharmacology, Azerbaijan Medical University;
Musayeva E.M. – Candidate of Biological Sciences, lecturer of the Chair of Pharmacology, Azerbaijan Medical University;
Huseinova G.A. – Candidate of Medical Sciences, associate professor of the Chair of Pharmacology, Azerbaijan Medical University;
Kasymova S.V. – senior laboratory assistant of the Chair of Family Medicine, Azerbaijan Medical University;
Jafarova R.A. – Doctor of Biological Sciences, head of the Department of Toxicology of the Scientific Research Center, Azerbaijan Medical University.

Correspondence address: Azerbaijan, AZ1022, Baku, 23 Bakikhanov str., Azerbaijan Medical University, Scientific Research Center, Department of Toxicology. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Rana A. Jafarova.

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