STM Journals Peer-reviewed research from Consortium e-Learning Network

OmniScience: A Multi-disciplinary Journal Review Article IMSEMTI 2024

Treatment of Hepatotoxicity

  1. Priyanka Department of Pharmacology, School of Pharmaceutical Sciences, CT University, Ludhiana
  2. Priyanka Rai Department of Pharmacology, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar,
  3. Samriti Bhardwaj Department of Pharmaceutics, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar
  4. Yashika Department f Pharmacology, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar

Abstract

An instantaneous or prolonged response to a synthetic or natural substance is known as drug-induced liver injury, or drug-induced hepatotoxicity (DILI). There are two distinct pathways that lead to hepatotoxicity: the more unpredictable idiosyncratic mechanism and the dose-dependent intrinsic mechanism. Several pathways, some known and others speculated, may be involved in the emergence of drug-induced damage. Drug-induced liver impairment can have several causes, and elevated liver tests are one of them. Excluding all alcoholic, nonalcoholic fatty liver, autoimmune, and hepatitis-like viral causes of liver illness is crucial. The best line of treatment is to cease taking any drugs that put undue strain on the liver and replace them with ones that mitigate or control the side effects of hepatotoxicity. Stopping up alcohol may also reduce your chance of developing hepatotoxicity. It has been demonstrated that intravenous carnitine and rapid N-acetylcysteine administration following an acetaminophen overdose can be used to treat liver disease and acute valproate-induced hepatotoxicity, respectively. A herbal hepatoprotective medication silymarin, a lavonolignan produced from Silybum marianum, often known as milk thistle, functions by blocking lipid peroxidation, reducing inflammation, stabilizing membranes, enhancing the immune system, and encouraging liver regeneration.

Keywords

References (47)

  1. Fisher K, Vuppalanchi R, Saxena R. Drug-Induced Liver Injury. Arch Pathol Lab Med. 2015;139(7):876–887.
  2. Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. United States Drug Induced Liver Injury Network. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340–1352.e7.
  3. Katarey D, Verma S. Drug-induced liver injury. Clin Med (Lond). 2016;16(Suppl 6):s104–s109.
  4. Kuna L, Bozic I, Kizivat T, Bojanic K, Mrso M, Kralj E, et al. Models of Drug Induced Liver Injury (DILI) - Current Issues and Future Perspectives. Curr Drug Metab. 2018;19(10):830–838.
  5. Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950–966; quiz 967.
  6. Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363–373.
  7. Tujios SR, Lee WM. Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy. Liver Int. 2018;38(1):6–14.
  8. European Medicines Agency. [(accessed on 1 May 2015)].
  9. Physician Desk Reference (PDR) [accessed on 1 May 2015].
  10. Bjornsson ES, Jacobsen EI, Einarsdottir R, Chalasani N. Discrepancies in Liver Disease Labeling in the Package Inserts of Commonly Prescribed Medications. Gastroenterology. 2015;148(2):269-273. doi:10.1053/j.gastro.2014.12.007
  11. Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the attractive hazard. Expert Opinion on Drug Safety. 2009;8(6):709-714. doi:10.1517/14740330903397378
  12. Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, et al. Drug-induced liver injury following positive drug rechallenge. Regulatory Toxicology and Pharmacology. 2009;54(1):84-90. doi:10.1016/j.yrtph.2009.03.003
  13. Zimmerman HJ. Drug-induced liver disease. In: Sciff ER, Sorrell MF, Maddrey WC, editors. Diseases of the Liver. 8th ed. Philadelphia: Schiff’s Lippincott-Raven Publishers; 1999. pp. 973–1064.
  14. Agarwal VK, McHutchison JG, Hoofnagle JH. Important Elements for the Diagnosis of Drug-Induced Liver Injury. Clinical Gastroenterology and Hepatology. 2010;8(5):463-470. doi:10.1016/j.cgh.2010.02.008
  15. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, et al. An Oficial ATS Statement: Hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174:935–952.
  16. Naruse K, Tang W, Makuuchi M. Artiicial and bioartiicial liver support: A review of perfusion treatment for hepatic failure patients. World J Gastroenterol. 2007;13:1516–1521.
  17. Zimmerman HJ. Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. Philadelphia: Lippincott Williams & Wilkins; 1999.
  18. Watkins PB. Mechanisms of drug-induced liver disease. In: Schiff ER, Sorrell M, Maddrey WC, eds. Schiff’s Diseases of the Liver, 9 ed. Philadelphia: Lippincott Williams & Wilkins; 2003. pp. 1129–1145.
  19. Pessayre D, Fromenty B, Mansouri A, et al. Hepatotoxicity due to mitochondrial injury. In: Kaplowitz N, DeLeve LD, eds. Drug-Induced Liver Disease, 1st ed. New York: Marcel Dekker; 2003. pp. 55–83.
  20. Berson A, De Beco V, Lettéron P, Robin MA, Moreau C, Kahwaji JE, et al. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology. 1998;114(4):764-774. doi:10.1016/s0016-5085(98)70590-6
  21. Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003;348:529–537.
  22. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions. JAMA. 2001;286(18):2270. doi:10.1001/jama.286.18.2270
  23. Evans WE, McLeod HL. Pharmacogenomics: Drug disposition, drug targets, and side effects. N Engl J Med. 2003;348:538–547.
  24. Beaune P, Dansette PM, Mansuy D, Kiffel L, Finck M, Amar C, et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proceedings of the National Academy of Sciences. 1987;84(2):551-555. doi:10.1073/pnas.84.2.551
  25. Lucena MI, Andrade RJ, Kaplowitz N, García‐Cortes M, Fernández MC, Romero‐Gomez M, et al. Phenotypic characterization of idiosyncratic drug‐induced liver injury. Hepatology. 2009;49(6):2001-2009. doi:10.1002/hep.22895
  26. Chalasani N, Bjo¨rnsson E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology. 2010;138(7):2246–2259.
  27. Meng X, Maggs JL, Usui T, Whitaker P, French NS, Naisbitt DJ, et al. Auto-oxidation of Isoniazid Leads to Isonicotinic-Lysine Adducts on Human Serum Albumin. Chemical Research in Toxicology. 2014;28(1):51-58. doi:10.1021/tx500285k
  28. Larrey D, Vial T, Micaleff A, Babany G, Morichau-Beauchant M, Michel H, et al. Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases. Gut. 1992;33(3):368-371. doi:10.1136/gut.33.3.368
  29. Huang YS, Chern HD, Su WJ, Wu JC, Chang SC, Chiang CH, et al. Cytochrome P450 2E1 Genotype and the Susceptibility to Antituberculosis Drug–Induced Hepatitis. Hepatology. 2003;37(4):924-930. doi:10.1053/jhep.2003.50144
  30. Russmann S, Kullak-Ublick GA, Grattagliano I. Current concepts of mechanisms in drug-induced hepatotoxicity. Curr Med Chem. 2009;16(23):3041–3053
  31. Andrade RJ, Robles M, Ulzurrun E, Lucena MI. Drug-Induced Liver Injury: Insights from Genetic Studies. Pharmacogenomics. 2009;10(9):1467-1487. doi:10.2217/pgs.09.111
  32. for the DILIGEN study, Daly AK, International SAE Consortium, Donaldson PT, Bhatnagar P, Shen Y, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature Genetics. 2009;41(7):816-819. doi:10.1038/ng.379
  33. Lammert C, Bjornsson E, Niklasson A, Chalasani N. Oral Medications With Significant Hepatic Metabolism at Higher Risk for Hepatic Adverse Events. Hepatology. 2010;51(2):615-620. doi:10.1002/hep.23317
  34. Lammert C, Einarsson S, Saha C, et al. Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals. Hepatology. 2008;47(6):2003–2009.
  35. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, et al. Causes, Clinical Features, and Outcomes From a Prospective Study of Drug-Induced Liver Injury in the United States. Gastroenterology. 2008;135(6):1924-1934.e4. doi:10.1053/j.gastro.2008.09.011
  36. Gayam V, Khalid M, Shrestha B, Hossain MR, Dahal S, Garlapati P, et al. Drug-Induced Liver Injury: An Institutional Case Series and Review of Literature. J Investig Med High Impact Case Rep. 2018;6:2324709618761754
  37. Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol. 2008;14(44):6774–6785.
  38. Polson J, Lee WM. AASLD position paper: the management of acute liver failure. Hepatology. 2005;41:1179–1197.
  39. Bohan TP, Helton E, McDonald I, König S, Gazitt S, Sugimoto T, et al. Effect of l -carnitine treatment for valproate-induced hepatotoxicity. Neurology. 2001;56(10):1405-1409. doi:10.1212/wnl.56.10.1405
  40. Bhragual DD, Kumar N, Garg VK, Sharma PK. Review on plants having hepatoprotective activity. J Pharm Res. 2010;3:2077–2082.
  41. Mohamed Saleem TS, Madhusudhana Chetty C, Ramkanth S, Rajan VST, Mahesh Kumar K, et al. Hepatoprotective herbs – A review. Int J Res Pharm Sci. 2010;1:1–5.
  42. Vishnu Priya V, Niveda S, Pratiksha G, Gayathri R. A review of hepatoprotective natural products. Recent Res Sci Technol. 2010;2:49–52.
  43. Deshwal N, Sharma AK, Sharma P. Review on hepatoprotective plants. Int J Pharm Sci Rev Res. 2011;7:15–26.
  44. Pradhan SC, Girish C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res. 2006;124:491–504.
  45. Xu JJ, Diaz D, O’Brien PJ. Applications of cytotoxicity assays and prelethal mechanistic assays for assessment of human hepatotoxicity potential. Chemico-Biol Interact. 2004;150(1):115–128.
  46. CDER. Report to the Nation: Improving Public health through Human Drugs. Food and Drug Administration, Centre for Drug Evaluation and Research, US Department of Health and Human Services; 2005.
  47. Goldkind L, Laine L. A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiology and Drug Safety. 2006;15(4):213-220. doi:10.1002/pds.1207
Support