Treatment of Hepatotoxicity

Year : 2025 | Volume : 15 | Special Issue 01 | Page : 31 37
    By

    Priyanka,

  • Priyanka Rai,

  • Samriti Bhardwaj,

  • Yashika,

  1. Research Scholar, Department of Pharmacology, School of Pharmaceutical Sciences, CT University, Ludhiana, Punjab, India
  2. Research Scholar, Department of Pharmacology, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar,, Punjab, India
  3. Assistant Professor, Department of Pharmaceutics, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar, Punjab, India
  4. Research Scholar, Department f Pharmacology, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar, Punjab, India

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: Hepatotoxicity, drug induced liver injury(DILI), cyP450

[This article belongs to Special Issue under section in OmniScience: A Multi-disciplinary Journal (osmj)]

How to cite this article:
Priyanka, Priyanka Rai, Samriti Bhardwaj, Yashika. Treatment of Hepatotoxicity. OmniScience: A Multi-disciplinary Journal. 2025; 15(01):31-37.
How to cite this URL:
Priyanka, Priyanka Rai, Samriti Bhardwaj, Yashika. Treatment of Hepatotoxicity. OmniScience: A Multi-disciplinary Journal. 2025; 15(01):31-37. Available from: https://journals.stmjournals.com/osmj/article=2025/view=195240


References

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;148:269–273. 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 Opin. Drug Saf. 2009;8:709–714. 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. Regul Toxicol Pharmacol. 2009;54:84–90. 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. Clin Gastroenterol Hepatol. 2010;8:463–470. 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, DeBeco V, Lette´ron P, Robin MA, Moreau C, El Kahwaji J, 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):2270–2279. 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. Proc Natl Acad Sci USA. 1987;84(2):551–555. doi: 10.1073/pnas.84.2.551.
25. Lucena MI, Andrade RJ, Kaplowitz N, García-Cortes M, Carmen Fernández M, Romero-Gomez M, et al. Phenotypic characterization of idiosyncratic drug-induced liver injury: The influence of age and sex. 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 isonicotiniclysine adducts on human serum albumin. Chem Res Toxicol. 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 Y-S, Chern H-D, Su W-J, Wu J-C, Chang S-C, Chiang C-H, 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. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, et al. HLA-B* 5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 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, 1934.e1-4. 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, Konig 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. Pharmacoepidemiol Drug Saf. 2006;15(4):213–220. doi: 10.1002/pds.1207.

Special Issue Subscription Review Article
Volume 15
Special Issue 01
Received 14/10/2024
Accepted 08/11/2024
Published 23/01/2025
Publication Time 101 Days
326

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