Drugs-induced liver injury associated with non-steroidal anti-inflammatory drugs: a case report and clinical insights

Cover Page

Cite item

Abstract

Aim: To raise the awareness of general practitioners with special characteristics of the clinical manifestations of the drug-induced liver injury (DILI), which can manifest with various signs, symptoms and types of morphological injury, from asymptomatic increase in transaminases and liver steatosis to chronic hepatitis with advanced fibrosis.
Key points: NSAID is one of the most commonly prescribed groups of agents worldwide. Most of them have low risk of liver toxicity. However, prolonged uncontrolled intake of NSAID by patients without proper medical follow-up and monitoring may lead to serious liver injury, illustrated by the clinical case presented. The case manifested as an extremely rare liver injury in the form of chronic hepatitis with advanced fibrosis that developed after prolonged NSAID use.
Conclusion: DILI usually occur as idiosyncratic (non-predictable) reactions. This is an exclusion diagnosis requiring comprehensive medical knowledge and awareness on potential drug-induced liver toxicity, including that associated with drug interactions. To minimize potential risk of liver toxicity induced by NSAID, it is recommended to take them in the lowest effective dose and for a minimally required period. A thorough assessment of a patient's past history, monitoring of clinical chemistry parameters, and clinical judgment of the physician remain to be decisive for prevention, timely diagnosis, and treatment of DILI.

About the authors

Yu. G. Sandler

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Author for correspondence.
Email: sandlerjulia2012@gmail.com
ORCID iD: 0000-0003-4291-812X

Yuliya G. Sandler – MD, PhD, Senior Researcher, Department of Hepatology

86 Shosse Entuziastov, Moscow, 111123

Russian Federation

E. V. Vinnitskaya

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Email: e.vinnitskaya@mknc.ru
ORCID iD: 0000-0002-0344-8375

Elena V. Vinnitskaya – MD, PhD, Head of Department of Hepatology

86 Shosse Entuziastov, Moscow, 111123

Russian Federation

K. G. Saliev

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Email: fake@neicon.ru
ORCID iD: 0000-0002-4581-7052

Kirill G. Saliev – MD, Laboratory Researcher, Department of Hepatology

86 Shosse Entuziastov, Moscow, 111123

Russian Federation

S. G. Khomeriki

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Email: fake@neicon.ru
ORCID iD: 0000-0003-4308-8009

Sergey G. Khomeriki – MD, PhD, Professor, Head of Laboratory of Pathomorphology

86 Shosse Entuziastov, Moscow, 111123

Russian Federation

T. Yu. Кhaimenova

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Email: fake@neicon.ru
ORCID iD: 0000-0002-4599-4040

Tat'yana Yu. Khaymenova – MD, PhD, Head of Department of Liver Diseases

86 Shosse Entuziastov, Moscow, 111123

Russian Federation

References

  1. Björnsson E. Review article: drug-induced liver injury in clinical practice. Aliment Pharmacol Ther. 2010;32(1):3–13. doi: 10.1111/j.1365-2036.2010.04320.x.
  2. Leise MD, Poterucha JJ, Talwalkar JA. Drug-induced liver injury. Mayo Clin Proc. 2014;89(1): 95–106. doi: 10.1016/j.mayocp.2013.09.016.
  3. Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065–76. doi: 10.1002/hep.23937.
  4. Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, Watkins PB, Navarro V, Barnhart H, Gu J, Serrano J; 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): 1340–52.e7. doi: 10.1053/j.gastro.2015.03.006.
  5. Stine JG, Chalasani N. Chronic liver injury induced by drugs: a systematic review. Liver Int. 2015;35(11):2343–53. doi: 10.1111/liv.12958.
  6. 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):950–66; quiz 967. doi: 10.1038/ajg.2014.131.
  7. Shin J, Hunt CM, Suzuki A, Papay JI, Beach KJ, Cheetham TC. Characterizing phenotypes and outcomes of drug-associated liver injury using electronic medical record data. Pharmacoepidemiol Drug Saf. 2013;22(2):190–8. doi: 10.1002/pds.3388.
  8. Ettel M, Gonzalez GA, Gera S, Eze O, Sigal S, Park JS, Xu R. Frequency and pathological characteristics of drug-induced liver injury in a tertiary medical center. Hum Pathol. 2017;68:92–8. doi: 10.1016/j.humpath.2017.08.029.
  9. Cornberg M, Tacke F, Karlsen TH; European Association for the Study of the Liver. Clinical Practice Guidelines of the European Association for the study of the Liver – Advancing methodology but preserving practicability. J Hepatol. 2019;70(1):5–7. doi: 10.1016/j.jhep.2018.10.011.
  10. Stine JG, Chalasani NP. Drug Hepatotoxicity: Environmental Factors. Clin Liver Dis. 2017;21(1): 103–13. doi: 10.1016/j.cld.2016.08.008.
  11. Wehling M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol. 2014;70(10):1159–72. doi: 10.1007/s00228-014-1734-6.
  12. Haque T, Sasatomi E, Hayashi PH. Drug-Induced Liver Injury: Pattern Recognition and Future Directions. Gut Liver. 2016;10(1):27–36. doi: 10.5009/gnl15114.
  13. Day RO, Graham GG. Non-steroidal anti-inflammatory drugs (NSAIDs). BMJ. 2013;346:f3195. doi: 10.1136/bmj.f3195.
  14. Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26(4):285–91. doi: 10.1016/j.ejim.2015.03.008.
  15. Motola D, Vargiu A, Leone R, Cocci A, Salvo F, Ros B, Meneghelli I, Venegoni M, Cutroneo PM, Vaccheri A, Velo G, Montanaro N. Hepatic adverse drug reactions: a case/non-case study in Italy. Eur J Clin Pharmacol. 2007;63(1):73–9. doi: 10.1007/s00228-006-0222-z.
  16. Pillans PI, Ghiculescu RA, Lampe G, Wilson R, Wong R, Macdonald GA. Severe acute liver injury associated with lumiracoxib. J Gastroenterol Hepatol. 2012;27(6):1102–5. doi: 10.1111/j.1440-1746.2011.07036.x.
  17. Björnsson ES. Drug-induced liver injury: an overview over the most critical compounds. Arch Toxicol. 2015;89(3):327–34. doi: 10.1007/s00204-015-1456-2.
  18. Bessone F. Non-steroidal anti-inflammatory drugs: What is the actual risk of liver damage? World J Gastroenterol. 2010;16(45):5651–61. doi: 10.3748/wjg.v16.i45.5651.
  19. Rubenstein JH, Laine L. The hepatotoxicity of non-steroidal anti-inflammatory drugs. Alimentary Pharmacology and Therapeutics. 2004;20(4):373–80. doi: 10.1111/j.1365-2036.2004.02092.x.
  20. Sriuttha P, Sirichanchuen B, Permsuwan U. Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials. Int J Hepatol. 2018;2018:5253623. doi: 10.1155/2018/5253623.
  21. Gunter BR, Butler KA, Wallace RL, Smith SM, Harirforoosh S. Non-steroidal anti-inflammatory drug-induced cardiovascular adverse events: a meta-analysis. J Clin Pharm Ther. 2017;42(1):27–38. doi: 10.1111/jcpt.12484.
  22. Donati M, Conforti A, Lenti MC, Capuano A, Bortolami O, Motola D, Moretti U, Vannacci A, Rafaniello C, Vaccheri A, Arzenton E, Bonaiuti R, Sportiello L, Leone R; DILI-IT Study Group. Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug-induced liver injury case-control study in Italy. Br J Clin Pharmacol. 2016;82(1):238–48. doi: 10.1111/bcp.12938.
  23. Rostom A, Goldkind L, Laine L. Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients. Clin Gastroenterol Hepatol. 2005;3(5):489–98. doi: 10.1016/S1542-3565(04)00777-3.
  24. Danan G, Benichou C. Causality assessment of adverse reactions to drugs – I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol. 1993;46(11): 1323–30. doi: 10.1016/0895-4356(93)90101-6.
  25. Rockey DC, Seeff LB, Rochon J, Freston J, Chalasani N, Bonacini M, Fontana RJ, Hayashi PH; US Drug-Induced Liver Injury Network. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the Roussel-Uclaf causality assessment method. Hepatology. 2010;51(6):2117–26. doi: 10.1002/hep.23577.
  26. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924–34, 1934.e1–4. doi: 10.1053/j.gastro.2008.09.011.
  27. Fontana RJ, Seeff LB, Andrade RJ, Björnsson E, Day CP, Serrano J, Hoofnagle JH. Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology. 2010;52(2):730–42. doi: 10.1002/hep.23696.
  28. Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB, Hayashi PH, Davern TJ, Navarro V, Reddy R, Talwalkar JA, Stolz A, Gu J, Barnhart H, Hoofnagle JH; Drug-Induced Liver Injury Network (DILIN). Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology. 2014;59(2):661–70. doi: 10.1002/hep.26709.
  29. Guttmacher AE, Collins FS. Realizing the promise of genomics in biomedical research. JAMA. 2005;294(11):1399–402. doi: 10.1001/jama.294.11.1399.
  30. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461(7262):399–401. doi: 10.1038/nature08309.
  31. Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010;139(1):120–9.e18. doi: 10.1053/j.gastro.2010.04.013.
  32. Zucman D, Truchis Pd, Majerholc C, Stegman S, Caillat-Zucman S. Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007;45(1):1–3. doi: 10.1097/QAI.0b013e318046ea31.
  33. Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, Barnhart HX, Bondon-Guitton E, Hayashi PH, Bessone F, Carvajal A, Cascorbi I, Cirulli ET, Chalasani N, Conforti A, Coulthard SA, Daly MJ, Day CP, Dillon JF, Fontana RJ, Grove JI, Hallberg P, Hernández N, Ibáñez L, Kullak-Ublick GA, Laitinen T, Larrey D, Lucena MI, Maitland-van der Zee AH, Martin JH, Molokhia M, Pirmohamed M, Powell EE, Qin S, Serrano J, Stephens C, Stolz A, Wadelius M, Watkins PB, Floratos A, Shen Y, Nelson MR, Urban TJ, Daly AK; International Drug-Induced Liver Injury Consortium, Drug-Induced Liver Injury Network Investigators, and International Serious Adverse Events Consortium. Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study. Gastroenterology. 2017;152(5):1078–89. doi: 10.1053/j.gastro.2016.12.016.
  34. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, Daly MJ, Goldstein DB, John S, Nelson MR, Graham J, Park BK, Dillon JF, Bernal W, Cordell HJ, Pirmohamed M, Aithal GP, Day CP; DILIGEN Study; International SAE Consortium. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009;41(7):816–9. doi: 10.1038/ng.379.
  35. Weiler S, Merz M, Kullak-Ublick GA. Drug-induced liver injury: the dawn of biomarkers? F1000Prime Rep. 2015;7:34. doi: 10.12703/P7-34.
  36. Шабров АВ, Успенский ЮП, ред. Поражения органов пищеварения, индуцированные приемом нестероидных противовоспалительных препаратов. СПб.: ИнформМед; 2013. 284 с.
  37. Zimmerman HJ. Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver. 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. 789 p.
  38. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation [Internet]. Drug Safety; 2009. Available from: https://www.fda.gov/media/116737/download.
  39. Licata A, Calvaruso V, Cappello M, Craxì A, Almasio PL. Clinical course and outcomes of drug-induced liver injury: nimesulide as the first implicated medication. Dig Liver Dis. 2010;42(2): 143–8. doi: 10.1016/j.dld.2009.06.009.
  40. Kwon J, Kim S, Yoo H, Lee E. Nimesulide-induced hepatotoxicity: A systematic review and meta-analysis. PLoS One. 2019;14(1):e0209264. doi: 10.1371/journal.pone.0209264.

Supplementary files

There are no supplementary files to display.


Copyright (c) 2019 Sandler Y.G., Vinnitskaya E.V., Saliev K.G., Khomeriki S.G., Кhaimenova T.Y.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies