Generic placeholder image

The International Journal of Gastroenterology and Hepatology Diseases

Editor-in-Chief

ISSN (Print): 2666-2906
ISSN (Online): 2666-2914

Case Report

Severe DILI in a Patient under Polypharmacy Including Rosuvastatin: Diagnostic Challenges and Lessons from a Case Report Assessed Using the Updated RUCAM Algorithm

Author(s): Luis Díaz-Orozco, Fernando Quiroz-Compean, Jorge Aquino-Matus, Rolf Teschke and Nahum Méndez-Sánchez*

Volume 1, Issue 1, 2022

Published on: 24 June, 2022

Article ID: e250422203997 Pages: 8

DOI: 10.2174/2666290601666220425104715

Price: $65

conference banner
Abstract

Background: Drug-induced liver injury (DILI) and the causative drug in patients under polypharmacy medication represent a challenging diagnosis.

Case Report: A 73 years old multimorbid man receiving polypharmacy, including rosuvastatin among other drugs, presented with high values of alanine aminotransferase (950 U/L) and aspartate aminotransferase (702 U/L), associated with a normal value of alkaline phosphatase (46 U/L), which turned out as DILI due to the hepatocellular injury type with an R-value of 29.8 as calculated from liver test values. Causality for each drug was assessed using the updated RUCAM (Roussel Uclaf Causality Assessment Method) prospectively. Causality for rosuvastatin and diltiazem was highly probable based on a RUCAM score of 9, but no reports of DILI caused by diltiazem were found. In addition, the causality grade for other drugs included in the patient’s medication was “probable” based on a RUCAM score of 6 to 8. The patient experienced a favorable outcome after discontinuation of all medication.

Discussion: The medication history, as well as the prospective and proactive causality evaluation by the updated RUCAM, helped establish the diagnosis of severe DILI by two highly suspected causative drugs, considering also several drugs with a “probable” causality grade in this case. Statins may cause direct damage to the liver, interact with other drugs, and enhance the susceptibility to DILI caused by commonly safe drugs

Conclusion: In this case, the DILI was caused by rosuvastatin as evidenced by a high score in the updated RUCAM, but a large number of comedications may have a co-triggering effect.

Keywords: Drug induced liver injury (DILI), case report, liver injury, roussel uclaf causality assessment method (RUCAM), statins.

Graphical Abstract

[1]
Marrone, G.; Vaccaro, F.G.; Biolato, M.; Miele, L.; Liguori, A.; Araneo, C.; Ponziani, F.R.; Mores, N.; Gasbarrini, A.; Grieco, A. Drug-induced liver injury 2017: The diagnosis is not easy but always to keep in mind. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(1)(Suppl.), 122-134.
[PMID: 28379587]
[2]
Hoofnagle, J.H.; Björnsson, E.S. Drug-induced liver injury - Types and phenotypes. N. Engl. J. Med., 2019, 381(3), 264-273.
[http://dx.doi.org/10.1056/NEJMra1816149] [PMID: 31314970]
[3]
Danan, G.; Teschke, R. RUCAM in drug and herb induced liver injury: The update. Int. J. Mol. Sci., 2015, 17(1), 14.
[http://dx.doi.org/10.3390/ijms17010014] [PMID: 26712744]
[4]
Danan, G.; Bénichou, 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), 1323-1330.
[http://dx.doi.org/10.1016/0895-4356(93)90101-6] [PMID: 8229110]
[5]
Bénichou, C.; Danan, G.; Flahault, A. Causality assessment of adverse reactions to drugs--II. An original model for validation of drug causality assessment methods: Case reports with positive rechallenge. J. Clin. Epidemiol., 1993, 46(11), 1331-1336.
[http://dx.doi.org/10.1016/0895-4356(93)90102-7] [PMID: 8229111]
[6]
Bénichou, C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J. Hepatol., 1990, 11(2), 272-276.
[http://dx.doi.org/10.1016/0168-8278(90)90124-A] [PMID: 2254635]
[7]
NCBI. LiverTox: Clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Rosuvastatin, 2012. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548620/
[8]
Chalasani, N.; Bonkovsky, H.L.; Fontana, R.; Lee, W.; Stolz, A.; Talwalkar, J.; Reddy, K.R.; Watkins, P.B.; Navarro, V.; Barnhart, H.; Gu, J.; Serrano, J. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology, 2015, 148(7), 1340-52.e7.
[http://dx.doi.org/10.1053/j.gastro.2015.03.006] [PMID: 25754159]
[9]
NCBI. LiverTox: Clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Diltiazem, 2012. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547898/
[10]
Björnsson, E.S.; Hoofnagle, J.H. Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports. Hepatology, 2016, 63(2), 590-603.
[http://dx.doi.org/10.1002/hep.28323] [PMID: 26517184]
[11]
Björnsson, E.S. Hepatotoxicity by drugs: The most common implicated agents. Int. J. Mol. Sci., 2016, 17(2), 224.
[http://dx.doi.org/10.3390/ijms17020224] [PMID: 26861310]
[12]
Teschke, R. Top-ranking drugs out of 3312 drug-induced liver injury cases evaluated by the Roussel Uclaf causality assessment method. Expert Opin. Drug Metab. Toxicol., 2018, 14(11), 1169-1187.
[http://dx.doi.org/10.1080/17425255.2018.1539077] [PMID: 30354694]
[13]
Rosenberg, J.; Higley, C.; Lewis, J.H. Selected highlights from the recent literature of newly reported herbal and dietary supplement-induced liver injury. Adv. Res. Gastroenterol. Hepatol., 2020, 15(1)555904
[http://dx.doi.org/10.19080/ARGH.2020.15.555904]
[14]
Traverse, J.H.; Swenson, L.J.; McBride, J.W. Acute hepatic injury after treatment with diltiazem. Am. Heart J., 1994, 127(6), 1636-1639.
[http://dx.doi.org/10.1016/0002-8703(94)90402-2] [PMID: 8197999]
[15]
Teschke, R.; Danan, G. Worldwide use of RUCAM for causality assessment in 81,856 idiosyncratic DILI and 14,029 HILI cases published 1993-mid 2020: A comprehensive analysis. Medicines (Basel), 2020, 7(10), 1-39.
[http://dx.doi.org/10.3390/medicines7100062] [PMID: 33003400]
[16]
Shah, J.; Lingiah, V.; Pyrsopoulos, N.; Galan, M. Acute liver injury in a patient treated with rosuvastatin: A rare adverse effect. Gastroenterol. Res., 2019, 12(5), 263-266.
[http://dx.doi.org/10.14740/gr1212] [PMID: 31636777]
[17]
Shepherd, J.; Hunninghake, D.B.; Stein, E.A.; Kastelein, J.J.P.; Harris, S.; Pears, J.; Hutchinson, H.G. Safety of rosuvastatin. Am. J. Cardiol., 2004, 94(7), 882-888.
[http://dx.doi.org/10.1016/j.amjcard.2004.06.049] [PMID: 15464670]
[18]
Hwang, N.K.; Park, J.S.; Cha, K.S.; Kang, J.S. Hepatotoxicity associated with a short course of rosuvastatin. Chin. Med. J. (Engl.), 2015, 128(12), 1693-1694.
[http://dx.doi.org/10.4103/0366-6999.158382] [PMID: 26063377]
[19]
Naiqiong, W.; Liansheng, W.; Zhanying, H.; Yuanlin, G.; Chenggang, Z.; Ying, G.; Qian, D.; Dongchen, L.; Yanjun, Z.; Jianjun, L. A multicenter and randomized controlled trial of bicyclol in the treatment of statin-induced liver injury. Med. Sci. Monit., 2017, 23, 5760-5766.
[http://dx.doi.org/10.12659/MSM.904090] [PMID: 29200411]
[20]
Famularo, G.; Miele, L.; Minisola, G.; Grieco, A. Liver toxicity of rosuvastatin therapy. World J. Gastroenterol., 2007, 13(8), 1286-1288.
[http://dx.doi.org/10.3748/wjg.v13.i8.1286] [PMID: 17451217]
[21]
Teschke, R. Idiosyncratic DILI: Analysis of 46,266 cases assessed for causality by RUCAM and published from 2014 to early 2019. Front. Pharmacol., 2019, 10, 730.
[http://dx.doi.org/10.3389/fphar.2019.00730] [PMID: 31396080]
[22]
Teschke, R.; Zhu, Y. Paracetamol (acetaminophen), alcohol, and liver injury: Biomarkers, clinical issues, and experimental aspects. SL Pharmacol. Toxicol., 2018, 1, 113.
[23]
Teschke, R. Acetaminophen syn. paracetamol: Acute liver injury and acute on chronic liver failure with case analysis and causality assessment using RUCAM.In: Liver Failure: Acute and Acute on Chronic; Pyrsopoulos, N.T., Ed.; Springer Nature: Cham, Switzerland, 2020.
[http://dx.doi.org/10.1007/978-3-030-50983-5_12]
[24]
Uetrecht, J. Mechanistic studies of idiosyncratic DILI: Clinical implications. Front. Pharmacol., 2019, 10, 837.
[http://dx.doi.org/10.3389/fphar.2019.00837] [PMID: 31402866]
[25]
Teschke, R.; Uetrecht, J. Mechanism of idiosyncratic drug induced liver injury (DILI): Unresolved basic issues. Ann. Transl. Med., 2021, 9(8), 730.
[http://dx.doi.org/10.21037/atm-2020-ubih-05] [PMID: 33987428]
[26]
Lammert, C.; Einarsson, S.; Saha, C.; Niklasson, A.; Bjornsson, E.; Chalasani, N. Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals. Hepatology, 2008, 47(6), 2003-2009.
[http://dx.doi.org/10.1002/hep.22272] [PMID: 18454504]
[27]
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.
[http://dx.doi.org/10.1002/hep.23317] [PMID: 19839004]
[28]
Thakkar, S.; Chen, M.; Hong, H.; Liu, Z.; Fang, H.; Tong, W. Drug-induced liver injury (DILI) classification and its application on human DILI risk prediction.In: Drug-Induced Liver Toxicity; Chen, M.; Will, Y., Eds.; Springer Nature, 2018, pp. 45-59.
[http://dx.doi.org/10.1007/978-1-4939-7677-5_3]
[29]
Chen, M.; Borlak, J.; Tong, W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. Hepatology, 2013, 58(1), 388-396.
[http://dx.doi.org/10.1002/hep.26208] [PMID: 23258593]
[30]
Chen, M.; Suzuki, A.; Borlak, J.; Andrade, R.J.; Lucena, M.I. Drug-induced liver injury: Interactions between drug properties and host factors. J. Hepatol., 2015, 63(2), 503-514.
[http://dx.doi.org/10.1016/j.jhep.2015.04.016] [PMID: 25912521]
[31]
Weng, Z.; Wang, K.; Li, H.; Shi, Q. A comprehensive study of the association between drug hepatotoxicity and daily dose, liver metabolism, and lipophilicity using 975 oral medications. Oncotarget, 2015, 6(19), 17031-17038.
[http://dx.doi.org/10.18632/oncotarget.4400] [PMID: 26220713]
[32]
Björnsson, E.; Jacobsen, E.I.; Kalaitzakis, E. Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketing. J. Hepatol., 2012, 56(2), 374-380.
[http://dx.doi.org/10.1016/j.jhep.2011.07.023] [PMID: 21889469]
[33]
Bader, T. The myth of statin-induced hepatotoxicity. Am. J. Gastroenterol., 2010, 105(5), 978-980.
[http://dx.doi.org/10.1038/ajg.2010.102] [PMID: 20445507]
[34]
Bader, T. Yes! Statins can be given to liver patients. J. Hepatol., 2012, 56(2), 305-307.
[http://dx.doi.org/10.1016/j.jhep.2011.08.016] [PMID: 21963520]
[35]
Schulze, J.; Glass, X. Statin hepatotoxicity and the dilemma of causality in rare hepatic adverse drug reactions. J. Hepatol., 2012, 57(3), 702-703.
[http://dx.doi.org/10.1016/j.jhep.2012.03.010] [PMID: 22510260]
[36]
Bader, T. Reply to: “Statin hepatotoxicity and the dilemma of causality in rare hepatic adverse drug reactions. J. Hepatol., 2012, 57(3), 703-704.
[http://dx.doi.org/10.1016/j.jhep.2012.04.001]
[37]
Teschke, R. Hepatotoxicity associated with statins. Ann. Hepatol., 2012, 11(3), 418-420.
[http://dx.doi.org/10.1016/S1665-2681(19)30943-3] [PMID: 22481466]
[38]
Ke, L.; Lu, C.; Shen, R.; Lu, T.; Ma, B.; Hua, Y. Knowledge mapping of drug-induced liver injury: A scientometric investigation (2010-2019). Front. Pharmacol., 2020, 11, 842.
[http://dx.doi.org/10.3389/fphar.2020.00842] [PMID: 32581801]
[39]
Sarges, P.; Steinberg, J.M.; Lewis, J.H. Drug-Induced liver injury: Highlights from a review of the 2015 literature. Drug Saf., 2016, 39(9), 801-821.
[http://dx.doi.org/10.1007/s40264-016-0427-8] [PMID: 27142208]
[40]
Shahbaz, O.; Mahajan, S.; Lewis, J.H. Highlights of drug - and herb- induced liver injury in the literature from 2016: How best to translate new information into clinical practice? Expert Opin. Drug Metab. Toxicol., 2017, 13(9), 935-951.
[http://dx.doi.org/10.1080/17425255.2017.1362391] [PMID: 28772086]
[41]
Teschke, R.; Schulze, J.; Eickhoff, A.; Danan, G. Drug induced liver injury: Can biomarkers assist RUCAM in causality assessment? Int. J. Mol. Sci., 2017, 18(4), 803.
[http://dx.doi.org/10.3390/ijms18040803] [PMID: 28398242]
[42]
Teschke, R.; Eickhoff, A.; Brown, A.C.; Neuman, M.G.; Schulze, J. Diagnostic biomarkers in liver injury by drugs, herbs, and alcohol: Tricky dilemma after EMA correctly and officially retracted letter of support. Int. J. Mol. Sci., 2019, 21(1), 212.
[http://dx.doi.org/10.3390/ijms21010212] [PMID: 31892250]
[43]
Teschke, R.; Andrade, R.J. Drug-induced liver injury: Expanding our knowledge by enlarging population analysis with prospective and scoring causality assessment. Gastroenterology, 2015, 148(7), 1271-1273.
[http://dx.doi.org/10.1053/j.gastro.2015.04.027] [PMID: 25921378]
[44]
Teschke, R.; Andrade, R.J. Drug, herb, and dietary supplement hepatotoxicity. Int. J. Mol. Sci., 2016, 17(9), 1488.
[http://dx.doi.org/10.3390/ijms17091488] [PMID: 27608014]
[45]
Teschke, R.; Danan, G. Drug induced liver injury with analysis of alternative causes as confounding variables. Br. J. Clin. Pharmacol., 2018, 84(7), 1467-1477.
[http://dx.doi.org/10.1111/bcp.13593] [PMID: 29607530]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy