Pharmacovigilance of drug-induced liver injury in search for frequency and outcomes in a Brazilian hospital: Challenges in future cases using a robust causality assessment method such as the updated RUCAM
DOI:
https://doi.org/10.12970/2308-8044.2020.08.08Keywords:
Chemical and drug-induced liver injury, Pharmacovigilance, Pharmacoepidemiology, Pharmacy service hospital, Drug-related side effects and adverse reactions, Adverse drug reaction reporting systems, Roussel Uclaf Causality Assessment Method.Abstract
Background and Aims: Drug-induced liver injury (DILI) is the main cause of drug withdrawal from the market. It is an adverse reaction that even when it was not observed in clinical trials, it can be subsequently detected when marketed. This study aimed to identify DILI frequency and outcomes evaluating various pharmacovigilance strategies. Methods: A retrospective study was done evaluating strategies for screening DILI. The first strategy was based on gathering data from the ICDs related to toxic hepatitis K71 and acute liver failure K72 for 10 years. The second strategy was to gather 5 years of retrospective pharmacovigilance data. We excluded other hepatobiliary disorders as confounders. Results: For K71 we identified 24 DILI cases from a total of 36, with one death. For K72, we found 15 DILI cases out of 300, with 8 deaths. Pharmacovigilance had 5,203 reports, 17 cases related to the hepatic system with nine DILI cases identified. DILI is estimated to occur around 21/100,000 patients but in reality, this frequency probably may be higher due to underreporting and underdiagnosing. There was no report of causality algorithm use. Conclusions: The search through K71 was more sensitive, K72 detected the most severe cases, and the pharmacovigilance were the least severe. None DILI case identified by the ICD was reported in the pharmacovigilance and vice-versa, which gives evidence to the lack of interaction between the services and health professionals about adverse drug reactions. There was no record of the use of diagnostic algorithms to assess causality like the updated RUCAM (Roussel Uclaf Causality Assessment Method), a particular challenge for future DILI cases.References
Hoffman KB, Dimbil M, Kyle RF, et al. A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes. J Manag Care Spec Pharm 2015; 21: 1134-43c. https://doi.org/10.18553/jmcp.2015.21.12.1134
Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329: 15-9. https://doi.org/10.1136/bmj.329.7456.15
Hopf Y, Watson M, Williams D. Adverse-drug-reaction related admissions to a hospital in Scotland. Pharm World Sci 2008; 30: 854-62. https://doi.org/10.1007/s11096-008-9240-5
van der Hooft CS, Dieleman JP, Siemes C, et al. Adverse drug reaction-related hospitalisations: a population-based cohort study. Pharmacoepidemiol Drug Saf 2008; 17: 365- 71. https://doi.org/10.1002/pds.1565
Alexopoulou A, Dourakis SP, Mantzoukis D, et al. Adverse drug reactions as a cause of hospital admissions: a 6-month experience in a single center in Greece. Eur J Intern Med 2008; 19: 505-10. https://doi.org/10.1016/j.ejim.2007.06.030
Pedrós C, Formiga F, Corbella X, Arnau JM. Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features. Eur J Clin Pharmacol 2016; 72: 219-26. https://doi.org/10.1007/s00228-015-1974-0
Miguel A, Azevedo LF, Araujo M, Pereira AC. Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2012; 21: 1139-54. https://doi.org/10.1002/pds.3309
Carrasco-Garrido P, de Andres LA, Barrera VH, de Miguel GA, Jimenez-Garcia R. Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006). BMC Health Serv Res 2010; 10: 287. https://doi.org/10.1186/1472-6963-10-287
Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother 2008; 42: 1017-25. https://doi.org/10.1345/aph.1L037
Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279: 1200-5. https://doi.org/10.1001/jama.279.15.1200
Ernst FR, Grizzle AJ. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc 2001; 41:192-9. https://doi.org/10.1016/s1086-5802(16)31229-3
Bootman JL, Harrison DL, Cox E. The health care cost of drug-related morbidity and mortality in nursing facilities. Arch Intern Med 1997; 157: 2089-96.
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: 213-20. https://doi.org/10.1002/pds.1207
Stevens JL, Baker TK. The future of drug safety testing: expanding the view and narrowing the focus. Drug Discov Today 2009; 14: 162-7. https://doi.org/10.1016/j.drudis.2008.11.009
Olivier P, Montastruc JL. The nature of the scientific evidence leading to drug withdrawals for pharmacovigilance reasons in France. Pharmacoepidemiol Drug Saf 2006; 15: 808-12. https://doi.org/10.1002/pds.1248
Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med 2016; 14: 10. https://doi.org/10.1186/s12916-019-1294-9
Sgro C, Clinard F, Ouazir K, et al. Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology 2002; 36: 451-5. https://doi.org/10.1053/jhep.2002.34857
Bjornsson ES, Bergmann OM, Bjornsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25, 25. e1-3; quiz e19-20. https://doi.org/10.1053/j.gastro.2013.02.006
Mugusi S, Ngaimisi E, Janabi M, et al. Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz-based HAART with or without tuberculosis coinfection in Tanzania. PloS one 2012; 7: e40180. https://doi.org/10.1371/journal.pone.0040180
Yimer G, Gry M, Amogne W, et al. Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients. PloS One 2014; 9: e94271. https://doi.org/10.1371/journal.pone.0094271
Watkins PB, Seligman PJ, Pears JS, Avigan MI, Senior JR. Using controlled clinical trials to learn more about acute druginduced liver injury. Hepatology 2008; 48: 1680-9. https://doi.org/10.1002/hep.22633
Ou P, Chen Y, Li B, et al. Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital. Springer Plus 2015; 4: 802. https://doi.org/10.1186/s40064-015-1600-8
Meier Y, Cavallaro M, Roos M, et al. Incidence of druginduced liver injury in medical inpatients. Eur J Clin Pharmacol 2005; 61: 135-43. https://doi.org/10.1007/s00228-004-0888-z
Woo HJ, Kim HY, Choi ES, et al. Drug-induced liver injury: A 2-year retrospective study of 1169 hospitalized patients in a single medical center. Phytomedicine 2015; 22: 1201-5. https://doi.org/10.1016/j.phymed.2015.10.002
Chen SS, Yu KK, Huang C, et al. The characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital: A retrospective cohort study. Medicine 2016; 95: e4683. https://doi.org/10.1097/md.0000000000004683
Jinjuvadia K, Kwan W, Fontana RJ. Searching for a needle in a haystack: use of ICD-9-CM codes in drug-induced liver injury. Am J Gastroenterol 2007; 102: 2437-43. https://doi.org/10.1111/j.1572-0241.2007.01456.x
Danan G, Teschke R. RUCAM in drug and herb induced liver injury: The update. Int J Mol Sci 2016; 17(1): 14. https://doi.org/10.3390/ijms17010014
Andrade RJ, Lucena MI, Fernandez MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to theSpanish registry over a 10-year period. Gastroenterology 2005; 129: 512-21. https://doi.org/10.1053/j.gastro.2005.05.006
Bessone F, Hernandez N, Lucena MI, Andrade RJ. The Latin American DILI Registry Experience: A Successful Ongoing Collaborative Strategic Initiative. Int J Mol Sci 2016; 17: 313. https://doi.org/10.3390/ijms17030313
Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with druginduced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol 2010; 105: 2396-404. https://doi.org/10.1038/ajg.2010.287
Baekdal M, Ytting H, Skalshøi Kjær M. Drug-induced liver injury: a cohort study on patients referred to the Danish transplant center over a five-year period. Scand J Gastroenterol 2017; 52: 450-4. https://doi.org/10.1080/00365521.2016.1267790
Larson AM, Polson J, Fontana RJ, et al. Acetaminopheninduced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005; 42: 1364- 72. https://doi.org/10.1002/hep.20948
Goldberg DS, Forde KA, Carbonari DM, et al. Populationrepresentative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system. Gastroenterology 2015; 148: 1353-61. e3. https://doi.org/10.1053/j.gastro.2015.02.050
Bjornsson ES. Hepatotoxicity by Drugs: The Most Common Implicated Agents. Int J Mol Sci 2016; 17: 224. https://doi.org/10.3390/ijms17020224
Chalasani N, Bonkovsky HL, Fontana R, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. e7. https://doi.org/10.1053/j.gastro.2015.03.006
Bareille MP, Montastruc JL, Lapeyre-Mestre M. [Liver damage and nonsteroidal anti-inflammatory drugs: case noncase study in the French Pharmacovigilance Database]. Therapie 2001; 56: 51-5. https://doi.org/10.1053/j.gastro.2015.03.006
Barritt AS, Lee J, Hayashi PH. Detective Work in Druginduced Liver Injury: Sometimes It's All about Interviewing the Right Witness. Clin Gastroenterol Hepatol 2010; 8: 635- 7. https://doi.org/10.1016/j.cgh.2010.03.020
Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. https://doi.org/10.1002/hep.23937
Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 2000; 283: 74-80. https://doi.org/10.1001/jama.283.1.74
