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Abstract

Drug-induced liver injury (DILI) remains a challenge in clinical practice and is still a diagnosis of exclusion. Although it has a low incidence amongst the general population, DILI accounts for most cases of acute liver failure with a fatality rate of up to 50%.

Case : A 56-year-old male was transferred to the Intensive Care Unit (ICU) with fever and severe thrombocytopenia,17,000. The patient was diagnosed with suspected sepsis and potential disseminated intravascular coagulation (DIC). Consequently, the patient was put on cefepime, administered 2g three times daily for over 30 minutes, and combined with amikacin at 1500 mg to be infused over 60 minutes. We adjusted the pharmacokinetics of cefepime on day three by changing the administration time from a 30-minute infusion to a 4-hour infusion. We discontinued amikacin on day five and continued cefepime. On day seven, the patient looked jaundiced at the sclera and skin. Upon drug chart review, we discovered that cefepime was associated with jaundice, according to post-marketing data. We ceased cefepime and ordered a Liver Function Test (LFT). The LFT results showed total bilirubin of 12 mg/dL and alkaline phosphatase nearly 1.5 times the normal level. Using the RUCAM score, the cholestatic injury was classified as mixed type with an R score of 4. Three days after discontinuing cefepime, serum total bilirubin and direct bilirubin levels decreased to 10.2 and 6.8 mg/dL, respectively. By day 25, the total bilirubin and alkaline phosphatase levels returned to near normal.

References

ndrade, R. J., Aithal, G. P., Björnsson, E. S., Kaplowitz, N., Kullak-Ublick, G. A., Larrey, D., & Karlsen, T. H. (2019). EASL clinical practice guidelines: Drug-induced liver injury. Journal of Hepatology, 70(6), 1222–1261. https://doi.org/10.1016/j.jhep.2019.02.014 

Björnsson, E. S., & Hoofnagle, J. H. (2015). Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports. Hepatology, 63(2), 590–603. https://doi.org/10.1002/hep.28323 

Björnsson, H. K., Snorrason, B. L., & Björnsson, E. S. (2025). DILI is an important cause of Hepatocellular and mixed liver Injury—A nationwide prospective study on elevated liver enzymes. Liver International, 45(10), e70327–e70327. https://doi.org/10.1111/liv.70327 

Chalasani, N., & Björnsson, E. (2010). Risk factors for Idiosyncratic Drug-Induced liver injury. Gastroenterology, 138(7), 2246–2259. https://doi.org/10.1053/j.gastro.2010.04.001 

Drugbank Online. (2007). In go.drugbank.com. https://go.drugbank.com/drugs/DB01413 

Hosack, T., Djamil Damry, & Biswas, S. (2023). Drug-induced liver injury: A comprehensive review. Sage Journals, 16, 175628482311634–175628482311634. https://doi.org/10.1177/17562848231163410 

Kang, Y., et al. (2020). Evaluation of Drug-Induced liver injury developed during hospitalization using electronic health record (EHR)-based algorithm. Allergy, Asthma & Immunology Research, 12(3), 430–442. https://doi.org/10.4168/aair.2020.12.3.430 

Katarey, D., Verma, S. (2016). Drug-induced liver injury. Clinical Medicine, 16 (Suppl_6), s104-s109. https://doi.org/10.7861/clinmedicine.16-6-s104 

Kullak-Ublick, G. A. (2013). Drug-Induced cholestatic liver Disease. Madame Curie Bioscience Database - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK6102/ 

Lammert, C., Bjornsson, E., Niklasson, A., & Chalasani, N. (2009). Oral medications with significant hepatic metabolism at higher risk for hepatic adverse events. Hepatology, 51(2), 615–620. https://doi.org/10.1002/hep.23317 

LiverTox: Clinical and research information on Drug-Induced liver injury [internet]. (2012). In PubMed. https://pubmed.ncbi.nlm.nih.gov/31643176/ 

Lucena, M. I., Kaplowitz, N., Hallal, H., Castiella, A., García-Bengoechea, M., Otazua, P., Berenguer, M., Fernandez, M. C., Planas, R., & Andrade, R. J. (2011). Recurrent drug-induced liver injury (DILI) with different drugs in the spanish registry: The dilemma of the relationship to autoimmune hepatitis. Journal of Hepatology, 55(4), 820–827. https://doi.org/10.1016/j.jhep.2010.12.041 

Malhotra, K., Fazylov, R., & Friedman-Jakubovics, M. (2021). A Case-Report of Drug-Induced mixed liver injury resulting from Cefepime exposure. Journal of Pharmacy Practice, 36(1), 164–167. https://doi.org/10.1177/08971900211015046 

Ortega, A. J., S. Reshad Ghafouri, Vu, L., Edwards, B., & Nickel, N. (2021). Cefepime-Induced encephalopathy in a High-Risk patient with renal insufficiency and cirrhosis. Cureus. https://doi.org/10.7759/cureus.18767 

Perez, M.-J., & Briz, O. (2009). Bile-acid-induced cell injury and protection. World Journal of Gastroenterology, 15(14), 1677–1689. https://doi.org/10.3748/wjg.15.1677 

Stephens, C. et.al (2021). Comprehensive analysis and insights gained from long-term experience of the spanish DILI registry. Journal of Hepatology, 75(1), 86–97. https://doi.org/10.1016/j.jhep.2021.01.029

Sundaram, V., & Björnsson, E. S. (2017). Drug-induced cholestasis. Hepatology Communications, 1(8), 726–735. https://doi.org/10.1002/hep4.1088 

Yao-Kuang Wu, P.-F. L., & Hsin Yi Chen. (2019). A rare case of cefepime-induced cholestatic liver injury. Semantic Scholar. https://www.semanticscholar.org/paper/A-rare-case-of-cefepime-induced-cholestatic-liver-Liao-Wu/25befa06d31a29dcbdd878ee30e01413f4c3cc34 

UpToDate Inc. (2024). Cefepime [Drug information]. Lexi-Drugs, UpToDate Lexidrug. October 10, 2024, from http://online.lexi.com 

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