Drug-Induced Liver Injury Associated with the Use of Everolimus in a Liver Transplant Patient

Abstract

Drug-induced liver injury (DILI) has not been previously reported as a complication of treatment with everolimus. A 56-year-old Caucasian male liver transplant recipient developed DILI after receiving everolimus. Elevations in transaminase levels occurred within a week of starting everolimus and an upward trend in the transaminase levels continued with supporting histopathologic changes confirmed by liver biopsy. Within one week of drug discontinuation, his liver enzymes normalized to baseline. This report includes a brief review of the pharmacokinetic properties of everolimus, a review of the relevant literature, and an analysis using the RUCAM and Naranjo algorithms.

Worldwide Use of RUCAM for Causality Assessment in 81,856 Idiosyncratic DILI and 14,029 HILI Cases Published 1993–Mid 2020: A Comprehensive Analysis

“…Among these were a broad range of departments, which in most cases include departments of Hepatology and Gastroenterology, ensuring careful clinical evaluation of patients with suspected DILI and associated causality assessment for the offending drug(s). To a lesser degree, other departments were contributors, for instance, Pharmacology, or Pharmacy and Pharmaceutical sciences [ 170 ].…”

Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians

“…Latency varies between one week for erlotinib [49-51], sorafenib [52], regorafenib [53], and more than six months for gefitinib [54,55], dasatinib [56], ibrutinib [57], imatinib [58,59], nindetanib [60], and sunitinib [61]. DILI related to MKI use is hepatocellular (elevated aminotransferase levels with either no or a small increase in alkaline phosphatase levels), but cases of mixed DILI (elevation of both aminotransferase and alkaline phosphatase levels) have been published for dasatinib [56], imatinib [62], pazopanib [63], sorafenib [52], everolimus [64], and vemurafenib [65]. Elevated bilirubin levels meeting Hy's law criteria (hepatocellular type injury seen concurrently with bilirubin > 2X ULN) has been reported for crizotinib (2 cases -death) [35,66] [61,81], and the vemurafenib-ipilimumab association (2 casesrecovery) [48] (Table 2).…”

Drug‐Induced Liver Injury After Liver Transplantation

“…Apart from these series, isolated cases of DILI have been reported in LT recipients. Patel et al (14) reported a case of an LT patient with liver toxicity due to everolimus, and liver toxicity due to tacrolimus has been described in LT recipients, especially in children, as well as in solid organ transplantation, which is different from liver. (15)…”

“…(49) However, series of transplant patients treated with everolimus show no relevant liver toxicity, (50) except for an isolated patient already mentioned. (14) A patient series of sirolimus hepatotoxicity has been reported in LT patients with active HCV infection. (51) Liver biopsy findings included sinusoidal congestion and eosinophilia, with liver enzymes returning to normal levels after drug withdrawal.…”