Topical Diclofenac-Induced Hepatotoxicity

Abstract

The hepatotoxic potential of diclofenac, a commonly used non-steroidal anti-inflammatory agent, is well established in literature. However, cases of diclofenac-induced liver disease have occurred almost exclusively with the oral formulation of this medication. We report the case of an elderly man with Paget’s disease and osteoarthritis who developed acute hepatotoxicity, as evidenced by laboratory diagnostics, four months after use of topical diclofenac 1% gel. Once diclofenac gel was discontinued, repeat blood work three weeks after discharge demonstrated return of liver function tests to baseline. Given the temporal relationship between the initiation and escalation of topical diclofenac and the changes in liver function tests, the likelihood of diclofenac-induced liver injury was deemed possible using a well-recognized causality assessment tool. Further research on topically administered non-steroidal anti-inflammatory agents is needed to identify monitoring intervals for early detection and avoidance of adverse effects in patients using topical diclofenac.

The Phytochemical Profiling, In Vitro Antioxidant, and Hepatoprotective Activity of Prenanthes purpurea L. and Caffeoylquinic Acids in Diclofenac-Induced Hepatotoxicity on HEP-G2 Cells

“…A potential role in idiosyncratic hepatotoxicity is played by the generation of reactive quinone imine metabolites and ROS in the first phase of diclofenac’s metabolism and the subsequent impairment of mitochondrial function [ 8 , 9 , 10 , 11 ]. Undergoing drug glucuronidation in the conjugation phase facilitates the formation of glucuronide–protein adducts with neoantigenic properties, thus inducing an autoimmune response culminating in hepatocyte death [ 9 , 12 , 13 ]. In light of these findings, inducing the intrinsic antioxidant defense system of hepatocytes has been the most lucrative strategy for shielding the organ from oxidative stress damage, which is recognized as a primary pathogenetic factor in DILI, as well as other liver diseases.…”