Trial and error: investigational drug induced liver injury, a case series report.

This is a case report series of four patients who exhibited signs and symptoms of acute liver dysfunction during participation in a Phase I trial of a novel non-steroidal anti-inflammatory drug (NSAID) designed to inhibit microsomal prostaglandin synthase 1 (MPGES1). Within one month of trial initiation, all four patients presented with epigastric pain, fatigue, nausea, and increasing liver function tests (LFTs). Two out of four patients required hospitalization, underwent liver biopsies, and were treated with N-acetylcysteine. The remaining two patients were managed as outpatients. Liver biopsies were consistent with drug induced liver injury (DILI). Within three months of stopping the investigational drug, symptoms subsided and LFTs normalized in all patients. This case report series signifies the importance of NSAIDs and novel drug agents in general as potentially hepatotoxic substances, the need for a high level of suspicion of DILI when considering possible etiologies of acute liver failure, and the need for prompt withdrawal of the causative agent in management of patients presenting with DILI.