Clinical course and outcomes of drug-induced liver injury: Nimesulide as the first implicated medication

Abstract

a b s t r a c tBackground and aims: Drug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute liver failure. The aim of our study was to evaluate the number of DILI cases admitted to our Unit and to identify the drugs responsible. Thus, we reviewed all clinical records of patients with DILI admitted to our Unit from 1996 to 2006. Patients and methods: A database was constructed, reporting demographic, clinical features at onset, laboratory results, suspected drugs and follow-up. Liver damage was defined as hepatocellular, cholestatic or mixed, according to clinical and laboratory data. Results: Forty-six patients were admitted with a diagnosis of DILI. Presentation was jaundice in 22 patients and hepatic failure in 3 (all attributed to nimesulide). Liver damage was of a cytolytic pattern in 19 cases (41%), cholestatic in 15 (33%) and mixed in 12 (26%). Jaundice was found to be higher in nimesulideinduced liver damage compared to other drugs (p = 0.007). Three out of 14 patients with nimesulideinduced DILI developed encephalopathy and/or ascites. Time of recovery in the nimesulide group was significantly lower than DILI from other drugs (p < 0.001). Conclusion: Non-steroidal anti-inflammatory drugs, psychotropic drugs and antimicrobials are the most common causes of DILI. Nimesulide-induced DILI is usually reversible upon discontinuation of the drug, but occasionally progresses to liver failure.

Hyaluronic acid&ndash;nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo

“…64 The toxicity of nimesulide to hepatocytes has been previously observed 65,66 which is attributed mainly to the nitro group in its structure. 67 After reduction, NiNH 2 exhibits reduced toxicity than nimesulide in hepatocytes because nimesulide is a powerful protonophoretic uncoupler and NAD(P)H oxidant.…”

Adverse drug reactions and organ damage: The liver

“…Nimesulide was the most commonly implicated NSAID, responsible for hepatocellular DILI in women and the cholestatic/mixed type in men [30,36]. Among antibiotics, we reported the impact of AMCinduced [37] and fluoroquinolone-induced [38] liver injury.…”

Autoimmune hepatitis unmasked by nimesulide

“…Among these, NSAIDs are among the drugs most responsible for DILI 10 18–22. More specifically, nimesulide's safety was reviewed in 2007 and again in 2010 by the European Medicines Agency (EMEA), because of concerns with liver injury 18 23. The Agency's Committee for Medicinal Products for Human Use concluded that nimesulide was associated with an increased risk of liver toxicity compared with other anti-inflammatory treatments and that systemic nimesulide should not be used for long-term treatment 24…”