Transplantation for Acute Liver Failure in Patients Exposed to NSAIDs or Paracetamol (Acetaminophen)

Abstract

BackgroundMost NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain.ObjectivesThe aim of the study was to estimate population event rates for NSAID-associated ALFTMethodsThis was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY).ResultsIn the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose).Event rates per MTY were 1.59 (95 % CI 1.1–2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2–3.9) for ibuprofen, 1.9 (95 % CI 0.8–3.7) for nimesulide, 1.6 (95 % CI 0.6–3.4) for diclofenac and 1.6 (95 % CI 0.3–4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6–4.1) without overdoses and 7.8 (95 % CI 6.8–9.0) including overdoses.ConclusionsALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-012-0013-7) contains supplementary material, which is available to authorized users.

Acute pain: a multifaceted challenge – the role of nimesulide

“…The multinational SALT study 7 evaluated the population event rates for NSAID-associated acute liver failure leading to liver transplantation. This non-interventional, retrospective study was agreed with the European Medicines Agency (EMA) to provide estimates of the rates of acute liver failure leading to registration for liver transplantation in patients who had been exposed to NSAIDs or paracetamol within 30 days before first clinical symptoms of liver injury.…”

“…Liver damage is a rare adverse event that has already been known for the entire class of NSAIDs; recent pharmaco-epidemiological studies concluded that safety concerns with nimesulide are no higher than with other NSAIDs, and that the risk/benefit profile for hepatic side effects is comparable with other drugs of its class [5][6][7] . The purpose of this commentary is to provide current evidence on the efficacy and in particular safety of nimesulide in the treatment of a variety of clinical conditions characterized by the presence of acute inflammatory pain.…”

Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions

“…Adverse event rates in single-dose trials are no different from placebo with ibuprofen or paracetamol (Toms et al, 2008;Derry et al, 2009), although a large randomized trial for common pain in general practice indicated a lower incidence of gastrointestinal adverse events for ibuprofen compared with paracetamol (Moore et al, 2003). There is no evidence of any cardiovascular risk with ibuprofen used at non-prescription doses (Moore et al, 2014a), but non-overdose paracetamol-exposed liver failure was twice as common than NSAIDexposed liver failure (Gulmez et al, 2013). Cancer pain and paediatric pain will most often be treated with prescribed analgesics.…”

Attenuation of copaiba oil in hepatic damage in rats

“…Acute liver failure (ALF) is characterized as a syndrome with sudden progression and severe hepatocellular dysfunction 1 .…”