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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.

Residual confounding by a matching variable and different definitions of the exposure time window explained differences in results. In case-control studies of drug use and fracture risk, broad matching criteria for age should be avoided and the selection of the time-window for exposure should be carefully considered.

Scientists and regulators in Europe and the United States continue to seek methods and strategies to improve knowledge on rational use of medicines for pregnant and breastfeeding populations, an important subset of women's health. Regulatory agencies have made strides toward improvement, but much more is needed. Recognizing the importance of international collaboration, we have begun to consider how to address these important public health issues more globally. The health of the child begins with the health of the mother.

The simultaneous start of ABC and NVP in first-line antiretroviral regimens should be avoided because of a high (20%) incidence of HSR. Short-term therapy with prednisolone did not prevent HSR in patients using ABC with or without NVP.