Gulmez Sinem Ezgi, Unal Ulku Sur, Lassalle Régis, Chartier Anaïs, Grolleau Adeline, Moore Nicholas
Bordeaux PharmacoEpi, INSERM CIC1401, Université de Bordeaux, Bordeaux, France.
Tekirdağ Çerkezköy Tepe Emlak Family Medicine Centre,, Cumhuriyet District Tepe Emlak Part 2, Çerkezköy-Tekirdağ, Turkey.
Pharmacoepidemiol Drug Saf. 2018 Nov;27(11):1174-1181. doi: 10.1002/pds.4640. Epub 2018 Aug 16.
The SALT study found similar per-user risks of acute liver failure (ALF) leading to transplantation (ALFT) between NSAIDs and a threefold higher risk in nonoverdose paracetamol (NOP) users. The objective of EPIHAM was to identify the risks of hospital admission for acute liver injury (ALI) associated with NSAIDs and NOP.
Case-population study in the 1/97 sample of the French population claims database. Acute liver injury was identified from hospital discharge summaries, from 2009 to 2013. Exposure for cases was dispensing of NSAID or NOP resulting in exposure within 30 days before admission. Population exposure was the number of patients using the drugs over the study timeframe and total number of DDD dispensed.
Of 63 cases of ALI, 13 had been exposed to NSAIDs and 24 to NOP. Events per million DDD (95% CI) ranged from 0.46 (0.09-1.34) (ketoprofen) to 1.43 (0.04-7.97) (diclofenac combinations), 0.43 (0.23-0.73) all NSAIDs combined, 0.58 (0.37-0.86) for NOP. There was no association with average duration of treatment. Per patient risk ranged from 19.5 (5.31-49.9) (ibuprofen) per million users to 37.2 (19.8-63.6) all NSAIDs combined, 58.0 (37.2-86.3) for NOP. There was a linear relationship between average treatment duration and per-user risk (R = 0.51, P < .05 for NSAIDs, R = 0.97, P < .01 for NOP).
Risk of hospital admission for ALI with NSAIDs and NOP was similar and indicative of a dose and duration-related effect (pharmacological) effect. Acute liver injury rates were not predictive of ALFT risk.
SALT研究发现，非甾体抗炎药（NSAIDs）导致急性肝衰竭（ALF）并进而需要肝移植（ALFT）的个体风险相似，而未过量服用对乙酰氨基酚（NOP）的使用者发生这种情况的风险则高出三倍。EPIHAM研究的目的是确定与NSAIDs和NOP相关的急性肝损伤（ALI）住院风险。
在法国人群索赔数据库的1/97样本中进行病例群体研究。通过2009年至2013年的医院出院总结来确定急性肝损伤。病例的暴露情况是在入院前30天内使用NSAIDs或NOP。群体暴露是指在研究时间段内使用这些药物的患者数量以及药物的限定日剂量（DDD）总数。
在63例ALI病例中，13例曾暴露于NSAIDs，24例曾暴露于NOP。每百万DDD的事件发生率（95%置信区间）范围为0.46（0.09 - 1.34）（酮洛芬）至1.43（0.04 - 7.97）（双氯芬酸复方制剂），所有NSAIDs联合使用时为0.43（0.23 - 0.73），NOP为0.58（0.37 - 0.86）。与平均治疗持续时间无关。每位患者的风险范围为每百万使用者中19.5（5.31 - 49.9）（布洛芬）至所有NSAIDs联合使用时的37.2（19.8 - 63.6），NOP为58.0（37.2 - 86.3）。平均治疗持续时间与每位使用者的风险之间存在线性关系（NSAIDs的R = 0.51，P <.05；NOP的R = 0.97，P <.01）。
NSAIDs和NOP导致ALI住院的风险相似，表明存在剂量和持续时间相关的效应（药理学效应）。急性肝损伤率不能预测ALFT风险。
