Ishihara M, Ohmiya N, Nakamura M, Funasaka K, Miyahara R, Ohno E, Kawashima H, Itoh A, Hirooka Y, Watanabe O, Ando T, Goto H
Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Aliment Pharmacol Ther. 2014 Sep;40(5):538-47. doi: 10.1111/apt.12858. Epub 2014 Jul 4.
The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised.
To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease.
Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays.
Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and 13SNPs were unrelated. The use of meloxicam and CYP2C93SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively).
The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.
非甾体抗炎药（NSAID）所致小肠损伤的病因尚未完全明确。
确定有症状的NSAID所致小肠损伤（包括隔膜病）的危险因素。
在1262例行视频胶囊内镜检查和/或双气囊小肠镜检查的有症状患者中，连续156例患者被证实服用过NSAID。采用Taqman 5'-核酸酶分析法通过等位基因鉴别确定其CYP2C9*2、3和13单核苷酸多态性（SNP）。
在156例NSAID使用者中，31例（20%）被诊断为NSAID所致小肠损伤。多因素分析表明，合并症的存在以及使用昔康类药物（美洛昔康、安吡昔康和氯诺昔康）或双氯芬酸与NSAID所致小肠损伤风险增加相关（校正OR分别为2.97，95%CI：1.05 - 8.41，P = 0.041；校正OR为7.05，95%CI：2.04 - 24.40，P = 0.002）。阿司匹林与非阿司匹林NSAID联合使用比单独使用阿司匹林的损害更大。年龄、性别、质子泵抑制剂的联合使用、NSAID使用指征、NSAID使用时长以及CYP2C92、3和13 SNP均无关联。美洛昔康的使用和CYP2C93 SNP与隔膜病风险增加显著相关（校正OR分别为183.75，95%CI：21.34 - 1582.38；P < 0.0001；校正OR为12.94，95%CI：1.55 - 108.36，P = 0.018）。
特定NSAID的使用以及干扰NSAID代谢的因素可能与小肠损伤相关，尤其是与隔膜病相关。
