非甾体类抗炎药致小肠黏膜损伤危险因素的系统评价
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摘要
目的 系统评价非甾体类抗炎药(NSAIDs)致小肠黏膜损伤的危险因素。方法 计算机检索WanFang Data、CNKI、Web of Science、EBSCO、PubMed和The Cochrane Library数据库,搜集关于NSAIDs致小肠黏膜损伤危险因素的病例-对照研究,检索时限均从建库截至2018年5月1日。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.2和STATA 12.0软件进行系统评价。结果 共纳入6个病例-对照研究,其中病例组小肠黏膜损伤阳性265例,对照组小肠黏膜损伤阴性301例。Meta分析结果显示,PPI应用[OR=1.59,95%CI(1.07,2.35),P=0.02]是NSAIDs致小肠黏膜损伤的独立危险因素;同时,有骨关节炎[OR=2.44,95%CI(1.11,5.36),P=0.03]或类风湿性关节炎[OR=3.04,95%CI(1.31,7.03),P=0.01]患者应用NSAIDs致小肠黏膜损伤风险更高;而性别、年龄、吸烟史、饮酒史、H_2RA及瑞巴派特用药史、合并心血管疾病及脑血管疾病与小肠黏膜损伤无关,差异均无统计学意义。结论 PPI使用是NSAIDs致小肠黏膜损伤的独立危险因素,但仍需更多大样本、高质量研究来进一步证实PPI对小肠黏膜损伤的影响大小。
Objectives To systematically review the risk factors for intestinal injury induced by non-steroidal anti-inflammatory drugs(NSAIDs). Methods We comprehensively searched WanFang Data, CNKI, Web of Science,EBSCO, PubMed and The Cochrane Library databases to collect studies on risk factors of NSAIDs-induced intestinal injury. Two reviewers independently screened literature, extracted data and assessed risk of bias, and then, meta-analysis was performed by using RevMan 5.2 and STATA 12.0 software. Results A total of 6 case-control studies were included,in which 265 patients were in the case group and 301 patients in the control group. The results of meta-analysis showed that PPI was an independent risk factor for NSAIDs-induced intestinal injury(OR=1.59, 95%CI 1.07 to 2.35, P=0.02). In addition, patients with osteoarthritis(OR=2.44, 95% CI 1.11 to 5.36, P=0.03) or rheumatoid arthritis(OR=3.04, 95% CI1.31 to 7.03, P=0.01) was associated with intestinal mucosal injury induced by NSAIDs. Gender, age, smoking history,drinking history, H_2RA and rebamipide medication history, cardiovascular disease and cerebrovascular disease were not associated with intestinal injury. Conclusions PPI is an independent risk factor for NSAIDs-induced intestinal injury.However, studies with high-quality, larger sample size are required to further verify that PPI increases the prevalence of intestinal injury.
Objectives To systematically review the risk factors for intestinal injury induced by non-steroidal anti-inflammatory drugs(NSAIDs). Methods We comprehensively searched WanFang Data, CNKI, Web of Science,EBSCO, PubMed and The Cochrane Library databases to collect studies on risk factors of NSAIDs-induced intestinal injury. Two reviewers independently screened literature, extracted data and assessed risk of bias, and then, meta-analysis was performed by using RevMan 5.2 and STATA 12.0 software. Results A total of 6 case-control studies were included,in which 265 patients were in the case group and 301 patients in the control group. The results of meta-analysis showed that PPI was an independent risk factor for NSAIDs-induced intestinal injury(OR=1.59, 95%CI 1.07 to 2.35, P=0.02). In addition, patients with osteoarthritis(OR=2.44, 95% CI 1.11 to 5.36, P=0.03) or rheumatoid arthritis(OR=3.04, 95% CI1.31 to 7.03, P=0.01) was associated with intestinal mucosal injury induced by NSAIDs. Gender, age, smoking history,drinking history, H_2RA and rebamipide medication history, cardiovascular disease and cerebrovascular disease were not associated with intestinal injury. Conclusions PPI is an independent risk factor for NSAIDs-induced intestinal injury.However, studies with high-quality, larger sample size are required to further verify that PPI increases the prevalence of intestinal injury.
引文
1 Shiotani A, Kamada T, Haruma K. Low-dose aspirin-induced gastrointestinal diseases:past, present, and future. J Gastroenterol,2008, 43(8):581-588.
2 Matsumoto T, Kudo T, Esaki M, et al. Prevalence of non-steroidalanti-inflammatory drug-induced enteropathy determined by double-balloon endoscopy:a Japanese multicenter study. Scand J Gastroenterol, 2008, 43(4):490-496.
3 Yamada A, Niikura R, Maki K, et al. Proton pump inhibitor therapy did not increase the prevalence of small-bowel injury:a propensity-matched analysis. PLoS One, 2017, 12(8):e0182586.
4 Washio E, Esaki M, Maehata Y, et al. Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury:a randomized, placebo-controlled Trial. Clin Gastroenterol Hepatol, 2016, 14(6):809-815.
5 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in metaanalyses. Eur J Epidemiol, 2010, 25(9):603-605.
6 Isomura Y, Yamaji Y, Yamada A, et al. Irsogladine improves smallintestinal injuries in regular users of nonsteroidal antiinflammatory drugs. Gastrointest Endosc, 2014, 80(1):118-125.
7 Endo H, Sakai E, Taniguchi L, et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users:data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc, 2014, 80(5):826-834.
8 Ishihara M, Ohmiya N, Nakamura M, et al. Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease. Aliment Pharmacol Ther, 2014, 40(5):538-547.
9 Watanabe T, Tanigawa T, Nadatani Y, et al. Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage. Dig Liver Dis, 2013, 45(5):390-395.
10 Muraki M, Fujiwara Y, Machida H, et al. Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users. Scand J Gastroenterol,2014, 49(3):267-273.
11 王娉.非甾体抗炎药引发小肠不良反应因素分析及处理.国际医药卫生导报, 2017, 23(9):1421-1423.
12 Konaka A, Kato S, Tanaka A, et al. Roles of enterobacteria, nitric oxide and neutrophil in pathogenesis of indomethacin-induced small intestinal lesions in rats. Pharmacol Res, 1999, 40(6):517-524.
13 Watanabe T, Higuchi K, Kobata A, et al. Non-steroidal antiinflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut, 2008, 57(2):181-187.
14 Watanabe T, Nishio H, Tanigawa T, et al. Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury:involvement of lactic acid. Am J Physiol Gastrointest Liver Physiol, 2009, 297(3):G506-G513.
15 Casado Arroyo R, Polo-Tomas M, Roncalés MP, et al. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy:long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart, 2012, 98(9):718-723.
16 Wallace JL, Syer S, Denou E, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology, 2011, 141(4):1314-1322.
17 Omatsu T, Naito Y, Handa O, et al. Reactive oxygen speciesquenching and anti-apoptotic effect of polaprezinc on indomethacin-induced small intestinal epithelial cell injury. J Gastroenterol, 2010, 45(7):692-702.
18 Mayo SA, Song YK, Cruz MR, et al. Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci. Physiol Rep, 2016, 4(6):e12725.
19 ZhouY, Dial EJ, Doyen R, et al. Effect ofindomethacin on bile acidphospholipid interactions:implication for small intestinal injury induced by nonsteroidal anti-inflammatory drngs. Am J Physiol Gastrointest Liver Physiol, 2010, 298(5):G722-G731.
20 Narabayashi K, Ito Y, Eid N, et al. Indomethacin suppresses LAMP-2 expression and induces lipophagy and lipoapoptosis in rat enterocytes via the ER stress path way. J Gastroenterol, 2015, 50(4):541-554.
21 Edogawa S, Sakai A, Inoue T, et al. Down-regulation of collagen I biosynthesis in intestinll epithelill cells exposed to indomethacin:a comparative proteome analysis. J Proteomics, 2014, 103:35-46.
22 Nuki Y, Umeno J, Washio E, et al. The influence of CYP2C19polymorphisms on exacerbating effect of rabeprazole in celecoxibinduced small bowel injury. Aliment Pharmacol Ther, 2017, 46(3):331-336.
23 Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol, 2009, 104(7):1633-1641.
24 Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. The changing face of hospitalisation due to gastrointestinal bleeding and perforation. Aliment Pharmacol Ther, 2011, 33(5):585-591.
25 Montalto M, Gallo A, Curigliano V, et al. Clinical trial:the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy-a randomized, double-blind, cross-over, placebocontrolled study. Aliment Pharmacol Ther, 2010, 32(2):209-214.
26 Lanas A. We are using too many PPIs, and we need to stop:a European perspective. Am J Gastroenterol, 2016, 111(8):1085-1086.
27 Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol:a pilot study. Clin Gastroenterol Hepatol, 2008, 6(11):1279-1282.
28 Kurata S, Nakashima T, Osaki T, et al. Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model. J Clin Biochem Nutr, 2015, 56(1):20-27.
29 Kurokawa S, Katsuki S, Fujita T, et al. A randomized, doubleblinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury. J Gastroenterol, 2014, 49(2):239-244.
30 Watanabe T, Takeuchi T, Handa O, et al. A multicenter,randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-tosevere small intestinal damage. PLoS One, 2015, 10(4):e0122330.
31 Kojima Y, Takeuchi T, Ota K, et al. Effect of long-term proton pump inhibitor therapy and healing effect of irsogladine on nonsteroidal anti-inflammatory drug-induced small-intestinal lesions in healthy volunteers. J Clin Biochem Nutr, 2015, 57(1):60-65.
32 Xiong L, Huang X, Li L, et al. Geranylgeranylacetone protects against small-intestinal injuries induced by diclofenac in patients with rheumatic diseases:a prospective randomized study. Dig Liver Dis, 2015, 47(4):280-284.
2 Matsumoto T, Kudo T, Esaki M, et al. Prevalence of non-steroidalanti-inflammatory drug-induced enteropathy determined by double-balloon endoscopy:a Japanese multicenter study. Scand J Gastroenterol, 2008, 43(4):490-496.
3 Yamada A, Niikura R, Maki K, et al. Proton pump inhibitor therapy did not increase the prevalence of small-bowel injury:a propensity-matched analysis. PLoS One, 2017, 12(8):e0182586.
4 Washio E, Esaki M, Maehata Y, et al. Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury:a randomized, placebo-controlled Trial. Clin Gastroenterol Hepatol, 2016, 14(6):809-815.
5 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in metaanalyses. Eur J Epidemiol, 2010, 25(9):603-605.
6 Isomura Y, Yamaji Y, Yamada A, et al. Irsogladine improves smallintestinal injuries in regular users of nonsteroidal antiinflammatory drugs. Gastrointest Endosc, 2014, 80(1):118-125.
7 Endo H, Sakai E, Taniguchi L, et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users:data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc, 2014, 80(5):826-834.
8 Ishihara M, Ohmiya N, Nakamura M, et al. Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease. Aliment Pharmacol Ther, 2014, 40(5):538-547.
9 Watanabe T, Tanigawa T, Nadatani Y, et al. Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage. Dig Liver Dis, 2013, 45(5):390-395.
10 Muraki M, Fujiwara Y, Machida H, et al. Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users. Scand J Gastroenterol,2014, 49(3):267-273.
11 王娉.非甾体抗炎药引发小肠不良反应因素分析及处理.国际医药卫生导报, 2017, 23(9):1421-1423.
12 Konaka A, Kato S, Tanaka A, et al. Roles of enterobacteria, nitric oxide and neutrophil in pathogenesis of indomethacin-induced small intestinal lesions in rats. Pharmacol Res, 1999, 40(6):517-524.
13 Watanabe T, Higuchi K, Kobata A, et al. Non-steroidal antiinflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut, 2008, 57(2):181-187.
14 Watanabe T, Nishio H, Tanigawa T, et al. Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury:involvement of lactic acid. Am J Physiol Gastrointest Liver Physiol, 2009, 297(3):G506-G513.
15 Casado Arroyo R, Polo-Tomas M, Roncalés MP, et al. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy:long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart, 2012, 98(9):718-723.
16 Wallace JL, Syer S, Denou E, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology, 2011, 141(4):1314-1322.
17 Omatsu T, Naito Y, Handa O, et al. Reactive oxygen speciesquenching and anti-apoptotic effect of polaprezinc on indomethacin-induced small intestinal epithelial cell injury. J Gastroenterol, 2010, 45(7):692-702.
18 Mayo SA, Song YK, Cruz MR, et al. Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci. Physiol Rep, 2016, 4(6):e12725.
19 ZhouY, Dial EJ, Doyen R, et al. Effect ofindomethacin on bile acidphospholipid interactions:implication for small intestinal injury induced by nonsteroidal anti-inflammatory drngs. Am J Physiol Gastrointest Liver Physiol, 2010, 298(5):G722-G731.
20 Narabayashi K, Ito Y, Eid N, et al. Indomethacin suppresses LAMP-2 expression and induces lipophagy and lipoapoptosis in rat enterocytes via the ER stress path way. J Gastroenterol, 2015, 50(4):541-554.
21 Edogawa S, Sakai A, Inoue T, et al. Down-regulation of collagen I biosynthesis in intestinll epithelill cells exposed to indomethacin:a comparative proteome analysis. J Proteomics, 2014, 103:35-46.
22 Nuki Y, Umeno J, Washio E, et al. The influence of CYP2C19polymorphisms on exacerbating effect of rabeprazole in celecoxibinduced small bowel injury. Aliment Pharmacol Ther, 2017, 46(3):331-336.
23 Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol, 2009, 104(7):1633-1641.
24 Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. The changing face of hospitalisation due to gastrointestinal bleeding and perforation. Aliment Pharmacol Ther, 2011, 33(5):585-591.
25 Montalto M, Gallo A, Curigliano V, et al. Clinical trial:the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy-a randomized, double-blind, cross-over, placebocontrolled study. Aliment Pharmacol Ther, 2010, 32(2):209-214.
26 Lanas A. We are using too many PPIs, and we need to stop:a European perspective. Am J Gastroenterol, 2016, 111(8):1085-1086.
27 Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol:a pilot study. Clin Gastroenterol Hepatol, 2008, 6(11):1279-1282.
28 Kurata S, Nakashima T, Osaki T, et al. Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model. J Clin Biochem Nutr, 2015, 56(1):20-27.
29 Kurokawa S, Katsuki S, Fujita T, et al. A randomized, doubleblinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury. J Gastroenterol, 2014, 49(2):239-244.
30 Watanabe T, Takeuchi T, Handa O, et al. A multicenter,randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-tosevere small intestinal damage. PLoS One, 2015, 10(4):e0122330.
31 Kojima Y, Takeuchi T, Ota K, et al. Effect of long-term proton pump inhibitor therapy and healing effect of irsogladine on nonsteroidal anti-inflammatory drug-induced small-intestinal lesions in healthy volunteers. J Clin Biochem Nutr, 2015, 57(1):60-65.
32 Xiong L, Huang X, Li L, et al. Geranylgeranylacetone protects against small-intestinal injuries induced by diclofenac in patients with rheumatic diseases:a prospective randomized study. Dig Liver Dis, 2015, 47(4):280-284.