Abstract：
Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI.
This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn\'s disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 μg/g of stool provides good evidence of EPI, and levels of 100-200 μg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.
This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn\'s disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 μg/g of stool provides good evidence of EPI, and levels of 100-200 μg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.
摘要：
方法：胰腺外分泌功能不全（EPI）是由于胰腺无法将最小/阈值水平的特定胰腺消化酶输送到肠道而引起的疾病，导致营养素和大量营养素消化不良，导致他们的可变缺陷。EPI经常被诊断不足，因此,患者往往得不到适当的治疗。迫切需要提高对这种情况的认识和治疗。美国胃肠病学协会（AGA）临床实践更新专家审查的目的是提供流行病学的最佳实践建议。评估，和EPI的管理。
方法：本专家评审是由美国胃肠病学协会（AGA）研究所临床实践更新委员会（CPUC）和AGA理事会委托并批准的，目的是就对AGA会员具有很高临床重要性的主题提供及时的指导。并接受了CPUC的内部同行评审和通过胃肠病学标准程序的外部同行评审。这些最佳实践建议声明来自对已发表文献的回顾和专家意见。因为没有进行系统评价，这些最佳实践建议声明没有对证据质量或所提出考虑因素的强度进行正式评级。最佳实践建议声明最佳实践建议1：高风险临床疾病患者应怀疑EPI，比如慢性胰腺炎,复发性急性胰腺炎，胰腺导管腺癌,囊性纤维化,和以前的胰腺手术。最佳实践建议2：在具有中等风险临床状况的患者中，应考虑使用EPI。比如十二指肠疾病，包括乳糜泻和克罗恩病；既往肠道手术；长期糖尿病；和高分泌状态（例如，Zollinger-Ellison综合征）。最佳实践建议3：EPI的临床特征包括有或没有腹泻的脂肪泻，减肥,腹胀,过度的肠胃气胀,脂溶性维生素缺乏症，和蛋白质卡路里营养不良。最佳实践建议4：粪便弹性蛋白酶测试是最合适的初始测试，必须在半固体或固体粪便标本上进行。粪便弹性蛋白酶水平<100μg/g粪便提供了EPI的良好证据，对于EPI，100-200μg/g的水平是不确定的。最佳实践建议5：在胰腺酶替代疗法时可以进行粪便弹性蛋白酶测试。最佳实践建议6：粪便脂肪测试很少需要，必须在高脂肪饮食时进行。定量测试对于常规临床使用通常是不实际的。最佳实践建议7：对胰腺酶治疗试验的反应对于EPI诊断是不可靠的。最佳实践建议8：横截面成像方法（计算机断层扫描，磁共振成像，和内窥镜超声）无法识别EPI，尽管它们在良性和恶性胰腺疾病的诊断中起着重要作用。最佳实践建议9：呼吸测试和直接胰腺功能测试有望，但在美国并不广泛。最佳实践建议10：一旦确诊为EPI，需要使用胰酶替代疗法（PERT）进行治疗。如果不进行EPI治疗,它会导致与脂肪吸收不良和营养不良有关的并发症，对生活质量有负面影响。最佳实践建议11:PERT制剂全部来自猪源,并且在等效剂量下同样有效。需要使用非肠溶包衣制剂的H2或质子泵抑制剂疗法。最佳实践建议12:PERT应该在用餐期间服用，在成人中，每餐初始治疗至少40,000USP单位的脂肪酶，其中一半用零食治疗。随后的剂量可以根据膳食大小和脂肪含量来调整。最佳实践建议13：常规补充和监测脂溶性维生素水平是合适的。饮食调整包括低-中等脂肪饮食，经常小餐和避免极低脂肪饮食。最佳实践建议14：PERT成功治疗的措施包括减少脂肪泻和相关的胃肠道症状；体重增加，肌肉质量，和肌肉功能；并改善脂溶性维生素水平。最佳实践建议15：应监测EPI并获得营养状况的基线测量值（体重指数，生活质量衡量标准，和脂溶性维生素水平)。应获得基线双能X射线吸收法扫描，每1-2年重复一次。
方法：本专家评审是由美国胃肠病学协会（AGA）研究所临床实践更新委员会（CPUC）和AGA理事会委托并批准的，目的是就对AGA会员具有很高临床重要性的主题提供及时的指导。并接受了CPUC的内部同行评审和通过胃肠病学标准程序的外部同行评审。这些最佳实践建议声明来自对已发表文献的回顾和专家意见。因为没有进行系统评价，这些最佳实践建议声明没有对证据质量或所提出考虑因素的强度进行正式评级。最佳实践建议声明最佳实践建议1：高风险临床疾病患者应怀疑EPI，比如慢性胰腺炎,复发性急性胰腺炎，胰腺导管腺癌,囊性纤维化,和以前的胰腺手术。最佳实践建议2：在具有中等风险临床状况的患者中，应考虑使用EPI。比如十二指肠疾病，包括乳糜泻和克罗恩病；既往肠道手术；长期糖尿病；和高分泌状态（例如，Zollinger-Ellison综合征）。最佳实践建议3：EPI的临床特征包括有或没有腹泻的脂肪泻，减肥,腹胀,过度的肠胃气胀,脂溶性维生素缺乏症，和蛋白质卡路里营养不良。最佳实践建议4：粪便弹性蛋白酶测试是最合适的初始测试，必须在半固体或固体粪便标本上进行。粪便弹性蛋白酶水平<100μg/g粪便提供了EPI的良好证据，对于EPI，100-200μg/g的水平是不确定的。最佳实践建议5：在胰腺酶替代疗法时可以进行粪便弹性蛋白酶测试。最佳实践建议6：粪便脂肪测试很少需要，必须在高脂肪饮食时进行。定量测试对于常规临床使用通常是不实际的。最佳实践建议7：对胰腺酶治疗试验的反应对于EPI诊断是不可靠的。最佳实践建议8：横截面成像方法（计算机断层扫描，磁共振成像，和内窥镜超声）无法识别EPI，尽管它们在良性和恶性胰腺疾病的诊断中起着重要作用。最佳实践建议9：呼吸测试和直接胰腺功能测试有望，但在美国并不广泛。最佳实践建议10：一旦确诊为EPI，需要使用胰酶替代疗法（PERT）进行治疗。如果不进行EPI治疗,它会导致与脂肪吸收不良和营养不良有关的并发症，对生活质量有负面影响。最佳实践建议11:PERT制剂全部来自猪源,并且在等效剂量下同样有效。需要使用非肠溶包衣制剂的H2或质子泵抑制剂疗法。最佳实践建议12:PERT应该在用餐期间服用，在成人中，每餐初始治疗至少40,000USP单位的脂肪酶，其中一半用零食治疗。随后的剂量可以根据膳食大小和脂肪含量来调整。最佳实践建议13：常规补充和监测脂溶性维生素水平是合适的。饮食调整包括低-中等脂肪饮食，经常小餐和避免极低脂肪饮食。最佳实践建议14：PERT成功治疗的措施包括减少脂肪泻和相关的胃肠道症状；体重增加，肌肉质量，和肌肉功能；并改善脂溶性维生素水平。最佳实践建议15：应监测EPI并获得营养状况的基线测量值（体重指数，生活质量衡量标准，和脂溶性维生素水平)。应获得基线双能X射线吸收法扫描，每1-2年重复一次。
