系统回顾与荟萃分析发现胰酶替代疗法对慢性胰腺炎有效

　　2016年12月9日，《英国医学杂志》旗下《肠道》在线发表英国利物浦大学皇家医院、西班牙圣地亚哥-德孔波斯特拉大学医院、中国四川大学华西医院的研究报告，发现胰酶替代疗法能够治疗慢性胰腺炎患者的胰腺外分泌功能不全。

　　胰腺外分泌功能不全可减少脂溶性维生素、必需氨基酸、叶酸、维生素B1、钙、锌、镁的吸收，同时可降低慢性胰腺炎确诊后的中位生存。严重腹痛、腹泻、体重下降和脂肪泻的症状对生活质量产生不利影响，而且与之相关的营养不良增加骨质疏松症、感染、和心血管疾病的风险。胰腺外分泌功能不全会影响确诊为慢性胰腺炎一半以上的患者，并在确诊5～10年时恶化。

　　胰酶替代疗法利用猪消化酶（胰淀粉酶，蛋白酶和脂肪酶），其中脂肪酶是最重要的成分。这些药物的不同在于是否有肠溶衣和剂型（颗粒、微片、微球或微型微球）。

　　该研究发现，胰酶替代疗法可以缓解疼痛，减少粪便中脂肪排泄物，降低粪便氮排出，并且减轻排泄量；同时改善氮和脂肪吸收，提高生活质量；也缓解营养缺乏。

　　该研究对1965～2015年的数据库文献进行检索，确认17项研究511例慢性胰腺炎患者进行定性评定，根据14项研究合成定量数据。主要结局为脂肪吸收系数，通过脂肪摄入和粪便排泄计算。次要结局为氮吸收系数、粪便脂肪排泄、粪便氮排泄、粪便重量、性状和频次、腹痛和胃肠道症状、体重、生活质量、不良反应。将胰酶替代疗法与基线、安慰剂以及相互之间不同剂型、剂量、给药时间进行比较。

　　结果发现，胰酶替代疗法与基线（83.7±6.0比63.1±15.0，P＜0.00001；I2=89%）和安慰剂（83.2±5.5比67.4±7.0，p=0.0001；I2=86%）相比，可以提高脂肪吸收系数。

　　胰酶替代疗法提高氮吸收系数，减少粪便中脂肪排泄物，减少粪便氮排泄，减轻粪便重量和缓解腹痛，并且无显著不良反应。

　　随访研究表明，胰酶替代疗法增加血浆营养指标，改善胃肠道症状和生活质量，且无显著不良事件。

　　高剂量或肠溶包衣酶与低剂量或非肠溶包衣相比更有效。

　　亚组、敏感性荟萃回归分析显示，样本量、慢性胰腺炎诊断标准、研究设计、酶剂量与异质性相关，卫生不均等数据缺乏。

　　因此，胰酶替代疗法可以纠正胰腺外分泌功能不全和营养不良，并且可通过提高剂量、增加肠溶包衣、在进食和酸抑制过程中给药获得优化。

　　进一步研究需要确定最佳治疗方案，以解决卫生不均等对数据的影响，同时观察对营养的长期影响。

Gut. 2016 Dec 9. [Epub ahead of print]

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

de la Iglesia-García D, Huang W, Szatmary P, Baston-Rey I, Gonzalez-Lopez J, Prada-Ramallal G, Mukherjee R, Nunes QM, Domínguez-Munoz JE, Sutton R; NIHR Pancreas Biomedical Research Unit Patient Advisory Group.

Collaborators: Cameron G, Donaldson K, Jones G, Lancaster J, Lucas A, Manby K, McLaren T, Rodgers C, Rodgers J, Swindlehurst W, Symon N, Warrington D, Whitby M.

Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK; University Hospital of Santiago de Compostela, Compostela, Spain; West China Hospital, Sichuan University, Chengdu, China; University of Santiago de Compostela, Compostela, Spain.

OBJECTIVE: The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.

DESIGN: Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.

RESULTS: A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.

CONCLUSIONS: PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.

KEYWORDS: exocrine pancreatic function; nutrient absorption; pancreatic enzymes; pancreatitis

PMID: 27941156

PII: gutjnl-2016-312529

DOI: 10.1136/gutjnl-2016-312529