title: Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK.|Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Compostela, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: de la Iglesia-García
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK.|Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmary
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Compostela, Spain.
authors.forename: Iria
authors.initials: I
authors.lastname: Baston-Rey
authors.affiliation: Department of Pharmacy, University Hospital of Santiago de Compostela, Compostela, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gonzalez-Lopez
authors.affiliation: Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Compostela, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Prada-Ramallal
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Mukherjee
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK.
authors.forename: Quentin M
authors.initials: QM
authors.lastname: Nunes
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Compostela, Spain.
authors.forename: J Enrique
authors.initials: JE
authors.lastname: Domínguez-Muñoz
authors.affiliation: NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK.
authors.forename: Robert
authors.identifier: 0000-0001-6600-562X
authors.initials: R
authors.lastname: Sutton
mesh_terms: D004041:Dietary Fats / Q000378:metabolism; D057487:Enzyme Therapy; D004798:Enzymes / Q000008:administration & dosage; D010188:Exocrine Pancreatic Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005243:Feces / Q000737:chemistry; D006801:Humans; D009752:Nutritional Status; D010179:Pancreas / Q000201:enzymology*; D050500:Pancreatitis, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic
chemical_list: D004041:Dietary Fats; D004798:Enzymes
keywords: EXOCRINE PANCREATIC FUNCTION; NUTRIENT ABSORPTION; PANCREATIC ENZYMES; PANCREATITIS