Exocrine Pancreatic Insufficiency After Acute Pancreatitis and Pancreatic Enzyme Replacement Therapy
Summary
Acute pancreatitis represents an acute inflammatory process of the pancreas, which undergoes local and systemic complications, associated with non-negligible morbidity and mortality, and significant economic and quality of life impact. Even after the recovery phase, the development and persistence of sequelae from the inflammatory/necrotic process, including exocrine and endocrine pancreatic insufficiencies, are frequent. Although well documented as consequence of other pancreatic conditions, exocrine pancreatic insufficiency (EPI) after acute pancreatitis is poorly studied and probably underdiagnosed. The prevalence, diagnosis, independent risk factors and therapeutic approaches for EPI after acute pancreatitis need further investigation. Recent evidence suggests the involvement of the pancreas-intestinal axis and immunological dysfunction in several pancreatic pathologies, although their role in the development of EPI after acute pancreatitis is still scarce. Pancreatic enzyme replacement therapy (PERT) is the only treatment currently available in EPI, but the timing for start and duration of this therapy in acute pancreatitis remain to be established. This study have the following objectives: to determine the prevalence, clinical, analytical and nutritional biomarkers and duration of EPI after acute pancreatitis, as well as changes in gut microbiota and immunologic response, and quality of life in EPI and response to PERT after acute pancreatitis; and to determine the prevalence and biomarkers associated with endocrine pancreatic insufficiency following acute pancreatitis and the presence of gut dysbiosis and immunologic changes in acute pancreatitis according to its severity.
Timeline
- Start
- 2022-05-01
- Primary completion
- 2023-12-31
- Completion
- 2024-12-31
Publications
- Results Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol. 2019 Aug;16(8):479-496. doi: 10.1038/s41575-019-0158-2.
- Results Roberts SE, Morrison-Rees S, John A, Williams JG, Brown TH, Samuel DG. The incidence and aetiology of acute pancreatitis across Europe. Pancreatology. 2017 Mar-Apr;17(2):155-165. doi: 10.1016/j.pan.2017.01.005. Epub 2017 Jan 19.
- Results Xiao AY, Tan ML, Wu LM, Asrani VM, Windsor JA, Yadav D, Petrov MS. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016 Sep;1(1):45-55. doi: 10.1016/S2468-1253(16)30004-8. Epub 2016 Jun 28.
- Results Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.
- Results Hollemans RA, Hallensleben NDL, Mager DJ, Kelder JC, Besselink MG, Bruno MJ, Verdonk RC, van Santvoort HC; Dutch Pancreatitis Study Group. Pancreatic exocrine insufficiency following acute pancreatitis: Systematic review and study level meta-analysis. Pancreatology. 2018 Apr;18(3):253-262. doi: 10.1016/j.pan.2018.02.009. Epub 2018 Feb 20.
- Results Huang W, de la Iglesia-Garcia D, Baston-Rey I, Calvino-Suarez C, Larino-Noia J, Iglesias-Garcia J, Shi N, Zhang X, Cai W, Deng L, Moore D, Singh VK, Xia Q, Windsor JA, Dominguez-Munoz JE, Sutton R. Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis. Dig Dis Sci. 2019 Jul;64(7):1985-2005. doi: 10.1007/s10620-019-05568-9. Epub 2019 Jun 4.
- Results Gravito-Soares M, Gravito-Soares E, Gomes D, Almeida N, Tome L. Red cell distribution width and red cell distribution width to total serum calcium ratio as major predictors of severity and mortality in acute pancreatitis. BMC Gastroenterol. 2018 Jul 5;18(1):108. doi: 10.1186/s12876-018-0834-7.
- Results Das SL, Singh PP, Phillips AR, Murphy R, Windsor JA, Petrov MS. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut. 2014 May;63(5):818-31. doi: 10.1136/gutjnl-2013-305062. Epub 2013 Aug 8.
- Results Ahmed Ali U, Issa Y, Hagenaars JC, Bakker OJ, van Goor H, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Brink MA, Schaapherder AF, Dejong CH, Spanier BW, Heisterkamp J, van der Harst E, van Eijck CH, Besselink MG, Gooszen HG, van Santvoort HC, Boermeester MA; Dutch Pancreatitis Study Group. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis. Clin Gastroenterol Hepatol. 2016 May;14(5):738-46. doi: 10.1016/j.cgh.2015.12.040. Epub 2016 Jan 6.
- Results Pendharkar SA, Salt K, Plank LD, Windsor JA, Petrov MS. Quality of life after acute pancreatitis: a systematic review and meta-analysis. Pancreas. 2014 Nov;43(8):1194-200. doi: 10.1097/MPA.0000000000000189.
- Results Sankaran SJ, Xiao AY, Wu LM, Windsor JA, Forsmark CE, Petrov MS. Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis. Gastroenterology. 2015 Nov;149(6):1490-1500.e1. doi: 10.1053/j.gastro.2015.07.066. Epub 2015 Aug 20.
- Results Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO. Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1220-1228.e4. doi: 10.1016/j.cgh.2018.01.027. Epub 2018 Jan 31.
- Results Loser C, Brauer C, Aygen S, Hennemann O, Folsch UR. Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an indirect pancreatic function test. Scand J Gastroenterol. 1998 Mar;33(3):327-34. doi: 10.1080/00365529850170946.
- Results Adolph TE, Mayr L, Grabherr F, Schwarzler J, Tilg H. Pancreas-Microbiota Cross Talk in Health and Disease. Annu Rev Nutr. 2019 Aug 21;39:249-266. doi: 10.1146/annurev-nutr-082018-124306.
- Results Zhu Y, He C, Li X, Cai Y, Hu J, Liao Y, Zhao J, Xia L, He W, Liu L, Luo C, Shu X, Cai Q, Chen Y, Lu N. Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice. J Gastroenterol. 2019 Apr;54(4):347-358. doi: 10.1007/s00535-018-1529-0. Epub 2018 Dec 5.
- Results Leal C, Almeida N. Predicting Severity in Acute Pancreatitis: A Never-Ending Quest.... GE Port J Gastroenterol. 2019 Jul;26(4):232-234. doi: 10.1159/000499680. Epub 2019 Apr 16. No abstract available.
- Results Almeida N, Fernandes A, Casela A. Predictors of Severity and In-Hospital Mortality for Acute Pancreatitis: Is There Any Role for C-Reactive Protein Determination in the First 24 Hours? GE Port J Gastroenterol. 2015 Jul 3;22(5):187-189. doi: 10.1016/j.jpge.2015.05.004. eCollection 2015 Sep-Oct. No abstract available.
- Results Rao SA, Kunte AR. Interleukin-6: An Early Predictive Marker for Severity of Acute Pancreatitis. Indian J Crit Care Med. 2017 Jul;21(7):424-428. doi: 10.4103/ijccm.IJCCM_478_16.
- Results Deng LH, Hu C, Cai WH, Chen WW, Zhang XX, Shi N, Huang W, Ma Y, Jin T, Lin ZQ, Jiang K, Guo J, Yang XN, Xia Q. Plasma cytokines can help to identify the development of severe acute pancreatitis on admission. Medicine (Baltimore). 2017 Jul;96(28):e7312. doi: 10.1097/MD.0000000000007312.
- Results Nieminen A, Maksimow M, Mentula P, Kyhala L, Kylanpaa L, Puolakkainen P, Kemppainen E, Repo H, Salmi M. Circulating cytokines in predicting development of severe acute pancreatitis. Crit Care. 2014 May 21;18(3):R104. doi: 10.1186/cc13885.
- Results de la Iglesia-Garcia D, Huang W, Szatmary P, Baston-Rey I, Gonzalez-Lopez J, Prada-Ramallal G, Mukherjee R, Nunes QM, Dominguez-Munoz JE, Sutton R; NIHR Pancreas Biomedical Research Unit Patient Advisory Group. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut. 2017 Aug;66(8):1354-1355. doi: 10.1136/gutjnl-2016-312529. Epub 2016 Dec 9.
- Results Dominguez-Munoz JE. Pancreatic enzyme replacement therapy: exocrine pancreatic insufficiency after gastrointestinal surgery. HPB (Oxford). 2009 Dec;11 Suppl 3(Suppl 3):3-6. doi: 10.1111/j.1477-2574.2009.00132.x.
- Results Kahl S, Schutte K, Glasbrenner B, Mayerle J, Simon P, Henniges F, Sander-Struckmeier S, Lerch MM, Malfertheiner P. The effect of oral pancreatic enzyme supplementation on the course and outcome of acute pancreatitis: a randomized, double-blind parallel-group study. JOP. 2014 Mar 10;15(2):165-74. doi: 10.6092/1590-8577/797.
- Results Dominguez-Munoz JE, Nieto-Garcia L, Lopez-Diaz J, Larino-Noia J, Abdulkader I, Iglesias-Garcia J. Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis. BMC Cancer. 2018 May 5;18(1):534. doi: 10.1186/s12885-018-4439-x.
- Results Layer P, Kashirskaya N, Gubergrits N. Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency. World J Gastroenterol. 2019 May 28;25(20):2430-2441. doi: 10.3748/wjg.v25.i20.2430.
- Results American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S13-S27. doi: 10.2337/dc18-S002.
- Results Dominguez-Munoz JE. Diagnosis and treatment of pancreatic exocrine insufficiency. Curr Opin Gastroenterol. 2018 Sep;34(5):349-354. doi: 10.1097/MOG.0000000000000459.
- Results Ferreira PL. [Development of the Portuguese version of MOS SF-36. Part I. Cultural and linguistic adaptation]. Acta Med Port. 2000 Jan-Apr;13(1-2):55-66. Portuguese.
- Results Pais-Ribeiro J, Pinto C, Santos C. Validation study of the portuguese version of the QLC-C30-V.3. Psic, Saúde & Doenças. 2008;9(1):89-102.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Kreon | Protein / enzyme biologic | 25000 unknown | — |
| Subject | Kreon | Protein / enzyme biologic | 50000 unknown | — |
| Comparator | Omeprazole | Other / unclassified | 20 mg | — |