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PERSISTENT EXOCRINE PANCREATIC INSUFFICIENCY AFTER ACUTE PANCREATITIS AND PREDICTIVE FACTORS FOR ITS OCCURRENCE: A PROSPECTIVE LONGITUDINAL AND RANDOMIZED CONTROLLED TRIAL STUDY WITH LONG-TERM FOLLOW-UP

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PERSISTENT EXOCRINE PANCREATIC INSUFFICIENCY AFTER ACUTE PANCREATITIS AND PREDICTIVE FACTORS FOR ITS OCCURRENCE: A PROSPECTIVE LONGITUDINAL AND RANDOMIZED CONTROLLED TRIAL STUDY WITH LONG-TERM FOLLOW-UP

Marta Gravito-Soares 1, Elisa Gravito-Soares 1, Nuno Peres Almeida 1, Barbara Rocha 2, Pedro Narra Figueiredo 1

Affiliations

1 Gastroenterology Department, Hospitais Universidade Coimbra, Unidade Local Saúde Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Coimbra, Portugal

2 Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Celular biology, University of Coimbra, Coimbra, Portugal, Coimbra, Portugal

Summary

AI Generated

Exocrine pancreatic insufficiency developed in 47.6% of patients after acute pancreatitis, persisted for at least 6 months in 58% of those affected, and responded better to pancreatic enzyme replacement therapy than placebo in severe cases (20% vs. 12% resolution, p=0.04).

In 105 patients with first-episode acute pancreatitis, 50 (47.6%) developed exocrine pancreatic insufficiency, with 60% classified as severe and 38% occurring even in mild AP.
Persistent exocrine pancreatic insufficiency (lasting ≥6 months) occurred in 58% (n=29) of affected patients, including 31% with mild AP.
In the randomized trial, pancreatic enzyme replacement therapy (4000 IU with meals, 20000 IU with snacks) led to significantly more EPI resolution than placebo in patients with severe EPI (20% vs. 12%, p=0.04), though overall EPI resolution rates were similar (44% vs. 40%, p=0.598).
Independent predictors of persistent EPI included previous diabetes (OR 15.382, p=0.001), endocrine pancreatic insufficiency (OR 9.906, p=0.042), recurrent AP (OR 7.182, p=0.028), non-biliary etiology (OR 5.744, p=0.037), severe AP (OR 21.386, p<0.001), pancreatic necrosis (OR 21.05, p=0.007), and low magnesium (OR 45.690, p=0.045).
Endocrine pancreatic insufficiency was diagnosed in 17.1% of patients overall.
The presenter recommended screening all acute pancreatitis patients for exocrine insufficiency using fecal elastase-1 and starting enzyme replacement therapy early in diagnosed cases.

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Abstract

Introduction

Exocrine pancreatic insufficiency (EPI) following acute pancreatitis (AP) has been reported heterogeneously with unclear recovery timeline.

Aims & Methods

Aim: To determine the prevalence of EPI after AP and the prevalence and predictors of persistent EPI after AP for at least 6 months.
Methods: Prospective longitudinal study of consecutive adult patients diagnosed with first episode of AP. Excluded patients with previous EPI, follow-up after AP <12months and after EPI <6months. EPI was assessed by elastase fecal-1 and endocrine pancreatic insufficiency (EnPI) by fasting serum glucose, HbA1c and oral glucose tolerance test. Patients with AP who developed EPI were randomized to receive pancreatic enzyme replacement therapy (PERT, 4000IU with each meal and 20000IU with snacks; clinicaltrials.gov NCT05480241) vs. placebo. Clinical, inflammatory, nutritional and immunological factors were evaluated. Evaluated predictors for persistent EPI (≥6months) and compared with transient EPI (<6months) and AP with no EPI groups.

Results

A total of 105 patients (65.7%(n=69) males; mean age:63.8±17.1yo) were enrolled and followed-up, 65.7% with alcoholic/biliary etiology. AP was moderately-severe in 32.4% and severe in 16.2%. EPI (mean elastase fecal-1 176.9±175.8 (vs. 425.1±105.0; p<0.001) was observed in 50 (47.6%) patients, being severe in 60% and 38% of patients with mild AP: 64% at the time, 14% at 1 month, 16% at 3 months and 6% at 6 months of AP diagnosis. EnPI was diagnosed in 17.1%(n=18) and 19.0%(n=20) has previous diabetes mellitus. EPI was persistent (≥6 months after EPI diagnosis) in 58%(n=29; mean elastase fecal-1 83.8±58.5 (vs. 373.6±118.4; p<0.001)), being 31%(n=9) with mild AP. 6-month post-randomization, 44%(n=11/25) under PERT and 40%(n=10/25) under placebo resolved EPI (p=0.598), with statically significance for severe EPI (resolved EPI: PERT-20%; placebo-12%; p=0.04).
After univariate/multivariate analysis, factors significantly associated with persistent EPI were previous diabetes (OR 15.382; p=0.001), EnPI (OR 9.906; p=0.042), recurrent AP (OR 7.182; p=0.028), non-biliary etiology (OR 5.744; p=0.037), increasing AP severity (OR 21.386; p<0.001), mMarshal score ≥2 (OR 23.026; p=0.001), intermediate/intensive care unit admission (OR 19.583; p=0.003), pancreatic necrosis (OR 21.05; p=0.007) and low magnesium (OR 45.690; p=0.045).

Conclusion

EPI following AP is a non-negligible condition, present in almost half of patients during first 6months after AP diagnosis, being severe in about 2/3 of patients and persists for at least 6 months in more than half of patients, Previous diabetes, EnPI, recurrent AP, non-biliary etiology, severe AP and low magnesium were strongly and independent associated with persistent PEI. Since can occur and be persistent even in mild AP, is crucial understand injury mechanisms, stratify patient’s risk, tailoring screening and start PERT early.

References

Phillips AE, Beijani J, Culp S, Chennat J, Lee PJ, Machicado JD, et al. Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort study. E Clinical Medicine 2024;75:102774.
Huang W, de la Iglesia-García D, Baston-Rey I, Calviño-Suarez C, Lariño-Noia J, Iglesias-Garcia J, et al. Exocrine pancreatic insufficiency following acute pancreatitis: Systematic review and meta-analysis. Dig Dis Sci 2019;64(7):1985-2005.
Jawaid S, Forsmark CE. Exocrine pancreatic insufficiency following acute pancreatitis: true association or EPIphenomenon?. Dig Dis Sci 2019;67(7):1731-1733.

Event

UEG Week Berlin 2025

Topics

Pancreas

Submission format

Abstract

Session

From The Lion King to Waterland: A journey through pancreatitis

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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