Published online Nov 6, 2021. doi: 10.12998/wjcc.v9.i31.9469
Peer-review started: April 1, 2021
First decision: June 23, 2021
Revised: July 3, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: November 6, 2021
Pancreatic exocrine insufficiency (PEI) is a consequence of impaired production, drainage or function of pancreatic enzymes. The classical presenting symptom is steatorrhoea, however testing for PEI is often recommended in patients with non-specific symptoms, such as abdominal pain or diarrhoea. PEI is a known sequela of chronic pancreatitis, pancreatic cancer, and pancreatic resection. It is also thought to be associated with numerous other conditions, including: Previous acute pancreatitis, coeliac disease, diabetes, upper gastrointestinal (GI) surgery, liver cirrhosis, smoking, alcohol excess, human immunodeficiency virus infection, cardiac failure, chronic kidney disease, hyperparathyroidism, haemochromatosis and older age. However, the evidence base supporting the above associations is very heterogeneous.
The evidence base supporting many associations with PEI is weak. Strengthening the evidence base will prevent unnecessary investigation in low risk patients, and the identification of potential new associations may impact clinical practice and guide the direction of future research.
This study aimed to explore all previously reported associations with PEI simultaneously, in a large cohort of general gastroenterology outpatients. In addition, we studied three associations not previously explored: Proton pump inhibitor (PPI) therapy, cholecystectomy, and bile acid malabsorption, all of which are physiologically plausible causes of PEI.
A retrospective cohort study was performed. General gastroenterology outpatients tested for PEI with faecal elastase-1 (FE1) were identified and information retrieved from the electronic patient record. PEI was defined as FE1 < 200 μg/g. Multiple imputation, an advanced statistical technique that reduces bias, was used to handle missing data. Univariable logistic regression was used to study which presenting symptoms predicted PEI. Multivariable logistic regression was used to explore the relationship between all previously reported associations and PEI.
Steatorrhoea and weight loss were the only symptoms that predicted PEI. Chronic pancreatitis, pancreatic cancer, previous upper GI surgery and type 2 diabetes were confirmed to be associated with PEI; and between them explained over half of the cases. None of the other purported associations were found to be associated with PEI. This is the first study to investigate, and detect, an association between PPI therapy and PEI.
The threshold for testing for PEI should be low in patients with one or more significant risk factor. Symptoms, apart steatorrhoea and weight loss, are not predictive of PEI, and the diagnostic yield will be low in the absence of a risk factor. Patients on PPI therapy who have a low (positive) FE1 result should, where possible, discontinue PPI therapy and have the test repeated after a washout period.
We recommend that our finding that PPI therapy may be associated with PEI or a falsely positive FE1 result is now investigated with a prospective interventional study.