Andres Gelrud, MD, is a gastroenterologist at Baptist Health Miami Cancer Institute, part of Baptist Health South Florida

Andres Gelrud, MD

Beyond Chronic Pancreatitis, Rethinking Who Gets EPI and How We Treat It, With Andres Gelrud, MD

remains a misunderstood disease, leading to gaps and unmet needs in patient care across multiple etiologies, with clinicians reassessing the future of the therapeutic landscape.

Many clinicians lack awareness of how far-reaching EPI can be, mainly focusing on its presentation in patients with chronic pancreatitis, pancreatic cancer, post–pancreatic resection, and cystic fibrosis. There's an unmet need in identifying EPI in patients with type 1 and 2 diabetes, post-gastric resection and gastric bypass patients, celiac disease, and severe acute pancreatitis, who are at an increased risk.

"The ones that are frequently left behind and that we don't tend to think too much about are patients, for example, with diabetes, type one, type two, patients with gastric resections, patient with gastric bypass that they have a completely normal looking and functional pancreas, but for other reasons, you know, they're developing exocrine pancreatic insufficiency," said Andres Gelrud, MD, a gastroenterologist at Baptist Health Miami Cancer Institute, part of Baptist Health South Florida, in an interview with HCPLive. "So these are conditions actually that we don't tend to think about, but it's very important, because now we do recognize them as patients that may have exocrine pancreatic insufficiency, and starting treatment will have a major impact in their quality of life."

 due to its symptoms overlapping with common gastrointestinal disorders, including irritable bowel syndrome and celiac disease, which include bloating, diarrhea, and weight loss. Patients may wait years before approaching a doctor about these symptoms due to their non-specificity and embarrassment to broach the subject of GI issues. Often, symptoms will not manifest until significant pancreatic damage has already occurred, leading to a harder-to-treat patient.

commonly utilized test for diagnosing EPI i

s the fecal elastase-1 (FE-1). However, this test lacks sensitivity for mild to moderate cases, and furthermore, false positives are common when stool is watery or diluted, underscoring the need to interpret results in clinical context. For context, an FE-1 result < 200 µg/g is abnormal, with values < 100 µg/g indicating a high likelihood of EPI and levels between 100 to 200 µg/g indeterminate.

Furthermore, clinicians who treat EPI are witness to the major pill burden their patients face. Right now, pancreatic enzyme replacement therapy has been supported as the best available option, but patients do not find it ideal.

"One of the biggest unmet needs that I see is that patients frequently complain of the number of pills that they have to take, the size of the pill that they have to take,” said Gerlund. “This is an issue that I tend to hear over and over and over."

To address this pill burden, the field would have to discover new pharmaceutical formulations to make disease management easier for patients. 

Barkin JA, Delk TB, Powell VJ. Symptoms, burden, and unmet needs of patients living with exocrine pancreatic insufficiency: a narrative review of the patient experience. 

https://doi.org/10.1186/s12876-024-03188-w

Radlinger B, Ramoser G, Kaser S. Exocrine Pancreatic Insufficiency in Type 1 and Type 2 Diabetes. 

https://doi.org/10.1007/s11892-020-01304-0

Epidemiology, evaluation and management of exocrine pancreatic insufficiency (EPI). American Gastroenterological Association. Published April 2, 2024. 

https://gastro.org/clinical-guidance/epidemiology-evaluation-management-exocrine-pancreatic-insufficiency/

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Gerlud explains unmet needs in EPI, including underdiagnosed patient populations, and the intense pill burdens patients face. 

Diagnosing and Managing Exocrine Pancreatic Insufficiency

To diagnose exocrine pancreatic insufficiency, clinicians should combine careful "detective work" on symptoms and risk factors with imaging and fecal elastase testing, while recognizing the test's limitations, especially with watery stools, and not relying on it in isolation. 

"So making the diagnosis of EPI at the beginning can be very challenging... it's super important to do the detective work, look for risk factors... you really have to take your time if you want to make this diagnosis early," said Andres Gelrud, MD, a gastroenterologist at Baptist Health Miami Cancer Institute, part of Baptist Health South Florida, in an interview with HCPLive.

A fecal elastase-1 result below 200 µg/g is considered abnormal, with values below 100 µg/g indicating a high likelihood of EPI and levels between 100 and 200 µg/g considered indeterminate, though false positives are common when stool is watery or diluted, underscoring the need to interpret results in clinical context.¹

Once the diagnosis is made, clinicians should promptly initiate adequately dosed pancreatic enzyme replacement therapy taken with meals and evaluate for fat-soluble vitamin deficiencies, bone disease, and diabetes. Per the 2023 AGA Clinical Practice Update, PERT should be initiated at a minimum of 40,000 USP units of lipase per main meal in adults, with half that dose for snacks, adjusted based on meal size and fat content and taken during the meal — not before or after. For patients on non-enteric-coated preparations, concurrent H2 blocker or PPI therapy is recommended.² This combination both relieves malabsorptive symptoms and addresses the broader metabolic consequences of EPI.

Symptoms of EPI are often nonspecific and overlap with other gastrointestinal conditions, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, and small intestinal bacterial overgrowth. Despite this, fewer than 7% of patients with chronic pancreatitis or pancreatic cancer are tested for EPI. This gap is significant given that EPI develops in approximately 20% of patients after acute pancreatitis, rising to 30% after severe episodes, and in 47–76% of those with autoimmune pancreatitis.³ As a result, clinicians should remain alert to symptoms such as bloating, diarrhea, and unexplained weight loss.

Monitoring after treatment initiation should focus on clinical response rather than repeat fecal elastase testing, which is not a reliable indicator of treatment efficacy. Per the AGA's Best Practice Advice, markers of successful PERT include reduction in steatorrhea and gastrointestinal symptoms, weight gain, improved muscle mass and function, and normalization of fat-soluble vitamin levels (A, D, E, and K). Baseline measurements of BMI, quality of life, and fat-soluble vitamins should be obtained at diagnosis, along with a baseline DEXA scan repeated every one to two years given EPI's association with metabolic bone disease.²

"Once we start to supplement the patient with pancreatic enzymes, you see that the symptoms very, very quickly start to resolve... as soon as you start to take the enzymes, the symptoms very, very fast start to improve," said Gelrud.

Whitcomb DC, Buchner AM, Forsmark CE. AGA clinical practice update on the epidemiology, evaluation, and management of exocrine pancreatic insufficiency: expert review. 

. 2023;165(5):1292-1301. doi:10.1053/j.gastro.2023.07.007

Capurso G, Traini M, Piciucchi M, Signoretti M, Arcidiacono PG. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. 

. 2019;12:129-139. doi:10.2147/CEG.S168266

Diagnosing and Managing Exocrine Pancreatic Insufficiency, With Andres Gelrud, MD

Why Exocrine Pancreatic Insufficiency Is Frequently Underdiagnosed, With Andres Gelrud, MD

 remains underdiagnosed and undertreated, but improving awareness could help address persistent gaps in clinical care.

Many clinicians and patients remain unaware of EPI’s strong association with diabetes and other pancreatic diseases, contributing to delays in diagnosis.

“Exocrine pancreatic insufficiency is a condition that is caused by multiple reasons, but mainly inadequate production of pancreatic enzymes,” said Andres Gelrud, MD, a gastroenterologist at Baptist Health Miami Cancer Institute, part of Baptist Health South Florida, in an interview with HCPLive. “It’s also defined as inadequate delivery or activity of the pancreatic enzymes needed for normal digestion, and here we’re talking about lipase, protease, and amylase.”

EPI results from inadequate secretion and/or delivery of pancreatic enzymes and bicarbonate into the duodenum, impairing normal digestion. Disruption of acinar cell function, reduced enzyme output, or ductal obstruction limits the availability of key digestive enzymes, including lipase, protease, and amylase. Lipase activity is typically affected earliest, leading to impaired fat digestion before carbohydrate and protein malabsorption. This progressive enzyme deficiency underlies the characteristic features of maldigestion and nutrient malabsorption seen in EPI.

The likelihood of developing EPI is increased in high-risk populations. Among patients with chronic pancreatitis, approximately 60%–90% develop EPI. Prevalence is also high in cystic fibrosis (~85%) and pancreatic cancer (66%–92%), with additional risk observed following pancreatic or bariatric surgery.

Symptoms of EPI are often nonspecific and overlap with other gastrointestinal conditions, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, and small intestinal bacterial overgrowth. Despite this, fewer than 7% of patients with chronic pancreatitis or pancreatic cancer are tested for EPI. As a result, clinicians should remain alert to symptoms such as bloating, diarrhea, and unexplained weight loss.

“If the patient tells you that they have gas, bloating, soft bowel movements, but they’re losing weight, that weight loss should be a major red flag that something is going on,” Gelrud said.

Ruling out EPI in these cases is critical, particularly among patients who report planning meals around anticipated bowel movements. By the time classic symptoms such as steatorrhea emerge, severe pancreatic dysfunction, often reflecting up to 90% loss of exocrine function, may already be present.

To learn more about diagnostic tools for EPI, follow part 2 of this interview.

Editor’s Note: Gelrud reports no relevant disclosures.

de Rijk FEM, van Veldhuisen CL, Besselink MG, et al. Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study. 

https://doi.org/10.1016/j.pan.2022.03.013

Ghodeif AO, Azer SA. Pancreatic Insufficiency. PubMed. Published 2023. 

https://www.ncbi.nlm.nih.gov/books/NBK555926/

Gerlud explains why exocrine pancreatic insufficiency is often missed, even in high-risk patients. 


Andres Gelrud, MD

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