a day ago
Q&A: PERT in Exocrine Pancreatic Insufficiency
John W. Birk, MS, MD
The primary treatment for exocrine pancreatic insufficiency (EPI) is dose-based pancreatic enzyme replacement therapy (PERT). The aim with PERT is to supplement pancreatic lipase and thus address symptoms, including steatorrhea and weight loss.[1] Enteric-coated formulations prevent the enzymes from being denatured in the stomach, and both enteric-coated and non-enteric-coated formulations have been approved by the FDA for the treatment of EPI. Medscape spoke with John W. Birk, MD, FACG, a professor of medicine and chief of the Division of Gastroenterology and Hepatology at UConn Health, about common pitfalls of PERT use in patients with EPI.
In our previous conversation, you stressed the importance of tailoring EPI treatment to the patient's need. Can you expand on that?
For sure. My first concern when managing patients with EPI is to support smoking cessation, treat alcohol use disorder, and lower elevated triglyceride levels when appropriate — that is, manage all modifiable risk factors associated with this condition.[1] Smoking profoundly affects the course of chronic pancreatitis — the most common cause of EPI — through different mechanisms, including the release of various pro-inflammatory cytokines, immune cell activation, and oxidative stress. In addition to lifestyle behavior changes and nutritional guidance, vitamins play an important role as antioxidants and in the prevention of common complications associated with maldigestion and malabsorption. Vitamin D supplementation is essential to prevent osteoporosis. Antioxidant supplements that package together selenium and vitamins C, A, K, and E are also recommended and have shown to decrease pain.[1]
How do you prescribe PERT?
I prescribe PERT according to the patient's weight, symptom severity, and lifestyle. In my experience, higher doses (≥ 40,000 IU twice daily) are more effective in symptom relief and treatment compliance; guidelines recommend 30,000-40,000 IU with each meal and 15,000-20,000 IU with snacks.[1] The response to treatment is typically good for such symptoms as diarrhea, bloating, steatorrhea, and weight loss. Pain is harder to manage; I typically refer patients to pain clinics. Often, they have a history of substance use disorder. Treatment response is based on symptom control and nutritional parameters, including a maximum of two bowel movements per day, stool consistency, loss of visible fat or oily droplets in the stool, and weight gain.
On top of that, you should assess for osteoporosis with a DEXA scan.[1] The prevalence of osteoporosis and sarcopenia is significant in chronic pancreatitis.[2,3]
I should mention that uncoated PERT formulations have been shown to decrease pain in a very narrow subgroup of patients with small pancreatic duct disease.[4] Uncoated formulations should be administered with proton pump inhibitors to avoid enzyme damage and inactivation by the stomach's low pH.
What are the next steps if a patient's symptoms do not improve?
Initially, I assess treatment compliance and then I investigate other conditions such as small-intestinal bacterial overgrowth (SIBO), underlying celiac disease, and inflammatory bowel disease. You can check for SIBO using a breath test that measures exhaled hydrogen and methane, indirect measures of microbial overgrowth.[5] The test is accessible, safe, and inexpensive. The antibiotics recommended to treat SIBO are neomycin 500 mg twice daily or rifaximin 550 mg twice daily.[6]
If the diagnosis of these conditions is excluded, you should increase the enzyme therapy dose. Your next concern will probably be about prescribing an excessive dose. I don't go over 72,000 IU three times a day, due to the risk for colonic strictures. I have never had a patient with this complication, but cases have been reported involving pediatric patients with cystic fibrosis.[7] You should follow-up any patient presenting with abdominal masses on exam or increased bowel sounds with colonoscopy or CT.[1]
Are these complications related to an advanced disease stage?
We have been talking about maldigestion treatment by replacing enzymes that the pancreas is no longer producing in sufficient quantity. Later in the disease, symptoms caused by malabsorption are also prominent, including vitamin B 12 deficiency, a potentially severe condition that can be prevented or managed if diagnosed early.[8] Dietary vitamin B 12 can bind three transport proteins: haptocorrin produced by salivary glands, intrinsic factor produced by parietal cell in the gastric mucosa, and transcobalamin. Pancreatic proteases are needed to degrade haptocorrin and trigger the transfer of B 12 to intrinsic factor in the duodenum, which will then be absorbed in the distal ileum.[9] In EPI, the lack of pancreatic proteases can interfere in vitamin B 12 absorption and cause deficiency, evidenced by symptoms such as anemia, fatigue, numbness, memory loss, depression, or psychosis. I have seen many EPI patients with B 12 deficiency. Treatment include sublingual or injection vitamin B 12 supplementation, patient education, and monitoring.[10,11]
Are there more concerns when using PERT in advanced stages of EPI?
Close blood glucose monitoring is recommended to all patients using PERT,[1,11] but toward the late stages of the disease, the patient develops type 3c diabetes, or pancreatogenic diabetes,[12] where damage to the pancreas extends to islet cells and affects insulin production. A study including patients diagnosed with diabetes found a prevalence of 9.2% of type 3c diabetes, associated mainly with chronic pancreatitis.[13] Insulin levels become unstable and may lead to hyperglycemia or hypoglycemia. At this stage, it is very likely that glucagon production is also impaired, so the use of EPI and the management of glycemia becomes very complex.
