Bile acid diarrhea (BAD) is an under-recognized explanation for persistent watery diarrhea. Once I see sufferers with the fellows within the normal gastrointestinal (GI) clinic, it’s additionally one of many extra satisfying diagnoses to make, as a result of the precise remedy can change a life. The basic clues for BAD – like prior cholecystectomy or ileal resection – are useful however usually missing. Typically we diagnose BAD by way of remedy. However which remedy? The reply(s) are rising, and they’re doing so on the again of tales that spotlight the thrill of scientific investigation.
The Commonplace: Bind and Hope
The standard strategy is a bile acid sequestrant reminiscent of cholestyramine or colesevalam. This works by binding extra bile acids within the colon to allow them to’t drive secretory diarrhea. It really works. However not at all times. Only half of patients on colesevelam obtain a higher than or equal to 25% discount in stool frequency.
The Twist: GLP-1 Receptor Agonists
In 2019, Knop and colleagues reported on two patients with BAD from Copenhagen. They went into remission on liraglutide prescribed to deal with their diabetes. The authors proposed a chic mechanism. Liraglutide slows higher GI motility, giving the small gut extra contact time to passively and actively reabsorb bile acids earlier than they attain the colon. That reabsorption boosts FGF19 secretion from enterocytes, which alerts the liver by way of FXR to cut back bile acid synthesis.
Subsequent comes essentially the most inspiring half.
That mechanistic speculation held up in an actual trial revealed in 2022. The Lancet Gastroenterology & Hepatology revealed these investigators’ randomly assigned, double-blind, active-comparator trial of liraglutide versus colesevelam in 52 sufferers with SeHCAT-confirmed BAD. The first final result was a higher than or equal to 25% stool-frequency discount. Liraglutide achieved this for 77% of sufferers versus 50% on colesevelam.
I’ve noticed these results in my very own clinic. With liraglutide but in addition semaglutide. It’s at all times a celebration. Of be aware, these experiences don’t make for sturdy proof, and these authors additionally imagine different GLP-1 receptor agonists are unlikely to be efficient. Additional real-world proof is required to information clinicians like me and determine which sufferers and therapies work.
What’s Subsequent: Statins
The identical Copenhagen group is now testing a totally completely different angle: atorvastatin. Statins decrease intracellular ldl cholesterol in hepatocytes, which is the substrate for bile acid synthesis. Once more, the story begins in the clinic with an observation. As with GLP-1 receptor agonists, the authors proceed to encourage. They’re testing their principle in a scientific trial: NCT07042165. “Therapy of Bile Acid Diarrhea With Atorvastatin,” led by Dr. Asger Lund, is now underway.
Why This Issues
For a situation this underdiagnosed and this treatable, it’s a pleasant reminder to maintain BAD on the differential for unexplained persistent diarrhea, and to know there’s a couple of instrument within the field when first-line sequestrants fail.
There are few instances in my profession that I’ve been really excited to learn a paper. I vividly bear in mind studying about liraglutide in 2022. I like instructing the fellows in regards to the physiology behind it, each to enhance affected person outcomes and to unfold the enjoyment of scientific investigation. The enjoyment that comes from carrying scientific inspirations by way of to trials that may change apply.
