Feb. 14, 2020
Bile acid diarrhea (BAD) is a common cause of chronic diarrhea and is characterized by excess bile acids (BAs) within the colon, resulting in increased colonic motility and secretion. Patients with BAD can also present with urgency and abdominal cramping.
In a commentary published in the April 2019 issue of Gastroenterology, Michael Camilleri, M.D., a gastroenterologist and researcher at Mayo Clinic's campus in Rochester, Minnesota, provides an overview of BAD and new developments in diagnostic approaches.
Who is at risk of developing bile acid diarrhea?
Bile acid diarrhea is subdivided into four major categories:
- Type I includes any ileal disease preventing the reabsorption of bile acids from the terminal ileum. This includes Crohn's disease, ileal resection and radiation ileitis.
- Type II is considered idiopathic, with no clear underlying cause. This type often presents as chronic diarrhea or diarrhea-predominant irritable bowel syndrome.
- Type III results from underlying diseases that are associated with malabsorption or biliopancreatic diseases, including chronic pancreatitis, celiac disease, cholecystectomy and some other diseases.
- Type IV stems from conditions that involve excessive BA synthesis without a clear source of impaired BA reabsorption. This type can occur in patients with hypertriglyceridemia or those treated with metformin.
What is the prevalence of BAD?
BAD is reported in about 25% to 33% of patients presenting with chronic diarrhea. Based on this data, BAD is estimated to affect approximately 1% of the population.
What diagnostic tests are available to detect BAD?
Currently, there are three major types of diagnostic tests available for BAD:
- The 75selenium homotaurocholic acid test (75SeHCAT)
- Serum biomarkers of hepatic BA synthesis (serum C4 and FGF19)
- Total and individual fecal BAs
The 75SeHCAT is considered the current gold standard for the diagnosis of BAD. However, it is not available in the United States. In the United States, the 48-hour total and individual fecal BAs are the gold standard. Although the serum testing is much more convenient, the sensitivity of the serum tests is not high enough for definitive diagnosis, and therefore the serum tests are best used as screening tests.
What does the 75 SeHCAT assess, and how is the test performed?
The 75SeHCAT is an imaging test that measures retention of radiolabeled bile acids. A gamma camera measures radiolabeled BA retained within the body at baseline (after ingestion of radiolabeled BA) and at seven days. Decreased retention of the radiolabeled BA suggests loss of BAs into the colon that is consistent with BAD.
What do serum biomarkers of hepatic BA synthesis measure, and how useful are these tests in diagnosing BAD?
The fasting serum testing for 7⍺-hydroxy-4-cholesten-3-one (C4) directly reflects hepatic BA synthesis; the higher the C4 value, the greater the hepatic BA synthesis. C4 is measured with high-performance liquid chromatography (HPLC) with mass spectrometry.
Fasting serum fibroblast growth factor 19 (FGF19) is an indirect marker of hepatic BA synthesis. FGF19 is a hormone produced within the ileum that provides negative feedback to the liver for hepatic BA synthesis; the higher the value of FGF19, the lower the hepatic BA synthesis. FGF19 is measured with enzyme-linked immunosorbent assay (ELISA). This is still a research test in the United States.
These fasting serum tests are ideally measured before 10 a.m. because of diurnal variation and meal-induced changes in serum C4 and FGF19. Overall, the serum fasting biomarkers are convenient, but they lack diagnostic accuracy when performed on their own. Fasting serum C4 is appropriate as a screening tool and is available via Mayo Medical Laboratories and other commercial testing facilities.
How useful are tests measuring total and individual BAs in stool?
Measurements of total and individual fecal BAs provide the most direct measure of excess BAs exiting the colon. Within the United States, a 48-hour measurement of total and individual fecal BAs provides the most efficient and accurate method to diagnose BAD. Research has established a significant correlation of total fecal BAs with the 75SeHCAT results, but no direct evaluation to determine sensitivity and specificity is available to date.
Currently, there are three validated definitions for bile acid diarrhea:
- Total fecal BAs greater than 2,337 µmol/48 hours
- Primary fecal bile acids greater than 10%
- Primary fecal bile acid greater than 4% with total fecal bile acids greater than 1,000 µmol/48 hours
What new testing options and improvements are currently in development?
Currently, the 48-hour fecal bile acid test requires a four-day, 100-gram fat diet and 48-hour stool collection. Researchers are currently testing the accuracy of a single, random stool sample together with a fasting serum C4 to determine whether this would be an acceptable alternative to the 48-hour fecal bile acid test. Refining the method by which total and individual fecal BAs are measured may help identify more individuals with BAD and help clinicians provide individualized care for these patients.
For more information
Vijayvargiya P, et al. Current practice in the diagnosis of bile acid diarrhea. Gastroenterology. 2019;156:1233.