From the Guidelines
The 7alphaC4 test is a blood test used to diagnose bile acid malabsorption, measuring the level of 7alphaC4, an intermediate product in bile acid synthesis, with elevated levels indicating bile acid malabsorption. This test is particularly useful for diagnosing the cause of chronic diarrhea, especially in patients with irritable bowel syndrome with diarrhea (IBS-D) or those who have had their gallbladder removed 1. The test requires a fasting blood sample, typically drawn in the morning when levels are most stable.
Key Points
- The 7alphaC4 test measures the level of 7alphaC4, which is an intermediate product in bile acid synthesis.
- Elevated levels of 7alphaC4 indicate that the body is producing more bile acids than normal, suggesting bile acid malabsorption.
- The test is preferred over older methods like the SeHCAT test because it's simpler, faster, and doesn't involve radiation.
- Results are typically available within a few days, and if bile acid malabsorption is confirmed, treatment with bile acid sequestrants like cholestyramine, colestipol, or colesevelam is usually recommended.
- A level of 7alphaC4 above 47.1 ng/mL is indicative of bile acid diarrhea, with a negative predictive value of 95% and a positive predictive value of 74% compared to SeHCAT testing 1.
Diagnostic Criteria
- The test has a negative predictive value of 95% and a positive predictive value of 74% compared to SeHCAT testing.
- A level of 7alphaC4 above 47.1 ng/mL is indicative of bile acid diarrhea.
- The test is useful in diagnosing bile acid malabsorption in patients with chronic diarrhea, especially those with IBS-D or those who have had their gallbladder removed.
Treatment
- If bile acid malabsorption is confirmed, treatment with bile acid sequestrants like cholestyramine, colestipol, or colesevelam is usually recommended.
- The treatment aims to reduce the symptoms of bile acid malabsorption, such as diarrhea, and improve the patient's quality of life.
From the Research
Definition of 7alphaC4 Test
- The 7alphaC4 test is a method for monitoring the enzymatic activity of hepatic cholesterol 7alpha-hydroxylase (C7alphaOH; CYP7A1) by assaying the stable bile acid intermediate 7alpha-hydroxy-4-cholesten-3-one (C4) in peripheral blood 2, 3.
- This test is used to determine the relative rates of bile acid production in humans, as the level of C4 in peripheral blood serum or plasma shows a strong correlation to the enzymatic activity of hepatic C7alphaOH 3, 4.
Mechanism of the Test
- 7alpha-hydroxy-4-cholesten-3-one (C4) is an oxidative enzymatic product of cholesterol metabolism via cholesterol 7alpha-hydroxylase, an enzyme also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) 5.
- C4 is a stable intermediate in the rate-limiting pathway of bile acid biosynthesis, and its plasma levels reflect the activity of CYP7A1 5, 6.
Clinical Applications
- The 7alphaC4 test can be used to clarify the regulation of bile acid synthesis in vivo in laboratory animals and humans, allowing for the monitoring of hepatic C7alphaOH activity using peripheral blood samples 2.
- This test has been applied to pre-clinical studies and can be used to determine the relative rates of bile acid production in humans, making it a convenient marker for the semiquantitative assessment of bile acid synthesis 5, 4.