Biochemical Diagnosis of Bile Acid Diarrhea: Prospective Comparison With the 75Seleno-Taurohomocholic Acid Test

Abstract

INTRODUCTION: The diagnosis of bile acid diarrhea is often missed because the availability of the 75seleno-taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test. METHODS: Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537). RESULTS: Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19–46) vs 8 (7–11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROCAUC) for C4 was 0.83 (0.72–0.93). C4 < 15 ng/mL had 85% (74%–96%) negative predictive value; C4 > 48 ng/mL had 82% (59%–100%) positive predictive value. Twenty patients had C4 values 15–48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53–146) vs 119 (84–240) (P = 0.004); ROCAUC was 0.71 (0.58–0.83). Stimulated FGF19 responses did not differ (P = 0.54). DISCUSSION: We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).

Effect of cholecystectomy on bile acid diarrhoea biomarkers: A prospective clinical study

“…The dotted lines show cut‐offs suggestive of bile acid diarrhoea; ie. FGF19 < 60 pg/mL 13 and C4 > 30 13,15 or >48 16,31,32 …”

“…We included seven patients with a history of cholecystectomy in a previous study on the biochemical diagnosis of bile acid diarrhoea. 13 The seven patients had a median 1-week SeHCAT retention of 8.7%…”

“…We therefore retrieved data on relevant cases from a previous study. 13 Further studies should include stool samples for assessment of microbiota [36][37][38] and faecal bile acids. 9,39 We conclude that cholecystectomy increased the FGF19 response, which may reflect an accelerated enterohepatic circulation of bile acids.…”

“…1 The bile synthesis rate may be assessed with plasma 7α-hydroxy-4-cholesten-3-one (C4), 8,9 whereas ileal reabsorption of bile acids may be assessed with plasma fibroblast growth factor 19 (FGF19). 10,11 Patients with bile acid diarrhoea diagnosed with the gold standard 75-seleno Tauro-homocholic acid (SeHCAT) retention test have lower fasting FGF19 12,13 and higher fasting C4 [13][14][15][16] than diarrhoea controls as does patients with postcholecystectomy bile acid diarrhoea. [12][13][14] Reports on the specific effects of cholecystectomy on the biomarkers are limited-however, two studies found substantial changes in FGF19 and C4 but only minor impact on bowel habits.…”

“…10,11 Patients with bile acid diarrhoea diagnosed with the gold standard 75-seleno Tauro-homocholic acid (SeHCAT) retention test have lower fasting FGF19 12,13 and higher fasting C4 [13][14][15][16] than diarrhoea controls as does patients with postcholecystectomy bile acid diarrhoea. [12][13][14] Reports on the specific effects of cholecystectomy on the biomarkers are limited-however, two studies found substantial changes in FGF19 and C4 but only minor impact on bowel habits. 17,18 The reference ranges for FGF19 and C4, therefore, may need adjustment for cholecystectomy status.…”