Table 1.

Characteristics and main findings of included articles. Se - sensitivity, Sp – Specificity

Author, (year), reference	Country	Study design	Number of patients /females	Study population	Method used to identify BAM	Se	Sp	Main findings
Vijayvargiya. P, 2019 [14]	USA	Retrospective case-control study	n = 124(109)	IBS-D, IBS-C and healthy volunteers	Total fecal 48-h BA in combination with primary fecal BAs	49%	91%	Primary BAs > 10% identified patients with increased fecal weight (sensitivity 49% and specificity 91%) and rapid colonic transit (sensitivity 48% and specificity 87%
Vijayvargiya. P, 2019 [15]	USA	Retrospective case-control study	n = 220(171)	HV, IBS-D and IBS-C	Fecal bile acids and fecal fat	76%	72%	Reduced total and primary fecal bile acids and increased fecal lithocholic acid were significant predictors of decreased fecal weight, frequency and consistency.
Battat R., 2019 [16]	USA	Prospectively cross-sectional study	n = 78 (47)	Crohn’s disease (CD) - IR, NR-CD and UC	C4	90%	84%	A cutoff concentration of C4 of 48.3 ng/mL or greater identified patients with diarrhea attributable to BAM with 90.9% sensitivity, 84.4% specificity
Donato L., 2018 [17]	USA	Prospectively cross-sectional study	n = 184 (110)	IBS-C, IBS-D, Healthy subjects	C4	82%	53%	Higher levels of C4 was found in patients with BAM compared to those without BAM with sensitivity/specificity of 82%/53%.
Vijayvargiya P., 2017 [18]	USA	Prospectively cross-sectional study	n = 101 (n = 83)	IBS-D	C4 and FGF19	50%	65%	Data demonstrated a higher specificity (83%) with a higher cut-off of 52.5 ng/mL.
Camilleri M., 2014 [19]	USA	Prospectively cross-sectional study	n = 124 (111)	IBS-D, IBS-C and HS	Total fecal 48-h BA in combination with primary fecal Bas	75%	75%	Estimated the specificity of the individual traits or models at 60% sensitivity for discriminating between the groups, with specificity ranging from 75% for IBS-D versus health, to 90% for IBS-D versus IBS-C
Pattni S., 2013 [11]	UK	Prospectively cross-sectional study	n = 72 (47)	Chronic diarrhoea of unknown aetiology	FGF19 compare to SeHCAT	67%	77%	NPV and PPV of FGF19 ≤ 145 pg/mL for a SeHCAT < 10% were 82 and 61%. Data suggest that FGF19 could predict response to sequestrant therapy
Pattni S., 2012 [20]	UK	Prospectively cross-sectional study	n = 258 (180)	patients with chronic diarrhea	FGF-19 + C4	58% 74%	79% 72%	The sensitivity and specificity of FGF19 at 145 pg/ml for detecting a C4 level > 28 ng/ml were 58 and 79%, respectively. For C4 > 60 ng/ml, these were 74 and 72%;
Brydon WG., 2011 [21]	Scotland	Prospectively cross-sectional study	n = 196 (108)	Patients with unexplained diarrhea	C4 BAM type 1 C4 BAM type 2 compare to SeHCAT	97% 90%	74% 77%	ROC analysis yielded a sensitivity/specificity of 90%/77% for type 1 BAM (ileal disease/resection) and 97%/74% for type 2 BAM (idiopathic) using 30 ng/mL as the upper limit of normal for serum C4
Lenicek M., 2011 [22]	Czech Republic	Prospectively cross-sectional study	n = 466 (267)	Crohn’s disease, Ilear Crohn’s resection and Healthy Subjects	FGF19 and C4	80%	68%	FGF19 levels maximizing precision was set to < 60 ng/L. In this case, the sensitivity and specificity of FGF19 as a marker of BAM reached 80 and 68%. BAM was also present in a substantial number of the patients with CD
Sauter GH, 1999 [23]	Germany	Prospective cross-sectional study	n = 129 (68)	HS + chronic diarrhea of unknown origin	C4 Compare to SeHCAT	90%	79%	75SeHCAT test yielded the same results in 19/23 (83%) patients. BAM was identified by an increase of C4 in serum with a sensitivity of 90% and a specificity of 79%.
Brydon WG, 1996 [24]	UK	Prospective case-control study	n = 164 (108)	chronic diarrhoea investigated prospectively	C4 Compare to SeHCAT	NPV 74% 100%	PPV 94% 96%	The positive predictive value of serum C4 was 74%. The high negative predictive value (98%) of serum c4
Balzer K, 1993 [25]	Germany	Prospective case-control study	n = 64	HS and patients with ileal disease or resection	SeHCAT	80%	96%	75SeHCAT retention test: sensitivity 80%, specificity 98%, accuracy 89%
Scheurlen C, 1988 [26]	Germany	Prospective case-control study	n = 64	Crohn’s disease	SeHCAT	59.6%	100%	At a specificity of 100% the sensitivity of the SeHCAT test was 59.6% and the efficiency was 67.2%.
Sciarretta G, 1987, [27]	Italy	Prospective case-control study	n = 46 (26)	healthy volunteers, distal ileum resection, Crohn’s and chronic diarrhea	SeHCAT	100%	94%	SeHCAT found to be the most suitable for differentiating between the groups, giving the 75SeHCAT test a 94% sensitivity and a 100% specificity. The data show that this test is a valid indicator of bile acid loss.
Merrick MV, 1985 [28]	UK	Prospective case-control study	n = 42	IBS and Ileal resection	SeHCAT	97%	80–99%	The diagnosis was established by measuring the proportion of SeHCAT, a synthetic bile salt, retained 1 week after oral administration of a tracer dose of less than 100F/kg of the compound labelled with 40 kBq (1. Ci) of selenium-75.