Table 1 Characteristics and main findings of included articles. Se - sensitivity, Sp – Specificity

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.