Date of study |
Author |
Country |
Method of assessing DGER |
Definition of pathologic DGER |
Patient population/subgroups |
Number of participants |
Prevalence of bile reflux |
Degree of bile reflux |
1988 |
Johnsson et al8 |
Sweden |
Oesophageal bile aspiration |
Not predefined |
HV vs GERD |
Total participants: 28 10 HV vs 18 patients |
Total DGER among patients: 94% (17/18) |
Not presented |
1993 |
Iftikhar et al70 |
UK |
Oesophageal bile aspiration |
Total bile acid concentration, >1105 μmol/L (95% centile upper limit, healthy controls) |
HV vs GERD vs Barrett's |
Total participants: 60 15 HV vs 30 Barrett's vs 15 GERD |
Erosive GERD 20% (3/15) Barrett's 50% (15/30) |
Erosive GERD: median 817.3 μmol/L (range 123.8–5721) Barrett's: median 1351.7 μmol/L (range 0–14 011) |
1994 |
Stein et al71 |
United States |
Oesophageal bile aspiration |
Total bile acid concentration >88 μmol/L (>95 centile for healthy controls) |
HV vs GERD |
Total participants: 95 43 HV vs 52 GERD |
Not presented |
GERD: Supine mean 107.7 μmol/L ± 24.6 SEM |
1994 |
Champion et al30 |
United States |
Bilitec 2000 |
% time absorbance >0.14 |
HV vs GERD vs Barrett's |
Total participants: 45 (35 applicable for this review) 12 HV vs 13 GERD vs 10 Barrett's (10 partial gastrectomy not reviewed) |
Not presented as total number |
Time absorbance was pathological: GERD absorbance mean ~12% Barrett's absorbance mean ~42% |
1995 |
Caldwell et al72 |
Ireland |
Bilitec 2000 |
% time absorbance >0.15 |
HV vs GERD vs Barrett's |
Total participants: 36 11 HV vs 13 GERD vs 12 Barrett's |
Not presented |
Time absorbance was pathological: GERD supine median 2.4% (range 0–37.9) Barrett's supine median % 12.9 (range 0–92.5) |
1996 |
Vaezi et al28 |
United States |
Bilitec 2000 |
% time absorbance >0.14, abnormal: >1.8% time >0.14 (95th centile of healthy controls) |
HV vs GERD vs Barrett's |
Total participants: 70 20 HV vs 16 NERD vs 14 erosive oesophagitis vs 20 Barrett's |
NERD 63% (10/16) Erosive oesophagitis 79% (11/14) Barrett's 95% (19/20) |
Time absorbance was pathological: NERD median 3.2% (range 0%-37%) Erosive oesophagitis median 14.6% (range 0–44) Uncomplicated Barrett's 23% (range 0–44) Complicated Barrett's median 46% (range 21–78) |
1997 |
Marshall et al48 |
UK |
Bilitec 2000 |
% time absorbance >0.14, or 2 min either side of symptom event having >10 s of absorbance >0.14 |
GERD split in two groups: With acid reflux vs no acid reflux |
Total participants: 59 |
Not presented |
Time absorbance was pathological: With acid reflux median 13.25% (IQR 5.3–26.5) Non acid reflux patients median 0.1% (IQR 0–1.7) |
1997 |
Kauer et al73 |
Germany |
Oesophageal bile aspiration |
Pathological bile reflux was defined by the 95th centile cut-off from their healthy population |
HV vs GERD |
Total participants: 80 43 HV vs 37 GERD |
Trace bile detected in GERD patients 86% (32/37) |
Not presented |
1998 |
Marshall et al74 |
UK |
Bilitec 2000 |
% of time absorbance >0.14 |
HV vs GERD vs Barrett's |
Total participants: 128 15 HV vs 63 NERD vs 23 erosive oesophagitis vs 27 Barrett's |
Not presented |
Time absorbance was pathological: NERD median 2.6% (IQR 0–8) Erosive oesophagitis median 9.1% (IQR 0.7–37.5) Barrett's median 16% (IQR 5–38.2) |
1998 |
Stein et al29 |
Germany |
Bilitec 2000 |
% of time absorbance >0.25, abnormal >6.9% of time >0.25 absorbance (95th centile cut-off of healthy controls) |
HV vs NERD vs erosive oesophagitis vs Barrett's no dysplasia vs Barrett's with adenocarcinoma |
Total participants: 131 20 HV vs 19 NERD vs 45 erosive oesophagitis vs 33 Barrett's without dysplasia vs 12 Barrett's with early adenocarcinoma vs 2 Barrett's with High grade dysplasia |
NERD 10.5% (2/19) Erosive oesophagitis 22% (10/45) Barrett's 62% (29/47) |
Not presented |
1998 |
Oberg et al19 |
United States |
Bilitec 2000 |
% time absorbance >0.2 Abnormal: >1.7% time absorbance >0.2 |
NERD vs erosive oesophagitis vs Barrett's (short segment vs long segment) |
Total participants: 262 130 NERD vs 70 erosive oesophagitis vs 30 short segment Barrett's, 32 long segment Barrett's |
NERD 30% (39/130) Erosive oesophagitis 61.4% (43/70) Barrett's 79% (49/62) |
NERD median 0.1% (IQR 0–2.6) Erosive oesophagitis median 4.2% (IQR 0.2–21.7) Short segment Barrett's median 7.9% (IQR 1.2–18.4) Long segment Barrett's median 15.7% (IQR 4.2–30.5) |
1999 |
Nehra et al75 |
UK |
Oesophageal bile aspiration |
Not predefined |
HV vs GERD & Barrett's |
Total participants: 40 10 HV vs 10 NERD vs 10 erosive oesophagitis vs 10 Barrett's |
Not presented |
NERD median peak bile acids 14 mmol/L (range 0–257) Erosive oesophagitis peak bile acid 124 mmol/L (range 6–1020) Barrett's median peak bile acids 181 mmol/L (range 30–820) |
2000 |
Marshall et al76 |
UK |
Bilitec 2000 |
% time absorbance >0.14. Abnormal >7% of time absorbance >0.14 |
GERD |
Total participants: 113 |
All participants with GERD 51% (58/113) NERD 17% (7/41) Erosive oesophagitis 64% (29/45) Barrett's 81% (22/27) |
Time absorbance was pathological: All patients mean (range): Bile reflux only mean 12.2% (range 6.5–20.7) Acid and bile reflux mean 18.1% (range 3.6–61) |
2000 |
Cuomo et al77 |
Belgium |
Bilitec 2000 |
% time absorbance >0.14, abnormal was >9.6% of time >0.14 absorbance |
GERD with erosive oesophagitis |
Total participants: 84 |
NERD 38% (17/45) Erosive oesophagitis and Barrett's 46% (18/39) |
Time absorbance was pathological: NERD mean 6.1% ± 1.5 SEM Grade I-II mean 8.2% ± 2.6 SEM Grade III-IV and Barrett's mean 16.1% ± 4.2 SEM |
2001 |
Campos et al27 |
United States |
Bilitec 2000 |
Abnormal absorbance >0.2 for >1.7% of time |
GERD patients being evaluated for Barrett's, subset with Bilitec |
Total participants: 502 (only 206 completed Bilitec) All patients GERD on pH, 174 of 502 with Barrett's |
Not presented |
Time absorbance was pathological: GERD: median 3.0% (IQR 0.1–10.7) Short segment Barrett's median 13.3% (IQR 2.8–26.5) Long segment Barrett's median 17.3% (IQR 6.9–34.4) |
2001 |
Menges et al32 |
Germany |
Bilitec 2000 |
% of time absorbance >0.2 |
Erosive oesophagitis vs Barrett's |
Total participants: 43 20 erosive oesophagitis vs 23 Barrett's |
Not presented |
Time absorbance was pathological: Erosive oesophagitis median 12.8% (IQR 1.9–74.9) Barrett's median 34.7% (IQR 0.3–84.6) |
2001 |
Koek et al13 |
Belgium |
Bilitec 2000 |
% time absorbance >0.14, >0.14 for more than 10 s, episodes >5 min >0.10 |
GERD |
Total participants: 72 |
Not presented |
Of 544 symptom episodes 2 min window prior to symptom episode: mean absorbance 0.11 (±0.007) 4 min window mean absorbance 0.13 (±0.007) 2 min window for symptom association probability 7% SAP for DGER with 10% SAP for mixed (Acid & DGER) reflux |
2002 |
Osugi et al78 |
Japan |
Bilitec 2000 |
>% of time absorbance >0.15, Abnormal >5% time >0.15 |
HV vs GERD |
Total participants: 53 10 HV vs 43 GERD |
NERD 50% (3/6) Erosive oesophagitis 97% (36/37) |
Not presented |
2002 |
Zaninotto et al25 |
Italy |
Bilitec 2000 |
% time absorbance >0.2 |
HV vs GERD vs Barrett's |
Total participants: 78 12 HV vs 32 GERD vs 17 long segment Barrett's vs 8 short segment Barrett's vs 9 with ultra short segment Barrett's |
Not presented |
Long segment Barrett's had significantly greater % time absorbance >0.2. Mean ~12.5% (number not provided) |
2003 |
Tack et al20 |
Belgium |
Bilitec 2000 |
% of time absorbance >0.14 episode was considered >0.14 for greater than 10 s, upper limit of normal from healthy subjects used but not documented |
HV vs GERD |
Total participants: 251 40 HV vs 211 GERD |
NERD • Solid meals ~10%, (of 45 patients) • Liquid meals ~30% (of 54 patients) Erosive oesophagitis • Solid meals ~30% (of 26 patients) • Liquid meals ~44% (of 34 patients) |
NERD solid meals: median 7.7% (IQR 3.7–17), NERD liquid meals median 0.8% (IQR: 0–8.9) Erosive oesophagitis solid meals median 15.3% (IQR 4–42.1) Erosive oesophagitis liquid meals 3.8% (IQR 0.5–14.5) |
2003 |
Tack et al79 |
Belgium |
Bilitec 2000 |
% of time absorbance >0.14 |
Patients with GERD |
Total participants: 26 |
GERD patients 11/21 (52%) |
Time absorbance was pathological: Median 5.8% (IQR 0.7%-12.6%) |
2004 |
Cool et al80 |
Belgium |
Bilitec 2000 |
Absorbance >0.14 Pathological defined as previous identified >95th centile of HV population (not presented) |
HV vs GERD |
Total participants: 366 20 HV vs 346 GERD |
53% (183/346) |
Not presented |
2006 |
Xu et al23 |
China |
Bilitec 2000 |
Abnormal if absorbance >0.14 for >2.53% |
GERD |
Total participants: 95 |
NERD 48% (21/44) Erosive oesophagitis 71% (36/51) |
Time absorbance was pathological: NERD mean 7.26% ± 11.08 SD Erosive oesophagitis mean 19.05 ± 23.44 SD |
2007 |
Wolfgarten et al22 |
Germany |
Bilitec 2000 |
% of time absorbance >0.25, abnormal if >1.1% of time >0.25 |
HV vs erosive oesophagitis vs Barrett's. |
Total participants: 64 19 HV vs 24 Barrett's vs 21 erosive oesophagitis |
Erosive oesophagitis 71% (15/21) Barrett's 75% (18/24) |
Time absorbance was pathological: Erosive oesophagitis median 3.5% (IQR 0.1–13.5) Barrett's median 7.8% (IQR 1.6–17.8) |
2007 |
Gadel-hak et al81 |
Egypt |
Bilitec 2000 |
% time absorbance >0.14, abnormal if >0.14 for >1.9% |
HV vs GERD vs Barrett's |
Total participants: 91 Patients |
63% (57/91) NERD patients 36% (4/11) Erosive oesophagitis 62% (44/71) Barrett's 100% (9/9) |
Time absorbance was pathological: In all participants (including Barrett's) mean 8.46% ± 14.05. NERD mean 4.48 ± 8.99 SD Erosive oesophagitis mean 8.18% ± 11.28 SD Barrett's mean 15.48% ± 30.48 SD |
2008 |
Xiong et al21 |
China |
Bilitec 2000 |
Abnormal if absorbance >0.14 >1.9% of time |
NERD |
Total participants: 82 |
52% (43/82) |
Time absorbance was pathological: Mean 12.37% ± 22.1 SD |
2008 |
Koek et al49 |
Belgium |
Bilitec 2000 |
% time absorbance >0.14, episodes >5 min >0.14 |
GERD & Barrett's |
Total participants: 422 Suspected GERD 422 • Erosive oesophagitis 164 • Barrett's 30 |
51% (215/422) |
Time absorbance was pathological: All patients median 4.9% (IQR 0.8–20.2) NERD median 2.8% (IQR 0.3–12.4) Erosive oesophagitis median 8.8% median (IQR 2–25) Barrett's median 27.4% (IQR 12–4) |
2020 |
De Bortoli et al |
Italy |
Bilitec 2000 |
% time absorbance >0.14, >1.8% of time |
NERD, with acid exposure >4%, Partially responsive to PPI |
Total participants: 42 |
50% (21/42) |
Time absorbance was pathological: Median time bile reflux pathological 9.6% (IQR 8%-13%) |