Systematic Review

Duodenogastroesophageal (Biliary) Reflux Prevalence, Symptoms, Oesophageal Lesions and Treatment

Chamara Basnayake; Annelies Geeraerts; Ans Pauwels; Ger Koek; Michael Vaezi; Tim Vanuytsel; Jan Tack


Aliment Pharmacol Ther. 2021;54(6):755-778. 

In This Article

Abstract and Introduction


Background: The prevalence of duodenogastroesophageal reflux (DGER) and its effect on symptoms and oesophageal lesions in gastroesophageal reflux disease (GERD) is unclear.

Aims: To conduct a systematic review to determine the prevalence of DGER among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER.

Methods: We searched Pubmed and MEDLINE for full text, English language articles until October 2020 that evaluated DGER prevalence among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER.

Results: We identified 3891 reports and included 35 which analysed DGER prevalence in GERD, 15 which evaluated its effect in non-erosive reflux disease (NERD), 17 on erosive oesophagitis, 23 in Barrett's, and 13 which evaluated the treatment of DGER. The prevalence of DGER, when evaluated by Bilitec, among all GERD patients ranged from 10% to 97%, in NERD 10%-63%, in erosive oesophagitis 22%-80% and in Barrett's 50%-100%. There were no differences in the presence or degree of DGER among patients who were asymptomatic or symptomatic on proton pump inhibitors (PPI). The most commonly evaluated treatments for DGER were PPIs and DGER reduced post-PPI therapy in all studies.

Conclusions: The prevalence of DGER increased with more advanced oesophageal lesions and did not explain persisting symptoms among patients taking PPI therapy. PPIs appear to be effective in the treatment of DGER. DGER remains an important consideration in patients with GERD and future therapies deserve more study.


Gastroesophageal reflux disease (GERD) is defined by refluxed gastric content into the oesophagus causing symptoms and/or oesophageal lesions. Oesophageal lesions range from erosive oitis to Barrett's ous and many patients with typical GERD symptoms have a macroscopically normal appearance of the oesophagus.[1] Traditionally, oesophageal injury in GERD patients was conceptualised as the result of chemical caustic effects from luminal factors, with the key factors in this paradigm thought to be acid and pepsin, causing direct injury to the epithelium.[2] Since the advent of effective acid suppressive therapies, such as proton pump inhibitors (PPIs), there has been significant improvement in controlling symptoms and complications which arise from GERD.[3] However, a substantial proportion of patients continue to suffer from symptoms and complications of GERD despite adequate PPI therapy. The contributing factors to symptoms in patients with GERD are complex, as significant numbers of patients have symptoms in the absence of erosive changes or significant acid reflux detected on 24 hours pH monitoring.[1] Furthermore, oesophageal lesions can develop, despite an absence of gastric acid, such as in achlorhydria[4] or after gastrectomy[5] which counters the idea that acid is the sole mediator of oesophageal injury in GERD. In this context other injurious and symptom inducing substances in the oesophagus, besides acid, should be considered.

Duodenogastroesophageal reflux (DGER), commonly referred to as "bile reflux", is the pathophysiological entity which is the reflux of duodenal content, including bile, by way of the stomach into the oesophagus. Duodeno-gastric reflux is a normal physiological phenomenon which occurs after meals in both health and disease.[6] GERD involves the reflux of gastric content which can include bile and other duodeno-gastric refluxate constituents.[6] Various methods have been utilised to establish the presence of duodenal contents, such as bile acids in the oesophagus, to support the presence of DGER. Early studies demonstrated the presence of bile, trypsin and alkaline substances by aspiration,[7,8] endoscopic biopsies[9,10] and scintigraphy.[11] Several studies, both in vivo and in vitro, have implicated duodenal contents in the pathogenesis of oesophageal GERD lesions. More contemporary studies have replaced aspiration measurements with ambulatory fiberoptic spectrophotometric bilirubin readings, for example, Bilitec 2000 (Medtronic), which quantify DGER by measuring bilirubin. Bilirubin, a constituent of bile, has a characteristic absorption wavelength of 450 mm which is measured by the Bilitec probe. Validation studies have shown that fiberoptic readings with the Bilitec system correlate well with aspiration measures of bilirubin.[12]

Since the widespread availability of oesophageal pH-impedance monitoring, the use of the Bilitec 2000® has almost completely disappeared. The underlying assumption is often that impedance monitoring accounts for "non-acid" reflux detection. However, this is not an equivalent of "bile reflux" as ambulatory pH and Bilitec 2000 studies in the absence of acid suppressive therapy have shown that DGER usually occurs at an acidic pH.[13–15] Furthermore, recent trials[16] which have directly attempted to address bile as a constituent of GERD, have demonstrated improved symptoms and lesions in patients with GERD. Despite this knowledge, there has been a little systematic examination of the literature regarding the prevalence of DGER, its effect on symptoms and oesophageal lesions and which treatments are effective. In this systematic review, we aimed to evaluate the prevalence of DGER, the effect of DGER on symptoms and oesophageal lesions. We also aimed to evaluate the treatment of DGER.