Esophageal Visceral Sensitivity to Bile Salts in Patients with Functional Heartburn and in Healthy Control Subjects

Abstract

Patients with nonerosive gastroesophageal reflux disease often have relatively low esophageal acid exposure and respond suboptimally to gastric acid suppression. In these patients, other constituents of gastric contents may induce esophageal symptoms. We have demonstrated that gastric contents can cause heartburn when the gastric pH >4. (Aliment Pharm Ther 14:129-134, 2000). The aim of this study was to determine relative sensitivities to chenodeoxycholic and ursodeoxycholic acids, and 0.1 N HCl, administered as provocative perfusion tests. Patients with functional heartburn and healthy control subjects were evaluated. Patients underwent a modified Bernstein acid infusion test and esophageal Barostat balloon distention. Time and volume to pain were recorded. Barostat balloon distention was performed using our standard protocol. Stepwise distentions were performed and pain was recorded. Sensitivity to chenodeoxycholic acid (Cheno) and Ursodeoxycholic acid (Urso) were assessed similarly to the Bernstein test using 2 mM concentrations of each, followed immediately by 5 mM if no pain was reported with 2 mM. Volume of bile acid infusion and length of time until pain was induced were assessed and compared to the same endpoints for acid sensitivity. "Total" time and "total" volume to induce pain were calculated for Cheno and Urso. Least-squares means were generated and two-tailed t-tests and regression analyses were performed (P < 0.05 level of significance). Ten functional heartburn patients and six healthy controls were evaluated (3 M, 13 F; age range, 19 to 56 years). Since five of six controls had pain with acid infusion (hypersensitive), all subjects were analyzed as one group. Only three subjects (all controls) had no pain with infusion of 2 mM Cheno and received the follow-up infusion of 5 mM. These same three subjects tolerated the maximum infusion (150 ml and 15 min) of 5 mM Cheno. Nine subjects did not have pain with 2 mM Urso and received the follow-up infusion of 5 mM Urso (five functional heartburn, four controls). Significantly more subjects tolerated the maximum bile acid infusion of 2 mM Urso vs 2 mM Cheno (nine vs three; P < 0.05, Chi-square test). The pain threshold (volume and time) for Urso was significantly higher than that for Cheno and acid (P < 0.05), and the pain threshold for Cheno was significantly higher than that for acid (P < 0.05). Conclusions are as follows: (1) Bile acids differ in their ability to induce pain. (2) Changing bile acid composition by treatment with Urso may change symptom presentation and symptom severity in patients with bile acid-induced esophageal pain.

Yield of 24-Hour Esophageal pH and Bilitec Monitoring in Patients with Persisting Symptoms on PPI Therapy

“…The nature of the stimulus that induces heartburn during weakly acidic reflux events has not been identified, but besides acid acting at pH above 4, bile is a potentially important contributor [21]. Esophageal perfusion with bile acids is able to induce a sensation of heartburn [22], and bile reflux has previously been implicated in the pathogenesis of heartburn in patients with pernicious anemia [23]. The Bilitec Ò 2000, a fiber-optic spectrophotometric probe, was developed to quantify duodeno-gastro-esophageal reflux (DGER) in an ambulatory fashion, and validation studies confirmed a good correlation between Bilitec Ò measurements and bile acid concentrations [24][25][26].…”

Clinical Case Report of PPI-refractory Gastro-Esophageal Reflux Disease (GERD) with Korean Medicine Treatment - A Focus on Evaluation of the Abdominal Examination

“…This finding also supports the non-acid-dependent role of esophageal hypersensitivity in the presentation of reflux symptoms (43). Interestingly, another study showed that infusion of bile salts into the esophagus can induce pain in 100% of patients previously diagnosed with functional heartburn and also induced pain in some of the healthy controls (44).…”

Weakly Acidic Reflux

“…Bile components are one valid candidate, as esophageal perfusion of bile acids is also able to induce heartburn [14] , and as similarly, bile reflux monitoring on PPI revealed a higher proportion of symptom episodes related to duodenogastroesophageal reflux as compared to acid reflux events [20] . On the other hand, the relationship between bile reflux and weakly acidic reflux is poorly studied, and the available evidence suggests that bile reflux most often accompanies acid reflux events, while many nonacid reflux episodes do not seem to contain bile [26,27] .…”

“…During ambulatory pH monitoring studies, less than half of the reported heartburn episodes in GERD patients were associated with acid reflux [9] . Finally, esophageal perfusion of bile acids is also able to induce heartburn [14] .…”