Introduction

Acute variceal bleeding is a life-threatening decompensating event in the natural history of cirrhosis. Endoscopic variceal ligation (EVL) along with non-selective beta blockers or carvedilol are current standard of care for patients with acute esophageal variceal bleeding. Use of proton pump inhibitors (PPI) in post EVL period is more of a personal choice as various society guidelines do not recommend continuation of PPI after EVL owing to low quality of evidence to support their use. The literature regarding the benefits of PPI in post EVL re-bleeding and mortality is heterogeneous without any clear answer particularly for mortality.

Aims & Methods

We conducted a single centre, outcome assessor blinded prospective randomized control trial where patients of liver cirrhosis with suspected or documented acute variceal bleeding were screened and those who underwent EVL were randomized into PPI or No-PPI group. Patients in the PPI group received Tab esomeprazole 40 mg once a day in addition to standard of care for all the patients. Both groups were followed up at 2 weeks post index EVL after randomization for occurrence of rebleeding and a repeat upper gastrointestinal endoscopy (UGIE) to document presence or absence of post EVL ulcers, their number and size. All patients were again followed up at 3 months for development of recurrent bleeding, mortality and adverse effect like pain and dysphagia post EVL. Primary outcome was to compare the rate of recurrent bleeding after EVL between the 2 groups. Secondary outcomes were to assess the difference in mortality, number and size of post EVL ulcers and adverse effects in the form of pain and dysphagia post EVL. Association between categorical outcomes was assessed by cross tabulation and comparison of percentages. Chi square test was used to test statistical significance. The association between quantitative variables was assessed by independent sample t-test to assess statistical significance. A p value of <0.05 was considered significant.

Results

A total of 246 patients were screened from June 2023 to April 2024 and 170 patients were randomized to both the groups. Baseline parameters were comparable between the groups. In the primary outcome, number of patients who developed recurrent bleeding episode were 23 (28.05%) in the no-PPI group, which were significantly more in comparison to 9 (11.54%) in the PPI group (p=0.009). Among the secondary outcomes, incidence of mortality was higher in the no-PPI group [16 (19.51%) vs 13 (16.67%) respectively], although statistically non-significant (p=0.640). All 16 (100%) deaths in the no-PPI group were related to rebleeding episode in comparison to only 5 (38.46%) deaths in the PPI group (p=0.035). Incidence of post EVL ulcers was significantly more in the no-PPI group [65 (86.67%) vs 22 (30.99%) respectively; p<0.001]. Median post EVL ulcer number and size were also significantly higher in the no-PPI group [1 (IQR 1,2) vs 0 (IQR 0,1) (p=<0.001); 6 mm (IQR 5,8) vs 5 mm (IQR 5,6) (p=0.0061) respectively]. At 2 weeks, chest pain was reported by 7 (9.33%) patients in the no PPI group vs 2 (2.82%) patients in the PPI group (p=0.167). No patient reported dysphagia at 2 weeks. No patient reported chest pain or dysphagia at 3 months.

Conclusion

Prescription of PPI after EVL in patients of liver cirrhosis with acute esophageal variceal bleeding is beneficial as it significantly decreases the recurrent bleeding episodes as well as mortality in such patients.

Introduction

Pathological esophageal acid exposure may persist in patients with Barrett’s esophagus (BE) despite standard proton pump inhibitor (PPI) therapy and symptom control, although current guidelines recommend at least standard-dose PPI for all patients with BE.¹

Aims & Methods

Aim was to evaluate the role of esophageal function testing in assessing acid exposure in BE patients on PPI therapy and in predicting neoplastic progression. We conducted a multicenter retrospective study including asymptomatic BE patients (defined by GerdQ total score <8 and a score of 0 on the first GerdQ item) who underwent high-resolution manometry and 24-hour pH impedance monitoring while on various PPI regimens. Maximal PPI therapy included esomeprazole 40 mg, pantoprazole 40 mg, rabeprazole 20 mg, or lansoprazole 30 mg, all administered twice daily. All other regimens were considered standard dosing. Index upper endoscopy with biopsies was performed under the same therapeutic regimen. Histologically, presence and degree of neoplasia (all confirmed by a second pathologist) was recorded. Acid exposure time (AET) <4% was defined as adequate acid control; AET >6% as pathological reflux. Predictors of pathological reflux and neoplasia were assessed using logistic regression analysis.

Results

A total of 135 patients (2016-2025) were included (mean age 58 ± 15 years; 73% male). Median BE length was C1 (range 0–3 cm) and M2 (range 1–5 cm), with 41% (n=56) classified as having long-segment BE. Sixty-seven patients (50%) were on standard-dose PPI. Pathological reflux was identified in 37 patients (27%), of whom 25 (67%) were on standard-dose therapy. Fourteen patients (10%) had borderline AET values (4–6%). Among the 84 patients (62%) with adequate acid control, 33 (39%) were taking standard-dose PPI. On multivariable analysis, standard-dose PPI (OR 3.04; 95% CI 1.34–6.89; p=0.008) and type III esophagogastric junction morphology (OR 2.52; 95% CI 1.01–5.01; p=0.047), consistent with manometric hiatal hernia, were independently associated with pathological reflux. Non-dysplastic BE was found in 112 patients, while 13 (10%) had neoplasia at index endoscopy (8 low-grade dysplasia, 3 high-grade dysplasia, 2 intramucosal adenocarcinoma). Pathological reflux was the only independent predictor of neoplasia (OR 10.41; 95% CI 2.65–41.26; p<0.001).

Table 1. Logistic regression analysis for factors associated with neoplasia on index endoscopy.

Conclusion

Nearly one-third of asymptomatic BE patients exhibit pathological reflux on pH-monitoring despite PPI treatment, predominantly among those on standard-dose and with manometric hiatal hernia. Nonetheless, adequate acid control is achieved in over one-third of patients on standard PPI therapy. Pathological reflux is associated with a 10-fold increased risk of neoplasia.

References

1. Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol. 2022;117(4):559-587.