Introduction

Gastroesophageal varices are present in approximately 50% of cirrhotic patients¹. The cirrhosis-related age-standardized mortality is high². Gastroesophageal variceal bleeding is a medical emergency with a mortality rate of approximately 10-20% at six weeks¹, and rebleeding incidence ranged from 32% to 84%³, and even higher, around 90%, in patients receiving no antiviral therapy⁴. Endoscopic variceal ligation (EVL) and endoscopic variceal obliteration (EVO) with cyanoacrylate are recommended for patients with acute variceal bleeding⁵, but both treatments have no impact on portal pressure⁶. Portal hypertension is the primary pathophysiological mechanism underlying gastroesophageal varices. Non-selective beta-blockers (NSBBs) induce vasodilation by targeting beta-receptors on blood vessels and the heart, reduce cardiac output through negative inotropic effects, thereby reducing portal blood flow and associated portal pressure^{7, 8}. Gastroesophageal varices type 1 (GOV1) and type 2 (GOV2) are varices in direct continuity from the esophagus to the stomach (lesser and greater curvatures, respectively)⁹. We chose EVL after EVO for treatment of GOV1 and GOV2, which tended to have a better secondary prophylactic effect according to our clinical experience. However, no prior research has evaluated the effect of additional NSBB under these circumstances. It remains unclear whether the addition of NSBB provides further benefit after combined use of tissue adhesive and endoscopic variceal ligation for bleeding gastroesophageal varices.

Aims & Methods

We retrospectively analyzed cirrhotic patients (mainly due to hepatitis B and C) who received endoscopic combined treatment of gastroesophageal varices and were assigned or not to NSBB treatment as a second prophylaxis. Subanalysis was done for ascites, portal vein thrombosis, splenectomy, and Child-Pugh grade. 5-year overall survival and rebleeding rates were compared between treatment groups.

Results

A total of 490 patients were analyzed, and 130 patients received additional NSBB treatment. Although the additional NSBB treatment did not lead to a statistically significant difference in overall 5-year survival (Log-rank test, p = 0.133), it did reduce the 5-year rebleeding rate from 45.7% to 30.64% (Log-rank test, p = 0.002, univariate COX analysis, HR 0.57, 95% CI 0.39-0.82), consistent with the comparison after propensity score matching. Neither overall survival nor bleeding differed significantly between propranolol and carvedilol. NSBB (HR 0.54, 95% CI 0.37-0.79, p = 0.001) and splenectomy (HR 0.65, 95% CI 0.44-0.96, p = 0.030) were independent factors in reducing rebleeding, rather than improving survival, in cirrhotic patients who received combined endoscopic treatment. In patients without splenectomy, NSBB treatment improved overall survival (Log-rank test, p = 0.019, univariate COX analysis, HR 0.43, 95% CI 0.21-0.89) and reduced rebleeding rates (Log-rank test, p = 0.001, univariate COX analysis, HR 0.52, 95% CI 0.34-0.78).

Conclusion

We show for the first time that adding NSBB to combined endoscopic therapy significantly reduced recurrent variceal bleeding (GOV1 & GOV2) in cirrhotic patients, yet did not improve overall survival, except for patients without splenectomy. The addition of NSBB for patients receiving combined endoscopic treatment of gastroesophageal varices provides benefits but does not prolong overall survival.

References

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