Early Rebleeding Following Endoscopic Variceal Ligation Associated With Increased Mortality Risk

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Time to rebleeding was a significant predictor of mortality risk following an endoscopic variceal ligation procedure.

Patients who had early rebleeding following endoscopic variceal ligation were at greater risk for death than patients with late or no rebleeding. Results of this retrospective, observational study were published in Digestive and Liver Disease.

All patients admitted to one hospital in Barcelona, Spain with confirmed hematemesis or melena between 2000 and 2014 were enrolled in a prospective gastrointestinal bleeding register. Patients (n=369) who had recovered from a first variceal bleed were retrospectively included in this study and followed until 2017. At baseline, patients were assessed by blood and hemodynamic tests as well as imaging studies. Nadolol or propranolol were administered at a dose of 80 mg/d, increasing to 240 mg/d. A secondary hemodynamic study was conducted 1 to 3 months after non-selective β-blocker treatment began. A hemodynamic response was defined as a hepatic venous pressure gradient decrease of >20% from baseline or below 12 mmHg. Endoscopic variceal ligation was performed until variceal eradication.

During the study period, 12% of patients had early rebleeding (within 6 weeks), 20% had late rebleeding (after 6 weeks), and 68% did not have a rebleeding incident. Bleeding was due to lesions from portal hypertension (96% early vs 95% late) and esophageal varices (89% early vs 84% late). Therapeutic failure was high (early: 96% vs late: 95%). Balloon tamponade was used in 10 patients, and a rescue transjugular intrahepatic portosystemic shunt was placed in 35 patients.

Over the course of long-term follow-up, mortality risk was increased in the early rebleeding group compared with the late rebleeding group (hazard ratio [HR], 0.476; 95% CI, 0.318-0.712; P <.001). Mortality risk was increased, although not significantly, for the patients who had a late rebleed compared with the patients with no rebleeding (HR, 0.902; 95% CI, 0.749-1.086; P =.271).

Patients with ascites, encephalopathy, high Child-Pugh scores, or high Model for End-Stage Liver Disease (MELD) scores at baseline were more likely to have an early rebleed. Independent predictors of an early rebleed included baseline hepatic venous pressure gradient (HR, 1.07; 95% CI, 1.01-1.15), baseline MELD score (HR, 1.09; 95% CI, 1.03-1.14), and the presence of ascites and/or encephalopathy (HR, 2.07; 95% CI, 0.99-6.06). After adjusting for significant baseline factors, early rebleeding was an independent predictor of mortality (HR, 1.58; 95% CI, 1.02-2.45; P =.04).

One limitation of this study was the retrospective design, which always has a risk for selection bias.

The study authors concluded that endoscopic variceal ligation rebleeding within 6 weeks among patients with hematemesis or melena had a higher mortality risk when compared with patients with late or no rebleeding episodes. “Our study suggests that stratification of risk of early rebleeding to guide therapy is desirable,” they concluded. “Future studies should elucidate whether strategies such as early preemptive [transjugular intrahepatic portosystemic shunt] may improve prognosis in patients at high risk [for] early rebleeding.”

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Ardevol A, Alvarado-Tapias E, Garcia-Guix M, et al. Early rebleeding increased mortality of variceal bleeders on secondary prophylaxis with β-blockers and ligation [published online July 8, 2020]. Dig Liver Dis. doi: 10.1016/j.dld.2020.06.005