Currently, an optimal treatment for acute cardiofundal variceal bleeding has not been confirmed. In this study, we directly compared EVO with RTO for acute cardiofundal variceal bleeding in patients with cirrhosis and found that all-variceal rebleeding rates at 2 years were statistically similar between the two groups (P = 0.150). However, the GV rebleeding rate at 2 years was significantly higher in the EVO group than in the RTO group (P = 0.003), and EVO (vs. RTO) was the only predictor of higher risk of GV rebleeding. On PSM analysis, both all-variceal and GV rebleeding rates were significantly higher in the EVO group than in the RTO group (all P < 0.05). Finally, we found that both EVO and RTO were effective for bleeding control (> 96.5%) and had low complication rates (< 3.5%). No difference was observed in the mortality between the two groups.
This study has several important clinical implications. In the present study, 1- and 2-year all-variceal rebleeding rates were statistically similar between the two groups (11.2% and 32.4% in the EVO group vs. 11.1% and 20.8% in the RTO group, P = 0.150. However, when patients were analyzed for GV rebleeding, the EVO group had significantly higher 1- and 2-year GV rebleeding rates than those in the RTO group (11.2% and 32.4% vs. 5.4% and 12.8%, P = 0.003). In addition, EVO was the only predictor of higher GV rebleeding risk (HR = 3.132, P = 0.005), while it was not associated with all-variceal bleeding in the cox-regression analysis.
The difference between all-variceal and GV rebleeding rates could be explained by the high EV rebleeding rate after RTO. Rebleeding from EVs developed in seven patients treated with RTO; 6 out of 7 did not receive EVL after RTO. In the present study, 14.8% of patients in the EVO group and 27.9% of patients in the RTO group developed worsening of EVs after bleeding control (P < 0.001). A recent randomized controlled study reported an EV worsening rate of 30% and 43.5% in the EVO and BRTO groups, respectively (29), and similar results have been frequently reported in previous studies (9, 30–33). Because RTO completely obliterates the portosystemic shunts that supply GVs, worsening of portal hypertension and its complications have been widely observed (34, 35). Thus, screening endoscopy and appropriate prophylaxis with EVL could decrease EV rebleeding after RTO (29).
To minimize the potential bias according to the differences in baseline characteristics between the EVO and RTO groups, particulary in MELD scores, PSM analysis was performed. On PSM analysis, both 1- and 2-year all-variceal and GV rebleeding rates were significantly higher in EVO group than in RTO group (12.1% and 37.3% vs. 8.3% and 20.0%, respectively, P = 0.032; 12.1% and 37.3% vs. 3.6% and 12.5%, respectively, P < 0.001). All these results suggest that RTO is superior to EVO in preventing all-variceal and GV rebleeding after treatment.
To our knowledge, three studies directly compared EVO and BRTO in terms of GV bleeding, and all studies demonstrated the superiority of BRTO over EVO in preventing variceal rebleeding (27, 29, 36). A retrospective study of cardiofundal variceal bleeding found lower rates of rebleeding following BRTO compared to EVO; however, 16/71 patients who underwent BRTO had simultaneous transjugular intrahepatic portosystemic shunts, which could improve portal hypertension and further decrease GV rebleeding (36). Recently, a randomized controlled study compared EVO with BRTO for secondary prophylaxis of cardiofundal GV bleeding (29). However, the number of patients was small (32 patients in EVO group vs. 32 patients in BRTO group). Additionally, 67.2% of patients were transferred patients who had recovered from a previous GV bleeding within 4 weeks. A prospective study also found a higher variceal rebleeding rate for EVO than for BRTO (71.4% vs. 15.4%); however, BRTO was performed only in patients without active bleeding (27).
The rates of recurrence and rebleeding of GVs after successful RTO are low, possibly because the injected sclerosing agent completely destroys the venous endothelium. (30, 31). The higher rebleeding rate in patients treated with EVO may be related to incomplete impaction of cyanoacrylate, leading to less or delayed obturation of GVs and their feeding vessels. Additionally, the results of EVO vary according to the clinician’s experience. Therefore, clinicians should seek the best option for each patient based on the patient’s general condition and access to appropriate medical resources and expertise in clinical practice.
In the present study, bleeding control rates of both treatments were sufficient (97.8% in the EVO group and 96.5% in RTO group). In addition, low prevalence of treatment-related complications (three patients had worsened ascites and two patients developed encephalopathy) was observed, supporting the safety of both modalities in patients with acute GV bleeding.
The one of most common causes of death after acute cardiofundal variceal bleeding was variceal rebleeding (27.5%), emphasizing the need for proper prevention of variceal rebleeding after bleeding control is achieved. There was no significant difference in transplantation-free survival between the EVO and RTO groups (86.7% vs. 88.4% at 6 months; 83.9% vs. 85.8% at 12 months), and a higher MELD score was the only predictor of increased mortality, consistent with the results of previous studies (27, 29).
The major limitation of our study is its retrospective design, which could have resulted in selection bias. Therefore, we conducted robust PSM analysis with large number of variables to minimize potential bias. In addition, due to the small number of patients who received beta-blockers, whether adding beta-blockers can reduce rebleeding from GVs has not been elucidated by the current results. Finally, this study included both BRTO and PARTO, which are different treatment modalities that use different sclerosing agents. Only one patient developed variceal rebleeding after PARTO. This result suggests that PARTO could further improve the treatment outcome of GV bleeding. Further randomized controlled studies with larger numbers of patients are needed to confirm the optimal treatment strategy for patients with acute cardiofundal variceal bleeding.
In conclusion, our study shows that both RTO and EVO are effective and safe methods, however, RTO is more effective than EVO in preventing all-variceal and GV rebleeding, with similar survival outcomes. The worsening of EVs after BRTO should be screened and managed appropriately. EVO could be another effective option for acute cardiofundal variceal bleeding, especially in a clinical setting that lacks resources or expertise for RTO.