This study aims to compare the efficacy and safety of early TIPS versus salvage TIPS in patients with liver cirrhosis complicated by AEVB, with a focus on their impacts on rebleeding, HE, and survival rate. The results indicated that although there was no significant difference in long-term survival rates between the two groups of patients, early TIPS significantly reduces the rebleeding rate (9% vs 18.52%) and the incidence of HE (22% vs 35.19%). Thereby, it prevents the further deterioration of liver function caused by recurrent bleeding and the medical burden associated with multiple hospitalizations. These findings suggest that for patients with liver cirrhosis and AEVB, early TIPS intervention at the time of the first bleeding episode may be more beneficial in reducing the risk of postoperative complications compared to salvage TIPS.
The findings of this study are partially consistent with the large randomized controlled trial by Lv et al. and Garcia-Pagán JC et al. (
13,
19), which demonstrated that early TIPS improves survival in high-risk patients. Although our study did not show a significant difference in survival rates, the advantage of early TIPS in reducing rebleeding aligns with previous findings (
20,
21). Notably, our research found a lower incidence of HE in the early TIPS group, which differs from some conventional perspectives (
22). However, recent studies (
23,
24) have shown that in the treatment of variceal bleeding, the incidence of HE is comparable between early preemptive TIPS and endoscopic therapy, and post-TIPS HE does not lead to an increase in mortality. This discrepancy may be attributed to the inclusion of a patient population with relatively better liver function in our study or may reflect advancements in intraoperative shunt pressure control techniques. Transjugular intrahepatic portosystemic shunt also improves prognosis by effectively treating the hemodynamic disorders associated with cirrhosis. Meanwhile, the higher incidence of HE in the salvage TIPS group is consistent with reports by Shalaby et al. (
25), suggesting that recurrent bleeding and failed endoscopic therapy may exacerbate liver injury and systemic inflammation, thereby increasing the risk of post-TIPS encephalopathy.
The superiority of early TIPS may stem from its ability to address the fundamental issue of portal hypertension at the hemodynamic level at an earlier stage. Portal hypertension is not only the direct cause of bleeding but also the trigger for intestinal barrier dysfunction, endotoxemia, and systemic inflammation, which are core factors driving the progression of cirrhosis and multiple organ failure. By rapidly reducing portal pressure, early TIPS potentially interrupts this vicious cycle, thereby reducing subsequent complications. In contrast, patients receiving salvage TIPS experience a longer duration of active bleeding and sustained portal hypertension before endoscopic treatment fails. This may lead to a more severe systemic inflammatory response and exhaustion of functional reserve in multiple organs. This "second hit" model implies that even after receiving TIPS, their subsequent recovery is more challenging. Additionally, portal hypertension persisted, and new variceal branches might form again, resulting in recurrent bleeding. Krige et al. (
26) demonstrated that after multiple failed endoscopic hemostasis attempts, liver function deteriorates, complications ensue, and outcomes are poor. This may explain why the control group had a higher mortality rate following repeated failed endoscopic treatments.
Transjugular intrahepatic portosystemic shunt achieves hemostasis by establishing a shunt between the portal vein and the hepatic vein, diverting part of the blood from the portal vein to the systemic circulation. This process helps reduce the portal vein pressure, thereby alleviating the severity of varicose veins (
27,
28). Hepatic encephalopathy is the most common complication after TIPS. The main reason for HE occurrence after TIPS is that ammonia cannot be converted by the liver and directly enters the brain from the intestines. This leads to the excessive activation of astrocytes and astrocyte edema, followed by a decrease in their detoxification capacity, and ultimately results in HE (
29). Relevant studies have shown that the incidence of overt hepatic encephalopathy (OHE) after TIPS in patients with liver cirrhosis is 30% - 35%, and up to 8% of these patients may progress to persistent overt hepatic encephalopathy (
30). In our study, the incidence of HE in the early TIPS group was 22%, while that in the control group was 35.16%, which is consistent with the above-mentioned research results. A study by Nardelli et al. (
24) has shown that HE after TIPS does not increase the mortality rate of patients with liver cirrhosis.
In this study, the general data and survival data of the early TIPS group and the TIPS group after repeated failed endoscopic therapy were compared. The results showed that early TIPS had significant advantages in reducing the degree of varices, decreasing rebleeding, and lowering the incidence of HE in patients. Relevant studies (
31,
32) have indicated that early TIPS can effectively control gastrointestinal bleeding and further improve the survival rate of patients.
In conclusion, for patients with advanced liver cirrhosis and acute variceal bleeding, early TIPS is superior to salvage TIPS performed after repeated failed endoscopic therapy in terms of improving survival rate, reducing further bleeding, and not increasing the risk of severe HE. Therefore, for patients with decompensated liver cirrhosis and acute variceal bleeding, it is recommended to receive TIPS treatment as early as possible, rather than undergoing salvage TIPS treatment when they have experienced multiple episodes of bleeding, repeated failed endoscopic therapy, and decompensation of liver and kidney function. The findings of this study support the more proactive consideration of an early TIPS strategy for select patients with AEVB, particularly those at high risk of endoscopic treatment failure, rather than salvage TIPS. This approach may help avert further liver function impairment caused by recurrent bleeding and improve patients' quality of life.
However, this study has several limitations. First, as a single-center retrospective design, it carries a potential risk of selection bias. Second, although the definitions of "early TIPS" and "salvage TIPS" were clearly outlined, their distinction may blur in real-world clinical practice. Additionally, the analysis did not fully account for detailed factors such as post-TIPS antiplatelet/anticoagulation strategies or shunt flow velocity, which may influence rebleeding rates and stent patency. Future prospective, multicenter studies are needed to validate these findings and to explore biomarkers or clinical scoring systems capable of precisely predicting the optimal timing for TIPS intervention.
5.1. Conclusions
This study demonstrates that for patients with liver cirrhosis complicated by acute esophageal and gastric variceal bleeding (AEVB), the early TIPS strategy is more effective in preventing rebleeding and HE without increasing the risk of mortality compared with salvage TIPS. Therefore, for eligible patients, consideration should be given to advancing the timing of TIPS intervention.