Comparison Between Portosystemic Shunts and Endoscopic Therapy for Prevention of Variceal Re-Bleeding: A Systematic Review and Meta-Analysis
Esophageal and gastric varices are among the most severe complications of cirrhotic portal hypertension, often leading to massive gastrointestinal hemorrhage. Approximately 50% of patients with cirrhosis develop gastroesophageal varices, and about one-third of these patients experience hemorrhage, which is a significant cause of early mortality, with rates ranging from 30% to 50% for the first variceal bleed. Patients who survive the initial episode face a high risk of re-bleeding, exceeding 60% within one year, and a mortality rate of approximately 20%. Therefore, secondary prophylaxis to prevent variceal re-bleeding is crucial for these patients.
This systematic review and meta-analysis aimed to compare the efficacy of three primary interventions for preventing variceal re-bleeding in patients with cirrhotic portal hypertension: surgical portosystemic shunts, transjugular intrahepatic portosystemic shunt (TIPS), and endoscopic therapy (ET). The study evaluated outcomes such as overall mortality, short-term and long-term survival, bleeding-related mortality, variceal re-bleeding rates, and the incidence of postoperative hepatic encephalopathy.
Background and Rationale
Portosystemic shunts, including surgical shunts and TIPS, have been used for decades to manage variceal bleeding in patients with cirrhotic portal hypertension. Surgical shunts, which include total, partial, selective, or super-selective decompression of the portal, splenic, mesenteric, and gastroesophageal variceal venous systems, were widely used from the 1960s to the 1980s. However, their use has declined with the advent of less invasive techniques like TIPS and ET.
TIPS is a minimally invasive procedure that creates a shunt between a hepatic vein and the intrahepatic portal vein using a metal stent. It has largely replaced surgical shunts due to its lower operative morbidity and mortality, especially in patients with advanced cirrhosis and refractory variceal bleeding. ET, which includes endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL), involves repetitive sessions to obliterate varices and has been shown to effectively control acute variceal bleeding and reduce re-bleeding and mortality.
Despite the widespread use of these interventions, there is ongoing debate about their comparative efficacy, particularly in terms of survival benefits. This meta-analysis sought to address this gap by systematically comparing the outcomes of surgical portosystemic shunts, TIPS, and ET.
Methods
The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Collaboration’s systematic review framework. A comprehensive literature search was conducted using PubMed, Embase, and the Cochrane Central Register of Controlled Trials, with no language restrictions. The search terms included “variceal hemorrhage,” “variceal bleeding,” “variceal re-bleeding,” “esophageal and gastric varices,” “portal hypertension,” and “liver cirrhosis.” The search was limited to randomized controlled trials (RCTs) published up to June 2017.
Inclusion criteria required that the studies be RCTs comparing surgical portosystemic shunts with TIPS, surgical shunts with ET, or TIPS with ET. Participants had to be patients with cirrhosis and portal hypertension who had experienced at least one episode of variceal bleeding. Studies had to report at least one of the following outcomes: overall mortality, 30-day or 6-week survival, bleeding-related mortality, variceal re-bleeding, or postoperative hepatic encephalopathy. Exclusion criteria included duplicate publications, insufficient data, and studies involving patients with non-cirrhotic portal hypertension.
Two independent reviewers screened the titles and abstracts of the identified studies, and discrepancies were resolved through discussion and consensus. Data extraction included study design, patient characteristics, interventions, follow-up, and outcomes. The quality of the included studies was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias.
Results
The meta-analysis included 26 publications comprising 28 RCTs and a total of 2845 patients. Of these, 496 patients were involved in studies comparing surgical portosystemic shunts with TIPS, 1244 in studies comparing surgical shunts with ET, and 1105 in studies comparing TIPS with ET.
Overall Mortality
There was no significant difference in overall mortality among the three interventions. Surgical portosystemic shunts did not significantly differ from TIPS (risk ratio [RR] = 0.64, 95% confidence interval [CI] = 0.36–1.13, P = 0.12) or from ET (RR = 0.82, 95% CI = 0.64–1.05, P = 0.11). Similarly, TIPS did not show a statistically significant difference in overall mortality compared to ET (RR = 1.13, 95% CI = 0.93–1.38, P = 0.22).
Short-Term Survival (30-Day or 6-Week)
There was no significant difference in 30-day or 6-week survival among the three interventions. Surgical portosystemic shunts did not significantly differ from TIPS (RR = 1.02, 95% CI = 0.88–1.19, P = 0.77) or from ET (RR = 1.03, 95% CI = 0.94–1.13, P = 0.49). TIPS also did not significantly differ from ET (RR = 0.92, 95% CI = 0.78–1.09, P = 0.34).
Bleeding-Related Mortality
Surgical portosystemic shunts were associated with significantly lower bleeding-related mortality compared to both TIPS (RR = 0.07, 95% CI = 0.01–0.32, P = 0.0007) and ET (RR = 0.17, 95% CI = 0.06–0.51, P = 0.002). TIPS showed a trend toward lower bleeding-related mortality compared to ET, but the difference was not statistically significant (RR = 0.53, 95% CI = 0.29–0.99, P = 0.05).
Variceal Re-Bleeding
Surgical portosystemic shunts were associated with significantly lower rates of variceal re-bleeding compared to both TIPS (RR = 0.21, 95% CI = 0.07–0.60, P = 0.004) and ET (RR = 0.10, 95% CI = 0.04–0.24, P < 0.00001). TIPS also showed a significantly lower rate of variceal re-bleeding compared to ET (RR = 0.46, 95% CI = 0.36–0.58, P < 0.00001).
Postoperative Hepatic Encephalopathy
There was no significant difference in the rate of postoperative hepatic encephalopathy between surgical portosystemic shunts and TIPS (RR = 0.52, 95% CI = 0.22–1.24, P = 0.14) or between surgical shunts and ET (RR = 1.09, 95% CI = 0.59–2.01, P = 0.78). However, TIPS was associated with a significantly higher rate of hepatic encephalopathy compared to ET (RR = 1.78, 95% CI = 1.34–2.36, P < 0.0001).
Discussion
The findings of this meta-analysis suggest that there is no significant difference in overall mortality or short-term survival among surgical portosystemic shunts, TIPS, and ET. However, surgical portosystemic shunts were associated with the lowest bleeding-related mortality and the lowest rate of variceal re-bleeding among the three interventions. TIPS was superior to ET in preventing variceal re-bleeding but at the cost of a higher incidence of postoperative hepatic encephalopathy.
Surgical portosystemic shunts may be the most effective intervention for preventing variceal re-bleeding without increasing the risk of hepatic encephalopathy. TIPS, while effective in reducing re-bleeding, carries a higher risk of hepatic encephalopathy, which is a significant drawback. ET, although less invasive, is associated with higher rates of re-bleeding and bleeding-related mortality.
The study highlights the importance of individualized treatment strategies based on patient characteristics, such as liver function and the severity of portal hypertension. For patients with good liver function and recurrent variceal bleeding, surgical portosystemic shunts may offer long-term benefits. In contrast, TIPS may be more suitable for patients with advanced cirrhosis and refractory variceal bleeding, despite the increased risk of hepatic encephalopathy.
Limitations
The meta-analysis has several limitations. The number of studies comparing surgical portosystemic shunts with TIPS was relatively small, which may affect the reliability of the results. Additionally, the quality of the included studies varied, and some studies had a high risk of bias. The follow-up periods differed among the studies, which could have influenced the outcomes. Furthermore, the study did not evaluate procedure-related complications, length of hospital stay, or medical expenses, which are important factors in clinical decision-making.
Conclusion
In conclusion, this meta-analysis found no significant difference in overall mortality or short-term survival among surgical portosystemic shunts, TIPS, and ET. However, surgical portosystemic shunts were associated with the lowest bleeding-related mortality and the lowest rate of variceal re-bleeding. TIPS was superior to ET in preventing re-bleeding but at the cost of a higher incidence of hepatic encephalopathy. These findings suggest that surgical portosystemic shunts may be the most effective intervention for preventing variceal re-bleeding, particularly in patients with good liver function. However, the choice of intervention should be tailored to individual patient characteristics and clinical circumstances.
doi.org/10.1097/CM9.0000000000000212
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