Esophagogastric variceal bleeding (EVB) is the most dangerous complication of decompensated cirrhosis (1). Most of the patients with liver cirrhosis have symptoms of esophagogastric varices, with an increase in the incidence by 7% per year (2). EVB is the main influencing factor for the increased mortality in patients with liver cirrhosis (3). The mortality of the first bleeding was about 20–30% if an active intervention was not carried out (4). Within 2 years after the first bleeding, the rebleeding rate and mortality increased significantly, which threatened the safety of patients (5). However, the secondary prevention of EVB in liver cirrhosis mainly includes endoscopic treatment, non-selective beta-blocker drugs (NSBBs), transjugular intrahepatic portosystemic shunt (TIPS), and surgical treatment (6); all these methods have limited curative effects. Although the evidence is not convincing, guidelines recommend the use of ligation and vasoactive drugs as first-line therapy for acute variceal bleeding (AVB) (7).

In the development of endoscopic therapy technology, sclerosing agent injection, tissue glue injection, vein ligation, and several other technical methods have emerged gradually to control acute bleeding and prevent rebleeding (8). Previous studies and meta-analyses have shown that vasoactive drugs and sclerotherapy are better than sclerotherapy alone (9). However, the clinical outcomes were not evaluated with respect to endoscopic variceal ligation (EVL) combined with endoscopic injection sclerotherapy (EIS). Thus, we conducted a meta-analysis to investigate the efficacy and safety of EVL+EIS to control AVB.

EVB patients have a high risk of rebleeding and death after bleeding control (19). If the EVB patients do not receive secondary preventive treatment for 1–2 years, the rebleeding rate is elevated to about 60%, and the mortality rate is 33% (20). At present, EVL and EIS are indispensable in the endoscopic treatment of the secondary prevention of EVB. The basic goal of the treatment is to eradicate or reduce the degree of esophageal varices in order to reduce the recurrence rate and mortality (21). Patients with a history of EVB should be treated routinely by endoscopy, and patients with acute EVB should continue to receive corresponding endoscopic treatment after the termination of bleeding (22).

In EVL technology, the negative pressure at the front end of the endoscope is inhaled into the esophageal varices that are then ligated with a rubber ring in the transparent cap (7). The physical ligation blocks the blood supply of the varices, resulting in thrombosis, tissue necrosis, and ulcers, finally leaving healing scars for the treatment and elimination of varices (23). EIS refers to the injection of a sclerosing agent into the tissue of varicose vein or adjacent to varicose vein, which shows ischemia and necrosis in the tissue of varicose vein, and then produces fibrosis, to eliminate varicose veins (24). With the continuous development of endoscopic technology and the evolution of sclerosing agents, the clinical application of EVL and EVs is also evolving (25).

The present meta-analysis did not detect any statistically significant difference in the efficacy of acute bleeding control (RR = 0.99, 95% CI: 0.63–1.56, P = 0.981), overall rebleeding (RR = 0.83, 95% CI: 0.52–1.31, P = 0.415), variceal eradication (RR = 1.01, 95% CI: 0.82–1.23, P = 0.960), and overall mortality (RR = 0.80, 95% CI: 0.52–1.24, P = 0.314), but a significant difference was observed in the overall complications (RR = 0.60, 95% CI: 0.41–0.87, P = 0.01). The main complications of EVL include chest pain or discomfort, dysphagia or pain, and erosion or ulcer at the ligation site, infection, or bacteremia (26). Rubber bands falling off and sliding can also form ulcers and after rebleeding (27). Compared to EVL alone, the effect of EIS combined with EVL varies in different studies. In patients with active bleeding, EVL uses ligation device, which limits the intraoperative field of vision, raising the technical requirements of endoscopic operators (28).

Due to various conditions, the present meta-analysis has some limitations. Firstly, the included studies were from different countries. Secondly, the frequency of follow-up and the total duration of follow-up were also incompatible. Thirdly, some disparities in medical technology and medical facilities were observed in the included literature. Therefore, EVL and EVs may show similar results in the treatment of esophageal variceal bleeding.

In conclusion, EVL is superior to the combination of EVL and EIS in safety, while no significant differences were noted in efficacy. Nonetheless, further studies should be designed based on a large sample size, multiple centers, RCTs to substantiate these two clinical interventions.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

JS and HZ contributed to the conceptualization, project administration, and writing and review. JS and MR contributed to the data curation. YX and YY contributed to the data analysis. JS, HZ, and LL contributed to the methodology. HZ and MR contributed resources. YX and LL contributed the software. HZ contributed to the supervision. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.