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A meta-analysis of combined generic-covered stent-graft with or without bare-metal stent for refractory variceal bleeding

 Department of Intervention Vascular, Aerospace Center Hospital, Beijing, China

Date of Submission14-Aug-2021
Date of Decision28-Jan-2022
Date of Acceptance10-Feb-2022
Date of Web Publication20-Jul-2022

Correspondence Address:
Mingchao Ding,
15, Yuquan Road, Haidian District, Beijing
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmas.jmas_262_21

PMID: 35915531


Objectives: The meta-analysis was conducted to systematically assess the efficacy and safety of generic stent-graft/bare-stent combination compared with Fluency stent alone in transjugular intrahepatic portosystemic shunt procedure for refractory variceal bleeding.
Methods: PubMed, EMBASE, Scopus, Web of Science and the Cochrane Database were searched for relevant studies from January 1990 to September 2020; outcome measures studied were primary patency, hepatic encephalopathy, survival, re-bleeding and portal venous pressure.
Results: Four studies (1 randomised controlled trial and 3 retrospective studies) with 449 subjects (157 patients in the combined stent group and 292 patients in the covered stent group) were included. No significant difference was observed in the incidence of mortality (hazard ratio [HR] = 1.069, 95% confidence interval [CI] [0.524, 2.178]), hepatic encephalopathy (odds ratio [OR] = 0.860, 95% CI [0.341, 2.169], P = 0.750) and re-bleeding (OR = 1.049, 95% CI [0.226, 4.881], P = 0.951). Compared with Fluency stent alone, combination therapy was associated with moderate decrease in outcomes on the post-operative portal venous pressure (standard mean difference [SMD] −0.210, 95% CI [−0.418, −0.001], P = 0.049) and was not associated with significant decrease in outcomes on the pre-operative portal venous pressure (SMD − 0.129, 95% CI [−0.336, 0.078], P = 0.223). The primary patency was significantly lower in the Fluency/bare-stent combination group (HR = 0.473, 95% CI [0.288, 0.776]).
Conclusions: Generic stent-graft/bare-stent combination therapy was associated with significantly lower primary patency compared to Fluency stent alone.

Keywords: Expand polytetrafluoroethylene covered stent, oesophagogastric variceal bleeding, transjugular intrahepatic portosystemic shunt

How to cite this URL:
Ren H, Ding M, Huang X, Wang B, Chi G, Shao C, Song S, Song W, Shi R. A meta-analysis of combined generic-covered stent-graft with or without bare-metal stent for refractory variceal bleeding. J Min Access Surg [Epub ahead of print] [cited 2022 Aug 14]. Available from:

  Introduction Top

Oesophagogastric variceal bleeding is a life-threatening complication of portal hypertension, associated with in-hospital mortality rate of 15%~16%.[1],[2] Transjugular intrahepatic portosystemic shunt (TIPS) is a recommended minimally invasive method for the treatment and prevention of variceal bleeding refractory to pharmacological and endoscopic therapy.[3],[4],[5] At present, expand polytetrafluoroethylene (ePTFE)-covered stent-grafts are preferred to the bare metal stent (BMS) during TIPS procedure with better shunt patency and treatment efficacy, especially for specialised ePTFE-covered Viatorr stent graft.[6],[7],[8],[9] Meanwhile, recent studies have demonstrated that Fluency ePTFE-covered stent or Fluency/BMS combination, related to considerable primary shunt patency rates and cost-effectiveness of TIPS, provides an alternative choice under conditions of limited availability of Viatorr endoprostheses in some regions.[6],[10],[11],[12],[13],[14],[15] It is uncertain, nevertheless, whether Fluency/BMS combination strategy performs better than Fluency stent alone. Dealing with this background, the meta-analysis was performed to assess the efficacy and safety of generic stent-graft/bare-stent combination compared with Fluency stent alone in TIPS procedure for refractory variceal bleeding.

  Methods Top

Study selection

A systematic search of PubMed, EMBASE, Scopus, Web of Science and the Cochrane Database from January 1990 up to September 2020 was performed. Search strategy was as follows: 'TIPS OR Corresponding Medical Subject Heading terms' AND 'Covered with bare stents OR Stent-graft/bare stent combination' AND 'Polytetrafluoroethylene covered OR Fluency'. Prospective randomised controlled trials (RCTs) and retrospective case–control studies were included. References for eligible literature were also manually searched. The non-human studies, case reports, editorials, conference, letters or comment and review articles were excluded.

Data extraction

Data were independently extracted by two authors (Hongcheng Ren and Bin Wang) according to the Cochrane Handbook for Systematic Reviews of Interventions, including the patient demographics, perioperative characteristics and clinical outcomes. The selected studies are summarised in [Table 1]. The clinical outcomes were primary patency, survival, hepatic encephalopathy, portal venous pressure and post-operative re-bleeding. Discrepancies were solved by discussing with a senior investigator (Mingchao Ding) until reaching a consensus if necessary.
Table 1: Characteristics of included studies

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Quality assessment

The quality of included RCTs and observational studies was independently assessed by two authors utilising Jadad composite scale[16] and the modified New Castle–Ottawa Scale,[17] respectively.

Statistical analysis

The hazard ratio (HR) and 95% confidence intervals (95% CIs) were evaluated for time-to-event data. The odds ratio (OR) and the standardised mean difference (SMD) were estimated for the dichotomous outcome and continuous outcomes, respectively. For studies without reporting HR, the survival data were obtained from the published Kaplan–Meier curves via Engauge Digitizer version 11.1 (Mark Mitchell, Baurzhan Muftakhidinov and Tobias Winchen et al., “Engauge Digitizer Software.” Webpage: Then, HR and 95% CI were estimated by adopting the method reported by Tierney et al.[18] Heterogeneity among studies was assessed using the I2 test and Q statistic. I2 >50% or P < 0.10 denotes statistically significant, and the random-effects model was employed to pool results. Otherwise, a fixed-effects model was used in the absence of significant heterogeneity. Publication bias was detected by Harbord test and Peters' test for binary data while Egger test and Begg test for enumeration data and time-to-event data. All analyses were performed with the Stata version 13.1 (Stata Corporation, College Station, TX, USA).

  Results Top

Characteristics of studies and patients

The initial search identified 906 potential records. After removing duplicates and examining the full text of each citation, four studies, including 1 RCT[19] and 3 retrospective studies[20],[21],[22] from 2015 to 2019, met the inclusion criteria and were suitable for further investigation [Figure 1]. The meta-analysis involves 394 patients (166 TIPS with the Fluency/BMS combination and 228 TIPS with Fluency-covered stent). The characteristics, quality assessment and demographics of the included studies are summarised in [Table 1] and [Table 2].
Table 2: Results of each study and pooled estimates for primary patency encephalopathy and survival

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Four studies reported the survival rate [Figure 2]. TIPS with combination stent did not significantly differ from Fluency stent alone under the fixed-effects model (HR = 1.069, 95% CI [0.524, 2.178]). No statistically significant heterogeneity was observed (P = 0.129, I2 = 47.1%). There was no proof of publication bias (Begg P = 0.308, Egger P = 0.187).

Primary patency

The meta-analysis of three studies with 107 patients in the combination stent group and 163 patients in the Fluency stent group was performed. The primary patency was significantly lower in the Fluency/Wallstent stent combination group (HR = 0.473, 95% CI [0.288, 0.776]) [Figure 3]. No statistical heterogeneity was observed (P = 0.650, I2 = 0.0%), and a fixed-effect model was chosen. There was no proof of publication bias (Begg P = 1.000, Egger P = 0.323).

Portal venous pressure

Compared with Fluency stent alone, combination therapy was associated with moderate decrease in outcomes on the post-operative portal venous pressure [SMD −0.210, 95% CI [−0.418, −0.001], P = 0.049) [Figure 4] under the random-effects model (P = 0.023, I2 = 68.4%) and was not associated with significant decrease in outcomes on the pre-operative portal venous pressure (SMD −0.129, 95% CI [−0.336, 0.078], P = 0.223) [Figure 4] under the fixed-effect model (P = 0.428, I2 = 0.0%). No evidence of publication bias (Begg P = 1.000, Egger P = 0.856; Begg P = 0.089, Egger P = 0.148) was observed.

Hepatic encephalopathy and re-bleeding

Meta-analysis of two studies indicated that hepatic encephalopathy rate and re-bleeding rate were similar between the two groups in a fixed-effects model (OR = 0.860, 95% CI [0.341, 2.169], P = 0.750; OR = 1.049, 95% CI [0.226, 4.881], P = 0.951) [Figure 5]. No significant difference between the two groups was detected regarding statistical heterogeneity (P = 0.335, I2 = 0.0%; P = 0.270, I2 = 17.8%) and publication bias (Harbord P = 1.000, Peters P = 1.000; Harbord P = 1.000, Peters P = 1.000).

  Discussion Top

To the best of our knowledge, no prior meta-analysis has compared the safety and efficacy of Fluency ePTFE-covered stent/BMS combination versus Fluency ePTFE-covered stent alone in TIPS procedure for refractory variceal bleeding. In the present meta-analysis, the variceal gastric coronary vein was embolised with coils. The placement of stent into the left portal vein branch and the selection of 8-mm Fluency stent were adopted in the majority of TIPS procedures. Just as some scholars have considered, the 8-mm stents may be the optimal choice for the prophylaxis of hepatic encephalopathy, appropriate diversion and prolonged survival.[23],[24] Despite four publications contains three non-RCTs, most of the citations included in this review were relatively high quality. Moreover, no heterogeneity among studies on most outcomes was observed.

TIPS has been created to decompress the portal pressure gradient (PPG) and thereby prevent variceal re-bleeding.[25] Furthermore, reduction PPG to less than 12 mmHg (1 mmHg = 0.133 kPa) or by 20% or more of baseline significantly reduces the risk of recurrent haemorrhage.[26],[27],[28] Portal venous pressure was decreased more than 20% of original among included studies. The pre-TIPS portal venous pressure was similar between both groups (SMD −0.129, 95% CI [−0.336,0.078], P = 0.223), and the post-TIPS portal venous pressure was significant decrease in Fluency/BMS combination therapy (SMD −0.210, 95% CI [−0.418, −0.001], P = 0.049). However, re-bleeding rate was comparable between the two groups in a fixed-effects model (OR = 1.049, 95% CI [0.226, 4.881], P = 0.951). The result is in agreement with earlier studies that lesser reduction of PPG for cirrhotic patients receiving secondary prevention may not be associated with a lower incidence of recurrent haemorrhage but with a higher incidence of hepatic encephalopathy and liver failure as an increase shunt flow.[6],[25],[29]

Shunt dysfunction is a major concern after the TIPS procedure, which related to thrombosis and pseudointimal hyperplasia in the parenchymal tract or the hepatic vein outflow tract.[30] In comparison with the bare metal stent, the advent of ePTFE-covered stent tends to diminish most parenchymal tract TIPS stenoses.[9] Meanwhile, the prevalence of hepatic vein end TIPS stenosis has relatively increased.[10],[31] As a result, extending the TIPS stent graft to the hepatic vein/inferior vena cava junction is critical for reducing hepatic venous end stenosis and improving shunt patency.[10],[13] Considering the condition of single Fluency ePTFE-covered stent fall short of the hepatic vein/inferior vena cava junction and straighten back to its original configuration over time, the additional BMS deployment must be required. However, in the present study, significantly lower primary patency was reported in Fluency ePTFE-covered stent/BMS combination than Fluency ePTFE-covered stent alone (HR = 0.473, 95% CI [0.288, 0.776]). One possible reason for explaining lower primary patency in Fluency/BMS combination was that combination therapy was prone to cause alteration of shunt configuration due to poor flexibility, such as a block of the stent-grafts. Another explanation might be different definitions of shunt dysfunction and assessment techniques used in each centre.

Hepatic encephalopathy is another main drawback following TIPS placement. The incidence of new or worsening post-TIPS encephalopathy approximately 30%, regardless of whether the ePTFE-covered stent or BMS is applied.[32] Data from the results demonstrated a relatively lower risk of hepatic encephalopathy, which might be explained that during TIPS placement, 8-mm stent-grafts were deployed, and invasive portosystemic pressure gradient was measured. Although most patients with hepatic encephalopathy respond to standard therapy, the occurrence of post-TIPS hepatic encephalopathy significantly impacts the patient's quality of life.[33] Therefore, the prevention of hepatic encephalopathy is essential through controlling precipitating factors and taking non-absorbable disaccharides.[34]

TIPS procedure-related complications such as intra-peritoneal bleeding and infection may cause perioperative death, nothing but the rate of mortality is rare. In two retrospective studies of 1750 and 389 patients, the incidence of fatal technical complications was 1.7%[6] and 0.5%,[35] respectively. These results are in accordance with the present study. In most situations, mortality following TIPS placement not be attributed to the TIPS procedure itself but the progression of underlying hepatic cirrhosis.[36] Child–Turcotte–Pugh and the model of end-stage liver diseases scores were the most common to predict hepatic reserve and mortality in patients after TIPS.[37]

Several potential limitations should be taken into account in this meta-analysis. First, over half of the studies were retrospective and the sample size was limited. Hence, the risk of certain selection and publication bias exists. Second, the type of bare metal stent and the measurement of portal venous pressure were heterogeneous. Third, all the studies are restricted to Asian populations. Last, clinical outcome data were not reported in some studies and the estimated HR data extracted from published Kaplan–Meier curves may not correspond with reality.

  Conclusions Top

Generic stent-graft/bare-stent combination therapy was associated with significantly lower primary patency compared to Fluency stent alone.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2]


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