Shunts compared with endoscopic intervention to prevent further episodes of variceal bleeding in people with liver cirrhosis

Background

People with scarring of the liver (cirrhosis) may develop high pressure in the portal vein (the vein that carries blood from the gut to the liver). This high pressure results in abnormally dilated veins (varices) in the gullet (oesophagus), in the stomach, or in the intestine, which may cause life-threatening bleeding. People who have bled once are at high risk of bleeding in the future, so it is important to prevent further bleeding episodes in these people. Different treatment options are available to prevent further bleeding. One option is endoscopic treatment, which uses a flexible camera to examine the affected area and to seal varices with elastic bands, or to inject the varices with a substance to close the veins. A second option is 'shunting', which diverts blood flow away from the problematic vein, reducing pressure and thereby reducing the chance of bleeding. There are three main types of shunts: total shunt, distal splenorenal shunt, and transjugular intrahepatic portosystemic shunt. Total shunt and distal splenorenal shunt were more commonly used in the past and require invasive surgical procedures. TIPS are now much more commonly used, as they do not require invasive surgery.

Review question

The aim of this Cochrane Review was to compare shunts versus endoscopic treatments with or without further medications in people with liver cirrhosis who had previously bled from varices, by collecting and analysing all relevant studies in this topic area and by reviewing the evidence.

Study characteristics

In June 2020, we reviewed the evidence. We found 27 randomised clinical trials (trials where participants are allocated to groups at random) involving 1828 participants. Three trials investigated total shunt (164 participants); five trials investigated distal splenorenal shunt (352 participants); and 19 trials investigated transjugular intrahepatic portosystemic shunt (1312 participants). The source of funding was unclear in 16 trials. Eleven trials were funded by the government or received grants from local hospitals or universities.

Results

Evidence suggesting whether shunt treatments compared with endoscopic treatments with or without further medications alter the overall risk of death from any cause (all-cause mortality), reduce the risk of bleeding from varices, or reduce the risk of dying from bleeding varices (death due to variceal bleeding) was very uncertain.

Evidence that people treated with shunts compared with endoscopic treatments with or without further medications are at increased risk of acute hepatic encephalopathy (brain dysfunction associated with liver disease) or chronic hepatic encephalopathy (brain dysfunction that occurs repeatedly or does not fully improve) was also very uncertain.

We could not conclude with certainty whether people treated with shunt stayed in hospital longer than people treated with endoscopy with or without further medications, or which treatment was more expensive, as we were not confident that combining the results from different studies would produce a meaningful result. No trials reported on the impact of treatments on patient quality of life.

Risk of bias

The results of our analyses must be interpreted with caution due to concerns about the quality of included trials. Weaknesses in the design of these studies could influence results, making them potentially misleading.

Conclusions

We cannot say for sure that portosystemic shunts when compared with endoscopic treatment associated sometimes with medical treatment modify the risk of overall death (all-cause mortality), reduce the risk of repeated episodes of bleeding, or increase the risk of developing hepatic encephalopathy. We need properly conducted trials assessing important outcomes for people with cirrhosis and health providers.

Authors' conclusions: 

Evidence on whether portosystemic shunts versus endoscopy interventions with or without medical treatment in people with cirrhosis and previous hypertensive portal bleeding have little or no effect on all-cause mortality is very uncertain. Evidence on whether portosystemic shunts may reduce bleeding and mortality due to bleeding while increasing hepatic encephalopathy is also very uncertain. We need properly conducted trials to assess effects of these interventions not only on assessed outcomes, but also on quality of life, costs, and length of hospital stay.

Read the full abstract...
Background: 

People with liver cirrhosis who have had one episode of variceal bleeding are at risk for repeated episodes of bleeding. Endoscopic intervention and portosystemic shunts are used to prevent further bleeding, but there is no consensus as to which approach is preferable.

Objectives: 

To compare the benefits and harms of shunts (surgical shunts (total shunt (TS), distal splenorenal shunt (DSRS), or transjugular intrahepatic portosystemic shunt (TIPS)) versus endoscopic intervention (endoscopic sclerotherapy or banding, or both) with or without medical treatment (non-selective beta blockers or nitrates, or both) for prevention of variceal rebleeding in people with liver cirrhosis.

Search strategy: 

We searched the CHBG Controlled Trials Register; CENTRAL, in the Cochrane Library; MEDLINE Ovid; Embase Ovid; LILACS (Bireme); Science Citation Index - Expanded (Web of Science); and Conference Proceedings Citation Index - Science (Web of Science); as well as conference proceedings and the references of trials identified until 22 June 2020. We contacted study investigators and industry researchers.

Selection criteria: 

Randomised clinical trials comparing shunts versus endoscopic interventions with or without medical treatment in people with cirrhosis who had recovered from a variceal haemorrhage.

Data collection and analysis: 

We used standard methodological procedures expected by Cochrane. When possible, we collected data to allow intention-to-treat analysis. For each outcome, we estimated a meta-analysed estimate of treatment effect across trials (risk ratio for binary outcomes). We used random-effects model meta-analysis as our main analysis and as a means of presenting results. We reported differences in means for continuous outcomes without a meta-analytic estimate due to high variability in their assessment among all trials. We assessed the certainty of evidence using GRADE.

Main results: 

We identified 27 randomised trials with 1828 participants. Three trials assessed TSs, five assessed DSRSs, and 19 trials assessed TIPSs. The endoscopic intervention was sclerotherapy in 16 trials, band ligation in eight trials, and a combination of band ligation and either sclerotherapy or glue injection in three trials. In eight trials, endoscopy was combined with beta blockers (in one trial plus isosorbide mononitrate). We judged all trials to be at high risk of bias. We assessed the certainty of evidence for all the outcome review results as very low (i.e. the true effects of the results are likely to be substantially different from the results of estimated effects). The very low evidence grading is due to the overall high risk of bias for all trials, and to imprecision and publication bias for some outcomes. Therefore, we are very uncertain whether portosystemic shunts versus endoscopy interventions with or without medical treatment have effects on all-cause mortality (RR 0.99, 95% CI 0.86 to 1.13; 1828 participants; 27 trials), on rebleeding (RR 0.40, 95% CI 0.33 to 0.50; 1769 participants; 26 trials), on mortality due to rebleeding (RR 0.51, 95% CI 0.34 to 0.76; 1779 participants; 26 trials), and on occurrence of hepatic encephalopathy, both acute (RR 1.60, 95% CI 1.33 to 1.92; 1649 participants; 24 trials) and chronic (RR 2.51, 95% CI 1.38 to 4.55; 956 participants; 13 trials). No data were available regarding health-related quality of life.

Analysing each modality of portosystemic shunts individually (i.e. TS, DSRS, and TIPS) versus endoscopic interventions with or without medical treatment, we are very uncertain if each type of shunt has effect on all-cause mortality: TS, RR 0.46, 95% CI 0.19 to 1.13; 164 participants; 3 trials; DSRS, RR 0.93, 95% CI 0.65 to 1.33; 352 participants; 4 trials; and TIPS, RR 1.10, 95% CI 0.92 to 1.31; 1312 participants; 19 trial; on rebleeding: TS, RR 0.28, 95% CI 0.14 to 0.56; 127 participants; 2 trials; DSRS, RR 0.26, 95% CI 0.11 to 0.65; 330 participants; 5 trials; and TIPS, RR 0.44, 95% CI 0.36 to 0.55; 1312 participants; 19 trials; on mortality due to rebleeding: TS, RR 0.25, 95% CI 0.06 to 0.96; 164 participants; 3 trials; DSRS, RR 0.31, 95% CI 0.13 to 0.74; 352 participants; 5 trials; and TIPS, RR 0.65, 95% CI 0.40 to 1.04; 1263 participants; 18 trials; on acute hepatic encephalopathy: TS, RR 1.66, 95% CI 0.70 to 3.92; 115 participants; 2 trials; DSRS, RR 1.70, 95% CI 0.94 to 3.08; 287 participants; 4 trials, TIPS, RR 1.61, 95% CI 1.29 to 1.99; 1247 participants; 18 trials; and chronic hepatic encephalopathy: TS, Fisher's exact test P = 0.11; 69 participants; 1 trial; DSRS, RR 4.87, 95% CI 1.46 to 16.23; 170 participants; 2 trials; and TIPS, RR 1.88, 95% CI 0.93 to 3.80; 717 participants; 10 trials.

The proportion of participants with shunt occlusion or dysfunction was overall 37% (95% CI 33% to 40%). It was 3% (95% CI 0.8% to 10%) following TS, 7% (95% CI 3% to 13%) following DSRS, and 47.1% (95% CI 43% to 51%) following TIPS. Shunt dysfunction in trials utilising polytetrafluoroethylene-covered stents was 17% (95% CI 11% to 24%).

Length of inpatient hospital stay and cost were not comparable across trials.

Funding was unclear in 16 trials; 11 trials were funded by government, local hospitals, or universities.

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