Abstract

Abstract Background

The presence of oesophageal varices is associated with the risk of upper gastrointestinal bleeding. Endoscopic variceal ligation is used to prevent this occurrence but the ligation procedure may be associated with complications.

To assess the beneficial and harmful effects of band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices.

We combined searches in the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 9 February 2019.

We included randomised clinical trials comparing band ligation verus no intervention regardless of publication status, blinding, or language in the analyses of benefits and harms, and observational studies in the assessment of harms. Included participants had cirrhosis and oesophageal varices with no previous history of variceal bleeding.

Three review authors extracted data independently. The primary outcome measures were all‐cause mortality, upper gastrointestinal bleeding, and serious adverse events. We undertook meta‐analyses and presented results using risk ratios (RRs) with 95% confidence intervals (CIs) and I² values as a marker of heterogeneity. In addition, we calculated the number needed to treat to benefit (NNTTB) for the primary outcomes . We assessed bias control using the Cochrane Hepato‐Biliary domains; determined the certainty of the evidence using GRADE; and conducted sensitivity analyses including Trial Sequential Analysis.

Six randomised clinical trials involving 637 participants fulfilled our inclusion criteria. One of the trials included an additional small number of participants (< 10% of the total) with non‐cirrhotic portal hypertension/portal vein block. We classified one trial as at low risk of bias for the outcome, mortality and high risk of bias for the remaining outcomes; the five remaining trials were at high risk of bias for all outcomes. We downgraded the evidence to moderate certainty due to the bias risk. We gathered data on all primary outcomes from all trials. Seventy‐one of 320 participants allocated to band ligation compared to 129 of 317 participants allocated to no intervention died (RR 0.55, 95% CI 0.43 to 0.70; I² = 0%; NNTTB = 6 persons). In addition, band ligation was associated with reduced risks of upper gastrointestinal bleeding (RR 0.44, 95% CI 0.28 to 0.72; 6 trials, 637 participants; I² = 61%; NNTTB = 5 persons), serious adverse events (RR 0.55, 95% CI 0.43 to 0.70; 6 trials, 637 participants; I² = 44%; NNTTB = 4 persons), and variceal bleeding (RR 0.43, 95% CI 0.27 to 0.69; 6 trials, 637 participants; I² = 56%; NNTTB = 5 persons). The non‐serious adverse events reported in association with band ligation included oesophageal ulceration, dysphagia, odynophagia, retrosternal and throat pain, heartburn, and fever, and in the one trial involving participants with either small or large varices, the incidence of non‐serious side effects in the banding group was much higher in those with small varices, namely ulcers: small versus large varices 30.5% versus 8.7%; heartburn 39.2% versus 17.4%. No trials reported on health‐related quality of life.

Two trials did not receive support from pharmaceutical companies; the remaining four trials did not provide information on this issue.

This review found moderate‐certainty evidence that, in patients with cirrhosis, band ligation of oesophageal varices reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared to no intervention. It is unlikely that further trials of band ligation versus no intervention would be considered ethical.

Author(s)

Sonam Vadera, Charles Wei Kit Yong, Lise Lotte Gluud, Marsha Y Morgan

Abstract

Plain language summary

Band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in people with cirrhosis and oesophageal varices

Background

Cirrhosis is a chronic disorder of the liver. People with cirrhosis may develop dilated veins in their oesophagus, and these may bleed. Variceal bleeding is potentially life‐threatening. Band ligation is a procedure in which a viewing instrument or endoscope is inserted through the mouth into the oesophagus and the varices are then tied off at their base, thereby cutting off the blood flow. The varices have to be sufficiently large to allow the bands to be applied. This procedure can be done before people bleed from their varices (primary prevention) or after they have suffered a bleed (secondary prevention).

Review question

We investigated the benefits and harms of band ligation compared with no treatment, for primary prevention of bleeding in people with cirrhosis and oesophageal varices by reviewing clinical trials in which people were randomly allocated (chosen by chance) to band ligation or no treatment.

Search date

9 February 2019.

Trial funding sources

Two of the included trials did not receive funding or support from for‐profit companies; the remaining four trials did not provide information on this issue.

Trial characteristics

We included six randomised clinical trials involving 637 participants. All randomised clinical trials compared band ligation to no treatment. One trial included participants with and without cirrhosis. The length of time taken to eradicate the varices, where reported, ranged from a mean of 28 to 76 days.

Key results

Our analyses showed a beneficial effect of band ligation on the rates of death, bleeding, and serious adverse events compared to no treatment.

Certainty of the evidence

In people with cirrhosis and oesophageal varices, the risk of death associated with variceal bleeding is very high as are the risks of other serious harms. Our review has found that band ligation reduces the risks of these problems when compared to no treatment. We are moderately confident in our estimates of the benefits and harms of band ligation. It is unlikely that any further trials comparing band ligation versus no intervention will be undertaken.

Author(s)

Sonam Vadera, Charles Wei Kit Yong, Lise Lotte Gluud, Marsha Y Morgan

Reviewer's Conclusions

Authors' conclusions

Implications for practice

This review includes randomised clinical trials evaluating the use of band ligation for the primary prevention of variceal bleeding. Our analyses has found evidence that band ligation reduces mortality, upper gastrointestinal bleeding, including variceal bleeding, and serious adverse events, when compared to no intervention. However, there were limitations in the amount and certainty of the evidence, little information about non‐serious adverse events, and no data concerning health‐related quality of life. Nevertheless, band ligation is recommended as one alternative treatment for primary prevention of variceal bleeding in people with medium to large varices, and is used widely in clinical practice, particularly where treatment with non‐selective beta‐blockers is either contraindicated or not tolerated.

Implications for research

Variceal bleeding is a medical emergency associated with a mortality rate which, in spite of recent progress, is still of the order of 10% to 20% at six weeks (Carbonell 2004). Guidelines have been formulated for the management of portal hypertension in a series of 'Baveno' consensus workshops undertaken at intervals from 1986; the latest of these, Baveno VI, was published in 2015 (Baveno VI 2015). The National Institute for Health and Care Excellence (NICE) has also provided guidance on aspects of the assessment and management of portal hypertension relevant to this review (NICE 2016).

Five of the trials included in the present review were undertaken between 1996 and 1999 prior to the publication of the recommendations of the Baveneo III to VI consensus workshops; the fifth trial was published in 2005 and hence prior to Baveno V and VI. All of the trials were performed before publication of the NICE Guidelines.

According to both sets of guidelines, endoscopic band ligation is not recommended as a treatment option for people with small varices (Baveno VI 2015; NICE 2016). People with small varices without signs of increased risk may be treated with non‐selective beta‐blockers to prevent bleeding; those with red wale marks or with severely decompensated cirrhosis are at increased risk of bleeding and should be treated with non‐selective beta‐blockers (Baveno VI 2015). The Baveno consensus recommends that people with medium to large varices should be treated with a non‐selective beta‐blocker or endoscopic band ligation for the prevention of the first variceal bleed (Baveno VI 2015).

Given the substantial mortality associated with variceal bleeding and the fact that band ligation is now an established and recommended treatment for primary prophylaxis of variceal bleeding in people with cirrhosis and medium to large varices, we do not believe that further trials of band ligation compared to no intervention could be justified on ethical grounds.