Elsevier

The Lancet

Volume 361, Issue 9361, 15 March 2003, Pages 952-954
The Lancet

Rapid Review
Prevention of variceal rebleeding

https://doi.org/10.1016/S0140-6736(03)12778-XGet rights and content

Summary

Context

Variceal bleeding is the most frequent severe complication of portal hypertension and a leading cause of death and liver transplantation in patients with cirrhosis. Patients surviving a variceal bleed are at high risk of rebleeding (over 60% at 1 year). Portacaval shunts and transjugular intrahepatic portasystemic shunts (TIPS) are effective for prevention of rebleeding but carry a high risk of hepatic encephalopathy. Endoscopic techniques include band ligation (EBL) and injection sclerotherapy (EIS). Drug approaches are based on non-selective β blocker with or without isosorbide-5-mononitrate (ISMN).

Starting point

David Patch and colleagues (Gastroenterology 2002; 123: 1013–19) randomised 102 patients surviving a variceal bleeding to EBL or drug therapy with propranolol with the addition of ISMN if target reductions in portal pressure (evaluated by the hepatic venous pressure-gradient [HVPG]) were not achieved at 3 months. Overall, results of drug therapy were similar to those of EBL (44% vs 54% rebleeding at 1 year). There were no differences in survival or nonbleeding complications. Christophe Bureau and colleagues (Hepatology 2002; 36: 1361–66) treated 34 patients with cirrhosis and portal hypertension with propranolol and measured HVPG after a median of 4 days. Target HVPG reductions were achieved in 13 “responders”. ISMN was added in the 21 “non-responders” and HVPG measured again: seven more patients achieved target HVPG reduction. Re-bleeding rates were lower in responders than in non-responders (10% vs 64%). Both studies suggest that drug therapy can be improved by adding ISMN to b blockers in those patients with an insufficient decrease in HVPG.

Where next?

Long-term drug therapy is emerging as effective treatment for the prevention of variceal rebleeding. The role of HVPG monitoring as a guide to identifying patients requiring further treatment needs to be further evaluated. Trials to determine the best treatment for patients who do not respond to drug therapies are also required.

Section snippets

Treatment of portal hypertension

In cirrhosis, portal hypertension is mainly due to increased resistance to portal blood-flow through the cirrhotic liver, and increased blood-flow in the portal and collateral circulation due to splanchnic vasodilatation and a hyperkinetic circulation. Portal hypertension can therefore be attenuated by decreasing intrahepatic resistance, reducing portal blood-flow, or both.3 Until recently, increased intrahepatic resistance could only be corrected by means of liver transplantation or

Problems with drug therapy

Although it has been customary to adjust the dose of β blockers to achieve a 25% fall in the resting heart-rate, this reduction by no means guarantees an effective fall in HVPG, and there is no correlation between changes in heart rate and changes in HVPG. Our approach is to titrate up to the maximum tolerated dose, with dose escalation every 2 days. Christophe Bureau and colleagues17 used a fixed dose of long-acting propranolol every other day, but this regimen has been criticised.20

HVPG

Conclusions

Drug therapy is a simple and safe way to prevent variceal rebleeding, provided target reductions in HVPG are achieved. Future steps forward include the development of non-invasive ways to assess the haemodynamic response so that therapy can be tailored not only in research studies, but also in clinical practice. However, this tailoring is not likely to be possible in the near future, and unless HVPG measurement is available, physicians will have to make decisions based on published results with

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