Wednesday, August 31, 2011

Early TIPS for Ascites Study Seeks to Improve Survival

September issue of Gastroenterology

Early TIPS for Ascites Study Seeks to Improve Survival

The possibility that we can improvethe quality and length of life for liver disease patients, without a transplant, is one of the most exciting potentia lopportunities in our field today. Ascites,the most common complication from cirrhosis, develops in 50% of patients within10 years.1 Development of ascites reflects decompensation of the liver and is associated with an increase in morbidity and mortality.

Initially, the ascites is usually controlled easily with diuretics, but as the liver disease worsens, higher and higher doses of diuretics are required to maintain patient comfort. Eventually, diuretic treatment fails and the patient is diagnosed with refractory ascites. The current standard of care for refractory ascites consists of large volume paracentesis (LVP), coupled with an aggressive pharmacotherapy regimen.

Transjugular intrahepatic portosystemicshunt (TIPS) therapy is regarded as the last line of defense, a bridge to liver transplantation.

However, these conclusions are based on trials in which bare stents were used to create the TIPS. With covered stents that are now available, better outcomes might be possible.

Interventional radiologists and hepatologists have come together in an international trial to determine if TIPS intervention can increase transplant-free survival compared to LVP when performed earlier in the ascitic patient population.

Previous studies comparing TIPS to LVP must be revisited. Conducted in the1990s and early 2000s, these studies may have failed to consistently demonstrate increased life expectancy for three reasons.

First, mostly end-stage patients with refractory ascites were included. Second, neither therapy changes the underlying liver disease, a reason why most therapies, except transplant, have failed to show a survival benefit.

Finally, bare metal stents,which had a high failure rate, were the only option for TIPS therapy at the time.

This study is being conducted to evaluate whether newer technology like covered stents with a lower failure rate will address this last potential pitfall. The Early TIPS for Ascites Study is a randomized, multi-center study, sponsored by Gore Medical in collaboration with both hepatologists and interventional radiologists.

Given the nature of the TIPS referral pathway, the team approach will lead to better patient care, more coordinated medical management, and improved recruitment. The goal of the study is to determine whether patients with difficult-to-treat ascites benefit most from early TIPS therapy using a covered stent or from continued LVP,based on transplant-free survival.

This study has survival as its primary endpoint, in contrast to previous trials, which looked at control of ascites. There is little question that TIPS is better than LVP in controlling the ascites. But controlled trials have shown that use of TIPS is associated with more encephalopathy than alternative forms of therapy.1

What is unclear is the balance of these two factors and the over all impact on survival. This study will also differ from prior studies that focused on refractory ascites, because the Early TIPS forAscites Study protocol allows for enrollment of patients prior to reaching the refractory stage as defined by TheInternational Ascites Club. This is also the first study of its kind in which the Modelfor End-Stage Liver Disease score is used for patient selection and will also be tracked during follow-up as a study end point.

Previous studies comparing TIPS with bare metal stents to LVP in patients with refractory ascites had mixed findings.2 Yet arecent meta-analysis of these studies found that TIPS patients had significantly longer transplant-free survival than paracentesis patients.3 And a study published last year in the New England Journal of Medicine4 compared early TIPS intervention with a covered stent to pharmacotherapy/endoscopicband ligation in high-risk variceal bleeding patients, with positive results.

TIPS therapy is a minimally invasive procedure done with closed surgery, as only a small puncture is made in the jugular vein for insertion of the device. A TIPS creates a functional side-to-side portocaval shunt to route blood flow through the damaged liver and into the main blood vessels that carry blood back to the heart.

With the TIPS procedure, alternative treatments such as medications and paracentes is for ascites, and endoscopic treatment of varices, may possibly not be needed as often. Some reports have shown significant improvements in TIPS therapy when using a covered stent versus a bare metal stent.5,6

As one of the national principal investigators for the Early TIPS for Ascites Study, I believe that the possibility of prolonging patient lives is one of the most exciting new questions in TIPS therapy that we must answer. Most treatments for complications of portal hypertension improve the patient’s condition without affecting survival. We believe that if survival improves in the TIPS cohort, the paradigm for management of cirrhotic ascites might change significantly.

■THOMAS D. BOYER, M.D., is Director ofthe Arizona Liver Research Institute,Professor of Medicine, and Medical Director of the University Medical CenterLiver Transplant Program, University ofArizona College of Medicine, Tucson.References1. Hepatology 2005;41:386-400.2. Hepatology 2009;49:2087-107.3.
Gastroenterology 2007;133:825-34.4. N. Engl. J. Med. 2010;362:2370-9.5. Hepatology 2003;38:1043-50.6. Liver International 2007;27:742-7

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