Shunt dysfunction: Is it suitable as the primary end point in transjugular intrahepatic portosystemic shunt trials?
Authors: Jingzhi Cai, Wengang Guo, Chuangye He, Guohong Han
Journal: Journal of Hepatology (2014)

Covered vs. uncovered stents for transjugular intrahepatic portosystemic shunt: A randomized controlled trialJournal of HepatologyVol. 60Issue 5PreviewThe first studies comparing covered stents (CS) and bare stents (BS) to achieve Transjugular Intrahepatic Portosystemic Shunt (TIPS) were in favor of CS, but only one randomized study has been performed. Our aim was to compare the primary patency of TIPS performed with CS and BS. Full-Text PDF Reply to: "Shunt dysfunction: Is it suitable as the primary end point in transjugular intrahepatic portosystemic shunt trials?"Journal of HepatologyVol. 62Issue 1PreviewWe are very honoured by the interest of Han and colleagues for our study [1]. In their letter two topics were discussed. The first topic was the type of dysfunction in which they underlined and illustrated the risk of initial stent malposition. The second topic was in relation with the primary end point of our study. Here, they suggested the use of clinical recurrence rather than haemodynamics, to qualify shunt dysfunction. Full-Text PDF Open Access We read with great interest the randomized controlled trial (RCT) by Perarnau et al. that was published in the Journal of Hepatology [[1]Perarnau J. Gouge A. Nicolas C. Alteroche L. Borentain P. Saliba F. et al.Covered versus uncovered stents for transjugular intrahepatic portosystemic shunt: a randomized controlled trial.J Hepatol. 2014; 60: 962-968Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar]. The first RCT on transjugular intrahepatic portosystemic shunt (TIPS), comparing PTFE-covered stents (CS) with bare stents (BS) on shunt patency and clinical outcomes, was published in 2004 [[2]Bureau C. Garcia-Pagan J.C. Otal P. Pomier-Layrargues G. Chabbert V. Cortez C. et al.Improved clinical outcome using polytetrafluoroethylene- coated stents for TIPS: results of a randomized study.Gastroenterology. 2004; 126: 469-475Abstract Full Text Full Text PDF PubMed Scopus (440) Google Scholar]. Ten years later, Perarnau et al. concluded that CS provided a significant reduction in shunt dysfunction compared to BS. No doubt, this paper has provided additional evidence to confirm the advantages of CS. However, we still believe that certain issues merit further discussion. To begin with, the shunt dysfunction rates in this paper (31.5% and 44.0% in the CS group vs. 53.8% and 63.6% in the BS group after 1 and 2 years) were higher than those in the first RCT (12.8% and 34% in the CS group vs. 43.9% and 74% in the BS group after 1 and 2 years) [1Perarnau J. Gouge A. Nicolas C. Alteroche L. Borentain P. Saliba F. et al.Covered versus uncovered stents for transjugular intrahepatic portosystemic shunt: a randomized controlled trial.J Hepatol. 2014; 60: 962-968Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar, 2Bureau C. Garcia-Pagan J.C. Otal P. Pomier-Layrargues G. Chabbert V. Cortez C. et al.Improved clinical outcome using polytetrafluoroethylene- coated stents for TIPS: results of a randomized study.Gastroenterology. 2004; 126: 469-475Abstract Full Text Full Text PDF PubMed Scopus (440) Google Scholar]. The authors attribute the outcome variance to differences in patient selection and shunt diameter [[1]Perarnau J. Gouge A. Nicolas C. Alteroche L. Borentain P. Saliba F. et al.Covered versus uncovered stents for transjugular intrahepatic portosystemic shunt: a randomized controlled trial.J Hepatol. 2014; 60: 962-968Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar]. However, this explanation may be incomplete. For example, the position of the stent may also influence the outcome of TIPS. A frequency of approximately 20% proximal or distal displacement was given in the previous American Association for the Study of Liver Disease (AASLD) guidelines [[3]Boyer T.D. Haskal Z.J. American Association for the Study of Liver Disease Practice Guidelines: the role of transjugular intrahepatic portosystemic shunt creation in the management of portal hypertension.J Vasc Interv Radiol. 2005; 16: 615-629Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar]. We also found that stent displacement may lead to a higher risk of shunt dysfunction in patients with variceal bleeding [[4]Bai M. He C. Qi X. Yin Z. Wang J. Guo W. et al.Shunting branch of portal vein and stent position predict survival after transjugular intrahepatic portosystemic shunt.World J Gastroenterol. 2014; 21: 20-23Google Scholar]. To illustrate the impact of stent position, we present the following case: A 62-year-old woman with a history of decompensated hepatitis B-related cirrhosis was admitted in our department to undergo TIPS insertion for the treatment of variceal bleeding. The portosystemic gradient decreased from 26 mmHg to 10 mmHg after the implantation of a 8/80 mm Fluency covered stent (Bard, Peripheral Vascular, Tempe, AZ, USA) (Fig. 1A) on April 17th, 2013. However, the patient developed variceal bleeding again on April 19th, 2013. Haemoglobin dropped from 99 g/L to 90 g/L, gastroesophageal varices and red-signs were seen during upper endoscopy. Direct portography confirmed that the top of the stent stood out against the upper wall of the right hepatic vein (Fig. 1B), raising the portosystemic gradient to 16 mmHg as a result. A new stent was inserted to extend the shunt to the junction of the hepatic vein and inferior vena cava (Fig. 1C). After TIPS revision, the portosystemic pressure gradient decreased to 10 mmHg, and the symptoms disappeared. The patient was free of variceal re-bleeding after one year of follow-up. Thus, the results could be cofounded by several factors if shunt dysfunction is used as the primary end point. Secondly, dysfunction was defined by the authors as an increase in the portosystemic pressure gradient (PPG) to ⩾12 mmHg and/or a reduction in the calibre of the stent by ⩾50% at portography [[1]Perarnau J. Gouge A. Nicolas C. Alteroche L. Borentain P. Saliba F. et al.Covered versus uncovered stents for transjugular intrahepatic portosystemic shunt: a randomized controlled trial.J Hepatol. 2014; 60: 962-968Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar]. However, the definition of shunt dysfunction may differ depending on the underlying liver disease (i.e. ascites, haemorrhage), which may result in different risks of shunt dysfunction [[5]Membreno F. Baez A. Pandula R. Walser E. Lau D. Differences in long-term survival after transjugular intrahepatic portosystemic shunt for refractory ascites and variceal bleed.J Gastroenterol Hepatol. 2005; 20: 474-481Crossref PubMed Scopus (32) Google Scholar]. We reviewed previous RCTs in TIPS, and found that RCTs about haemorrhage defined shunt dysfunction in one or several of the following criteria: (1) Doppler sonography: a 20–50% decrease in the stent flow, a portal blood-flow velocity lower than 10–60 cm/s or over 120 cm/s, or a change in the direction of the flow in the intrahepatic portal branches; (2) Angiography: a reduction in the calibre of the stent by ⩾50% or an occlusion of the shunt; (3) PPG: over 12–15 mmHg. Meanwhile RCTs on ascites identified shunt dysfunction through angiographic findings and a PPG over 12 mmHg except Doppler sonography. Thus, no consistent agreement has been reached among researchers as to the exact judgment criteria of shunt dysfunction. Notably, most physicians rely on Doppler sonography to monitor shunt dysfunction in practice, but the best indicator of shunt dysfunction is symptom recurrence according to the AASLD guidelines [[6]Boyer T.D. Haskal Z.J. AASLD practice guidelines: the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension.Hepatology. 2010; 51: 1-16Crossref PubMed Scopus (1) Google Scholar]. Furthermore, if shunt dysfunction occurs, what actions should be taken? Treatments, such as balloon angioplasty or new stent insertion were provided if shunt dysfunction was confirmed by the author [[1]Perarnau J. Gouge A. Nicolas C. Alteroche L. Borentain P. Saliba F. et al.Covered versus uncovered stents for transjugular intrahepatic portosystemic shunt: a randomized controlled trial.J Hepatol. 2014; 60: 962-968Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar], even though such interventions may not conform to the clinical reality. In practice, TIPS revision is only performed when symptoms occur [[7]Rössle M. TIPS: 25 years later.J Hepatol. 2013; 59: 1081-1093Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar]. Hence, the definition and management of shunt dysfunction still needs further exploration, and symptom recurrence may be more relevant to both clinical practice and scientific studies than shunt dysfunction. Therefore, shunt dysfunction may not be the suitable primary end point of TIPS trials. From our perspective, the best primary end point should be the problem for which the management was conducted. The recurrence of symptoms, such as variceal bleeding and hepatic ascites, may be considered the optimal primary end point. Thus, we use symptom recurrence to define shunt dysfunction in our study [[8]Han G. Qi X. He C. Yin Z. Wang J. Xia J. et al.Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic portal hypertension in liver cirrhosis.J Hepatol. 2011; 54: 78-88Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar]. We look forward to further discussions regarding the optimal primary end point of TIPS research. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.