Volume 42, Issue 7, Pages 462-467 (July 2010)

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Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: Time to update the guidelines?

Received 6 November 2009; accepted 15 November 2009. published online 28 December 2009.

Abstract

Since its first introduction in the 1980s, transjugular intrahepatic portosystemic shunt has played an increasingly important role in the management and treatment of the complications of portal hypertension. In 2005, the American Association for the Study of Liver Diseases published the Practice Guidelines for the use of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Since then, technical advances and new interesting data on transjugular intrahepatic portosystemic shunt have been presented in the literature. The present review focusses on the applications of transjugular intrahepatic portosystemic shunt and examines more recent studies on this topic; the current guidelines on the use of transjugular intrahepatic portosystemic shunt are also discussed. From the data presented in the most recent publications, it has become increasingly clear that the recommendations stemming from the current guidelines need to be reviewed and updated in several points. Changes in the American Association for the Study of Liver Diseases Practice Guidelines are needed for both common indications (variceal bleeding and refractory ascites) as well as uncommon ones (i.e., Budd-Chiari syndrome and portal cavernoma). In addition, a relevant technical advance has been the introduction of the polytetrafluoroethylene-covered stents, which greatly improved the patency and clinical efficacy of transjugular intrahepatic portosystemic shunt. Consequently, new studies are required to re-assess the role of transjugular intrahepatic portosystemic shunt performed with new covered stents as compared with other strategies in the management of portal hypertension.

Abbreviations: AASLD, American Association for the Study of Liver Diseases, BCS, Budd-Chiari syndrome, HVPG, Hepatic venous pressure gradient, MELD, Model end-stage liver disease, PTFE, Polytetrafluoroethylene, RCTs, Randomized controlled trials, TIPS, Transjugular intrahepatic porto-systemic shunt

Keywords: Budd-Chiari syndrome, Cirrhosis, Refractory ascites, Variceal bleeding

Article Outline

• Abstract

• 1. Introduction

• 2. TIPS and variceal bleeding

• 2.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 1

• 3. TIPS versus surgery

• 3.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 2

• 4. TIPS and refractory ascites

• 4.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 3

• 5. TIPS and uncommon indications: hepatic and portal veins thrombosis

• 5.1. TIPS and Budd-Chiari syndrome

• 5.1.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 4

• 5.2. TIPS and portal cavernoma

• 6. Conclusion

• Conflicts of interest statement

• References

• Copyright

1. Introduction

Since the first description of transjugular intrahepatic porto-systemic shunt (TIPS), the indications for the procedure have progressively expanded and, still today, the role of TIPS in the treatment of portal hypertension continues to evolve. In 2005, the Practice Guidelines for the use of TIPS in the management of portal hypertension were published by the American Association for the Study of Liver Diseases (AASLD) [1]. Further recommendations on the use of TIPS were discussed in the Baveno IV Consensus Conference on portal hypertension [2] and in the 2007 AASLD Practice Guidelines on the prevention and management of variceal bleeding [3]. Since then, technical advances and new studies on TIPS have been presented in the literature. This review is therefore aimed at examining more recent data on this topic and discussing the current recommendations on the use of TIPS.

2. TIPS and variceal bleeding

2.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 1

TIPS is effective in controlling acute variceal bleeding that is refractory to medical therapy and is preferred to surgery in this situation (evidence grade II-3).

TIPS should not be used for the prevention of rebleeding in patients who have bled only once from esophageal varices, and its use should be limited to those who fail pharmacological and endoscopic therapy (evidence: grade I).

TIPS was first used for variceal bleeding. According to the current guidelines [1], TIPS can be used for both the control of active variceal bleeding and the prevention of variceal rebleeding. In these clinical conditions, TIPS is considered a second-line therapy: it should be used only when medical and endoscopic treatments have failed (see Recommendation 1). The large majority of patients with acute variceal bleeding can in fact be controlled with a combination of drugs and endoscopic therapy. In those patients who continue to bleed despite these treatments, emergency TIPS represents an important rescue therapy and, although no randomized controlled trials (RCTs) are available, several observational studies [4], [5], [6], [7], [8], [9], [10] reported that TIPS is able to control variceal bleeding refractory to the medical and endoscopic treatment with a success rate ranging from 89 to 100%, a rebleeding rate of 15% and a mortality rate within the first month of 30%.

Regarding the prevention of variceal rebleeding, several RCTs have compared TIPS with endoscopic therapy [11], [12], [13], [14], [15], [16], [17], drugs [18] or a combination of these two [19], [20], [21], and three metanalyses [22], [23], [24] were published. These data demonstrated that, although the patients treated with TIPS experienced significantly fewer rebleeding episodes, no advantages in terms of survival were reported and, on the other hand, the incidence of hepatic encephalopathy resulted significantly greater than that observed in non-shunted control groups. For these reasons, TIPS was again considered as second-line treatment for the prevention of variceal rebleeding and current guidelines [1] suggest that it should not be used in patients who have bled only (see Recommendation 1).

In summary, TIPS is regarded as a second-line treatment for both acute variceal bleeding and rebleeding prevention. However, 10–20% of acute bleeders do not respond to first-line treatments (medical and endoscopic therapies) and, even when emergency TIPS is available, the mortality rate of patients not responding to the first-line therapy and eventually treated by TIPS remains high (around 30% within the first month). Moreover, in those patients surviving the first bleeding and undergoing medical and/or endoscopic treatments according to current guidelines, the one-year rebleeding rate ranges between 30 and 60%, depending on the treatment administered [25].

How could this strategy be ameliorated? The possibility of identifying — among those acutely bleeding — patients at a higher risk of rebleeding and mortality could be of help. In these patients, in fact, more aggressive management may be useful. Some recent data suggest that this approach might be possible; actually, it has been noted that an early measurement of hepatic venous pressure gradient (HVPG) in cirrhotic patients during an acute variceal bleeding provides significant prognostic information [26]. Those patients with an initial HVPG of >20mm Hg, in fact, proved to have a poor evolution of their bleeding episode (i.e., failure to control bleeding, early rebleeding and greater transfusion requirement) and, consequently, a worse survival. On the basis of this observation, a RCT [27] utilised this information (an HVPG value of >20mmHg measured within the first 24h after admission for acute variceal bleeding) to identify a group of high-risk patients. These subjects were then randomised to receive an early TIPS or traditional medical and endoscopic therapy. The outcome of the two randomised groups were compared with that of a low-risk patient group with an HVPG value of <20mmHg (Fig. 1). This study provided very interesting results by showing that, in the high-risk group (HVPG >20mmHg), the cases treated with early portal decompression (TIPS) had less treatment failures, transfusion requirements and need of intensive care. Moreover, in this group the survival rate was significantly higher than that observed in the high-risk group treated with medical and endoscopic therapy, and similar to that observed in the low-risk group (Fig. 1). This study demonstrated for the first time that it is possible to identify those subjects with acute variceal bleeding at very high-risk of rebleeding and death and that, in these patients, a more aggressive therapy — such as the employment of TIPS as a first-line treatment — is significantly more efficient than the traditional approach.

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Fig. 1. Summary of the results of a RCT on the use of early TIPS in high-risk cirrhotic patients with an acute variceal bleeding [27].

The use of this strategy in clinical practice is however limited by the fact that HVPG is hardly measurable in acutely bleeding patients. To overcome this problem, a recent study [28] showed that some simple parameters measured during an acute bleeding (such as an advanced Child-Pugh class or a systolic blood pressure of <100mmHg) seem to be as useful as HVPG measurement in identifying those patients at a higher risk of rebleeding Finally, a recent RCT [29] (though only in abstract form) suggests that in acutely bleeding subjects with a poor prognosis according to the above clinical parameters, an early TIPS with extended-polytetrafluoroethylene (PTFE)-covered stents reduces the rebleeding rate and improves survival compared to the control group treated with traditional methods (Table 1).

Table 1.

Summary of the results of a RCT comparing early TIPS and standard treatment in high-risk cirrhotic patients with an acute variceal bleeding [29].


	Medical/endoscopic treatment (n=31)	TIPS (n=32)	p
Failure to control acute variceal bleeding (n)	14	1	0.01
One-year cumulative rebleeding	97%	50%	< 0.001
One-year cumulative survival	60%	86%	0.02
One-year cumulative ascites	33%	13%	NS
One-year cumulative hepatic encephalopahty	40%	28%	NS

In conclusion, evidence has been now provided that the use of TIPS at an early stage may represent a new perspective and improve the outcome and survival of high-risk bleeding patients selected by simple clinical prognostic indicators. Therefore, the current recommendation [1] which considers the combination of vasoactive drugs and endoscopic therapy as first-line therapy in all cases, limiting the use of TIPS as a rescue therapy in case of failures, needs to be revised.

3. TIPS versus surgery

3.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 2

Pending further studies, in patients with good liver function, either a TIPS or a surgical shunt are appropriate choices for the prevention of rebleeding in patients who have failed medical therapy (evidence: grade II-2).

In patients with poor liver function, TIPS is preferred to surgical therapy in the prevention of rebleeding in patients who have failed medical therapy (evidence: grade III).

The indication that, according to current guidelines [1], surgical shunting is still to be considered as a possible alternative to TIPS for Child-A patients is, also, another issue to be reviewed. This recommendation is debatable in light of the results of two recent papers [30], [31], both based on the only available RCT which compared TIPS to distal spleno-renal shunting. In the first paper [30], TIPS resulted as effective as surgical shunting in preventing variceal bleeding and no differences were found in terms of hepatic encephalopathy and mortality. In the TIPS group there was a greater need for re-interventions due to shunt dysfunction. However, in this study, TIPS was constructed with traditional bare stents while, to date, several papers [32], [33], [34], [35], [36], [37], [38], [39], [40], [41] have clearly documented that the use of e-PTFE-covered stents has completely overcome the problem of TIPS dysfunction (Fig. 2). The second paper [31] demonstrated not only that TIPS is as effective as surgical shunting in preventing variceal bleeding, but also that it is more cost-effective. This study provides a solid rationale to support the use of TIPS in clinical practice. In the accompanying editorial by D’Amico and Luca [42], it has been suggested, as already established in clinical practice, that the era of surgical shunting for treatment of portal hypertension is over. On this issue also, therefore, the recommendations of current guidelines need to be revised.

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Fig. 2. Cumulative two-year probability of remaining free of shunt dysfunction in cirrhotic patients treated with TIPS constructed with PTFE-covered stents and with the conventional bare stents (data in the figure are derived by Refs. [41], [63]).

4. TIPS and refractory ascites

4.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 3

Although TIPS will decrease the need for repeated large-volume paracentesis in patients with refractory ascites associated with cirrhosis, it should be used only in those patients who are intolerant of repeated large-volume paracentesis (evidence: grade I).

Refractory ascites represents yet another indication for TIPS placement. Five trials [43], [44], [45], [46], [47] and three metanalyses [48], [49], [50] on the topic are currently available. All RCTs showed that TIPS significantly reduces the recurrence of ascites while mortality rate was reduced in one trial [47] only and was similar in the others. The cumulative incidence of hepatic encephalopathy was similar between the two groups. Hepatic encephalopathy episodes, however, were somewhat more frequent and more severe in the patients treated with TIPS than in those undergoing repeated paracentesis. Based on these results, the AASLD Guidelines [1] (see Recommendation 3) considered TIPS as a second-line treatment to be used only in patients intolerant to repeated large-volume paracentesis. However, recent data support a revision of these recommendations. Salerno et al. [51], by analysing the individual patient data of four of the five published RCTs, have shown that TIPS was able to significantly reduce not only the risk of recurrence of ascites but also the mortality rate of patients with refractory ascites when compared with repeated large-volume paracentesis. Interestingly, the superiority of TIPS in terms of survival was maintained also by dividing the patients into different classes of severity according to the model end-stage liver disease (MELD) score. This observation does not support the indication that limits the use of this technique only to those patients intolerant to repeated large-volume paracentesis, and suggests that, at least for selected cases, TIPS may become the first-line choice. The predictive factors of survival identified in the study were age, serum bilirubin and sodium levels, while the development of post-TIPS hepatic encephalopathy was predicted by the MELD score, the mean arterial pressure and the post-TIPS portal pressure gradient. Additional studies carried out in clinical practice might therefore address the better strategy to select those patients with refractory ascites who can obtain the advantage of TIPS on survival by minimising the incidence of hepatic encephalopathy. Presently, younger patients with a less compromised liver function and systemic haemodynamics may, however, benefit from TIPS as a first-line treatment for refractory ascites.

5. TIPS and uncommon indications: hepatic and portal veins thrombosis

Hepatic and portal vein thrombosis were considered by the AASLD Practice Guidelines as relative contraindications to TIPS because of the technical difficulties in constructing the shunt in the absence of a normal anatomy of the portal and the hepatic vein systems. However, recent data suggest that TIPS is not contraindicated in these rare conditions and that it may even play an important role in their management. Unfortunately, RCTs on this topic are not available and, probably, the infrequency of these pathologies discourages the possibility of carrying out RCTs with a sufficient number of patients. Nevertheless, in recent years several case reports and observational studies have used TIPS both in Budd-Chiari syndrome (BCS) and in portal vein thrombosis with promising results.

5.1. TIPS and Budd-Chiari syndrome

5.1.1. 2005 AASLD Practice Guidelines for the use of TIPS: Recommendation 4

The decision to create a TIPS in a patient with Budd-Chiari syndrome should be based on the severity of disease, and only patients with moderate disease appear to be reasonable candidates for a TIPS (evidence: grade II-3). Patients with BCS and mild disease can be managed medically, whereas those with more severe disease or acute hepatic failure are best managed by liver transplantation (evidence: grade II-3).

The above reported recommendations are still acceptable and are further supported by two recent papers. The first [52] reported the long-term results of TIPS in 124 BCS patients collected in several centers and demonstrated that TIPS is able to improve the estimated five-year orthotopic liver transplantation-free survival. According to the Rotterdam score, survival was 74% (95% CI: 65–83%) in the intermediate-risk patients group and 42% (95% CI: 28–56%) in the high-risk group. The post-TIPS corresponding values were: 82% (95% CI: 69–90%) in the intermediate-risk group and 71% (95% CI: 53–84%) in the high-risk group. The study showed that also in these patients the use of e-PTFE-covered stents for the TIPS construction is much more efficient. Finally, the paper identified serum bilirubin levels, age and INR/PT values as independent risk factors for mortality, and provided a specific prognostic model to estimate the one-year survival rate for BCS patients treated with TIPS.

The second paper [53] was an observational study in which a number of treatments, including TIPS, were sequentially applied; the Authors’ strategy was to introduce the treatments according to their increasing invasiveness and was based on treatment response rather than on the severity of the patients’ condition. Based on this algorithm, the lack of a complete response to a given treatment led to the shift to the following more invasive therapeutic option. Pharmacotherapy was the first option, followed by hepatic vein recanalisation in non-responders, followed by TIPS and, finally, liver transplantation. With this therapeutic strategy most patients achieved a complete clinical response with an excellent survival.

In summary, TIPS is technically and clinically successful in most patients with BCS and its role in the management of this disease is fully established. Consistent data indicate that, in patients in whom the disease is not fully controlled by the aforementioned options, the next step should be TIPS creation (and e-PTFE-covered stents should always be preferred). Whether the early use of TIPS could be more efficient in patients with mild symptoms remains to be established. Procedure-related complications and feasibility, the main limiting factors, are greatly influenced by technical skill and experience, therefore improved results can be expected in the near future.

5.2. TIPS and portal cavernoma

Recently, an interesting advance in the application of TIPS was achieved in the management of chronic portal vein thrombosis. Although TIPS placement is technically difficult when portal vein thrombosis is associated with a cavernous transformation, after some unsuccessful reports [54], [55], [56] several authors [57], [58], [59], [60] have presented their first satisfactory results by demonstrating that TIPS is technically feasible also in these subjects. Their experience is presently limited to case reports only and to small patient series, but it provides promising results (Table 2). In theory, TIPS might be useful in patients with non-cirrhotic portal hypertension both as a rescue therapy for acute variceal bleeding (and for those cases with ectopic varices) and in the prophylaxis of variceal rebleeding. In addition, the TIPS-induced acceleration of the portal blood flow may prevent the extension of thrombosis into the portal system or may reduce intestinal ischemia due to the extension of thrombosis to the superior mesenteric vein. Moreover, lifelong anticoagulation therapy, which, when indicated, has been associated with a reduction of further thrombotic events [61], is administered with difficulty in individuals with large varices at high-risk of bleeding or in those who have already bled. TIPS creation, by definitely eliminating varices, may therefore reduce the risks associated with anticoagulation therapy. This potential indication has been recently discussed [62]. More data are of course needed to fully establish the potential role of TIPS in portal cavernoma, but we believe that this procedure should be included in the algorithm for the management of patients with this infrequent cause of portal hypertension. Because of the technical difficulties related to TIPS creation in this condition, these patients should however be referred to selected Units with a large experience in TIPS procedure.

Table 2.

Available reports on the use of TIPS in patients with portal cavernoma.


		TIPS
	Radosevich et al. [54]	1/1 failed
	Walser et al. [55]	2/2 failed
	Jiang et al. [56]	4/4 failed
	Kawamata et al. [57]	1/1 successful
	Van Ha et al. [58]	3/4 successful (75%)
	Bauer et al. [59]	4/4 successful (100%)
	Senzolo et al. [60]	6/9 successful (67%)
	Riggio et al. (unpublished)	7/10 successful (70%)

6. Conclusion

Many recommendations of the current guidelines on the use and application of TIPS in clinical practice need to be extensively reviewed. Changes are needed regarding both more common (variceal bleeding and intractable ascites) and uncommon indications. In addition, the introduction of e-PTFE-covered stents is a major technical advance to be considered. In a recent RCT, these stents improved patients’ survival when compared with traditional bare ones. Because all available RCTs used bare stents, their conclusions might be deeply modified by the use of these newer devices. Controlled studies are definitely required to re-assess the role of TIPS performed with new covered stents as compared with other strategies, not only in terms of survival and clinical outcome but also quality of life and cost-effectiveness. Finally the choice of anaesthetic technique during TIPS is another developing issue. Total intravenous anaesthesia [64] has been recently successfully used, thus reducing logistic or organisational difficulties.

New revised guidelines on the use of TIPS should clarify:

-In which clinical setting and for which patients with acute variceal bleeding is TIPS indicated at an early stage.

-In which clinical setting and for which patients with refractory ascites is TIPS considered first-line treatment.

-The role of TIPS in patients with non-cirrhotic portal hypertension (BCS portal vein obstruction).

Author's note: At the time of publication of the present article, the AASLD published un update [65] of the original 2005 guidelines dealing with some of the points raised by this review.

Conflicts of interest statement

None declared.

References

[1]. [1]Boyer TD, Haskal ZJ. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology. 2005;41:396–400.

[2]. [2]de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005;43:167–176. Full Text | Full-Text PDF (174 KB) | CrossRef

[3]. [3]Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922–938. CrossRef

[4]. [4]Banares R, Casado M, Rodriguez-Laiz JM, et al. Urgent transjugular intrahepatic portosystemic shunt for control of acute variceal bleeding. Am J Gastroenterol. 1998;93:75–79. MEDLINE | CrossRef

[5]. [5]Jalan R, John TG, Redhead DN, et al. A comparative study of emergency transjugular intrahepatic portosystemic stent-shunt and esophageal transection in the management of uncontrolled variceal hemorrhage. Am J Gastronterol. 1995;90:1932–1937.

[6]. [6]La Berge JM, Somberg KA, Lake JR, et al. Two-year outcome following transjugular intrahepatic portosystemic shunt for variceal bleeding: results in 90 patients. Gastroenterology. 1995;108:1143–1151. Abstract | Full-Text PDF (827 KB) | CrossRef

[7]. [7]Le Moine O, Devier J, Ghysels M, et al. Transjugular intrahepatic portosystemic stent shunt as rescue treatment after sclerotherapy failure in variceal bleeding. Scand J Gastroenterol. 1994;207:23–28.

[8]. [8]Mc Cormick PA, Dick R, Panagou EB, et al. Emergency transjugular intrahepatic portosystemic stent-shunting as salvage treatment for uncontrolled variceal bleeding. Br J Surg. 1994;81:1324–1327. MEDLINE | CrossRef

[9]. [9]Sanyal AJ, Freedman AM, Luketic VA, et al. Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy. Gastroenterology. 1996;111:138–146. Full-Text PDF (52 KB) | CrossRef

[10]. [10]Gerbes AL, Gulberg V, Waggerhauser T, et al. Transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding in portal hypertension. Comparison of emergency and elective interventions. Dig Dis Sci. 1998;43:2463–2469. MEDLINE | CrossRef

[11]. [11]Cabrera J, Maynar M, Granados R, et al. Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage. Gastroenterology. 1996;110:832–839. Abstract | Full-Text PDF (123 KB) | CrossRef

[12]. [12]Sanyal AJ, Freedman AM, Luketic VA, et al. Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial. Ann Intern Med. 1997;126:849–857. MEDLINE

[13]. [13]Jalan R, Forrest EH, Stanley AJ, et al. A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices. Hepatology. 1997;26:1115–1122. MEDLINE | CrossRef

[14]. [14]Merli M, Salerno F, Riggio O, et al. Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: a randomized multicenter trial. Hepatology. 1998;27:40–45.

[15]. [15]Garcia-Villarreal L, Martinez-Lagares F, Sierra A, et al. Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal rebleeding after recent variceal hemorrage. Hepatology. 1999;29:27–32. MEDLINE | CrossRef

[16]. [16]Pomier-Layrargues G, Villeneuve JP, Deschênes M, et al. Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial. Gut. 2001;48:390–396. MEDLINE | CrossRef

[17]. [17]Cello JP, Ring EJ, Olcott EW, et al. Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial. Ann Intern Med. 1997;126:858–865. MEDLINE

[18]. [18]Escorsell A, Bañares R, García-Pagán JC, et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial. Hepatology. 2002;35:385–392. MEDLINE | CrossRef

[19]. [19]Rossle M, Deibert P, Haag K, et al. Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propanolol for prevention of variceal rebleeding. Lancet. 1997;349:1043–1049. Abstract | Full Text | Full-Text PDF (59 KB) | CrossRef

[20]. [20]Sauer P, Theilman L, Stremmer W, et al. Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propanolol for variceal rebleeding. Gastroenterology. 1997;113:1623–1631. Abstract | Full-Text PDF (369 KB) | CrossRef

[21]. [21]Sauer P, Hansmann J, Richter GM, et al. Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic portosystemic stent shunt: a long-term randomized trial. Endoscopy. 2002;34:690–697. CrossRef

[22]. [22]Luca A, D’Amico G, La Galla R, et al. TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of randomized clinical trials. Radiology. 1999;212:411–421. MEDLINE

[23]. [23]Burroughs AK, Vangeli M. Transjugular intrahepatic portosystemic shunt versus endoscopic therapy: randomized trials for secondary prophylaxis of variceal bleeding: an updated meta-analysis. Scand J Gastroenterol. 2002;37:249–252. MEDLINE | CrossRef

[24]. [24]Papatheodoridis GV, Goulis J, Leandro G, et al. Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: a meta-analysis. Hepatology. 1999;30:612–622. MEDLINE | CrossRef

[25]. [25]Bosch J, García-Pagán JC. Prevention of variceal rebleeding. Lancet. 2003;361:952–954[Review]. Abstract | Full Text | Full-Text PDF (66 KB) | CrossRef

[26]. [26]Moitinho E, Escorsell A, Bandi JC, et al. Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology. 1999;117:626–631. Abstract | Full Text | Full-Text PDF (175 KB) | CrossRef

[27]. [27]Monescillo A, Martınez-Lagares F, Ruiz-del-Arbol L, et al. Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding. Hepatology. 2004;40:793–801. MEDLINE | CrossRef

[28]. [28]Abraldes JG, Villanueva C, Bañares R, et al. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48:229–236. Abstract | Full Text | Full-Text PDF (148 KB) | CrossRef

[29]. [29]Garcia-Pagan JC, et al. An early decision for PTFE-TIPS improves survival in high risk cirrhotic patients admitted with acute variceal bleeding. A multicenter RCT. Hepatology. 2008;48:373;[Abs].

[30]. [30]Henderson JM, Boyer TD, Kutner MH, et al. Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial. Gastroenterology. 2006;130:1643–1651. Abstract | Full Text | Full-Text PDF (181 KB) | CrossRef

[31]. [31]Boyer TD, Henderson JM, Heerey AM, et al. Cost of preventing variceal rebleeding with transjugular intrahepatic portal systemic shunt and distal splenorenal shunt. J Hepatol. 2008;48:407–414. Abstract | Full Text | Full-Text PDF (147 KB) | CrossRef

[32]. [32]Cejna M, Peck-Radosavljevic M, Thurnher SA, et al. Creation of transjugular intrahepatic portosystemic shunts with stent-grafts: initial experiences with a polytetrafluoroethylene-covered nitinol endoprothesis. Radiology. 2001;221:437–446. MEDLINE | CrossRef

[33]. [33]Otal P, Smayra T, Bureau C, et al. Preliminary results of a new expanded-polytetrafluoroethylene-covered stent-graft for transjugular intrahepatic portosystemic shunt procedures. Am J Roentgenol. 2002;178:141–147.

[34]. [34]Maleaux G, Nevens F, Wilmer A, et al. Early and long-term clinical and radiological follow-up results of expanded polytetrafluoroethylene-covered stent-grafts for transjugular intrahepatic portosystemic shunt procedures. Eur Radiol. 2004;14:1842–1850. MEDLINE

[35]. [35]Angermayr B, Cejna M, Koeing F, et al. Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stent-grafts versus bare stents. Hepatology. 2003;38:1043–1050. MEDLINE | CrossRef

[36]. [36]Charon JPM, Alaedin FH, Pimphalwar SA, et al. Results of polytetrafluoroethylene-covered stent grafts for transjugular portosystemic shunt creation. J Vasc Interv Radiol. 2004;15:1219–1230. Abstract | Full Text | Full-Text PDF (1306 KB)

[37]. [37]Vignali C, Bargellini I, Grosso M, et al. TIPS with expanded polytetrafluoroethylene-covered stent: results of an Italian multicenter study. Am J Roentgenol. 2005;185:472–480.

[38]. [38]Barrio J, Ripoll C, Banares R, et al. Comparison of transjugular intrahepatic portosystemic shunt dysfunction in PTFE-covered stent-grafts versus bare stents. Eur J Radiol. 2005;55:120–124. | CrossRef

[39]. [39]Ockenga J, Kroencke TJ, Schuetz T, et al. Covered transjugular intrahepatic portosystemic stents maintain lower portal pressure and require fewer reinterventions than uncovered stents. Scand J Gastroenterol. 2004;10:994–999.

[40]. [40]Bureau C, Garcia-Pagan JC, Otal P, et al. Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study. Gastroenterology. 2004;126:469–475. Abstract | Full Text | Full-Text PDF (179 KB) | CrossRef

[41]. [41]Angeloni S, Merli M, Salvatori F, et al. Polytetrafluorethylene-covered stent-graft for TIPS procedure: 1-year patency and clinical results. Am J Gastroenterol. 2004;99:280–285. MEDLINE | CrossRef

[42]. [42]D’Amico G, Luca A. TIPS is a cost effective alternative to surgical shunt as a rescue therapy for prevention of recurrent bleeding from esophageal varices. J Hepatol. 2008;48:387–390. Full Text | Full-Text PDF (103 KB) | CrossRef

[43]. [43]Lebrec D, Giuily N, Hadengue A, et al. Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. J Hepatol. 1996;25:135–144. Abstract | Full-Text PDF (1184 KB) | CrossRef

[44]. [44]Rössle M, Ochs A, Gülberg V, et al. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites. N Engl J Med. 2000;342:1701–1717. MEDLINE | CrossRef

[45]. [45]Ginès P, Uriz J, Calahorra B, et al. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology. 2002;123:1839–1847. Abstract | Full Text | Full-Text PDF (106 KB) | CrossRef

[46]. [46]Sanyal AJ, Genning C, Reddy KR, et al. The North American study for the treatment of refractory ascites. Gastroenterology. 2003;124:634–641. Abstract | Full Text | Full-Text PDF (128 KB) | CrossRef

[47]. [47]Salerno F, Merli M, Riggio O, et al. Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites. Hepatology. 2004;40:629–635. MEDLINE | CrossRef

[48]. [48]Albillos A, Bañares R, González M, et al. A meta-analysis of transjugular intrahepatic portosystemic shunt versus paracentesis for refractory ascites. J Hepatol. 2005;43:990–996. Abstract | Full Text | Full-Text PDF (121 KB) | CrossRef

[49]. [49]Deltenre P, Mathurin P, Dharancy S, et al. Transjugular intrahepatic portosystemic shunt in refractory ascites: a meta-analysis. Liver Int. 2005;25:349–356. MEDLINE

[50]. [50]D’Amico G, Luca A, Morabito A, et al. Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a metaanalysis. Gastroenterology. 2005;129:1282–1293. Abstract | Full Text | Full-Text PDF (382 KB) | CrossRef

[51]. [51]Salerno F, Cammà C, Enea M, et al. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology. 2007;133:825–834. Abstract | Full Text | Full-Text PDF (287 KB) | CrossRef

[52]. [52]Garcia-Pagán J, Heydtmann M, Raffa S, et al. TIPS for Budd-Chiari Syndrome: long-term results and prognostics factors in 124 patients. Gastroenterology. 2008;135:808–815. Abstract | Full Text | Full-Text PDF (327 KB) | CrossRef

[53]. [53]Plessier A, Sibert A, Consigny Y, et al. Aiming at minimal invasiveness as a therapeutic strategy for Budd-Chiari syndrome. Hepatology. 2006;44:1308–1316. MEDLINE | CrossRef

[54]. [54]Radosevich PM, Ring EJ, LaBerge JM, et al. Transjugular intrahepatic portosystemic shunt in patients with portal vein occlusion. Radiology. 1993;186:523–527. MEDLINE

[55]. [55]Walser EM, McNees SW, DeLa Pena O, et al. Portal venous thrombosis: percutaneous therapy and outcome. J Vasc Interv Radiol. 1998;9:119–127. Abstract | Full-Text PDF (11097 KB) | CrossRef

[56]. [56]Jiang ZB, Shan H, Shen XY, et al. Transjugular intrahepatic portosystemic shunt for palliative treatment of portal hypertension secondary to portal vein tumor thrombosis. World J Gastroenterol. 2004;10:1881–1884. MEDLINE

[57]. [57]Kawamata H, Kumazaki T, Kanazawa H, et al. transjugular intrahepatic portosystemic shunt in a patient with cavernomatous portal vein occlusion. Cardiovasc Interv Radiol. 2000;23:145–149.

[58]. [58]Van Ha TG, Hodge J, Funaky B, et al. Transjugular intrahepatic portosystemic shunt placement in patients with cirrhosis and concomitant portal vein thrombosis. Cardiovasc Interv Radiol. 2006;29:785–790.

[59]. [59]Bauer J, Johnson S, Durham J, et al. The role of TIPS for portal vein patency in liver transplant patients with portal vein thrombosis. Liver Transpl. 2006;12:1544–1551. MEDLINE | CrossRef

[60]. [60]Senzolo M, Tibbals J, Cholongitas E, et al. Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without cavernous transformation. Aliment Pharmacol Ther. 2006;23:767–775. MEDLINE | CrossRef

[61]. [61]Condat B, Pessione F, Hillaire S, et al. Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology. 2001;120:490–497. Abstract | Full Text | Full-Text PDF (183 KB) | CrossRef

[62]. [62]Senzolo M, Patch D, Miotto D, et al. Interventional treatment should be incorporated in the algorithm for the management of patients with portal vein thrombosis. Hepatology. 2008;48:1352–1353. CrossRef

[63]. [63]Riggio O, Angeloni S, Salvatori FM, et al. Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts. Am J Gastroenterol. 2008;103:2738–2746.

[64]. [64]DeGasperi A, Corti A, Corso R, et al. Transjugular intrahepatic portosystemic shunt (TIPS): the anesthesiological point of view after150 procedures managed under total intravenous anesthesia. J Clin Monit Comput. 2009;[Epub ahead of print].

[65]. [65]Boyer TD, Haskal ZJ. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. Hepatology. 2009;[Epub ahead of print].

II Gastroenterologia, Dipartimento di Medicina Clinica, Università di Roma “La Sapienza”, Viale dell’Università 37, 00185 Rome, Italy

Corresponding author. Tel.: +39 0649972001; fax: +39 0649972001/453319.

PII: S1590-8658(09)00442-3

doi:10.1016/j.dld.2009.11.007

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