Elaborative role of TIPS in ascites in chronic liver disease patients.

1. TIPS in Ascites
Pratap Sagar Tiwari
Pic ref: https://www.sehatq.com/tindakan-medis/transjugular-intrahepatic-portosystemic-shunt-tips

2. Note
➢This is a compilation from various sources. References included. All credit goes to
original authors.
➢Only for academic purposes.
➢Do not edit, rename, copy or publish.
Thankyou
pratapsagartiwari@gmail.com

3. Ascites
• Ascites is the MC cause of decompensation in LC, as 5-10% of pts with compensated cirrhosis per year
develop this complication.1
• The appearance of ascites heralds a poor prognosis, as the five-year survival drops from about 80% in
compensated pts to about 30% in pts with DLC and ascites.2
• Refractoriness of ascites is associated with a poor prognosis, with a median survival of about six months.3
3
1. Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology 1987;7:122–128.
2. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006;44:217–231.
3. Salerno F, Borroni G, Moser P, Badalamenti S, Cassara L, Maggi A, et al. Survival and prognostic factors of cirrhotic patients with ascites: a study of 134 outpatients. Am J Gastroenterol 1993;88:514–519.

4. Refractory ascites (ra)
• In about 5-10% of cirrhotic pts per year and as liver disease progresses, response to sodium restriction
and diuretics diminishes, leading to RA.[1]
• RA is defined by the failure to mobilize ascites despite high-dose diuretics, typically about 400 mg/day
spironolactone and 160 mg furosemide or equivalent dose of loop-acting diuretic.[1]
• Ascites is also considered to be refractory when effective doses of diuretics cannot be used because of
development of diuretic-associated complications. RA is often a/with dilutional hyponatremia, type 2
HRS, SBP, and muscle wasting.[2]
Definition table in next slide
1. Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International ascites club. Hepatology 1996;23:164-176.
2. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004;350:1646-1654.

5. Definition & Diagnostic Criteria
5Moore KP, Wong F, Ginès P, et al. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology 2003;38:258–266.

6. Management of Refractory Ascites (summary)
• Large-volume paracentesis with albumin:
• Diuretics in patients with refractory ascites: continue if renal sodium excretion >30 mmol/day
• Non-selective beta-blockers in patients with refractory ascites: with caution
• Transjugular intrahepatic portosystemic shunts: HE significantly reduced from 50 % to about 18%
• Wang Q et al,2017. Eight mm covered TIPS does not compromise shunt function but reduces HE in
preventing RVH.
• Sauerbruch et al. 2015. Prevention of rebleeding from EV in pts receiving small-diameter stents vs.
hemodynamically controlled medical therapy.
• Indeed, underdilated 10 mm stent grafts passively expand to almost the full diameter within 1–6 weeks.
The final messages from Metaanalysis can be summarised as follow:
i) TIPS controlled ascites better than LVP
ii) TIPS is followed by a greater incidence of HE
iii) However, discrepant results were obtained with respect to survival.
Currently available data suggest that TIPS improves survival compared to LVP in pts with recurrent ascites, but it
does not in those with refractory ascites.
6For detailed management of Refractory Ascites, refer to my slide " Refractory Ascites"

7. Other management options tried in Studies
➢ a1-adrenergic agonist: midodrine
➢ a2-adrenoceptor agonist : clonidine
➢ Combinations of midodrine with either clonidine
➢ Antagonist of vasopressin V2-receptors: tolvaptan
➢ Terlipressin
➢ Octreotide and albumin
➢ Combined midodrine/rifaximin/diuretics
➢ Alfapump®: significant reduction of the number and volume of paracentesis, significantly improved
quality of life and nutritional parameters.AE: AKI
Inhibition of the AVP V2 receptor reduces the number of
aquaporin-2 water channels in the renal collecting duct and
decreases the water permeability of the collecting duct.
Collectively, agents that competitively block ADH action and
increase water excretion are called aquaretics.
7
Furthur-on, I will be discussing regarding the role of TIPS IN ASCITES only.

8. 1960s
Inadvertent portal access during
transjugular cholangiography
1969
Rosch [1] discussed the potential of a
“radiologic portocaval shunt”
1982
Colapinto [2] creates the first
human balloon dilated TIPS
1988
Richeter [3] creates the first
human Palmaz stent TIPS
Early to mid-
1990s
Widespread clinical use with self-
expanding bare stents
HISTORY OF TIPS
1. Rösch J, HanafeeWN, SnowH. Transjugular portal venography and radiologic portacaval shunt: an experimental study. Radiology 1969;92(5):1112–1114
2. Colapinto RF, Stronell RD, Gildiner M, et al. Formation of intrahepatic portosystemic shunts using a balloon dilatation catheter: preliminary clinical experience. AJR AmJ Roentgenol 1983;140(4): 709–714
3. Richter GM, Palmaz JC, Noldge G, et al. The transjugular intrahepatic portosystemic stent-shunt (TIPSS): a new nonoperative percutaneous procedure. Radiologie 1989;29:406–411
8

9. Mid- to late-
1990s
Animal experimentation using
silicone and e-PTFE coated stents to
improve TIPS patency [1-3]
2001
Procedure endpoint defined as a
reduction in PSG to <12 mm Hg
Early 2000s
• Early human e-PTFE covered stent-graft experience[4-7]
• Defining TIPS candidacy by prognostic parameters (e.g.,
MELD)
2005
AASLD places practice guidelines on the
“role of TIPS in the MX of PHTN”
2009
AASLD adds BCS as an additional
indication & considers e-PTFE
covered stent grafts as standard of
practice
HISTORY OF TIPS
9References are at the end of the slides

10. Transjugular intrahepatic portosystemic shunt
(TIPSS): Introduction
• TIPS involve creation of a low-resistance channel between
the hepatic vein and the intrahepatic portion of the
portal vein (usually the right branch) using angiographic
techniques.
• The tract is kept patent by deployment of an expandable
metal stent across it, thereby allowing blood to return to
the systemic circulation.
• A TIPS is placed to reduce portal pressure in pts with
complications related to PHTN.[1,2]
1. Colombato L. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension.
J Clin Gastroenterol. 2007 Nov-Dec. 41 Suppl 3:S344-51.
2. Gaba RC, Omene BO, Podczerwinski ES, Knuttinen MG, Cotler SJ, Kallwitz ER, et al. TIPS for Treatment of Variceal
Hemorrhage: Clinical Outcomes in 128 Patients at a Single Institution over a 12-Year Period. J Vasc Interv Radiol. 2011
Dec 16. Pic src: Sankar K, edt al. Transjugular Intrahepatic Portosystemic Shunts. JAMA. 2017;317(8):880.
10

11. Transjugular intrahepatic portosystemic shunt
©2018 UpToDate
• Creation of a vascular access by the puncture of the IJV, which
must be performed under US guidance.
• Catheterization of one of the HVs, which can be also punctured
percutaneously under real time US guidance when its ostium is
not easily accessible. When HVs are occluded (BCS), PV branches
can be reached by direct puncture from the IVC.
• Puncture through the liver parenchyma of one of the main
branches of PV with or without real time USG guidance .
• Measurement of the porto-systemic pressure gradient (PPG)
by a digital recording system properly set-up for venous pressure.
IVC and not RA BP should be subtracted to PV pressure to
calculate the gradient.
S. Fagiuoli, R. Bruno, and V. W. Debernardi, “Consensus conference on TIPS management: Techniques, indications, contraindications,”
Digestive and Liver Disease, vol. 49, no. 2, pp. 121–137, 2017. 11

12. Transjugular intrahepatic portosystemic shunt
©2018 UpToDate
• Balloon dilatation of the parenchymal tract between the hepatic
(or IVC) and PVs.
• Deployment of the stent within the parenchymal tract.
• Hemodynamic assessment of the resultant PPG reduction
followed by further balloon dilatation of the lumen to reach the
desired target of pressure gradient.
• Reduction of PPG to <12 mm Hg should be achieved when the
indication is bleeding from EV.
S. Fagiuoli, R. Bruno, and V. W. Debernardi, “Consensus conference on TIPS management: Techniques, indications, contraindications,”
Digestive and Liver Disease, vol. 49, no. 2, pp. 121–137, 2017. 12

13. TIPS PROCEDURE
©2018 UpToDate
13

14. TIPS procedure
• Intravenous heparin is given for prevention of shunt thrombosis (bolus dose of 2500–5000 U
followed by constant infusion for 1–2 weeks, targeted at an aPTT of 60–80 seconds.
• A color Doppler USG is obtained 24 hours after the procedure to show shunt patency.
• It is usually repeated one week later if it is an uncovered stent or one month later if it is covered.
After that, if there are no complications, the USG is repeated 3 months later and then every 6 months
until the clinical outcome.
14/56

15. Are blood products routinely required during
TIPS placement?
• FFP, or pro-haemostatic agents are not required in cirrhotic pts undergoing TIPS, irrespective of
INR value (1,2).
• Although the threshold of platelet count needed to ensure normal primary haemostasis in cirrhosis is
not clearly defined, the 50X109/L cut-off can be utilized for platelets infusion before TIPS (3).
1. Bosch J, Thabut D, Albillos A, Carbonell N, Spicak J, Massard J, et al. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial. Hepatology. 2008
May;47(5):1604–14.
2. Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion. 2005 Sep;45(9):1413–25.
3. Tripodi A, Primignani M, Chantarangkul V, Lemma L, Jovani M, Rebulla P, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int. 2013 Mar;33(3):362–7.
15

16. Post-TIPS assessment
16/56
LOREM
IPSUM
>50 cm/s, ideally between 90 to 150 cm/s, but
acceptable from 50 to 200~250 cm/s.
Velocity in the shunt device
Patency and flow direction in HVs
(esp. the segment between the device and the IVC, of
which we should determine the velocity)
Direction of flow in PV: Hepatopetal
Direction of main IHPV branches: retrograde/
stagnant.
Flow direction in PV & branches
If the flow in SV is hepatofugal before TIPS, should
be hepatopetal post-TIPS in a normal functionating
device.
Flow direction in Splenic Vein
>30 cm/s. Note that it should ↑ significantly
after TIPS (>50%).
Velocity of the mid PV
Reduction in the caliper of the collaterals;
(paraumbilical, left gastric, SRS).
Evaluation of the collateral vessels
Stent configuration / position

17. EARLY EVENTS: Bacteriemia
• Bacteriemia after TIPS (defined by fever >38.5°C, or leucocytosis >15.000 / ul and positive blood
cultures) ranges between 2-25%(2-4,6) and in a prospective RCT was not influenced by antibiotic
prophylaxis (1)
• A longer duration of procedure, multiple stenting and the maintenance of a central venous line
are a/with a higher risk of infection after TIPS.
• In pts with uncomplicated procedure, the transjugular venous access should be removed at the end of the
intervention (1,5).
• A single dose of long acting cephalosporin ↓ the incidence of bacterial infection (20% to 2.6%)
justifying its use in anticipated complex procedures (2).
1. Deibert P, Schwarz S, Olschewski M, Siegerstetter V, Blum HE, Rössle M. Risk factors and prevention of early infection after implantation or revision of transjugular intrahepatic portosystemic shunts: results of a
randomized study. Dig Dis Sci. 1998 Aug;43(8):1708–13.
2. Gulberg V, Deibert P, Ochs A, Rossle M, Gerbes AL. Prevention of infectious complications after transjugular intrahepatic portosystemic shunt in cirrhotic patients with a single dose of
ceftriaxone.Hepatogastroenterology. Jan;46(26):1126–30.
3. Ghinolfi D, De Simone P, Catalano G, Petruccelli S, Coletti L, Carrai P, et al. Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation. Clin Transplant.
Jan;26(5):699–705.
4. Moon E, Tam MDBS, Kikano RN, Karuppasamy K. Prophylactic antibiotic guidelines in modern interventional radiology practice. Semin Intervent Radiol. 2010 Dec;27(4):327–37.
5. Mizrahi M, Roemi L, Shouval D, Adar T, Korem M, Moses A, et al. Bacteremia and “Endotipsitis” following transjugular intrahepatic portosystemic shunting. World J Hepatol. 2011 May 27;3(5):130–6.
6. Navaratnam AM, Grant M, Banach DB. Endotipsitis: A case report with a literature review on an emerging prosthetic related infection. World J Hepatol. 2015 Apr 8;7(4):710–6.
17

18. LATE EVENTS: Endotipsitis
• Defined by the presence of sustained bacteriemia a/with the evidence of thrombus or vegetations
inside the TIPS. This clinical condition is rare (1%).
• Early endotipsitis (< 120 days of the procedure) is usually related to Gram-positive organisms and the
antibiotic therapy must be long-lasting (at least 3 months) to avoid recurrence (1).
• In pts with uncontrolled or recurrent infection LT should be considered(2).
• There is no evidence for adopting long-term prophylaxis for the prevention of endotipsitis.
1. Navaratnam AM, Grant M, Banach DB. Endotipsitis: A case report with a literature review on an emerging prosthetic related infection. World J Hepatol. 2015 Apr 8;7(4):710–6.
2. Kochar N, Tripathi D, Arestis NJ, Ireland H, Redhead DN, Hayes PC. Tipsitis: incidence and outcome-a single centre experience. Eur J Gastroenterol Hepatol. 2010 Jun;22(6):729–35.
3. Sanyal AJ, Reddy KR. Vegetative infection of transjugular intrahepatic portosystemic shunts. Gastroenterology. 1998;115:110-115.
The term “endotipsitis” was proposed by Sanyal and Reddy[3], who defined it as: (1) the presence of continuous
bacteremia indicating an infectious focus in continuity with the venous circulation and (2) failure to find an alternate
source of infection despite an extensive search.
18

19. Hepatic encephalopathy
• HE is one of the major complications of TIPS. The incidence of overt episodic or recurrent HE post-
TIPS varies between 15 and 67% in a 2-year follow-up. The incidence of persistent overt HE is
around 8% (1) and that of covert HE around 35% (2-9,12,13).
• Prophylaxis of post-TIPS HE with either lactulose or rifaximin is not routinely recommended (9).
• Stent lumen reduction or occlusion is effective in case of persistent overt post-TIPS HE (10,11).
References are present at the end of the slides. 19

20. Contraindications to TIPS positioning
• The absence of vascular accesses represents the only technical CI to TIPS (1).
• The presence of PVT resulting in a portal cavernoma is not an absolute CI in presence of a “portal”
landing zone with adequate flow and calibre to receive the device (2,3)
1. Gazzera C, Fonio P, Gallesio C, Camerano F, Doriguzzi Breatta A, Righi D, et al. Ultrasound-guided transhepatic puncture of the hepatic veins for TIPS placement. Radiol Med. 2013 Apr;118(3):379–85.
2. Senzolo M, Tibbals J, Cholongitas E, Triantos CK, Burroughs AK, Patch D. Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without cavernous transformation. Aliment Pharmacol
Ther. 2006 Mar 15;23(6):767–75.
3. Van Ha TG, Hodge J, Funaki B, Lorenz J, Rosenblum J, Straus C, et al. Transjugular intrahepatic portosystemic shunt placement in patients with cirrhosis and concomitant portal vein thrombosis. Cardiovasc
Intervent Radiol. Jan;29(5):785–90.
4. Chiva T, Ripoll C, Sarnago F, Rincón D, Gómez-Camarero J, Galindo E, et al. Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of portopulmonary hypertension. Liver Int. 2015
Feb;35(2):353–61.
S. Fagiuoli, “Consensus conference on TIPS management" 2017
Clinical contraindications to TIPS placement are:
• Advanced liver disease (CP > 11, serum bilirubin > 5 mg/dl, MELD >18) (4).
• Severe organic renal failure (serum creat > 3 mg/dl)
• Heart failure
• Severe porto-pulmonary HTN (mPAP>45mmHg)
• Recurrent or persistent overt HE grade > 2 (WH scale) despite adequate RX
• Uncontrolled sepsis
20

21. • Relative technical CIs are anatomical conditions a/with a reduction in technical success rate or with
an ↑ risk of complications, such as liver tumours, the presence of multiple hepatic cysts.
The clinical appropriateness of TIPS positioning should be evaluated on a case-by-case
basis according with the relevance of the indication and the presence of general CIs.
Indeed, in the context of a life-threatening condition such as AVH, a broader range can be
adopted (CP C score < 14).
21

22. TIPS: Bare stent Vs PTFE-covered stent
• A major complication after TIPS insertion using bare stent grafts is the development of HE, which
can occur in up to 50% of pts.[1,2]
• The incidence of this complication can be significantly reduced to about 18% with the use of PTFE-
covered stent grafts of 8 mm,[3] a result confirmed by a recent RCT comparing 8 mm and 10mm
stent grafts.[4]
• Dysfunction of TIPS with bare stent grafts because of stent thrombosis and stenosis can develop in
up to 80% of cases.[1] This complication has been significantly reduced with the use of PTFE-covered
stents.[5]
References are present at the end of the slides. 22
Note: Use of polytetrafluoroethylene coated stents was first reported in 1995 [6]

23. TIPS: Covered Vs Bare
Bureau et al. 2015[2] Perarnau et al. 2015[3]
39 Vs 41 66 Vs 71
After median follow-up of 300 days;
Shunt dysfunction: 13% Vs 44%,P < 0.001.
HE @1 yr: 21% Vs 41% (NS).
The 1-year and 2-year survival rates: 70.9 % and 64.5 %
Vs 59.5 % and 40.5 % (NS)
The use of CS improves shunt patency without increasing
the risk of HE.
Median follow-up :23.6 and 21.8 months, respectively.
Shunt dysfunction :RR= 0.60; 95% CI:0.38-0.96, p=0.032.
The 2-year rate of shunt dysfunction: 44.0% vs. 63.6% .
Risk of HE: 0.89; 95% CI: 0.53-1.49,NS
2-year survival: 70% vs. 67.5%, NS
CS provided a significant 40% reduction in dysfunction
compared to BS. No significant difference with regard to
HE or death.
Multi center single blind RCT
Stent diameter data: NA
Multi center single blind RCT
CS: 10.5 ± 0.9 versus BS: 11.7 ± 0.8 mm
In the recent meta-analysis by Qi et al[1], covered stents not only significantly
improved the shunt patency, but also significantly ↓the risk of death. Additionally,
the risk of HE was not ↑ by the use of covered stents.
23References are present at the end of the slides.

24. TIPS in mx of refractory ascites (ra)
• The goal of TIPS creation in the case for RA is to reduce the portosystemic pressure gradient to <12
mm Hg.[1]
• TIPS improves ascites via increased natriuresis through reduction in both proximal tubular sodium
reabsorption and activity in the RAAS.[2]
• Notably, even after TIPS creation, pts must continue to restrict their sodium intake, and a majority of pts
will require low dose diuretics to maintain an ascites-free state.
1. Sanyal AJ, Genning C, Reddy KR, Wong F, Kowdley KV, Benner K, et al. The North American study for the treatment of refractory ascites. Gastroenterology 2003;124:634-641.
2. Rossle M, Gerbes AL. TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. Gut 2010;59:988-1000.

25. Controlled studies and meta-analysis
• Numerous RCTs have compared LVP and TIPS.
• The clinical effects of TIPS with bare stents in pts with refractory or recurrent ascites have been
assessed in 6 prospective RCTs (next slide),[1-6] whose main features are reported.
• Based on these RCTs, 7 meta-analyses were performed.[7-13]
References are at the end of the slides
The final messages can be summarised as follow:
i) TIPS controlled ascites better than LVP,
ii) TIPS is followed by a greater incidence of HE.
However, discrepant results were obtained with respect to survival.
Note: Recurrent or recidivant ascites is a severe stage prior to further progression to refractory ascites and is defined
as ascites that recurs on at least 3 occasions within a 12-month period despite prescription of dietary sodium
restriction and adequate diuretic dosage.

26. Characteristics and results of 6 RCTs comparing
bared TIPS and LVP in pts with LC and RA.
References are at the end of the slides

27. Summary
• Thus, currently available data suggest that TIPS improves survival compared to LVP in pts with
Recurrent Ascites, but it does not in those with RA.
• A careful selection of pts is also crucial to maximise the beneficial effects of TIPS, as TIPS can even
be detrimental in pts with the most advanced stages of cirrhosis, such as those belonging to CP C.[1]
1. Lebrec D, Giuily N, Hadengue A, Vilgrain V, Moreau R, Poynard T, et al. Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a
randomized trial. French Group of Clinicians and a Group of Biologists. J Hepatol 1996;25:135–144.

28. Predictor of survival
• A risk score (R) system based on SCr, INR, serum bilirubin and aetiology of cirrhosis has been
proposed to predict survival after TIPS insertion for RA.[3] Pts with R > 1.8 had a median survival of
3 months or less. This model was superior to both the CP classification, as well as the CP score, in
predicting survival.
• Another simple predictor of survival suggested for pts receiving TIPS for RA consists of the
combination of serum bilirubin and platelet count.[1]
• Another factor that seems to influence mortality is the number of TIPS procedures performed in a
centre, as the risk of inpatient mortality is lower in hospitals performing ≥20 TIPS per year.[2]
1. Bureau C, Metivier S, D’Amico M, Peron JM, Otal P, Pagan JC, et al. Serum bilirubin and platelet count: a simple predictive model for survival in patients with refractory ascites treated by TIPS. J Hepatol
2011;54:901–907.
2. Sarwar A, Zhou L, Novack V, Tapper EB, Curry M, Malik R, et al. Hospital volume and mortality after trans-jugular intrahepatic portosystemic shunt creation in the United States. Hepatology 2017.
3. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000;31:864–871.

29. Models used for prediction of post–tips survival
• Numerous models have been used to predict post-TIPS survival (for any indication), of which the CP
score and MELD score have been the most used.[1]
• Of the two, the MELD score has shown to be superior to CP score as a predictor for short-term
outcomes.[2]
• In a meta-analysis by Salerno et al, a MELD score between 11 and 19 was found to have a significant
survival benefit in pts who underwent TIPS versus pts who underwent LVP.[3]
1. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000;31:864-871.
2. Salerno F, Merli M, Cazzaniga M, Valeriano V, Rossi P, Lovaria A, et al. MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic
shunt. J Hepatol 2002;36:494-500.
3. Salerno F, Camma C, Enea M, Rossle M, Wong F. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology 2007;133:825-834.

30. • In addition, a survival benefit for TIPS was seen across all MELD categories.
• Furthermore, in a recent single-center study of 100 pts who underwent TIPS placement, with an
expanding covered stent, the 1-year survival rate for a MELD score less than 15, 15 to 18, and greater
than 18 was 84%, 67%, and 54%, respectively.[1]
1. Bercu ZL, Fischman AM, Kim E, Nowakowski FS, Patel RS, Schiano TD, et al. TIPS for refractory ascites: a 6-year single-center experience with expanded polytetrafluoroethylene-covered stent-grafts. AJR Am J
Roentgenol 2015;204:654-661.

31. • Currently, no RCTs have evaluated TIPS for RA in pts with a MELD score greater than 20.
• As such, each pt with RA should be evaluated carefully by looking at other clinical factors that can
adversely affect outcomes. These factors include older age, high bilirubin, history of HE, and low sodium
concentration.[1]
• In those without severe hyperbilirubinemia or HE, TIPS may be considered in highly selected
individuals on a case-by-case basis and by individual assessment of risks and benefits.
1. Salerno F, Camma C, Enea M, Rossle M, Wong F. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology 2007;133:825-834.

32. Estimated 1-year mortality rate for various meld
scores of tips versus lvp
1. Rossle M, Gerbes AL. TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. Gut 2010;59:988-1000.
From Gut.[1] Copyright 2010, British Society of Gastroenterology.

33. Tips in other scenarios
➢TIPS in refractory/recidivant ascites/HRS/HH ?
➢TIPS in HPS/SOS?
➢TIPS in PVT ?
➢TIPS in NCIPH ?
➢TIPS in BCS ?

34. TIPS in refractory/recidivant ascites/HRS/HH ?
• TIPS is more effective than conservative/medical treatment to resolve refractory/recidivant
ascites, greatly reducing the need of paracentesis. TIPS should be considered in all pts with
refractory/recidivant ascites.
• TIPS is effective to treat type-II HRS associated to refractory/recidivant ascites. Cannot be
recommended in unselected patients with type-I HRS .
• TIPS can be considered in refractory hydrothorax (RH) aiming at resolution of hydrothorax and
reduction in number of thoracentesis. The effect of TIPS on survival are still not clearly defined in RH.
Thus, the final decision to insert a TIPS should be reached on an individual pt basis after a
multidisciplinary clinical evaluation.
S. Fagiuoli, R. Bruno, and V. W. Debernardi, “Consensus conference on TIPS management: Techniques, indications, contraindications,” Digestive and Liver Disease, vol. 49, no. 2, pp. 121–137, 2017.

35. TIPS in HPS/SOS?
• At present, there is no sufficient evidence to support the use of TIPS for the treatment of
hepatopulmonary syndrome.
• TIPS is not indicated in Sinusoidal Occlusion Syndrome in Bone Marrow Transplanted Patients, but
may be considered in individual basis in Solid Organ Transplant Recipient as stand-alone treatment or as
bridge to liver transplantation in a setting of multidisciplinary evaluation .
S. Fagiuoli, R. Bruno, and V. W. Debernardi, “Consensus conference on TIPS management: Techniques, indications, contraindications,” Digestive and Liver Disease, vol. 49, no. 2, pp. 121–137, 2017.

36. TIPS in PVT ?
• TIPS is feasible in pts with PVT with and without cirrhosis, but it bears higher failure and
complication rates when portal cavernoma, fibrous transformation of the main portal vein or
intrahepatic branches thrombosis, are present .
• Extension of the TIPS stent into the portal or SMV should be considered when recanalization of
PV/SMV is incomplete and the pt is not a LT candidate.
• TIPS can be considered to treat PVT in both cirrhotic and non-cirrhotic pts with progression of
thrombosis despite adequate anticoagulant treatment, or when there is an absolute CI to
anticoagulation, or with no response after a maximum of 6 months of anticoagulation treatment.
S. Fagiuoli, R. Bruno, and V. W. Debernardi, “Consensus conference on TIPS management: Techniques, indications, contraindications,” Digestive and Liver Disease, vol. 49, no. 2, pp. 121–137, 2017.

37. TIPS in NCIPH ?
• TIPS can be considered in NCIPH, applying the same indications utilized for the management of
portal hypertensive complications..
• Caution is needed in pts with refractory ascites, kidney failure and comorbidities.
S. Fagiuoli, R. Bruno, and V. W. Debernardi, “Consensus conference on TIPS management: Techniques, indications, contraindications,” Digestive and Liver Disease, vol. 49, no. 2, pp. 121–137, 2017.

38. TIPS in BCS ?
• In BCS pts, in a stepwise approach, TIPS with covered stent is indicated in case of failure of
anticoagulation (and angioplasty when feasible), represented by persistent ascites, AKI or elevated
transaminases .
• Listing for LT should be considered in case of a prognostic index score greater than 7 in pts candidate to
TIPS for BCS.
• When TIPS is attempted to treat hyper acute BCS with ALF presentation, the listing process for LT
should not be delayed.
BCS-TIPS PI (only for patients who underwent TIPS procedure): age × 0.08 + bilirubin × 0.16 + INR × 0.63[1].
1. Garcia-Pagán JC, Heydtmann M, Raffa S, Plessier A, Murad S, Fabris F, Vizzini G, Gonzales Abraldes J, Olliff S, Nicolini A, et al. TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in
124 patients. Gastroenterology. 2008;135:808–815.

39. End of Slides
39

40. History of TIPS
• The origins of TIPS date back to the 1960s with inadvertent portal access during the early years of transjugular cholangiography.
• In 1969, Rösch et al reported portal venography via a transjugular approach and discussed the potential of a “radiologic portocaval
shunt.” This was subsequently followed by animal experiments, initially with tract dilation utilizing dilators and then balloons.
• In 1982, Colapinto et al performed the first human balloon-dilated transjugular portosystemic shunt.
• However, it was in 1988 that the first human clinical procedure of a TIPS utilizing a metallic stent was documented (Palmaz stent) by
Goetz Richter (Freiburg, Germany).
• Subsequently, in the early to mid-1990s there was widespread clinical use of TIPS utilizing bare-metal stents. Selfexpanding stents
predominated as the primary stent utilized during TIPS (particularly the Wallstent, Boston Scientific, Natick, Massachusetts, United
States).
• In the second half of the 1990s, animal experimentation on covered stents using silicone coating and e-PTFE showed favorable
patency results for e-PTFE covered stents.
• Again, investigators at the Dotter Institute described a partly covered self-expanding stent, which the author believes has remarkable
resemblance to the currently commercially available Viatorr stent (Gore and Associates, Flagstaff, Arizona, United States).
• In the early 2000s, early human e-PTFE covered stent grafts for TIPS creation showed favorable and safe results with improved TIPS
patency.
• Finally, a decade ago (2003–2004) the Viatorr stent became commercially available in the United States and widespread utilization of
this e-PTFE covered stent grafts for TIPS occurred .

41. References: History
1. Saxon RR, Mendel-Hartvig J, Corless CL, et al. Bile duct injury as a major cause of stenosis and occlusion in transjugular intrahepatic
portosystemic shunts: comparative histopathologic analysis in humans and swine. J Vasc Interv Radiol 1996;7(4):487–497
2. Nishimine K, Saxon RR, Kichikawa K, et al. Improved transjugular intrahepatic portosystemic shunt patency with PTFE-covered stent-
grafts: experimental results in swine. Radiology 1995; 196(2):341–347
3. Haskal ZJ, Davis A, McAllister A, Furth EE. PTFE-encapsulated endovascular stent-graft for transjugular intrahepatic portosystemic
shunts: experimental evaluation. Radiology 1997;205(3): 682–688
4. Barrio J, Ripoll C, Bañares R, et al. Comparison of transjugular intrahepatic portosystemic shunt dysfunction in PTFE-covered stent-
grafts versus bare stents. Eur J Radiol 2005;55(1):120–124
5. Charon JP, Alaeddin FH, Pimpalwar SA, et al. Results of a retrospective multicenter trial of the Viatorr expanded polytetrafluoroethylene-
covered stent-graft for transjugular intrahepatic portosystemic shunt creation. J Vasc Interv Radiol 2004;15(11):1219–1230
6. Maleux 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(10):1842–1850
7. Hausegger KA, Karnel F, Georgieva B, et al. Transjugular intrahepatic portosystemic shunt creation with the Viatorr expanded
polytetrafluoroethylene-covered stent-graft. J Vasc Interv Radiol 2004;15(3):239–248
8. Angeloni S, Merli M, Salvatori FM, et al. Polytetrafluoroethylenecovered stent grafts for TIPS procedure: 1-year patency and clinical
results. Am J Gastroenterol 2004;99(2):280–285
41

42. References: Hepatic encephalopathy
1. Riggio O, Angeloni S, Salvatori FM, De Santis A, Cerini F, Farcomeni A, 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 Nov;103(11):2738–46.
2. Nolte W, Wiltfang J, Schindler C, Münke H, Unterberg K, Zumhasch U, et al. Portosystemic hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients
with cirrhosis: clinical, laboratory, psychometric, and electroencephalographic investigations. Hepatology. 1998 Nov;28(5):1215–25.
3. Berlioux P, Robic MA, Poirson H, Métivier S, Otal P, Barret C, et al. Pre-transjugular intrahepatic portosystemic shunts (TIPS) prediction of post-TIPS overt hepatic encephalopathy:
the critical flicker frequency is more accurate than psychometric tests. Hepatology. 2014 Feb;59(2):622–9.
4. Salerno F, Cammà C, Enea M, Rössle M, Wong F. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology .
2007 Sep;133(3):825–34.
5. Chalasani N, Clark WS, Martin LG, Kamean J, Khan MA, Patel NH, et al. Determinants of mortality in patients with advanced cirrhosis after transjugular intrahepatic portosystemic
shunting. Gastroenterology. 2000 Jan;118(1):138–44.
6. Kim HK, Kim YJ, Chung WJ, Kim SS, Shim JJ, Choi MS, et al. Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-
practice data. Clin Mol Hepatol. 2014 Mar;20(1):18–27.
7. Bai M, Qi X-S, Yang Z-P, Yang M, Fan D-M, Han G-H. TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites: an updated meta-analysis. World J
Gastroenterol. 2014 Mar 14;20(10):2704–14.
8. D’Amico G, Luca A, Morabito A, Miraglia R, D’Amico M. Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis. Gastroenterology. 2005
Oct;129(4):1282–93.
9. Riggio O, Masini A, Efrati C, Nicolao F, Angeloni S, Salvatori FM, et al. Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt:
a randomized controlled study. J Hepatol. 2005 May;42(5):674–9.
10. Fanelli F, Salvatori FM, Rabuffi P, Boatta E, Riggio O, Lucatelli P, et al. Management of refractory hepatic encephalopathy after insertion of TIPS: long-term results of shunt
reduction with hourglass-shaped balloon-expandable stent-graft. AJR Am J Roentgenol. 2009 Dec;193(6):1696–702.
11. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the
Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715–35.
12. Casado M, Bosch J, García-Pagán JC, Bru C, Bañares R, Bandi JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings.
Gastroenterology. 1998 Jun;114(6):1296–303.
13. Rössle M, Gerbes AL. TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. Gut. 2010 Jul;59(7):988–1000.
42

43. References: TIPS: Bare stent Vs PTFE-covered
stent
1. Casado M, Bosch J, Garcia-Pagan JC, Bru C, Banares R, Bandi JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt:
correlation with hemodynamic findings. Gastroenterology 1998;114:1296–1303.
2. Riggio O, Angeloni S, Salvatori FM, De Santis A, Cerini F, Farcomeni A, 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.
3. Sauerbruch T, Mengel M, Dollinger M, Zipprich A, Rossle M, Panther E, et al. Prevention of rebleeding from esophageal varices in patients
with cirrhosis receiving small-diameter stents vs. hemodynamically controlled medical therapy. Gastroenterology 2015;149:660–668.
4. Wang Q, Lv Y, Bai M, Wang Z, Liu H, He C, et al. Eight millimetre covered TIPS does not compromise shunt function but reduces hepatic
encephalopathy in preventing variceal rebleeding. J Hepatol 2017;67: 508–516.
5. Bureau C, Garcia-Pagan JC, 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;126:469–475.
6. Nishimine K, Saxon RR, Kichikawa K, Mendel-Hartvig J, Timmermans HA, Shim HJ, Uchida BT, Barton RE, Keller FS, Rösch J.
Improved transjugular intrahepatic portosystemic shunt patency with PTFE-covered stent-grafts: experimental results in swine. Radiology.
1995;196:341-347.
43

44. References: TIPS: Covered Vs Bare
1. Qi X, et al. Covered versus bare stents for transjugular intrahepatic portosystemic shunt: an updated meta-analysis of randomized controlled
trials. Therap Adv Gastroenterol. 2017 Jan; 10(1): 32–41.
2. Bureau C., Garcia-Pagan J., Otal P., Pomier-Layrargues G., Chabbert V., Cortez C., et al. (2004) Improved clinical outcome using
polytetrafluoroethylene-coated stents for TIPS: results of a randomized study. Gastroenterology 126: 469–475.
3. Perarnau J., Le Gouge A., Nicolas C., D’Alteroche L., Borentain P., Saliba F., et al. (2014) Covered vs. uncovered stents for transjugular
intrahepatic portosystemic shunt: a randomized controlled trial. J Hepatol 60: 962–968
44

45. References: Controlled studies and meta-analysis
1. Gines P, Uriz J, Calahorra B, Garcia-Tsao G, Kamath PS, Del Arbol LR, et al. Transjugular intrahepatic portosystemic shunting vs. paracentesis plus albumin for refractory ascites in
cirrhosis. Gastroenterology 2002;123:1839–1847.
2. Lebrec D, Giuily N, Hadengue A, Vilgrain V, Moreau R, Poynard T, et al. Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and
refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists. J Hepatol 1996;25:135–144.
3. Narahara Y, Kanazawa H, Fukuda T, Matsushita Y, Harimoto H, Kidokoro H, et al. Transjugular intrahepatic portosystemic shunt vs. paracentesis plus albumin in patients with refractory
ascites who have good hepatic and renal function: a prospective randomized trial. J Gastroenterol 2011;46:78–85.
4. Rossle M, Ochs A, Gulberg V, Siegerstetter V, Holl J, Deibert P, et al. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites. N Engl J
Med 2000;342: 1701–1707.
5. Salerno F, Merli M, Riggio O, Cazzaniga M, Valeriano V, Pozzi M, et al. Randomized controlled study of TIPS vs. paracentesis plus albumin in cirrhosis with severe ascites. Hepatology
2004;40:629–635.
6. Sanyal AJ, Genning C, Reddy KR, Wong F, Kowdley KV, Benner K, et al. The North American study for the treatment of refractory ascites. Gastroenterology 2003;124:634–641.
7. Albillos A, Banares R, Gonzalez M, Catalina MV, Molinero LM. A metaanalysis of transjugular intrahepatic portosystemic shunt vs. paracentesis for refractory ascites. J Hepatol
2005;43:990–996.
8. Bai M, Qi XS, Yang ZP, Yang M, Fan DM, Han GH. TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites: an updated meta-analysis. World J
Gastroenterol 2014;20:2704–2714.
9. Chen RP, Zhu Ge XJ, Huang ZM, Ye XH, Hu CY, Lu GR, et al. Prophylactic use of transjugular intrahepatic portosystemic shunt aids in the treatment of refractory ascites: metaregression
and trial sequential meta-analysis. J Clin Gastroenterol 2014;48:290–299.
10. D’Amico G, Luca A, Morabito A, Miraglia R, D’Amico M. Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis. Gastroenterology 2005;129:1282–
1293.
11. Deltenre P, Mathurin P, Dharancy S, Moreau R, Bulois P, Henrion J, et al. Transjugular intrahepatic portosystemic shunt in refractory ascites: a meta-analysis. Liver Int 2005;25:349–356.
12. Saab S, Nieto JM, Lewis SK, Runyon BA. TIPS vs. paracentesis for cirrhotic patients with refractory ascites. Cochrane Database Syst Rev 2006:CD004889.
13. Salerno F, Camma C, Enea M, Rossle M, Wong F. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology
2007;133:825–834.

46. References: Characteristics and results of 6 RCTs
comparing bared TIPS and LVP in pts with LC and RA.
1. Riggio O, Angeloni S, Salvatori FM, De Santis A, Cerini F, Farcomeni A, 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.
2. Sanyal AJ, Genning C, Reddy KR, Wong F, Kowdley KV, Benner K, et al. The North American study for the treatment of refractory ascites.
Gastroenterology 2003;124:634–641.
3. Salerno F, Merli M, Riggio O, Cazzaniga M, Valeriano V, Pozzi M, et al. Randomized controlled study of TIPS vs. paracentesis plus
albumin in cirrhosis with severe ascites. Hepatology 2004;40:629–635.
4. Narahara Y, Kanazawa H, Fukuda T, Matsushita Y, Harimoto H, Kidokoro H, et al. Transjugular intrahepatic portosystemic shunt vs.
paracentesis plus albumin in patients with refractory ascites who have good hepatic and renal function: a prospective randomized trial. J
Gastroenterol 2011;46:78–85.
5. Lebrec D, Giuily N, Hadengue A, Vilgrain V, Moreau R, Poynard T, et al. Transjugular intrahepatic portosystemic shunts:
comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians
and a Group of Biologists. J Hepatol 1996;25:135–144.
6. Rossle M, Ochs A, Gulberg V, Siegerstetter V, Holl J, Deibert P, et al. A comparison of paracentesis and transjugular
intrahepatic portosystemic shunting in patients with ascites. N Engl J Med 2000;342: 1701–1707.