the role of tips for portal vein patency in liver transplant patients with portal vein thrombosis

SHORT REPORT

The Role of TIPS for Portal Vein Patency in LiverTransplant Patients With Portal Vein ThrombosisJason Bauer,1 Stephen Johnson,1 Janette Durham,1 Michael Ludkowski,1 James Trotter,2

Thomas Bak,3 and Michael Wachs3

1Department of Radiology, Division of Interventional Radiology, 2Department of Internal Medicine, Divisionof Hepatology, and 3Department of Surgery, Division of Liver Transplant, University of Colorado HealthSciences Center, Denver, CO

The purpose of this research was to study the efficacy and outcomes of transjugular intrahepatic shunt (TIPS) in end-stage liverdisease (ESLD) patients with portal vein thrombosis (PVT) eligible for orthotopic liver transplant. Nine consecutive patients withPVT underwent TIPS as a nonemergent elective outpatient procedure. The primary indication for TIPS was to maintain portalvein patency for optimal surgical outcome. Eight patients underwent contrast enhanced computed tomography (CT) and 1magnetic resonance imaging diagnosing PVT. Shunt creation was determined by available targets at the time of TIPS and byprior imaging. Patients were followed with portography, ultrasound, CT, or magnetic resonance imaging, and the luminalocclusion was estimated before and after TIPS. Primary endpoints were transplantation, removal from the transplant list, ordeath. Stabilization, improvement, or complete resolution of thrombosis was considered successful therapy. Failures includedpropagation of thrombosis or vessel occlusion, and poor surgical anatomy due to PVT. Of 9 patients with PVT, TIPS wassuccessfully placed in all patients without complication or TIPS-related mortality. Eight of 9 patients (88.8%) had improvementat follow-up. One patient failed therapy and re-thrombosed. Two patients (22.2%) were transplanted without complication andhad no PVT at the time of transplant. Eight of 9 patients were listed for transplant at the time of their TIPS. Eight of 9 PVTswere nonocclusive. Four of 9 patients (44%) had evidence of cavernous transformation. Two patients expired during follow-up42 and 44 months after TIPS. Three patients remain on the transplant list. One patient has not been listed due tononprogression of disease. One patient has been removed from the transplant list because of comorbid disease. In conclusion,TIPS is safe and effective in patients with PVT and ESLD requiring transplant. Patients can be successfully transplanted withoptimal surgical anatomy. Liver Transpl 12:1544-1551, 2006. © 2006 AASLD.

Received January 16, 2006; accepted May 18, 2006.

Portal vein thrombosis (PVT) in the adult population israre. However, PVT is an accepted common complica-tion of chronic liver disease, reaching as high as 39%,1,2

and in transplant patients incidence of PVT ranges from2.1 to 26% preoperatively.3 In those with end-stage liverdisease (ESLD) who are eligible for transplant, PVT canexclude patients from surgery completely or complicatetransplantation with poor outcome. Routine screeningfor liver transplant eligibility will usually uncover PVT.Until recently, the condition was an absolute contrain-dication to transplant.4-8 Now, patients with PVT maybe transplanted, but the level of difficulty for the sur-

geon is increased as are the number of postoperativecomplications.9-13

Studies have shown that transjugular intrahepaticshunt (TIPS) is technically feasible in patients with PVT,but the studies include a wide range of patients withmalignancy, hypercoagulable states, and pancreatitisas the cause of PVT.14,15 In cirrhotics, TIPS have beenplaced successfully in patients with portal vein clot forthe standard indication of ascites and hemorrhage. Toour knowledge, there are few reports of TIPS placementto maintain portal vein patency for transplant. Since1992, we have performed over 300 TIPS at the Univer-

Abbreviations: PVT, portal vein thrombosis; ESLD, end-stage liver disease; TIPS, transjugular intrahepatic shunt; CT, computedtomography; SMV, superior mesenteric vein.Address reprint requests to Dr. Stephen Johnson, A030, 4200 East 9th Ave., Denver, CO 80262. Telephone: 303-372-6141; FAX: 303-372-6234;E-mail: [email protected]

DOI 10.1002/lt.20869Published online in Wiley InterScience (www.interscience.wiley.com).

LIVER TRANSPLANTATION 12:1544-1551, 2006

© 2006 American Association for the Study of Liver Diseases.

sity of Colorado. TIPS have been placed in patients withportal vein or splanchnic vein thrombosis. However,beginning in 1999 in conjunction with the Hepatologyand the Liver Transplant services, Interventional Radi-ology has been consulted to place TIPS in patients withPVT to maintain vessel patency in order to maximizesurgical outcome. The natural history of untreated PVTin this population is not clear, but in our experience,progression of thrombus is common and has excludedpatients from transplantation (Fig. 1A-C). Here, we de-scribe our experience with 9 consecutive patients whoreceived primary TIPS on a nonemergent basis to main-tain portal vein patency for future liver transplant.

PATIENTS AND METHODS

From 1999 through January 2005, 149 primary TIPSwere performed at our institution. Nine of 149 (6%)patients who received a primary TIPS for portal veinthrombosis were retrospectively identified. These pa-

tients represented a population of ESLD patients whoat the time of their TIPS did not require decompressionof varices or control of ascites and would not haveotherwise required TIPS. These 9 patients represent ourstudy group.

All but 1 patient was listed on the liver transplantregistry at the time TIPS was performed. Eight patientsunderwent a dual phase contrast enhanced computedtomography (CT), and 1 patient underwent an magneticresonance imaging prior to the procedure which di-agnosed the thrombosis. Long term follow up of portalvein patency was established with follow up CT, ul-trasound, magnetic resonance imaging, or Portogra-phy.

Data was retrospectively compiled and included thetype of PVT as well as extension of thrombus into thesuperior mesenteric vein (SMV) or the splenic vein.Findings on portography during TIPS placement,whether thrombectomy or thrombolytic therapy wasperformed, and the anatomy of the TIPS shunt and

Figure 1. Contrast enhanced CT in an ESLD patient without TIPS showing progression of portal vein thrombosis over one yearfrom Grade II to Grade IV, ultimately excluding this patient from transplant at our institution.

TIPS FOR PORTAL VEIN PATENCY IN LIVER TRANSPLANTATION 1545

LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases

device type used have been recorded for each case. Aswell, clot burden in portal, mesenteric, and splenicveins at the time of the procedure and at follow-upwas estimated (Patent: no detectable thrombus;Grade I: less than 25%; Grade II: 26-50%; Grade III:51-75%; and Grade IV: 76-100% occluded). The out-come of each TIPS, its long-term function, patientsurvival, and whether patients were transplantedwere also recorded (Tables 1, 2, and 3).

This retrospective review was approved by the Colo-rado Multiple Institution Review Board.

RESULTS

Two of 9 patients were female. Age at the time of TIPSranged from 26 to 61 years mean age. ESLD resultedfrom hepatitis and alcohol in 6 patients, autoimmunehepatitis in 1, and cryptogenic in the remaining 2.

One patient had documented PVT only. Four patientshad PVT and SMV thrombosis. Two patients had portalvein and splenic vein thrombosis, and 2 had thrombusin all 3 vessels. Four patients presented with cavernoustransformation of the portal vein.

No patient had a diagnosed hepatoma at the time ofTIPS. One patient developed a hepatoma during thefollow-up period.

All TIPS were performed from a right internal jugularvein approach using standard technique. A Ring TIPSset (Cook, Bloomington, IN) was used in all cases.Wedge CO2 portography was performed in 4 cases andmesenteric angiography in 2 cases. Hepatic to portalvein access was performed blindly under fluoroscopicguidance in the remaining cases. Because of the changein technology during this period, the 3 most recentshunt procedures were performed with the Viatorr stentgraft (Gore, Newark, DE ), 1 was performed with a Wall-stent (Boston Scientific, Natick, MA), and 3 were per-formed with the Smart stent (Cordis, New Brunswick,NJ ). Only 1 stent was used in all cases, and none wereplaced into the main portal vein to decrease the possi-bility of transplant complication.

TIPS was performed from the right hepatic vein to theright portal vein in 5 patients and from the middle

TABLE 1. Patient Prior to TIPS

PT Age

Cavernous

Transformation PVT SMVT SVT OLT

Listed*

at TIPS

Listed*

Now

1 26 Yes � � � Yes Yes No2 61 No � � � No Yes No3 45 Yes � � � No Yes No4 53 No � � � No Yes No5 28 No � � � No Yes Yes6 57 Yes � � � No Yes Yes7 52 Yes � � � No No No8 50 No � � � Yes Yes No9 54 No � � � No Yes Yes

Abbreviations: PT, patient; PVT, portal vein thrombosis; SMVT, superior mesenteric vein thrombosis; SVT, splenic veinthrombosis; OLT, orthotopic liver transplant �, thrombosis present; �, thrombosis absent.*Listed for liver transplantation at our institution.

TABLE 2. Pre-TIPS Degree of Thrombosis in the Main

Portal Vein, SMV, and Splenic Vein

PT MPV SMV SV

Cavernous

Transformation

1 Grade IV Grade II Patent Yes2 Grade II Grade IV Patent No3 Grade IV Grade IV Grade II Yes4 Grade III Grade III Patent No5 Grade IV Patent Grade II No6 Grade II Grade II Patent Yes7 Grade IV Grade III Patent Yes8 Grade IV Grade IV Grade IV No9 Grade IV Patent Grade IV No

Abbreviations: PT, patient; MPV, main portal vein; SMV,super mesenteric vein; SV, splenic vein.

TABLE 3. Post-TIPS Degree of Thrombosis in the Main

Portal Vein, SMV, and Splenic Vein

PT MPV SMV SV

1 Grade I Grade I Patent2 Grade I Grade I Patent3 Grade IV Grade IV Grade II4 Grade I Grade I Patent5 Grade II Patent Grade I6 Grade I Grade I Patent7 Grade IV Grade III Patent8 Patent Patent Patent9 Grade III Patent Grade III

NOTE: Luminal occlusion was estimated as follows: Patent(no detectable thrombus), Grade I (1-25% luminalocclusion), Grade II (26-50%), Grade III (51-75%), andGrade IV (76-100%).Abbreviations: PT, patient; MPV, main portal vein; SV,splenic vein.

1546 BAUER ET AL.


hepatic vein to the right portal vein in 1 patient. Onepatient had a shunt created from the left hepatic vein tothe left portal vein due to extensive right portal veinclot. All patients survived TIPS placement and weredischarged home with no complications. Follow-upranged from 2 to 45 months. Only 1 patient requiredshunt revision. While there was no clot identified, nar-rowing of the shunt from neointimal hyperplasia re-quired angioplasty and stenting at the 3-month fol-low-up in this patient.

Follow-up imaging included a combination of cathe-ter portography, CT, magnetic resonance imaging, andultrasound. Eight of 9 patients (88.8%) maintained por-tal vein patency. One patient with extensive chronicPVT and SMV thrombosis as well as cavernous trans-formation of the portal vein underwent portal veinthrombectomy with an Amplatz device (Microvena,White Bear Lake, MN) and with tissue plasminogenactivator (Genentech, South San Francisco, CA ) lacedinto the clot, on the day of the TIPS and again 2 daysfollowing TIPS. This patient received post-procedureCoumadin but never developed a patent portal vein andwas considered a failure of therapy. Occlusion wasdemonstrated on follow-up CT 4 months later and onmesenteric angiogram 41 months later performed forgastrointestinal bleeding. The patient also had a priorsplenectomy and inflow into the portal vein was de-creased compared to the other 8 patients. This patientdied 42 months after TIPS from massive variceal hem-orrhage.

Another patient (Fig. 1 and 2) with near occlusivethrombosis of the portal vein, SMV, and splenic veinsreceived adjunctive tissue plasminogen activator (20mg), Angiojet, (Possis Medical, Minneapolis, MN)thrombectomy, and Fogarty thrombectomy (EdwardsLife Sciences, Irvine, CA) at the time of TIPS. This suc-cessfully recanalized the portal vein, SMV, and splenicveins. On follow-up ultrasound at 2 weeks and portog-raphy at 3 months, there was complete resolution ofthrombus. This patient was successfully transplanted6 months after TIPS with a patent portal vein at the timeof surgery. In both patients for whom thrombectomywas performed, mechanical techniques were employedbefore shunt placement in order to minimize pulmo-nary embolization.

One patient with autoimmune hepatitis was trans-planted 8 months after TIPS. This patient developedextensive non-occlusive PVT with evidence of cavernoustransformation prior to TIPS (Fig. 2A-D). The portal veinwas patent at the time of surgery, and the transplantwas performed without complication. The patient isalive today and doing well. The remaining 6 patients(66.6%) have not been transplanted. Two patients havedied, the first at 44 months after TIPS, and the secondat 42 months after TIPS.

Of the remaining 5 patients who are alive and withouta liver transplant, 3 patients remain on the transplantlist, 1 has not been listed because of stable liver dis-ease, and 1 has been removed from the transplant listbecause of comorbidities (Fig. 3). All of the patients whoremain on the transplant list have patent portal veins

with improvement or resolution of clot within affectedveins (Fig. 4).

DISCUSSION

As experience has grown with liver transplantation,PVT has become only a relative contraindication. Thesurgical literature details many techniques for deal-ing with PVT at the time of transplantation includingthrombectomy, portal vein graft, extra-anatomic ve-nous reconstruction, and splenomesenteric or leftgastric vein recipient to donor portal vein anastomo-sis.8-13

Improved surgical survival and decreased complica-tion rates can be seen with partial vs. complete PVT andwith isolated PVT vs. extension in to the splenic and/orsuperior mesenteric vein.16 Because of advancing sur-gical techniques and the development of TIPS as a safeand efficacious procedure, there has been a naturalevolution utilizing TIPS to treat PVT and prevent pro-gression of clot in order to maintain candidacy for livertransplant. The pathophysiology of PVT in patients withcirrhosis is not clear but is likely due to increased re-sistance to flow. Therefore, shunt creation alone leadsto improved outflow with autothrombolysis regardlessof mechanical or pharmacologic therapy. This has beenreported in several small series where TIPS was per-formed for PVT in patients ultimately undergoing ortho-topic liver transplantation and was confirmed in ourpatients.17,18

Technical success in these 9 patients was 100% with85.7% patency of all veins. While a TIPS was success-fully placed and functioning in 1 patient with completePVT and cavernous transformation, the patient’s portalvein never recanalized despite mechanical thrombec-tomy, thrombolytics, and anticoagulation. This resultmay in part be due to poor inflow from a prior splenec-tomy as well as more chronic thrombosis. This patientmaintained his transplant eligibility until he died fromrenal failure and overwhelming sepsis 44 months afterTIPS.

Due to the retrospective nature of the study, post-TIPS imaging and the timeline of these studies are notuniform. As a result, estimation of clot burden followingTIPS was not standardized. The routine post-TIPS fol-low-up for our department in transplant-eligible pa-tients with PVT has now been standardized to include a3- and 9- month contrast-enhanced CT in asymptom-atic patients, or portography with possible shunt revi-sion in our symptomatic patients.

TIPS was safely performed for PVT in our patientswith no TIPS-related mortality. However, there are re-ports of higher complication rates and increased mor-tality in this population. A recent study by Ganger et al.reported a complication rate of 22%, including an 11%mortality rate in 11 patients with PVT. Nine patientshad a TIPS successfully placed, with 4 patients under-going liver transplantation.18 Complication and mortal-ity differences may be attributable to acute hemorrhagerequiring portal decompression with TIPS, while in our



small group of patients all procedures were performedon an elective outpatient basis.

Wasler et al. reported 20 patients with PVT, and 14TIPS were successfully placed. Decreased technicalsuccess and outcomes were attributable to clot burdenand chronicity of PVT.19 Radosevich et al. were able toplace TIPS in 3 of 6 patients through a transjugularapproach and in 4 of 4 patients using transhepaticportal vein recanalization followed by TIPS.14 All ofthese patients had portal vein occlusion, with subse-quent long-term patency at follow-up in 5 of 7 patients.Finally, Blum et al. successfully placed TIPS in 7 pa-

tients with partial PVT. There were no immediate com-plications.15 Fibrinolytic agents and balloon macera-tion were used in all patients. Five of 7 patients hadcomplete recanalization, and 2 of 7 experienced partialportal vein recanalization.

A diverse approach exists in the literature regardingthe recanalization of the portal vein. Two patients withcomplete thrombosis of the portal vein and/or SMV andsplenic veins received adjunctive lytic therapy and me-chanical thrombectomy. The remainder had only theTIPS placement. Eight of our patients maintainedportal vein patency with improvement in clot. Reports

Figure 2. Portography of a patient with autoimmune cirrhosis. (A) Cavernous transformation of the portal vein. (B) Grade IVPVT. (C) Patent TIPS and Grade I portal vein thrombosis one month and (D) five months after TIPS. The patient is alive today afterOLTX.

1548 BAUER ET AL.


Figure 3. A patient with hepatitis C cirrhosis. (A) Contrast enhanced CT showing Grade IV PVT. (B) Showing TIPS withintraluminal clot. (C) Follow up at 3 months with shunt narrowing but no PVT. The shunt was revised. (D) and (E) Gadolinium MRI(TR 150 TE 4.1) showing Grade I portal vein thrombosis 11 months after TIPS. This patient has been removed from thetransplant list due to comorbidities.



by Blum et al. and Wasler et al. used thrombectomy tech-niques in all their patients. This may increase proceduretime and cost but may be necessary for patients who havecomplete PVT and no antegrade flow.

There are only a few cases in the literature in whichthe primary indication for TIPS was to recanalize theportal vein to maintain transplant status. In 2001, Li-atsos et al. reported 2 patients, both with PVT andextension into the superior mesenteric vein.17 Both pa-tients underwent successful TIPS and received ortho-topic liver transplant at 31 and 27 days, respectively.Portal veins were patent at the time of transplant, andboth patients left the hospital without complication.Other reports were for patients whose primary indica-tion for TIPS was unrelated to maintaining optimal sur-gical anatomy for transplantation.

Patients with ESLD awaiting transplant who havepartial PVT do well with TIPS and will likely maintainportal vein patency. ESLD patients with complete PVTand cavernous transformation are technically morechallenging, and recanalization of the portal vein maynot be feasible.

Here, we have presented 9 patients who successfullyunderwent TIPS for PVT. The procedure is technicallyfeasible, and there was no procedure-related mortalityor significant complication in our group of patients.Clot lysis, prevention of clot propagation, and mainte-nance of portal vein patency seems achievable withtimely placement of TIPS following diagnosis of PVT intransplant-eligible patients.

Even if clot resolution is incomplete, halting its prop-agation is also valued for surgical success. With our

Figure 4. (A) Contrast enhanced CT in a patient with Grade II calcified chronic PVT. (B) CO2 portogram at the time of TIPS. (C)Grade I portal vein thrombosis at 6 month portogram. The patient remains on the transplant list.

1550 BAUER ET AL.


current outcomes, TIPS in this population is an effec-tive and safe technique for maintaining portal vein pa-tency.

REFERENCES

1. Nonami T, Yokoyama I, Iwatsuki S, Starzl T. The incidenceof portal vein thrombosis at liver transplantation. Hepa-tology 1992;16:1195-1198.

2. Okuda K, Ohnishi K, Kimura K, Matsutani S, Sumida M,Goto N, et al. Incidence of portal vein thrombosis in livercirrhosis: an angiographic study. Gastroenterology 1985;89:279-286.

3. Yerdel MA, Gunson B, Mirza D, Karayalcin K, Olliff S,Buckels J, et al. Portal vein thrombosis in adults under-going liver transplantation: risk factors, screening, man-agement, and outcome. Transplantation 2000;69:1873-1881.

4. Stieber AC, Zetti G, Todo S, Tzakis AG, Fung JJ, Marino I,et al. The spectrum of portal vein thrombosis in liver trans-plantation. Ann Surg 1991;213:199-206.

5. Langnas AN, Marujo WC, Stratta RJ, Wood RP, Ranjan D,Ozaki C, Shaw BW Jr. A selective approach to preexistingportal vein thrombosis in patients undergoing liver trans-plantation. Am J Surg 1992;63:132-136.

6. Moreno Gonzalez E, Garcia Garcia I, Gomez Sanz R,Gonzalez-Pinto I, Loinaz Segurola C, Jimenez Romero C.Liver transplantation in patients with thrombosis of theportal vein, splenic or superior mesenteric vein. Br J Surg1993;80:81-85.

7. Davidson BR, Gibson M, Dick R, Burroughs A, Rolles K.Incidence, risk factors, and outcome of portal vein abnor-malities at orthotopic liver transplantation. Transplanta-tion 1994;57:1174-1177.

8. Cherqui D, Duvoux C, Rahmouni A, Rotman N,Dhumeaux D, Julien M, Fagniez PL. Orthotopic livertransplantation in the presence of partial or total portalvein thrombosis: problems in diagnosis and management.World J Surg 1993;17:669-674.

9. Seu P, Shackleton CR, Shaked A, Imagawa DK, OlthoffKM, Rudich SR, et al. Improved results of liver transplan-

tation in patients with portal vein thrombosis. Arch Surg1996;131:840-845.

10. Orlando G, De Luca L, Toti L, Zazza S, Angelico M, Cas-ciani CU, Tisone G. Liver transplantation in the presenceof portal vein thrombosis: report from a single center.Transplant Proc 2004;36:199-202.

11. Shi LW, Verran D, Chang D, Drenckhahn C, Fisher J,Stewart G, McCaughan G. Primary liver transplantationwith preexisting portal vein thrombosis. Transplant Proc2003;35:354-355.

12. Molmenti EP, Roodhouse TW, Molmenti H, Jaiswal K,Jung G, Marubashi S, et al. Thrombendvenectomy fororganized portal vein thrombosis at the time of liver trans-plantation. Ann Surg 2002;235:292-296.

13. Czerniak A, Badger I, Sherlock D, Buckels J. Orthotopicliver transplantation in a patient with thrombosis of thehepatic portal and superior mesenteric veins. Transplan-tation 1990;50:334-335.

14. Radosevich PM, Ring EJ, LaBerge JM, Peltzer MY, HaskalZJ, Doherty MM, Gordon RL. Transjugular intrahepaticportosystemic shunts in patients with portal vein occlu-sion. Radiology 1993;186:523-527.

15. Blum U, Haag K, Rossle M, Ochs A, Gabelmann A, Boos S,Langer M. Noncavernomatous portal vein thrombosis inhepatic cirrhosis: treatment with transjugular intrahe-patic portosystemic shunt and local thrombolysis. Radiol-ogy 1995;195:153-157.

16. Manzanet G, Sanjuan F, Orbis P, Lopez R, Moya A, JuanM, et al. Liver transplantation in patients with portal veinthrombosis. Liver Transpl 2001;7:125-131.

17. Liatsos C, Vlachogiannakos J, Patch D, et al. Successfulrecanalization of portal vein thrombosis before liver trans-plantation using transjugular intrahepatic portosystemicshunt. Liver Transpl 2001;7:453-460.

18. Ganger DR, Klapman JB, McDonald V, Matalon TA, KaurS, Rosenblate H, et al. Transjugular intrahepatic porto-systemic shunt (TIPS) for Budd-Chiari syndrome or portalvein thrombosis. Am J Gastroenterol 1999;94:603-608.

19. Wasler E, McNees S, DeLa Pena O. Portal venous throm-bosis: percutaneous therapy and outcome. J Vasc IntervRadiol 1998;9:119-127.



the role of tips for portal vein patency in liver transplant patients with portal vein thrombosis

Documents