ORIGINAL ARTICLE

A Case-Controlled Study of the Safety andEfficacy of Transjugular IntrahepaticPortosystemic Shunts After Liver TransplantationAndrew King,1,2 Gail Masterton,4 Bridget Gunson,1,2 Simon Olliff,3 Doris Redhead,5

Kamarjit Mangat,3 Gabriel Oniscu,4 Peter Hayes,4 and Dhiraj Tripathi21Centre for Liver Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UnitedKingdom; 2Liver Unit and 3Department of Radiology, Queen Elizabeth Hospital, Birmingham, UnitedKingdom; 4Liver Unit and 5Department of Radiology, Royal Infirmary, Edinburgh, United Kingdom

The role of transjugular intrahepatic portosystemic shunt (TIPS) insertion in managing the complications of portal hypertensionis well established, but its utility in patients who have previously undergone liver transplantation is not well documented. Twenty-two orthotopic liver transplantation (OLT) patients and 44 nontransplant patients (matched controls) who underwent TIPS wereanalyzed. In the OLT patients, the TIPS procedure was performed at a median of 44.8 months (range ¼ 0.3-143 months) aftertransplantation. Eight (36.4%) had variceal bleeding, and 14 (63.6%) had refractory ascites. The underlying liver disease was cho-lestatic in 10 (45.4%) and viral in 4 (18.2%). The mean pre-TIPS Model for End-Stage Liver Disease (MELD) score was 13.4 65.1. There were no significant differences in age, sex, indication, etiology, or MELD score with respect to the control group. Themean initial portal pressure gradients (PPGs) were similar in the 2 groups (21.0 versus 22.4 mm Hg for the OLT patients and con-trols, respectively), but the final PPG was lower in the control group (9.9 versus 6.9 mm Hg, P < 0.05). The rates of both technicalsuccess and clinical success were higher in the control group versus the OLT group [95.5% versus 68.2% (P < 0.05) and 93.2%versus 77.2% (P < 0.05), respectively]. The rates of complications and post-TIPS encephalopathy were similar in the 2 groups,and there was a trend toward increased rates of shunt insufficiency in the OLT group. The mortality rate of the patients with a pre-TIPS MELD score > 15 was significantly higher in the OLT group [hazard ratio (HR) ¼ 4.32, 95% confidence interval (CI) ¼ 1.45-12.88, P < 0.05], but the mortality rates of the patients with a pre-TIPS MELD score < 15 were similar in the 2 groups. In the OLTgroup, the predictors of increased mortality were the pre-TIPS MELD score (HR ¼ 1.161, 95% CI ¼ 1.036-1.305, P < 0.05) andpre-TIPS MELD scores > 15 (HR ¼ 5.846, 95% CI ¼ 1.754-19.485, P < 0.05). In conclusion, TIPS insertion is feasible in trans-plant recipients, although its efficacy is lower in these patients versus control patients. Outcomes are poor for OLT recipients witha pre-TIPS MELD score > 15. Liver Transpl 17:771–778, 2011. VC 2011 AASLD.

Received October 19, 2010; accepted January 24, 2011.

Transjugular intrahepatic portosystemic shunt (TIPS)insertion has become an established therapeuticoption for the management of complications of portalhypertension. TIPS insertion is effective in controllingacute and recurrent variceal bleeding that is refractoryto medical and endoscopic therapy1-5 and reduces theneed for large-volume paracentesis in patients with re-fractory ascites.6-9 TIPS insertion may be used either

as a definitive treatment in patients with good liverfunction or as a bridge to liver transplantation inpatients with poor liver function. However, becauseTIPS placement precipitates hepatic encephalopathy inup to 30% of patients10,11 and can accelerate the pro-gression of hepatic failure, patient selection is crucial.

As the number of liver transplants performed eachyear rises and as patient survival increases because of

Abbreviations: CI, confidence interval; HR, hazard ratio; MELD, Model for End-Stage Liver Disease; NS, not significant; OLT,orthotopic liver transplantation; PPG, portal pressure gradient; PTFE, polytetrafluoroethylene; TIPS, transjugular intrahepaticportosystemic shunt.

Address reprint requests to Andrew King, M.D., Centre for Liver Research, Institute of Biomedical Research, 5th Floor Institute of BiomedicalResearch, University of Birmingham, Birmingham, United Kingdom B15 2TT. Telephone: þ44 121 415 8700; FAX: þ44 121 415 8701; E-mail:a.l.king@bham.ac.uk

DOI 10.1002/lt.22281View this article online at wileyonlinelibrary.com.LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases

LIVER TRANSPLANTATION 17:771-778, 2011

VC 2011 American Association for the Study of Liver Diseases.

surgical advances and improved immunosuppressiveregimes,12,13 disease recurrence and portal hyperten-sion in liver transplant recipients are being increasinglyrecognized.

Portal hypertension after transplantation may de-velop because of either an intrinsic hepatic problem(eg, allograft failure, rejection, or recurrent disease) orextrahepatic complications (eg, venous outflowobstruction, size mismatch, or portal vein thrombosisor stenosis).14-16 The therapeutic options for manag-ing the complications of portal hypertension in livertransplant recipients are essentially the same as thosefor the nontransplant population. Liver retransplanta-tion is a definitive treatment, but the risks of a secondliver transplant are significantly higher than those ofa first transplant, and transplant recipients may notbe suitable for retransplantation.

Little is known about the role of TIPS insertion inthe management of the complications of portal hyper-tension in liver transplant recipients. Data on thetechnical feasibility, safety, and efficacy are limitedbecause previous retrospective, uncontrolled studieshave included small numbers of patients predomi-nantly suffering from recurrent hepatitis C infec-tions.17-24 We need data to help us with patient selec-tion and the identification of those liver transplantrecipients for whom TIPS insertion would bebeneficial.

Here we report the outcomes of the largest series ofliver transplant recipients undergoing TIPS insertion;the procedure was performed at 2 liver transplantcenters in the United Kingdom with significant exper-tise in TIPS insertion. We compare their outcomes tothose of nontransplant patients (matched controls)undergoing TIPS insertion. We also identify factorsand characteristics that may predict the outcomes ofTIPS insertion for liver transplant recipients and helpus with patient selection for the procedure.

PATIENTS AND METHODS

Patients

A retrospective review of data for patients who hadundergone liver transplantation at 2 institutions(Queen Elizabeth Hospital, Birmingham, United King-dom, and Royal Infirmary, Edinburgh, United King-dom) was performed. IRB approval was not required.Between January 1991 and April 2009, 3618 patientsunderwent liver transplantation (2828 in Birminghamand 790 in Edinburgh), and 22 (0.6%) in whom TIPSinsertion had been attempted (18 in Birmingham and4 in Edinburgh) were identified. The first of these pro-cedures was performed in 1998.

A review of patients who had undergone TIPS inser-tion during this period was also performed (n ¼1365), and 2 control patients were identified for eachof the transplant recipients who had undergone TIPSinsertion. These patients were matched by age, sex,etiology of primary liver disease, indication for TIPSinsertion, and date of TIPS insertion. Data were col-

lected prospectively at the time of TIPS insertion; aretrospective review of the medical records, laboratoryresults, and radiological reports of these patients wasconducted; and the relevant data were collected.

Procedures

TIPS insertion was performed by highly experiencedinterventional radiologists at both centers (D.R., S.O.,and K.M.) with a previously described technique25;the procedure was modified to incorporate polytetra-fluoroethylene (PTFE)-covered stents in 2003 duringthe course of the study. The primary aim of the proce-dure was to reduce the portal pressure gradient (PPG)to less than 12 mm Hg. Technical success wasdefined by the Society of Interventional Radiologyguidelines as both the creation of a shunt and adecrease in the PPG to <12 mm Hg.26 PPG wasdefined as the difference (mm Hg) between the portalpressure and the right atrial pressure and wasrecorded at the beginning of the procedure (initialPPG) and at its completion (final PPG).

Outcomes

Transplant-free survival was used as an outcomethroughout the study, and patients were censored ifthey died, underwent liver retransplantation (thestudy population) or transplantation (the control pop-ulation), or were lost to follow-up.

Shunt patency was monitored with a combination ofultrasonography and portography, which were per-formed routinely according to the institutional proto-col (6-12 months) and when they were clinically indi-cated. Shunt insufficiency was defined as completestent occlusion, a PPG > 12 mm Hg, or a requirementfor radiological reintervention to maintain patency.Patients who died during follow-up were assumed tohave a patent shunt unless investigations demon-strated otherwise. The incidence of shunt insuffi-ciency was expressed as the number of insufficientshunts as a proportion of all shunts inserted.

Clinical success of TIPS insertion was defined as re-solution of the complication of portal hypertension,26

either (1) variceal rebleeding defined as endoscopicallyconfirmed active hemorrhage, stigmata of recenthemorrhage or the need for a red blood cell transfusion,or (2) clinically significant ascites requiring largevolume paracentesis in patients with ascites.

Encephalopathy was assessed and graded accord-ing to routine clinical practice, which was based onthe West Haven crtiteria.27 Post-TIPS encephalopathywas defined as the onset of clinically apparent new orworsening symptoms of portosystemic encephalop-athy after TIPS insertion.

Statistics

Baseline parametric data were expressed as meansand standard deviations, and any differences in thegroups were analyzed with the unpaired Student t

772 KING ET AL. LIVER TRANSPLANTATION, July 2011

test, the chi-square test, or the Mann-Whitney U testas appropriate. Cumulative survival and shunt insuf-ficiency were determined with the Kaplan-Meiermethod, and differences were assessed with the log-rank test. Cox proportional regression analysis wasused to assess variables predictive of mortality. SPSS15.0 software (SPSS, Inc., Chicago, IL) was used forthe analysis. P values less than 0.05 were consideredstatistically significant.

RESULTS

Patient Characteristics

Twenty-two liver transplant recipients were scheduledfor TIPS insertion at a median of 44.8 months (range¼ 0.3-143 months) after liver transplantation, andthey were followed up for a median of 6.5 months(range ¼ 0-85.5 months) after the procedure.

The etiology of the pretransplant primary liver dis-ease was cholestatic in 10 of the 22 patients (45.4%)and viral in 4 (18.2%). Posttransplant portal hyperten-sion had a vascular origin in 11 of the 22 patients(50%) and was due to recurrence of the primary liverdisease in 7 (31.8%; Table 1). Four of the 11 patientswith a vascular complication had a hepatic vein out-flow obstruction, and the TIPS was inserted through avascular Wallstent in the hepatic vein; 3 patients hadan intrahepatic inferior vena cava obstruction leadingto portal hypertension without obstructed hepaticveins; 2 patients had hepatic artery thrombosis lead-ing to liver failure and portal hypertension; and theremaining 2 patients had other vascular abnormal-ities. Before TIPS insertion, 2 patients received a sec-ond liver transplant, and 1 patient received a thirdliver transplant. All patients received full grafts fromheart-beating donors. Seventeen of the 22 patients

(77%) had a caval replacement transplant, whereasthe remaining 5 patients (23%) had a piggybacktransplant that used all 3 hepatic veins for outflowreconstruction.

The Model for End-Stage Liver Disease (MELD)score was calculated for all patients less than 24hours before the TIPS procedure. The differencebetween the mean MELD scores of the transplantgroup (13.4 6 5.1) and the control group (15.8 6 6.0)was not significant (NS). The proportions of patientswith MELD scores > 15 were similar in the 2 groups(36% versus 43%; Table 2).

Pre-TIPS renal function, which was estimated fromserum creatinine levels, was significantly higher inthe orthotopic liver transplantation (OLT) group ver-sus the control group (132 6 74 versus 102 6 78lmol/L, P < 0.05).

Forty-four matched controls were identified; no sig-nificant differences in the demographics of the controland transplant groups were identified (Table 2). Themedian follow-up time was 13.9 months (range ¼ 0-175 months).

Procedural and Hemodynamic Data

TIPS placement was not possible in 1 transplant re-cipient with a caval replacement because of failedcannulation of the hepatic veins. TIPS placement wassuccessful in all control patients.

The mean initial PPGs were similar in the OLT andcontrol groups (21.0 6 6.0 and 22.4 6 8.4 mm Hg,respectively, P ¼ NS), and both groups experienced asignificant reduction in the mean PPG. The mean finalPPG was significantly lower in the control group (6.96 3.6 mm Hg) versus the transplant recipient group(9.9 6 3.2 mm Hg, P < 0.01). There were significantlyfewer technically successful procedures in the

TABLE 1. Etiologies of Pretransplant Liver Disease and Causes of Posttransplant Portal Hypertension in Transplant

Recipients

Etiology of Pretransplant

Primary Liver Disease n

Cause of Posttransplant

Portal Hypertension n

Primary biliary cirrhosis 6 Recurrent primary biliary cirrhosis 2Vascular complication 2

Chronic rejection 1Veno-occlusive disease 1

Primary sclerosing cholangitis 4 Recurrent primarysclerosing cholangitis

2

Fibrosis of an unknown etiology 1Vascular complication 1

Fulminant hepatic failure 4 Vascular complication 3Azathioprine-induced

cholangiopathy1

Hepatitis C 3 Recurrent hepatitis C 3Alcoholic liver disease 2 Vascular complication 2Cryptogenic cirrhosis 1 Vascular complication 1Autoimmune hepatitis 1 Vascular complication 1Hepatitis B 1 Vascular complication 1Total 22 Total 22

LIVER TRANSPLANTATION, Vol. 17, No. 7, 2011 KING ET AL. 773

transplant group (the creation of a shunt and a reduc-tion in the PPG to <12 mm Hg) versus the controlgroup [15 patients in the OLT group (68.2%) and 42patients in the control group (95.5%), P < 0.05]. Therates of technical success in the transplant groupwere similar before (7/11) and after 2004 (8/11) andwith covered (8/12) and uncovered stents (7/10).

The mean numbers of stents used in each proce-dure were similar for the 2 groups (1.4 for the trans-plant group versus 1.3 for the control group, P ¼ NS);the proportion of covered stents was slightly higher inthe transplant group (54% versus 36%, P ¼ NS). Themean stent diameter for the transplant group waslower than that for the control group (9.3 6 0.9 versus10.3 6 1.6 mm, P < 0.05).

Clinical Efficacy

In the transplant recipient group, the rate of clinicalsuccess in controlling ascites after TIPS insertion was79%, and the rate of clinical success in preventingvariceal rebleeding was 75%. For 4 of the 5 patientsfor whom clinical success was not achieved, a vascu-lar complication was the cause of portal hypertension;graft implantation was performed with the piggybacktechnique in 3 of the 5 patients; and 3 of the 5patients did not achieve a PPG reduction to <12 mmHg. Two patients with ongoing variceal bleeding diedwithin 24 hours of the procedure, and 2 patients withpersisting ascites died within 6 months of the proce-dure (1 because of spontaneous bacterial peritonitisand 1 because of a complication of paracentesis).

In the control group, the rate of clinical success inpatients with ascites was 95.2%, and the rate of suc-cess in preventing variceal rebleeding was 91.3%.

Overall, the rate of clinical success in the transplantrecipient group was significantly lower than the ratein the control group (77.2% versus 93.2%, P < 0.05).

Complications

There were no procedure-related deaths in the trans-plant recipient group. One patient in the controlgroup died as a result of liver failure secondary toliver ischemia after TIPS insertion. One patient ineach group developed ischemic hepatitis that resolvedspontaneously, whereas another patient in the trans-plant recipient group developed a right-sided pleuraleffusion after the procedure that required no specifictreatment.

The rates of post-TIPS encephalopathy were similarin the 2 groups (27.2% in the transplant group and25% in the control group). Shunt occlusion or narrow-ing for post-TIPS encephalopathy refractory to medicaltherapy was undertaken in 3 patients (50%) in thetransplant group and in 3 patients (27%) in the con-trol group.

Shunt Insufficiency

There was no significant difference in the incidence ofshunt insufficiency during follow-up (Table 3). Therewas no significant difference in the number of reinter-vention procedures performed in each group. Eightreintervention procedures (1 restenting and 7 balloondilatations) were performed in the transplant recipientgroup, and 15 reintervention procedures (7 restent-ings and 8 balloon dilatations) were performed in thecontrol group.

Survival

Over the course of follow-up, 68% of the transplantpatients died at a median of 77 days (range ¼ 1-1293days) after the procedure, and 52% of the controlpatients died at a median of 50 days (range ¼ 2-2245days) after the procedure. The causes of death werecomparable in the 2 groups (Table 4).

TABLE 2. Characteristics of Both Patient Groups Before TIPS Insertion

Characteristic OLT Group (n ¼ 22) Control Group (n ¼ 44)

Age (years)* 49.4 6 12.2 (29-78) 53.6 6 12.5 (29-71)Male sex [n (%)] 9 (40.9) 20 (45.4)TIPS indication [n (%)]Ascites 14 (63.6) 21 (47.7)Variceal bleeding 8 (36.4) 23 (52.3)

Etiology [n (%)]Cholestatic 10 (45.4) 18 (40.9)Viral 4 (18.2) 9 (20.4)Alcohol-related 2 (9.1) 4 (9.1)Other 6 (27.3) 13 (29.5)

Emergency procedure [n (%)] 6 (27.3) 12 (27.3)Pre-TIPS MELD score† 13.4 6 5.1 15.8 6 6.0Pre-TIPS MELD score < 15 [n (%)] 14 (63.6) 25 (56.8)Pre-TIPS MELD score > 15 [n (%)] 8 (36.4) 19 (43.2)

NOTE: For all values, P was NS.*Values are presented as means and standard deviations (ranges are shown in parentheses).†Values are presented as means and standard deviations.

774 KING ET AL. LIVER TRANSPLANTATION, July 2011

Two patients in the transplant recipient group under-went retransplantation after the TIPS procedure (at 169and 170 days), whereas 8 patients in the control groupunderwent liver transplantation at a median of 337.5days (range ¼ 23-1589 days) after TIPS. Two morepatients in the transplant recipient group were listedfor retransplantation: one died on the transplant wait-ing list, whereas the other was subsequently delistedbecause of clinical improvement (the patient was stillalive at the end of the follow-up period).

Five patients (2 transplant recipients and 3 controlpatients) died within 7 days of the procedure. All hadundergone emergency procedures for variceal bleed-ing, and 3 of the procedures were technically unsuc-cessful (2 transplant recipients and 1 control patient).

There was no significant difference in the cumulativemortality over the course of follow-up between the trans-plant recipient group and the control group (Fig. 1 andTable 5). Among patients with pre-TIPS MELD scores <15, there was no significant difference in the cumulativemortality between the transplant recipient group and thecontrol group (P ¼ NS). Among patients whose pre-TIPSMELD scores were >15, there was a significantly highermortality rate in the transplant recipient group versusthe control group (P < 0.05; Table 5)

Outcome Predictors

The analysis of the factors predicting outcomes in theliver transplant recipient group is displayed in Table

6. The pre-TIPS MELD score [hazard ratio (HR) ¼1.161, 95% confidence interval (CI) ¼ 1.036-1.305, P< 0.05] and pre-TIPS MELD scores > 15 (HR ¼ 5.846,95% CI ¼ 1.754-19.485, P < 0.05) were the only vari-ables predictive of increased mortality in the livertransplant recipient group. In the transplant recipientgroup, the 1-year mortality rate was 87.5% for thosewith pre-TIPS MELD scores > 15 and 50% for thosewith pre-TIPS MELD scores < 15 (P ¼ 0.16).

DISCUSSION

Over the last 20 years, TIPS insertion has become anestablished treatment for patients with complicationsof portal hypertension and has been widely studied.Despite this, little is known about its role in the post–liver transplant setting. Our study represents the larg-est series of patients undergoing TIPS insertion afterliver transplantation. Our extensive experience inboth liver transplantation and TIPS procedures hasalso allowed the inclusion of a contemporaneous con-trol group of patients well matched for pre-TIPS char-acteristics; only 1 previous study has included such acontrol group.21 In contrast to previous studies inwhich the etiology of the liver disease for the studiedpatients was predominantly hepatitis C, the predomi-nant etiologies in our cohort were cholestatic liver dis-eases (primary biliary cirrhosis and primary scleros-ing cholangitis). This may represent either differencesin our transplant population as a whole (over thestudy period, 14.1% of the transplants in our centerswere performed for hepatitis C virus, and 13.6% ofthe patients in this study had hepatitis C as their pri-mary liver disease) or differences in our approach tothe management of portal hypertension after trans-plantation, which are reflected in the wide variationseen in the incidence of TIPS in liver transplant recipi-ents (from 0.6% in our population to 5% in somereports).

TABLE 3. Shunt Insufficiency

Time

(Months)

Incidence [% (n)]

OLT Group

(n ¼ 21)

Control Group

(n ¼ 44)

1 5 (1) 14 (6)3 24 (5) 16 (7)6 29 (6) 23 (10)12 38 (8) 30 (13)24 43 (9) 36 (16)

NOTE: The relative hazard for OLT patients versuscontrols over the follow-up period was 1.88 (95% CI ¼0.86-4.10). The P value was 0.115.

TABLE 4. Summary of the Causes of Death

Cause of Death

OLT Group

(n ¼ 15)

Control Group

(n ¼ 23)

Complications ofend-stage liverfailure [n (%)]

9 (60) 15 (65)

—Including uncontrolledvariceal rebleeding (n)

2 2

Sepsis [n (%)] 3 (20) 5 (22)Including spontaneous

bacterial peritonitis (n)1 1

Other [n (%)] 3 (20) 3 (13)

Figure 1. Kaplan Meier analysis of 36 month cumulativetransplant free survival after TIPS insertion.

LIVER TRANSPLANTATION, Vol. 17, No. 7, 2011 KING ET AL. 775

This study demonstrates the significance of theMELD score to outcomes after TIPS in liver transplantrecipients; this is perhaps not surprising because thiswas the original aim of the MELD scoring system.28

Overall, there was a trend toward lower survival overthe duration of follow-up in the transplant recipientgroup versus the control group. An important findingof the study is that a MELD score > 15 before TIPS inliver transplant recipients was a predictor of poor out-comes (HR ¼ 5.846, 95% CI ¼ 1.754-19.485, P <0.05); the 6-month transplant-free survival rate wasonly 12.5%. This was significantly worse than theresults for nontransplant patients with MELD scores> 15. Transplant recipients with MELD scores < 15had a survival rate similar to that of nontransplantpatients with MELD scores < 15. Even though themean MELD scores were similar in the 2 groupsbefore TIPS and, as we demonstrated, the survivalrate was much lower for the transplant recipientswith MELD scores > 15, the rate of subsequent livertransplantation or retransplantation was lower in theOLT group (9%) versus the control group (18%). Therate of subsequent retransplantation was lower than

that in previously published series (13%-33%)14-19:9% of all patients undergoing TIPS insertion at ourcenters subsequently undergo transplantation, andwe rarely use the TIPS procedure as a bridge to trans-plantation. It is likely that retransplantation was con-sidered too risky for our patients, and because of theworse outcomes with retransplantation,29,30 TIPSinsertion was considered the only option available tothem at the time. The survival benefit of transplanta-tion in patients with MELD scores > 15 has beenknown for some time,31 and the findings of this studysupport the notion of retransplantation as the therapyof choice in patients with MELD scores > 15. Whenthis is not feasible, it is unlikely that there will be anybenefit from TIPS insertion.

These findings also raise questions about the signif-icance of the MELD scoring system in the transplantpopulation. The mean serum creatinine concentrationwas significantly higher in the transplant recipientgroup versus the control group (132 6 74 versus 1026 78 lmol/L, P < 0.05), and this may be explained bylong-term nephrotoxic immunosuppression becausethe median time from OLT to TIPS was nearly 4 years.Despite this, the mean pre-TIPS MELD scores weresimilar in the 2 groups, and this suggests that theintrinsic liver disease in the transplant recipientgroup was less severe than that in the control group.Renal dysfunction in the transplant recipient groupmay also partly explain the lower rates of clinical suc-cess in patients with refractory ascites because lowerresponse rates have been seen in nontransplantpatients with established renal dysfunction.32

Despite differences in survival between the groups,the causes of death were similar in the 2 groups. Themajority of the deaths in both groups were due to

TABLE 5. Mortality

HR Over the Follow-Up

Period (95% CI)* P Value

Pre-TIPS MELDscore < 15

1.19 (0.46-3.08) 0.717

Pre-TIPS MELDscore > 15

4.32 (1.45-12.88) 0.009

*OLT patients versus controls.

TABLE 6. Cox Regression Analysis of Factors Predictive of Outcomes in the OLT Group

Factor

Mortality

HR 95% CI P Value

Age (years) 1.013 0.971-1.057 0.551Male sex 1.295 0.451-3.716 0.631Center location: Birmingham 2.078 0.465-9.296 0.339TIPS date: before 2004 0.764 0.274-2.129 0.607Etiology: cholestatic 1.097 0.394-3.052 0.859Anastomosis: piggyback 1.260 0.344-4.62 0.727Indication: ascites 1.686 0.520-5.462 0.384Emergency procedure 1.053 0.292-3.796 0.937Cause of portalhypertension: vascular

3.040 0.961-9.618 0.058

Initial PPG (mm Hg) 1.040 0.952-1.136 0.382Final PPG (mm Hg) 1.165 0.968-1.403 0.107Covered stent 0.724 0.259-2.020 0.537Stent number 1.701 0.806-3.587 0.163Stent diameter (mm) 1.100 0.847-1.428 0.476Pre-TIPS MELD score 1.161 1.036-1.305 0.010

Pre-TIPS MELD score > 15 5.846 1.754-19.485 0.004

OLT to TIPS time 1.000 1.000-1.000 0.676Technical success 0.640 0.199-2.057 0.454Clinical success 0.521 0.162-1.624 0.274

776 KING ET AL. LIVER TRANSPLANTATION, July 2011

complications of end-stage liver failure. It may be thatTIPS insertion accelerates the progression of liver fail-ure to a greater degree in transplant recipients versusnontransplant patients, although this is not clearfrom these data. Deaths due to sepsis were also simi-lar in the 2 groups because both groups were at riskof infection due to immunosuppression in the trans-plant recipients and immunoparesis secondary to liverdisease in the control group.

Our data demonstrate that TIPS insertion is techni-cally feasible in liver transplant recipients, regardless ofthe type of venous outflow reconstruction. Shunts weresuccessfully created in over 95% of the patients, andthis is in line with the bench mark of 95% recom-mended in the TIPS quality improvement guideline pub-lished by the Society of Interventional Radiologists in2003.26 However, there was a significantly lower rate ofhemodynamic success in the OLT group (68%) versusthe control group (95%), and this was reflected in thehigher mean final PPG seen in the OLT group (9.9 63.2 versus 6.9 6 3.6 mm Hg, P < 0.05). Therefore, it isnot surprising that clinical success was also signifi-cantly lower in the OLT group versus the control group.The OLT group failed to meet the target of 90% clinicalsuccess, whereas the control group exceeded this.

The mean stent diameter used in the OLT group wassignificantly lower than that in the control group (9.3 60.9 versus 10.3 6 1.6 mm, respectively, P < 0.05), andthis was also likely a factor in the lower rates of hemo-dynamic and clinical success. The use of smaller stentsmay be a reflection of the fact that these procedures aretechnically more challenging to complete. The differingpathophysiology of portal hypertension and the alteredvascular anatomy in transplant recipients with a piggy-back anastomosis may mean that despite the creationof a functioning shunt, portal decompression is notsuccessfully achieved. Our analysis indicates that post-transplant portal hypertension with a vascular etiologyis a predictor of increased mortality. This also addsweight to the notion that the pathophysiology of theportal hypertension in these patients may be differentfrom that of cirrhotic portal hypertension, which is par-ticularly important because of the increasing use of thepiggyback anastomosis.

Procedure-related complications were similar in the2 groups, and their frequency was within the accepted5% rate for major complications. The TIPS procedureappears to be both technically feasible and safe inliver transplant recipients. Post-TIPS encephalopathyoccurred with similar frequencies in the transplantrecipients and the controls within the overall expectedrate of 30%.33 This is in contrast to previous reportssuggesting that post-TIPS encephalopathy is more fre-quent in transplant recipients.21,23 The need for shuntocclusion was greater in the transplant recipientgroup; although this was not a statistically significantfinding, it may indicate that post-TIPS encephalop-athy is harder to control with standard medical ther-apy in transplant recipients.

PTFE-covered stents were introduced into clinicalpractice during the course of this series of patients,

and the proportions of covered stents were similar inthe 2 groups. However, the use of covered stents inpatients in the OLT group was not predictive ofimproved survival. Further study with a larger num-ber of patients with covered stents is necessary beforewe can make valid conclusions about the utility ofsuch stents in liver transplant recipients.

The low incidence of TIPS procedures in liver trans-plant recipients means that our study is a retrospectiveanalysis over a long period of time with a heterogeneouspatient population. However, the inclusion of a matchedcontemporaneous control group allows for any changesin procedural techniques (notably the introduction ofPTFE-covered stents) and for any posttransplant man-agement improvements. Certain data were not availablefor the analysis; in particular, we could not examine theeffect of alcohol consumption after TIPS insertion.

On the basis of our data, we suggest that TIPSinsertion has little or no benefit for transplant recipi-ents with MELD scores > 15, and if a patient is notsuitable for liver retransplantation, then TIPS place-ment should not be considered. These findings do,however, support a role for TIPS insertion in trans-plant recipients with MELD scores < 15. TIPS proce-dures in transplant patients, although feasible, maybe technically more difficult and may not achieve thedesired clinical outcomes. Therefore, they should beperformed only in centers with extensive experience inTIPS insertion as well as the management of livertransplant recipients.

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