Clinical Studies

The natural history of parallel transjugularintrahepatic portosystemic stent shuntsusing uncovered stent: the role of host-related factors

Ahmed Helmy1n, Doris N. Redhead2,Adrian J. Stanley3,n and Peter C.Hayes4

1Department of Liver Transplantation, King

Faisal Specialist Hospital & Research Center;

Riyadh, Saudi Arabia, 2Department of Radiology,

Royal Infirmary of Edinburgh, 3Department of

Gastroenterology, Glasgow Royal Infirmary,4Liver Unit, Department of Medicine, Royal

Infirmary of Edinburgh, Scotland.

Helmy A, Redhead, DN, Stanley AJ, Hayes, PC. The natural history ofparallel transjugular intrahepatic portosystemic stent shunts (TIPS) usinguncovered stent: the role of host-related factors.Liver International 2006: 26: 572–578.r2006 The Authors. Journal compilation r2006 Blackwell Munksgaard.

Abstract: Objectives: Parallel shunts (PS) are used in the management oftransjugular intrahepatic portosystemic stent-shunt (TIPS) insufficiency, amajor limitation of the technique. This study describes the natural history ofPS, and uses them as a model to assess the role of host factors in thedevelopment of primary shunt insufficiency. Methods: Out of 338 patientswith TIPS, 40 (11.8%) patients required insertion of a PS. Baseline andfollow-up data of these patients were collected. Regular shunt surveillanceinvolved biannual clinic visits and transjugular portography. Results: Thenon-PS group (group 1; n5 298) and the PS group (group 2; n5 40) hadsimilar baseline demographic and disease characteristics. Index shunts ofboth groups and the PS produced a significant portal pressure gradient drop(Po0.001), which was less in the index shunts of Group 2 (Po0.02 for both).PS had similar cumulative shunt patency rates to those of the index shunts ofGroup 1, and both were greater than those of index shunts in Group 2(Po0.001 for both). The intervention rate (number of interventions/numberof check portograms �100) was similar for PS and the index shunts of Group1 (38.7% and 43% respectively), but was significantly higher in the indexshunts of Group 2 (85.6%; Po0.01 for both). In Group 1 and Group 2, 144patients (48.3%) and 21 patients (52.5%) died during follow-up after amedian period of 23.4 and 8.9 months respectively. Conclusions: Thesefindings do not support the hypothesis that shunt insufficiency is related tohost factors.

Keywords: assisted patency – pathogenesis –

primary shunt insufficiency – shunt occlusion

Dr. Ahmed Helmy, Department of Liver Trans-

plantation, Hepatobiliary and Pancreatic Surgery,

King Faisal Specialist Hospital & Research Cen-

ter (KFSH&RC), MBC: 72. PO Box: 3354, Riyadh

11211, Saudi Arabia.

e-mail: ahsalem10@hotmail.com

Received 12 August 2005,

accepted 26 February 2006

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Since its introduction in 1989 (1), transjugularintrahepatic portosystemic stent-shunt (TIPS) hasbeen widely used in the management of complica-tions of portal hypertension (2–6). Shunt insuffi-ciency (SI), a major limitation of this technique, isreported to develop in up to 80% of patients.Therefore, regular portographic shunt surveil-

lance, with or without intervention, is requiredto preserve shunt patency (2, 4–9).

Many interventional techniques are used tomanage SI including balloon angioplasty, shuntrestenting, shunt extension, streptokinase injec-tion, and the creation of parallel shunts (PS). Thelatter procedure is usually reserved for the man-agement of shunt occlusion, occurring either asan acute shunt thrombosis or as a progressivepseudo-intimal hyperplasia to an extent whereshunt patency can no longer be preserved byballoon angioplasty and/or restenting. However,little is known about the natural history of PSincluding their efficacy, patency, and interventionrate.

Abbreviations: PPG, portal pressure gradient; PS, parallelshunts; SI, shunt insufficiency; TIPS, transjugular intrahepaticportosystemic shunt

nA. H. and A. J. S were formerly affiliated to the Liver Unit,Department of Medicine, Royal Infirmary of Edinburgh, Edin-burgh, Scotland.

Liver International 2006: 26: 572–578 r 2006 The AuthorsJournal compilation r 2006 Blackwell Munksgaard

DOI: 10.1111/j.1478-3231.2006.01264.x

572

The pathogenesis of SI is not clear. However,seepage of bile into the shunt has been suggestedas a possible contributing factor to the develop-ment of acute shunt thrombosis (10–13), How-ever, biliary fistulae are not always seen (14, 15).In addition, stent characteristics, technique-re-lated factors, host factors (e.g., diabetes mellitusand hypercoagulable states), decreased TGF se-cretion by the endothelial cells, and hitherto ill-defined factors associated with tissue injury andrepair, have all been cited as possible factorsleading to SI (10–19). A hypothesis that favorsa role for host-related factors in the developmentof SI would predict that the performance of thePS to be: (1) similar to that of the index TIPS inthe same group, as they will be exposed to thesame host factors; and (2) inferior to index TIPSof the cohort without PS.Therefore, this retrospective study aims to: (1)

describe the natural history of PS and (2) use thePS as a model to assess the role of host-relatedfactors in the pathogenesis of SI, through com-paring the performance of PS with that of theindex shunt in the same subgroup, and with thatof the index shunts in the cohort without PS.

Materials and methods

Patients

The Royal Infirmary of Edinburgh, Scotland, is atertiary referral center that has one of the biggestTIPS cohorts worldwide. We have selected 338patients who had successful TIPS insertion froma dedicated database of TIPS referrals afterexclusion of the patients who had technicallyunsuccessful procedure, those who had TIPSpostliver transplantation, those who entered aclinical trial involving modulation of the shuntsurveillance program (20), and those who under-went insertion of covered stents. This consecutiveseries of patients formed the basis of this study.Of these, 40 patients (11.8%) have required a PSat 0.03–22.8 months following the insertion of theindex TIPS. Summary of patients’ characteristicsis shown in Table 1.

Index TIPS placement

All TIPS procedures were performed or closelysupervised by a skilled interventional radiologistusing a standard technique described elsewhere(2). In our cohort, mesenteric angiography wasperformed pre-TIPS in the first 32 patients. In thesubsequent 27 patients, ultrasound was used tolocalize the site of portal vein bifurcation, but inthe remaining 279 patients, no preprocedureimaging was routinely carried out. Briefly, the

technique involves the preprocedure administra-tion of 1 g of cefotaxime and the administrationof sedation and analgesia in the form of mid-azolam and pethidine respectively. Using localanesthetic, the right internal jugular vein is cathe-terized and a 10Fg sheath introduced (WilliamCook Europe Tipsi set). A baseline measurementof the right atrial and the inferior vena cavapressure is obtained. Using a modified transjugu-lar liver biopsy needle, the right hepatic vein isselected and the needle directed towards theregion of the right branch of the portal vein. Afine stylet is passed down this needle and ad-vanced towards the portal branch. When a satis-factory position is achieved in the portal branch,a guide wire is introduced through the sheath ofthe stylet, into the portal system. A portogram isobtained and the pressure measured in the portalvein. The track is then dilated and stents (Walls-tents, Schneider, Minneapolis, MN) placed acrossthe track. Final portogram and pressure measure-ments are carried out. The procedure is usually

Table 1. Baseline characteristics of patients in both groups

Variable

Non-parallelshunt group(Group 1;n 5 298)

Parallelshunt group(Group 2;n 5 40)

Mean age � SEM (years) 53.4 � 12.7 51.3 � 10.8Age range (years) 8–83 32–71Male/Female n (%) 189 (63.4)/109 (36.6) 26 (65)/14 (35)Etiology of liver disease n (%)

Alcoholic liver disease 198 (66.4) 25 (62.5)Cryptogenic cirrhosis 24 (8.1) 4 (10)Primary biliary cirrhosis 27 (9.1) 3 (7.5)Hepatitis B/C 21 (7) 3 (7.5)Primary sclerosing

cholangitis6 (2) 2 (5)

Autoimmune hepatitis 7 (2.3) FOthers 15 (5) 3 (7.5)

Number with HCC n (%) 13 (4.4) 2 (5.0)INR 1.4 � 0.3 1.3 � 0.4Platelet count � 109/l 84 � 7 81 � 11Child–Pugh score(mean � SEM)

9.6 � 2.5 9.1 � 2.5

Child grade n (%)A 27 (9.1) 6 (15)B 113 (37.9) 15 (37.5)C 155 (52.1) 19 (47.5)Not applicable 3 (1) F

Indication n (%)Esophageal varices 197 (66.1) 22 (55)Gastric varices 44 (14.8) 8 (20)Refractory ascites 39 (13.1) 5 (12.5)Portal hypertensive

gastropathy8 (2.7) 3 (7.5)

Ectopic varices 8 (2.7) 1 (2.5)Others 2 (0.7) 1 (2.5)

Emergency procedure n (%) 127 (42.6) 13 (32.5)

n, number; SEM, standard error of the mean; HCC, hepatocellularcarcinoma; INR, international normalization ratio.

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The natural history of parallel shunts

completed within 1–2 h. No postprocedure antic-oagulation is used.

TIPS follow-up

All subjects were followed up till death, livertransplantation, time of data analysis, or loss tofollow-up according to a standard protocol.Briefly, Duplex Doppler ultrasound is performedwithin a week of TIPS insertion to ensure pa-tency, and a TIPS portogram is performed if thetrans-shunt flow appears inadequate. Followingdischarge, all patients are prospectively followed-up in a dedicated follow-up clinic with full clinicalexamination and biochemical profile at 6 weekspost-TIPS insertion and 4 monthly thereafter,and with regular portograms at 6 monthly inter-vals. During the direct portographic follow up,findings such as shunt thrombosis, pseudo-intimal hyperplasia, portal vein thrombosis, orhepatic vein stenosis are recorded and measure-ments of portal pressure gradient (PPG) arenoted.

Insertion of the PS

The procedure for this shunt is similar to place-ment of the initial (index) shunt. The second(parallel) shunt is placed alongside the first,usually from middle or left hepatic vein to theleft branch of the portal vein (Fig. 1). Theindications for PS insertion were: (1) all patientswith complete occlusion of the existing shunt(complete absence of flow through the shunt);(2) failure to achieve adequate final PPG despiteballoon angioplasty (three procedures); or (3) SIrequiring repeated balloon angioplasty (threeprocedures). No detectable complications of thePS procedure were observed.

Definitions

PPG is the portal pressure minus inferior venacava pressure, expressed as mmHg.

PPG drop is PPG pre-TIPS minus PPG post-TIPS. The % drop in PPG was calculated by theformula: %PPG drop5 (PPG pre-TIPS minusPPG post-TIPS) divided by PPG pre-TIPS multi-plied by 100.

SI is a �20% rise in PPG or an increase inPPG to �12mmHg together with portographicevidence of SI (10).

Shunt occlusion is the complete absence of flowthrough the shunt.

Primary shunt patency period is the preinterven-tion period, i.e., time from shunt insertion untilfirst intervention.

Assisted shunt patency period is the pre- pluspostintervention patency, i.e., time from shuntinsertion until the last portography.

Intervention rate equals the number of inter-ventions divided by the number of check porto-graphies, and multiplied by 100.

Data collection and statistical analysis

Data pertaining to baseline characteristics (demo-graphic features, details of liver disease, andindication for TIPS) were summarized in twogroups: (1) The Non-PS Group (Group 1;n5 298), which includes patients who had suc-cessful insertion of TIPS without need to place aPS during their follow-up; and (2) The PS Group(Group 2, n5 40), which includes patients whorequired PS placement. However, data regardingthe natural history of the shunt (duration ofprimary shunt patency, episodes of SI and typesof intervention for SI required) were studied andsubdivided into three groups:

Group 1: the index TIPS of patients who didnot require PS insertion (n5 298).Group 2: the index TIPS of subgroup thatrequired PS insertion (n5 40).Group 3: the PS (n5 40).

Results are expressed as mean� standard devia-tion (SD) unless otherwise stated. Paired Stu-dent’s t-test was used to compare paired data,whereas w2 test, and unpaired Student’s t-testwere used to compare unpaired data as appro-priate. Cox regression analysis was performed todetermine independent variables predicting therequirement of PS insertion. Cumulative primaryshunt patency was evaluated using Kaplan–Meierplots and differences between groups were ana-lyzed by the log-rank method. P-value of o0.05was taken as statistically significant.

Fig. 1. A portographic image represents a blocked index trans-jugular intrahepatic portosystemic stent-shunt (IS), a parallelshunt (PS), catheter (Ca), and coils (C) inside the esophagealvarices.

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Helmy et al.

Results

Patients in Group 1 (n5 298) and Group 2(n5 40) were similar with regard to age, sex,etiology of liver disease, Child grade, Child–Pugh score, platelet count, International Normal-ization Ratio, number of patients with hepatocel-lular carcinoma, TIPS indication, number ofemergency procedures, and in the size and typeof stents used (Tables 1 and 2).

Shunt efficacy

As shown in Table 2, TIPS insertion in Group 1and the PS produced a significant drop in PPG of61.0% and 71.6%, respectively (Po0.001 forPPG pre-TIPS vs. PPG post-TIPS in each group).However, the index TIPS of Group 2 performedsignificantly less well in reducing PPG comparedwith the PS, reducing PPG by 56.7% (Po0.01).In addition, the mean % drop in PPG was similarin the index shunt in Group 1 and the PS, andboth were significantly greater than the indexshunt in Group 2 (Po0.05 and Po0.01, respec-tively). Similarly, the absolute drop in the PPGwas significantly greater with the index shunt inGroup 1, and with the PS compared with theindex shunt in Group 2 (Po0.01 and Po0.02,respectively; Table 2).

The requirement of PS

Multivariate regression analysis of variables ofinterest (age, sex, Child–Pugh score, etiology ofliver disease, indication for TIPS, PPG pre-TIPS,PPG post-TIPS, PPG drop following index shunt,stent diameter) showed that increasing age(P5 0.01), higher Child–Pugh score (P5 0.03),and smaller stent diameter (P5 0.03) are thevariable that independently predict the require-ment of PS insertion.

SI

(1) Insufficiency of the index shunts in the non-PSgroup (Group 1; n5 298): During the mean fol-low-up period of 12.4 months (range 0.26–59.8),129 (43.3%) episodes of primary SI were docu-mented. Thirty four (26.4%) episodes occurredwithin the first month and 95 (73.6%) occurredthereafter. Primary SI episodes in the first monthwere caused by intimal hyperplasia (n5 12),shunt thrombosis (n5 18), hepatic vein stenosis(n5 2), portal vein thrombosis (n5 1) and shuntmigration (n5 1). Causes of primary SI after thefirst month were intimal hyperplasia (n5 61),hepatic vein stenosis (n5 22), shunt occlusion(n5 10), hepatic vein thrombosis (n5 1) andportal vein thrombosis (n5 1). In 499 portogramsthroughout the whole follow-up period, 215 in-terventions were undertaken giving an interven-tion rate of 43% to maintain shunt patency.These interventions included balloon angioplasty(n5 109), shunt extension (n5 54), PS (n5 40),shunt restenting (n5 11) and streptokinase injec-tion (n5 1).(2) Insufficiency of the index shunts in the PS

group (Group 2; n5 40): The mean follow-upperiod (period until insertion of a parallel stent)of the index shunt in Group 2 was 5.3 months(range 0.03–23.8), 40 (100%) episodes of primarySI were documented. Seventeen (42.5%) occurredwithin the first month and 23 (57.5%) occurredthereafter. Primary SI episodes in the first monthwere caused by shunt thrombosis (n5 11), intimalhyperplasia (n5 4), hepatic vein stenosis (n5 1),and shunt migration (n5 1). Causes of primarySI after the first month were intimal hyperplasia(n5 22), hepatic vein stenosis (n5 3), hepatic veinthrombosis (n5 1), and portal vein thrombosis(n5 1). In 67 portograms throughout the follow-up period, 58 interventions were undertaken giv-ing an intervention rate of 85.6% to maintain

Table 2. Comparison between the parallel shunts and the index shunts in both groups

Variable Group 1 (n 5 298) Group 2 (n 5 40) PS (n 5 40)

Stent diameter: millimeter 11.4 � 1.4 10.7 � 1.7 10.3 � 1.5Stent type: Wallstent/Palmaz stent (n) 275/23 37/3 40/0PPG pre-TIPS (mmHg) 19.6 � 7.4n 18.2 � 5.3n 20.4 � 6.6n

PPG post-TIPS (mmHg) 7.4 � 4.4 7.9 � 4.8 5.8 � 3.8PPG drop (mmHg) 12.4 � 7.1 10.4 � 5.4 13.9 � 8.3Drop in PPG (%) 61.0 56.7 71.4nn

Total SI episodes: n (%) 129 (43.3) 40 (100) 20 (50)SI episodes in first month: n (%) 34 (26.4) 17 (42.5) 2 (10)SI episodes after first month: n (%) 95 (73.6) 23 (57.5) 18 (90)Intervention rate (%) 43# 85.6 38.7#

Primary patency period:months 16.1 � 2.1 5.3 � 1## 12.7 � 2.3

Group 1,Index shunt of the non-parallel shunt group; Group 2,Index shunt of the parallel shunt group; data are expressed as Mean � SD; n, number; SI,shunt insufficiency; PPG, portal pressure gradient. nPo0.001 vs. PPG post-TIPS in each group. #P 5 0.01 vs. index shunts in Group 2. nnPo0.05 vs.index shunt of Group 1, and Po0.01 vs. the index shunt of Group 2. ##Po0.001 vs. the index shunts in Group 1 and the PS.

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The natural history of parallel shunts

shunt patency. These interventions included PSinsertion (n5 40), balloon angioplasty (n5 11),shunt extension (n5 5) and shunt restenting(n5 2).(3) Insufficiency of the PS: PS were followed

up for a mean period of 11.6 months (range: 0.3–40.6 months). During this time, 20 (50%) epi-sodes of primary SI were documented, of whichtwo (10%) occurred within 1 month and werebecause of shunt thrombosis, and 18 (90%)occurred thereafter. Causes of SI after the firstmonth included intimal hyperplasia (n5 10), he-patic vein stenosis (n5 5), and hepatic veinthrombosis (n5 3). In 62 portograms, 24 inter-ventions were required to maintain patency,translating to an intervention rate of 38.7%.These interventions included balloon angioplasty(n5 18), shunt restenting (n5 2), extension ofshunt (n5 4). The number of stents, includingthe index TIPS, inserted per patient ranged from2–3. Hepatic encephalopathy was severe enoughto require intervention in four (10%) patients.Intervention was in the form of narrowing(n5 2), occlusion with filter (n5 1) or coils(n5 1). Blockage of the PS has occurred in fourpatients; one underwent liver transplantation,one entered the variceal band ligation programand two died subsequently.

Primary and assisted shunt patency

The number (%) of primary SI episodes followingthe index shunt in Group 2 was 40 (100%). Thiswas statistically greater than following the PS inthe same group 20 (50%) and the index shunt inthe whole TIPS cohort, 129 (43.3%; Po0.01 forboth).Kaplan–Meier analysis and log rank test

showed that both the PS and the index shuntsin Group 1 behaved in a similar way regardingcumulative primary shunt patency rates at 6, 12,24 and 36 months (60.3%, 33.6%, 22.4% and 7%and 65.1%, 46.1%, 18.5% and 8.5%, respec-tively; P5 0.814). However, they were signifi-cantly greater than the patency rates of theindex shunts in Group 2 (27.5%, 15%, 0% and0%; Po0.01 and Po0.001, respectively; Fig. 2).Following portographic interventions, the cumu-lative ‘assisted’ shunt patency rates at 6, 12, 24and 36 months increased significantly in Group 2to 78%, 51.2%, 26.8% and 17.7% respectively,and in Group 1 to 89.9%, 81.4%, 70.3% and41.3% respectively (Po0.01 for both, as com-

pared with their primary patency rates).The mean� SEM primary patency period of

the PS (12.7� 2.3 months; time from PS place-ment until last portogram) was similar to that of

the index shunts in Group 1 (16.1� 2.1 months;time from index shunt placement until time offirst intervention). However, both were signifi-cantly greater than the primary patency period ofthe index shunt in Group 2 (5.3� 1 months; timefrom index shunt placement until time of firstintervention; Po0.001 for both. With interven-tions the mean� SEM assisted shunt patencyperiod Group 2 (from time of index shunt untillast portogram) increased to 14.5� 2.7 monthsand that in Group 1 increased to 46.9� 3.4months (Po0.01 for both).

Mortality

In Group 1 (n5 298), 144 patients (48.3%) diedduring follow-up after a median period of 23.4months (range: hours to 66.1 months). Causes ofdeath included liver and hepatorenal failure(n5 64; 44.4%), rebleeding (n5 24; 16.7%), pneu-monia (n5 18; 12.5%), sepsis (n5 8; 5.6%),hepatocellular carcinoma (n5 6; 4.2%), cerebro-vascular accident (n5 5; 3.5%), postcolectomy(n5 1; 0.7%), postliver transplantation (n5 1;0.7%), Gall bladder perforation (n5 1; 0.7%)and unknown (n5 16; 11.2%).

In Group 2 (n5 40), and following insertion ofthe PS, 21 patients (52.5%) died during follow-upafter a median period of 8.9 months (range: hoursto 66.1 months). Causes of death included liverfailure (n5 12; 57.1%), rebleeding (n5 2; 9.5%),pneumonia (n5 3; 14.4%), postcolectomy (n5 1;4.8%), unknown (n5 3; 14.4%).

Cumulative survival period in Group 1 at 12,24, and 60 months were 58.4%, 43.9%, and17.4% respectively, while those of Group 2 were56.2%, 28.1%, and 2.5% respectively (P5 0.41using Log Rank test; Fig. 3).

80706050403020100–10Period (months)

–0.2

0.0

0.2

0.4

0.6

0.8

1.0

Cum

ulat

ive

surv

ival

Fig. 2. Kaplan–Meier analysis of cumulative primary shuntpatency is similar in the parallel shunt group (n5 40, bold thickline) and the index shunt in the non-parallel shunt group(n5 298, dashed line); P5 0.81 and both are better than theindex shunt in the parallel shunt group (n5 40, thin line;Po0.001 for both).

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Discussion

The hypothesis favoring the role of host factors inthe development of SI would predict that theperformance of the PS to be similar to the indexTIPS in the same subgroup and inferior to theindex TIPS of the patients who did not require PSinsertion (Group 1). In this study, we have shownthat this is not the case and the performance ofthe PS is superior to the index TIPS in the samesubgroup. Indeed, the PS performed as well as theindex TIPS of Group 1 with regards to reducingportal pressure and primary shunt patency andintervention rate. This evidence would argueagainst a primary role for host-related factors inthe pathogenesis of SI. However, host factorsmay occasionally be affected by the insertion ofa PS, and therefore the improvement of perfor-mance of the PS can’t be attributed to shuntfactors alone. For example, extension of the PSclose to the junction of the hepatic vein and theinferior vena cava, makes host responses tohepatic veins injury almost impossible. Also,this hypothesis should be considered very care-fully. It is clear that patients requiring parallelTIPS formed a negative selection of all patientsundergoing TIPS. Whatever the reason, thesepatients did less well, perhaps to a large extent‘bad luck’ e.g., with respect to procedures com-plicated by bile leakage, and 100% eventuallyreceived parallel TIPS. A priori, the chance thatagain 100% would fail after the second procedureis likely to be lower. In other words, it seemshardly imaginable that the course after the par-allel procedure could have been worse than afterthe index procedure.PPG drop achieved by the index TIPS in the

Group 2 was significantly less than that achieved

by the PS or the index shunt of the Group 1. Thisobservation, we believe, is a further argumentagainst the role of host factors in the causationof SI, favoring other factors such as ‘techniquefactors’ or ‘shunt factors’. Although significant,the differences of the relative changes of thepressure gradients between the groups (61% vs.56.7%) is small questioning the relevance of thefinding. Other factors such as portal blood flow,length of shunt, and coagulation status should alsobe considered before concluding that the reducedPPG drop by the index shunt of Group 2 is entirelybecause of a reduced primary shunt function.Despite the proven effectiveness of TIPS in

reducing portal pressure and consequently therisk of rebleeding, the development of SI thatoccurs in almost all shunts over time is the‘Achilles Heel’ of this procedure. Therefore, reg-ular portography and intervention are necessaryfollow-up requirements to maintain shunt effi-ciency. However, this approach may discredit theTIPS treatment, and because shunt patency is asecondary endpoint, portography should only beperformed if clinically indicated, i.e., in presenceof risky varices or refractory ascites.In agreement with Dabos et al. (21), this study

shows the effectiveness and usefulness of the PSin reducing PPG and prolonging shunt patency.In addition, Haskal et al. (22) has shown thatplacement of a PS decompressed the portal sys-tem effectively after failure of the initial shunt toachieve that, but in their study they placed a PS atthe initial procedure where placement of a 10mmshunt failed to reduce the PPG and all stents were10mm in diameter.Mortality rates and causes are similar between

the groups. However, considering the shorterfollow-up period of the PS group (8.9 vs. 23.4months), the PS appears to increase mortality.Since we could not find any differences in thebiometrical and clinical variables between thegroups, this may be because of the higher reduc-tion in the PPG achieved by the PS. Accordingly,use of PS should be done with caution bearing inmind that it may increase mortality (and possiblyhepatic encephalopathy). Therefore, it may berecommended to implant smaller PS with a lesserreduction of the pressure gradient.The problem of occlusion of the PS despite

interventions has occurred in our population.Insertion of a third shunt is rarely feasible andthe alternative available programs are endoscopicmanagement, surgical shunts or liver transplanta-tion (23–25). The current alternative approachfor improving TIPS performance lie in the use ofcovered stents, which may probably overcomeboth stent and host related factors (26–28).

Period (months)706050403020100–10

Cum

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surv

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1.2

1.0

0.8

0.6

0.4

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Fig. 3. Kaplan–Meier analysis of cumulative survival of thenon-parallel shunt group (n5 298; continuous line) and theparallel shunt group (n5 40, dotted line); P5 0.41.

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The natural history of parallel shunts

In conclusion, primary SI is common andnecessitates regular check ups and interventions.PS placement is effective in the management ofSI. The requirement of a PS appears to be greaterin the patients who have smaller PPG dropfollowing their index TIPS placement. The super-iority of the performance of the PS over the indexshunts in the same patients and its similarity tothe index shunts in the whole TIPS populationmake the contribution of host factors in thedevelopment of primary SI unlikely.

Acknowledgements

We thank Drs. H. F. Lui, R. Jalan for their constructivecomments and help during collection of this data from the TIPSdatabase.

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