Clinics and Research in Hepatology and Gastroenterology (2014) 38, 155—163
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ORIGINAL ARTICLE
Impact of transjugular intrahepatic portosystemic shunting on liver transplantation: 12-year single-center experience Louise Barbier a,d,∗, Jean Hardwigsen a,d, Patrick Borentain b,d, Nicolas Biance a,d, Amine Daghfous a,d, Guillaume Louis c,d, Danielle Botta-Fridlund b,d, Yves-Patrice Le Treut a,d a
Department of Digestive Surgery and Liver Transplantation, AP—HM, Hôpital La Conception, 13005 Marseille, France b Department of Hepato-Gastro-Enterology, AP—HM, Hôpital La Conception, 13005 Marseille, France c Department of Radiology, AP—HM, Hôpital La Timone, 13005 Marseille, France d Aix-Marseille University, 13284 Marseille, France Available online 29 October 2013
Summary Background: The purpose of this study was to assess the impact of transjugular intrahepatic portosystemic shunting (TIPS) on liver transplantation (LT). Methods: Seventy-two patients transplanted after TIPS insertion between 1996 and 2008 were compared with 136 matched patients transplanted without prior TIPS. Results: At time of LT, 10% of the TIPS were occluded and 32% were misplaced. Shunt removal was difficult in 17% of the TIPS patients and required vena cava clamping in 10%. Collateral venous circulation was less extensive and intra-operative portocaval anastomosis was required more frequently in the TIPS group. No significant difference in transfusion requirements and operative times were observed between the two groups. Postoperatively, liver and renal function tests, in-hospital stay, graft rejection, re-transplantation and 1-year mortality rates were not statistically different. Ascites volume in the first week was greater in the TIPS group (7.6 L vs 6.9 L, P = 0.036). In the TIPS group, ascites and collateral circulation were greater if the shunt was occluded at the time of LT. Shunt misplacement or occlusion was not associated with higher intra-operative or postoperative complication rates. Conclusion: TIPS did not impair LT and can provide a safe bridge for LT in the end-stage cirrhotic patients. © 2013 Elsevier Masson SAS. All rights reserved. ∗ Corresponding author. Department of General Surgery and Liver Transplantation, Hôpital La Conception, 147, boulevard Baille, 13005 Marseille, France. Tel.: +33 4 91 38 36 58; fax: +33 4 91 36 16 55. E-mail addresses: [email protected], [email protected] (L. Barbier).
2210-7401/$ – see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.clinre.2013.09.003
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Introduction In the past decade, a shortage of donors and expanding indications, e.g. hepatocellular carcinoma (HCC), have increased the liver transplantation (LT) waiting list time of end-stage cirrhotic patients [1]. As a result, prevention and treatment of cirrhosis-related complications have become increasingly important. Transjugular intrahepatic portosystemic shunt (TIPS) was first proposed by Rössle et al. [2]. The goal of TIPS is to create a low-resistance channel of circulation by deployment of an expandable metal or, more recently, polytetrafluoroethylene (PTFE) covered stent between the hepatic vein and intrahepatic portion of the portal vein. The main indications are refractory or recurrent variceal bleeding, refractory ascites, and more marginally hepatorenal syndrome, hepatic hydrothorax, Budd—Chiari syndrome, and veno-occlusive disease [3,4]. Complications of TIPS may occur during the procedure, e.g. extra hepatic portal vein or bile duct or arterial lacerations/punctures, or during the postoperative period, e.g. heart failure (< 10%), acute hepatic failure, hepatic encephalopathy (up to 40%) and shunt dysfunction related to stenosis or occlusion (up to 90% with uncovered stents [3] and 40% with covered stents [5]). The risk of these complications must be offset by the benefits of the procedure, i.e., the prevention of portal hypertension-associated complications, improvement of general and nutritional state [6]. Hence, TIPS insertion has been proposed as a bridge to LT in patients with end-stage liver disease [7—11]. Access to LT has become difficult for patients with refractory ascites and a low Model For End-Stage Liver Disease (MELD) score since the introduction of MELD score in the graft allocation system. In France, refractory ascites and a MELD score < 15 is a condition corresponding to MELD score exception [12]. However, in the absence of contra-indications (advanced liver insufficiency, portal vein thrombosis, past episodes of encephalopathy, heart failure), TIPS insertion should be proposed as a first-line treatment [2]. By improving renal function including in hepatorenal syndrome [13], TIPS improve the patients’ condition and should extend the delay before they eventually require LT. In this setting, the impact of TIPS on intra-operative and postoperative outcomes of LT is a major issue. Most investigators have concluded that TIPS is useful and safe before LT, but only few previous studies [7,9,11] have involved large patient populations. Yet, some authors have reported that intra-operative portocaval shunting is required more often in patients undergoing LT after TIPS. Other questions have been raised about the consequences of stent occlusion and/or misplacement. While misplacement does not appear to unfavorably impact on blood products transfusions and patient and graft survivals in one study [7], consequences of occluded TIPS have never been studied. The purpose was to describe the impact of TIPS on intraoperative and postoperative outcomes of LT based on our 12-year experience, with a specific interest in misplaced and occluded subgroups.
L. Barbier et al.
Patients and methods After obtaining the approval of the Institutional Review Board of La Conception Hospital, data from the files of patients who underwent LT between 1996 and 2008 were retrospectively analyzed.
Patients From 1996 to 2008, 402 LT were performed in our centre. All cirrhotic patients who underwent orthotopic LT after TIPS (n = 72, 18%) have been included in the TIPS group. Patients who underwent re-transplantation and previous surgical portosystemic shunt were not included. A control group (n = 136) matched in the proportion of 2 to 1 for age, gender and Child-Pugh score was compiled by including cirrhotic patients who underwent LT without prior TIPS during the same time period.
TIPS All TIPS procedures were performed by the same team of experienced radiologists at La Timone Hospital in Marseille. Sixty-six (92%) of the stents were bare stents; PTFE-covered stents were occasionally used from 2004. Stent patency was routinely assessed by Doppler ultrasound before LT with the evaluation of specific parameters including color-Doppler, angle corrected velocity measurements in the main portal vein and the three segments of the shunt, and flow direction in the controlateral portal vein. Stent misplacement was defined as a protrusion of the device into the suprahepatic segment of inferior vena cava and/or below the portal vein bifurcation. Stent occlusion was defined as the absence of blood flow assessed by Doppler ultrasound within the shunt. In case of recurrence of PHT symptoms and occlusion of the TIPS at Doppler ultrasound, an angiography with shunt recanalization by transjugular approach was attempted.
LT and operative data Three senior transplant surgeons at La Conception Hospital in Marseille performed all the LT procedures. In all cases, the procedure consisted of orthotopic LT with conservation of the vena cava and piggyback technique. No venovenous bypass was performed. The first step of the LT procedure was exploration with assessment of ascites volume upon opening of the abdominal cavity and of venous collateral circulation that was scored on a scale of ‘‘0’’ (none) to 3 (extensive). Three TIPS-related parameters, i.e., misplacement, patency and removal difficulty, were also assessed. Portocaval anastomosis was performed [14,15] only after failure of triad clamping in case of splanchnic hyperemia or hemodynamic intolerance. Antibioprophylaxis was performed according to the hospital guidelines. Operative duration was expressed as explant time, i.e., time from skin incision to ablation of native liver and total procedure time, i.e., time from skin incision to closure.
TIPS before liver transplantation
157
Postoperative course
Results
Post-LT management including immunosuppressant regimen (as per the department policy), antibioprophylaxis, and thrombosis prevention was identical in the TIPS and control groups. Various postoperative factors potentially affected by TIPS were checked. Clinical parameters included total ascites volume in first week, prolonged ascites (> 1 month), and hemorrhage requiring transfusions. Laboratory values included acute renal failure requiring extra-renal epuration, cytolysis peaks, plasmatic creatinine on postoperative day (POD) 7, prothrombin time on POD 5, and days required for factor V to reach 65%. The need for post-LT cavoplasty (surgical or interventional radiological), acute graft rejection, re-transplantation, in-hospital stay and 1-year mortality were noted. The native liver specimen was examined for the presence of unsuspected HCC (incidentaloma).
TIPS and control groups
Statistical analysis Statistical analysis was performed using the GraphPad Prism version 5 software package. Probability values < 0.05 were considered to be statistically significant. Comparison of data was performed using the Fisher’s two-tailed exact test for qualitative variables and the unpaired two-tailed t-test for quantitative variables. For comparison of more than 2 groups, the chi-square test, one-way ANOVA analysis of variance and Bonferroni’s multiple comparison test were used. The results were expressed as medians with ranges, and mean ± standard deviation of the mean in square brackets if required. In tables, the values indicate medians with ranges for quantitative variables and number of cases (rate) for qualitative variables.
Table 1
The characteristics of patients in the two groups are listed in Table 1. As they were matched for age, gender and ChildPugh score, these items did not differ between groups. The frequency of alcoholic cirrhosis was higher and that of viral cirrhosis was lower in the TIPS group. The frequency of HCC (pre-LT diagnosis) was higher in the TIPS group. The difference in waiting list time was not statistically significant between the two groups.
TIPS procedures Indications for TIPS (n = 72) included upper gastrointestinal bleeding in 28 patients (39%), refractory ascites in 41 (57%) and hepatorenal syndrome in 3 (4%). The median interval between TIPS and LT was 7.9 months (0.2—74.5). Before LT, 2 (3%) patients required repeat TIPS and 16 (22%) required TIPS revision (dilatation and intra-TIPS stenting). At the time of LT, 5 (7%) patients presented documented TIPS occlusion due to thrombosis. In all but one case of occlusion, revision attempts failed; as the patients were already listed for LT, a new TIPS insertion was not performed.
Liver transplantation Intra-operative findings are summarized in Table 2. Seven stents (10%) were non-functional due to clotting, including 5 detected before LT. Stent misplacement was observed in twenty-three patients (32%) with protrusion of the device into the suprahepatic segment of the inferior vena cava in 7 patients, protrusion below the portal vein bifurcation in 10, and protrusion at both sites in 6. Stent removal
Characteristics of patients.
Age (years) Male gender Cirrhosis etiology Alcohol Viral Hepatitis B or/and C Unknown origin Multiple origins Autoimmune cirrhosis Thesaurismosisa Hepatocellular carcinomab Child-Pugh score Waiting list duration (months)
TIPS group (n = 72)
Control group (n = 136)
P
51 (19—63) 55 (76%)
49 (15—64) 99 (73%)
NS NS
42 (58%) 14 (19%) 5 (7%) 7 (10%) 3 (4%) 1 (1%) 12 (17%) 10 (5—13) 4.3 (0.2—9.6)
56 (41%) 51 (38%) 6 (4%) 13 (10%) 3 (2%) 7 (5%) 9 (7%) 10 (5—14) 3.4 (0—17.1)
0.020 0.008 NS NS NS NS 0.029 NS NS
Indications for TIPS: before LT indication: n = 35 (49%); as a bridge to LT: n = 37 (51%): for refractory ascites (n = 25) and for gastrointestinal bleeding (n = 12); NS: not statistically significant. Significant results are in bold font. a Thesaurismosis: Wilson disease, hemochromatosis, glycogenesis. b HCC diagnosed before LT.
158 Table 2
L. Barbier et al. Intra-operative criteria: comparison between TIPS and control groups.
Ascites at opening of abdominal cavity (L) Venous Collateral Circulation None Moderate Severe Extensive Transfusion (units) Red blood cells Platelets Fresh frozen plasma Autotransfusion Surgery time Explant time (min) Total operative time (h) Intra-operative portocaval anastomosis
TIPS group (n = 72)
Control group (n = 136)
P
0 (0—14) [1.2 ± 2.6]
0 (0—11) [1.5 ± 2.4]
NS
21 (29%) 34 (47%) 11 (15%) 6 (8%)
12 46 39 39
< 0.001 NS 0.040 < 0.001
3 1 8 4
(0—12) (0—18) (0—25) (0—21)
119 (48—260) 5.3 (3.5—9) 18 (25%)
(9%) (33%) (29%) (29%)
3 (0—15) 1 (0—25) 10 (0—28) 5 (0—24)
NS NS NS NS
131 (55—384)
NS
5.5 (3—10) 15 (11%)
NS 0.016
NS: not statistically significant. Significant results are in bold font.
was difficult in 12 cases (17%) but complete extraction was achieved in all cases even in cases associated with extensive vein—wall encapsulation. In all cases with inferior vena cava involvement, TIPS removal was performed by total vena cava exclusion without venovenous shunt. Major venous collateral circulation (stages 2 and 3) was significantly less frequent in the TIPS group. There was no significant difference between the two groups with regard to either total procedure time or explant time. Requirement for blood-derived products was also statistically similar. Portocaval anastomoses were required more frequently in the TIPS group (25% vs 11%, P = 0.016). No TIPS-related surgical revision was required.
Postoperative recovery Postoperative outcomes are summarized in Table 3. No statistically significant difference was observed in any of the laboratory values measured. Total ascites volume during the first week was greater in the TIPS group. The median hospital stay was 20 days (range, 5—55) in the TIPS group and 25 days (range, 2—70) in the control group (P = 0.98). There was no difference between the two groups with respect to hemorrhage, acute renal failure, acute graft rejection, re-transplantation, and 1-year mortality. Incidental HCC on the liver specimens was discovered in 2 cases in TIPS group (3%) versus 11 cases in control group (9%), P = NS. Follow-up (excluding immediate postoperative deaths) was 30 months (range, 1—95).
Subgroups analyses According to TIPS patency status Results of comparison of TIPS group patients with occluded versus patent stents (n = 7 and 65, respectively) and versus
control group are shown in Table 4. Venous collateral circulation was less extensive in patients whose stents were patent at the time of LT. This difference was not observed for patients with occluded stents. The need for portocaval anastomosis was more frequent in the TIPS groups regardless of stent status (patent vs. occluded). Total ascites volume during the first week was greater only in patients with occluded TIPS. No difference in ascites volume was observed for patients with patent TIPS at the time of LT.
According to TIPS misplacement Patients with stent misplacement (all locations, n = 23) were compared to patients with normally placed TIPS (n = 49) and to patients in the control group (n = 136) with regard to transfusion requirements, operative times, ascites volume at the time of opening of the abdominal cavity and total ascites volume during the first week. No statistical significant difference was found with regard to any of these parameters. Performance of inferior vena cava clamping in patients with stent misplacement (n = 7) did not significantly modify any of these parameters.
According to TIPS indications We performed a comparison with regard to venous collateral circulation, ascites at opening and during the first week, creatinine at POD 7 and requirement for a portosystemic shunt between subgroups according to TIPS indications: TIPS for refractory ascites as a bridge for LT (n = 25), TIPS for gastrointestinal bleeding as a bridge for LT (n = 12), TIPS set up before LT indication (n = 35). There was no difference between groups, apart from the requirement for intraoperative portosystemic shunt, which was more frequent if the TIPS were placed as a bridge for refractory ascites or gastrointestinal bleeding.
TIPS before liver transplantation Table 3
159
Postoperative course: comparison between TIPS and control groups. TIPS group (n = 72)
Control group (n = 136)
P
AST peak (UI/mL), (N < 35) ALT peak (UI/mL), (N < 45)
456 (29—8437) 364 (49—8206)
NS NS
Creatinine on POD 7 (mol/L) Prothrombin time on POD 5 (%) Days necessary for factor V > 65% Overall ascites during first week (L)
96.5 (37—387) 70 (30—100) 3 (1—22) 7.6 (0—64) [10.9 ± 2.6] 5 (8%) 5 (7%) 1 (1%) 2 (3%) 4 (6%) 7 (10%) 2 (3%) 10% 5 (7%)
285 (11—7110) 294.5 (31—6203) 86 (44—362) 69 (2—100) 3 (0—15) 6.9 (0—28) [8.1 ± 2.4] 5 (4%) 4 (3%) 6 (4%) 3 (2%) 19 (14%) 17 (13%) 5 (4%) 13% 4 (3%)
Hemorrhage requiring transfusion Ascitis over 1 month Acute renal failure requirinq postoperative extra-renal epuration Surgical or radiological cavoplasty Acute graft rejection Infectious complications Thrombotic complications 1-year mortality rate Re-transplantation
NS NS NS 0.036 NS NS NS NS NS NS NS NS NS
POD: postoperative day; NS: not statistically significant. Significant results are in bold font.
Discussion This study shows that TIPS is a safe procedure for the treatment of portal hypertension in end-stage cirrhotic patients awaiting LT. Despite requiring intra-operative portocaval anastomosis more often, prior TIPS did not have a detrimental effect on intra-operative outcomes of LT, nor improved the conditions of the procedure. Also, TIPS had no impact either on postoperative hepatic and renal functions or on mortality rate. These results are in line with those reported previously (Table 5). Most studies have shown no difference between patients with and without prior TIPS with regard to postoperative complications and in-hospital stays. One exception was the study of Tripathi et al. [9] who reported a lower rate of pulmonary infection, a higher rate of extra-renal epuration, and a longer in-hospital stay (but not in ICU) in TIPS patients but who observed no difference regarding postoperative course. Valdivieso et al. [16] as well reported more transfusions and a longer operative time in the TIPS group. Similarly, the only difference noted in graft and survival rates was a better 1-year patient survival rate in the TIPS group as described by Guerrini et al. [7]. In the present study, we focused on the impact of TIPS occlusion or misplacement. The intra-operative assessment of venous collateral circulation was correlated with TIPS patency: this subjective criterion was part of a systematic checklist after opening and was performed by 3 experienced surgeons, decreasing inter-individual bias. Total ascites volume during the first week was greater in the TIPS group, but this is to be attributed only to occluded TIPS, as shown in the subgroups analyses. However, it should be noted that we did not routinely perform intra-operative hemodynamic measurements; therefore, the rate of shunt dysfunction might have been slightly underestimated.
A comparison between bare stents and PTFE-covered stents could not be performed, since there was very few PTFE-covered stents. However, if further studies confirm a benefit of covered stents on occlusion rate [5], this problem should less occur with the wider use of covered TIPS. Two major issues in the transplantation surgical technique may be influenced by the presence of a stent: • the need of a transient portocaval anastomosis [14,15]; • the interruption of the vena cava flow. If the TIPS is patent, there is less collateral venous circulation; and triad clamping can be made difficult by splanchnic hyperemia and hemodynamic instability. In this case, a portocaval anastomosis is performed during LT. In the literature, the reported need of temporary portocaval shunt placement has varied, up to 66% depending on the centre [9]. The rate of portocaval anastomosis is this series was 25% of the patients with TIPS, which is sharply lower than the 65% reported in our series previously [11]. If the TIPS is misplaced, a total inferior vena cava clamping may be necessary, whereas we usually perform LT with a lateral clamping in order to preserve the caval flow. In most cases, TIPS devices should be placed beyond the portal bifurcation proximal to the hepatic vein—caval junction, as proposed by Guerrini et al. [7]. Misplacement occurred in one third of the cases in this series. In the literature, the occurrence of stent misplacement, an albeit poorly defined parameter, has been ranged from 20% [10] to 66% [17] of the cases. In our series, stent misplacement was observed in 32% of the cases. As reported by Guerrini et al. [7], no complications were attributable to stent misplacement. As some patients’ general state will be greatly improved by TIPS insertion, their time on the waiting list can extend (mean waiting time 7.9 months [0.2—74.5]). HCC being one
160
Table 4
Intra-operative and postoperative main criteria: subgroups comparisons between occluded TIPS, patent TIPS, and control groups.
Venous collateral circulation None Moderate Severe Extensive Transfusion Red blood cells Platelets Plasma Autotransfusion Operative times Explant time (min) Total operative duration (h) Ascites at opening of abdominal cavity (L) Portosystemic shunt Creatinine at POD 7 (mol/L) Overall ascites during 1st week (L) Hemorrhage requiring transfusion Prolonged ascites (1 mo) Acute renal failure requiring extra-renal epuration
Occluded TIPS (1) (n = 7)
Patent TIPS (2) (n = 65)
Control group (3) (n = 136)
P between the 3 groups
P between (1) and (2)
P between (1) and (3)
P between (2) and (3)
2 1 1 3
(29%) (14%) (14%) (43%)
19 (29%) 33 (51%) 10 (15%) 3 (5%)
12 46 39 39
< 0.001 0.028 NS < 0.001
NS NS
NS NS
< 0.001 0.030
0.010
NS
< 0.001
5 0 8 5
(0—7) (0—6) (0—20) (0—13)
3 1 8 4
3 (0—15) 1 (0—25) 10 (0—28) 5 (0—24)
NS
0.043
0.034
NS
< 0.001
NS
105 (95—195) 5.7 (5—7.3) 0 (0—5) [1.3 ± 2.2] 3 (43%) 95 (69—342) 10.1 (0—63) [18.4 ± 22.2] 0 0 0
(0—12) (0—18) (0—25) (1—21)
120 (48—260) 5.2 (3.5—9.0) 0 (0—14) [1.2 ± 2.7] 15 (23%) 97 (37—387) 7.3 (0—64) [10.1 ± 11.9] 5 (8%) 5 (8%) 1 (2%)
(9%) (34%) (29%) (29%)
131 (55—384) 5.5 (3—10) 0 (0—11) [1.5 ± 2.4] 15 (11%) 86 (44—362) 6.9 (0—28) [8.1 ± 2.4] 5 (4%) 4 (3%) 6 (4%)
NS NS NS NS NS NS NS NS 0.013 NS 0.008 NS NS NS
POD: postoperative day; NS: not statistically significant. Significant results are in bold font.
L. Barbier et al.
Main studies comparing TIPS vs no TIPS before LT.
Authors
Period
Groups (n)
Complications of TIPS at time of LT
Portocaval shunt or bypass
Blood loss and operative time
Postoperative complications
Hospital stay
Other criteria
Survival
Guerrini et al., 2009 [7]
1993—2007
TIPS: 61 Cont: 591
28% misplaced
TIPS: 31% Cont: 8% (P = 0.01)
ND
ND
ND (ICU stay)
Patient survival better in TIPS group at 1 year ND in patient and graft survivals at 3 and 5 years
Moreno et al., 2003 [8] Tripathi et al., 2002 [9]
1996—2002
TIPS: 26 Cont: 50 TIPS: 29 Cont: 53
18% occluded 52% misplaced 18%: occluded 21%: technical complications due to TIPS
?
ND
ND
ND
If displacement: ND in intraand postoperative, except longer bypass time during LT —
TIPS: 66% Cont: 68% (P = NS)
ND
TIPS: ↓pulmonary infection, ↑dialysis
ND for ICU stay TIPS: ↑hospital stay (41 vs 26 days, P = 0.005)
Zhou et al., 2002 [10]
?
TIPS: 5 Cont: 54
?
ND
TIPS: no complications
?
Castellani et al., 2001 [11] Dell’Era et al., 2005 [21]
1993—1999
TIPS: 31 Cont: 55
20% (n = 1) misplaced 3%: occluded
More transfusion requirements if technical complication due to TIPS. TIPS did not affect graft function —
ND
ND
ND
—
?
1992—2000
? TIPS: 17 Cont: 45 Surgical shunts: 28
TIPS: 65% Cont: 36% (P = NS) ?
ND
ND
ND
ND in patient and graft survival
Chui et al., 2000 [17]
1994—1998
TIPS: 9 Cont: 178
?
ND
?
?
Surgical shunts affecting hepatic hilum have a negative impact on LT —
1993—1999
77%: 1 occluded 6 misplaced
TIPS before liver transplantation
Table 5
ND in patient survival 1-year patient and graft survivals identical
?
?
161
162
Table 5 (Continued) Authors
Period
Groups (n)
Complications of TIPS at time of LT
Portocaval shunt or bypass
Blood loss and operative time
Postoperative complications
Hospital stay
Other criteria
Survival
Valdivieso et al., 2012 [16]
1996— 2010
TIPS: 49 Cont: 776
33% misplaced 25% partially or totally occluded
No
ND
ND
—
ND
Present study
1996—2008
TIPS: 72 Cont: 136
32% misplaced 10% occluded
TIPS: 25% Cont: 11% (P = 0.016)
More transfusions and longer operative time in TIPS group ND
ND
ND
ND in case of migration In case of occlusion: more venous collateral circulation and postoperative ascites, ND in complications rate
ND in patient survival at 1 year
TIPS: transjugular intrahepatic portosystemic shunting; LT: liver transplantation; ND: not different; Cont: control group; ICU: intensive care unit; NS: not statistically significant.
L. Barbier et al.
TIPS before liver transplantation of the main causes of patient dropout from LT waiting lists [18], the question of a higher incidence of HCC in TIPS patients as rose by Banares et al. [19] becomes important. In our series, HCC was a contra-indication to TIPS insertion. In 2 cases, TIPS were set up in emergency for gastrointestinal bleeding and HCC was not known previously. For other patients with HCC in the TIPS group, the TIPS were inserted before HCC was diagnosed and LT indicated. However, in our experience, when considered independently from others known risk factors, TIPS insertion was not associated with an increased risk of HCC [20]. Alike, the recurrence rate of HCC after LT was not different between TIPS group and control group (P = 0.652). In any case, a careful screening for HCC should always be performed before TIPS set up. In conclusion, TIPS insertion can be proposed to patients with symptomatic portal hypertension awaiting liver transplantation. Shunt misplacement or occlusion is not associated with higher intra-operative or postoperative complication rates. In case of occlusion, TIPS revision should be proposed in order to keep the beneficial effect on portal hypertension.
Disclosure of interest
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[8]
[9]
[10]
[11]
[12]
[13]
[14]
The authors declare that they have no conflicts of interest concerning this article. [15]
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transplantation for the outcome posttransplantation. Am J Transplant 2009;9:192—200. Moreno A, Meneu JC, Moreno E, Fraile M, García I, Loinaz C, et al. Liver transplantation and transjugular intrahepatic portosystemic shunt. Transplant Proc 2003;35:1869—70. Tripathi D, Therapondos G, Redhead DN, Madhavan KK, Hayes PC. Transjugular intrahepatic portosystemic stent-shunt and its effects on orthotopic liver transplantation. Eur J Gastroenterol Hepatol 2002;14:827—32. Zhou GW, Cai WY, Li HW, Zhu Y, Dodson F, Fung JJ. Transjugular intrahepatic portosystemic shunt for liver transplantation. Hepatobiliary Pancreat Dis Int 2002;1:179—82. Castellani P, Campan P, Bernardini D, Moulin G, Bartoli JM, Le Treut YP, et al. Is transjugular intrahepatic portosystemic shunt really deleterious for liver transplantation issue? A monocentric study on 86 liver transplanted patients. Transplant Proc 2001;33:3468—9. Francoz C, Belghiti J, Castaing D, Chazouillères O, DuclosVallée JC, Duvoux C, et al. Model for end-stage liver disease exceptions in the context of the french model for end-stage liver disease score-based liver allocation system. Liver Transpl 2011;17:1137—51. Rössle M, Gerbes AL. TIPS for treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. Gut 2010;59:988—1000. Belghiti J, Noun R, Sauvanet A, Durand F, Aschehoug J, Erlinger S, et al. Transplantation for fulminant and subfulminant hepatic failure with preservation of portal and caval flow. Br J Surg 1995;82:986—9. Figueras J, Llado L, Ramos E, Jaurrieta E, Rafecas A, Fabregat J, et al. Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study. Liver Transpl 2001;7:904—11. Valdivieso A, Ventoso A, Gastaca M, Bustamante J, Aguinaga A, Ruiz P, et al. Does transjugular intrahepatic portosystemic influence the outcome of liver transplantation? Transpl Proc 2012;44:1505—7. Chui AK, Rao AR, Waugh RC, Mayr M, Verran DJ, Koorey D, et al. Liver transplantation in patients with transjugular intrahepatic portosystemic shunts. Aust N Z J Surg 2000;70:493—5. Pleguezuelo M, Germani G, Gurusamy K, Calvaruso V. Dropout on the liver transplantation waiting list in a MELD-based allocation model. Systematic review and meta-analysis. J Hepatol 2011;50(Suppl. 1):S297 [abstract]. Banares R, Nunez O, Escudero M, Fernández C, Vaquero J, Beceiro I, et al. Patients with cirrhosis and bare-stent TIPS may have increased risk of hepatocellular carcinoma. Hepatology 2005;41:566—71. Borentain E, Ananian P, Garcia S, Hendon S, Barrantes C, BottaFridlund D, et al. Does transjugular intrahepatic portosystemic shunt increase hepatocellular carcinoma risk in patients with cirrhosis? Pathological study from explanted livers. J Hepatol 2013;44(Suppl. 2):S98. Dell’Era A, Grande L, Barros-Schelotto, Turnes J, Fuster J, Charco R, et al. Impact of prior portosystemic shunt on outcome of liver transplantation. Surgery 2005;137:620—5.
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ORIGINAL ARTICLE
Impact of transjugular intrahepatic portosystemic shunting on liver transplantation: 12-year single-center experience Louise Barbier a,d,∗, Jean Hardwigsen a,d, Patrick Borentain b,d, Nicolas Biance a,d, Amine Daghfous a,d, Guillaume Louis c,d, Danielle Botta-Fridlund b,d, Yves-Patrice Le Treut a,d a
Department of Digestive Surgery and Liver Transplantation, AP—HM, Hôpital La Conception, 13005 Marseille, France b Department of Hepato-Gastro-Enterology, AP—HM, Hôpital La Conception, 13005 Marseille, France c Department of Radiology, AP—HM, Hôpital La Timone, 13005 Marseille, France d Aix-Marseille University, 13284 Marseille, France Available online 29 October 2013
Summary Background: The purpose of this study was to assess the impact of transjugular intrahepatic portosystemic shunting (TIPS) on liver transplantation (LT). Methods: Seventy-two patients transplanted after TIPS insertion between 1996 and 2008 were compared with 136 matched patients transplanted without prior TIPS. Results: At time of LT, 10% of the TIPS were occluded and 32% were misplaced. Shunt removal was difficult in 17% of the TIPS patients and required vena cava clamping in 10%. Collateral venous circulation was less extensive and intra-operative portocaval anastomosis was required more frequently in the TIPS group. No significant difference in transfusion requirements and operative times were observed between the two groups. Postoperatively, liver and renal function tests, in-hospital stay, graft rejection, re-transplantation and 1-year mortality rates were not statistically different. Ascites volume in the first week was greater in the TIPS group (7.6 L vs 6.9 L, P = 0.036). In the TIPS group, ascites and collateral circulation were greater if the shunt was occluded at the time of LT. Shunt misplacement or occlusion was not associated with higher intra-operative or postoperative complication rates. Conclusion: TIPS did not impair LT and can provide a safe bridge for LT in the end-stage cirrhotic patients. © 2013 Elsevier Masson SAS. All rights reserved. ∗ Corresponding author. Department of General Surgery and Liver Transplantation, Hôpital La Conception, 147, boulevard Baille, 13005 Marseille, France. Tel.: +33 4 91 38 36 58; fax: +33 4 91 36 16 55. E-mail addresses: [email protected], [email protected] (L. Barbier).
2210-7401/$ – see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.clinre.2013.09.003
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Introduction In the past decade, a shortage of donors and expanding indications, e.g. hepatocellular carcinoma (HCC), have increased the liver transplantation (LT) waiting list time of end-stage cirrhotic patients [1]. As a result, prevention and treatment of cirrhosis-related complications have become increasingly important. Transjugular intrahepatic portosystemic shunt (TIPS) was first proposed by Rössle et al. [2]. The goal of TIPS is to create a low-resistance channel of circulation by deployment of an expandable metal or, more recently, polytetrafluoroethylene (PTFE) covered stent between the hepatic vein and intrahepatic portion of the portal vein. The main indications are refractory or recurrent variceal bleeding, refractory ascites, and more marginally hepatorenal syndrome, hepatic hydrothorax, Budd—Chiari syndrome, and veno-occlusive disease [3,4]. Complications of TIPS may occur during the procedure, e.g. extra hepatic portal vein or bile duct or arterial lacerations/punctures, or during the postoperative period, e.g. heart failure (< 10%), acute hepatic failure, hepatic encephalopathy (up to 40%) and shunt dysfunction related to stenosis or occlusion (up to 90% with uncovered stents [3] and 40% with covered stents [5]). The risk of these complications must be offset by the benefits of the procedure, i.e., the prevention of portal hypertension-associated complications, improvement of general and nutritional state [6]. Hence, TIPS insertion has been proposed as a bridge to LT in patients with end-stage liver disease [7—11]. Access to LT has become difficult for patients with refractory ascites and a low Model For End-Stage Liver Disease (MELD) score since the introduction of MELD score in the graft allocation system. In France, refractory ascites and a MELD score < 15 is a condition corresponding to MELD score exception [12]. However, in the absence of contra-indications (advanced liver insufficiency, portal vein thrombosis, past episodes of encephalopathy, heart failure), TIPS insertion should be proposed as a first-line treatment [2]. By improving renal function including in hepatorenal syndrome [13], TIPS improve the patients’ condition and should extend the delay before they eventually require LT. In this setting, the impact of TIPS on intra-operative and postoperative outcomes of LT is a major issue. Most investigators have concluded that TIPS is useful and safe before LT, but only few previous studies [7,9,11] have involved large patient populations. Yet, some authors have reported that intra-operative portocaval shunting is required more often in patients undergoing LT after TIPS. Other questions have been raised about the consequences of stent occlusion and/or misplacement. While misplacement does not appear to unfavorably impact on blood products transfusions and patient and graft survivals in one study [7], consequences of occluded TIPS have never been studied. The purpose was to describe the impact of TIPS on intraoperative and postoperative outcomes of LT based on our 12-year experience, with a specific interest in misplaced and occluded subgroups.
L. Barbier et al.
Patients and methods After obtaining the approval of the Institutional Review Board of La Conception Hospital, data from the files of patients who underwent LT between 1996 and 2008 were retrospectively analyzed.
Patients From 1996 to 2008, 402 LT were performed in our centre. All cirrhotic patients who underwent orthotopic LT after TIPS (n = 72, 18%) have been included in the TIPS group. Patients who underwent re-transplantation and previous surgical portosystemic shunt were not included. A control group (n = 136) matched in the proportion of 2 to 1 for age, gender and Child-Pugh score was compiled by including cirrhotic patients who underwent LT without prior TIPS during the same time period.
TIPS All TIPS procedures were performed by the same team of experienced radiologists at La Timone Hospital in Marseille. Sixty-six (92%) of the stents were bare stents; PTFE-covered stents were occasionally used from 2004. Stent patency was routinely assessed by Doppler ultrasound before LT with the evaluation of specific parameters including color-Doppler, angle corrected velocity measurements in the main portal vein and the three segments of the shunt, and flow direction in the controlateral portal vein. Stent misplacement was defined as a protrusion of the device into the suprahepatic segment of inferior vena cava and/or below the portal vein bifurcation. Stent occlusion was defined as the absence of blood flow assessed by Doppler ultrasound within the shunt. In case of recurrence of PHT symptoms and occlusion of the TIPS at Doppler ultrasound, an angiography with shunt recanalization by transjugular approach was attempted.
LT and operative data Three senior transplant surgeons at La Conception Hospital in Marseille performed all the LT procedures. In all cases, the procedure consisted of orthotopic LT with conservation of the vena cava and piggyback technique. No venovenous bypass was performed. The first step of the LT procedure was exploration with assessment of ascites volume upon opening of the abdominal cavity and of venous collateral circulation that was scored on a scale of ‘‘0’’ (none) to 3 (extensive). Three TIPS-related parameters, i.e., misplacement, patency and removal difficulty, were also assessed. Portocaval anastomosis was performed [14,15] only after failure of triad clamping in case of splanchnic hyperemia or hemodynamic intolerance. Antibioprophylaxis was performed according to the hospital guidelines. Operative duration was expressed as explant time, i.e., time from skin incision to ablation of native liver and total procedure time, i.e., time from skin incision to closure.
TIPS before liver transplantation
157
Postoperative course
Results
Post-LT management including immunosuppressant regimen (as per the department policy), antibioprophylaxis, and thrombosis prevention was identical in the TIPS and control groups. Various postoperative factors potentially affected by TIPS were checked. Clinical parameters included total ascites volume in first week, prolonged ascites (> 1 month), and hemorrhage requiring transfusions. Laboratory values included acute renal failure requiring extra-renal epuration, cytolysis peaks, plasmatic creatinine on postoperative day (POD) 7, prothrombin time on POD 5, and days required for factor V to reach 65%. The need for post-LT cavoplasty (surgical or interventional radiological), acute graft rejection, re-transplantation, in-hospital stay and 1-year mortality were noted. The native liver specimen was examined for the presence of unsuspected HCC (incidentaloma).
TIPS and control groups
Statistical analysis Statistical analysis was performed using the GraphPad Prism version 5 software package. Probability values < 0.05 were considered to be statistically significant. Comparison of data was performed using the Fisher’s two-tailed exact test for qualitative variables and the unpaired two-tailed t-test for quantitative variables. For comparison of more than 2 groups, the chi-square test, one-way ANOVA analysis of variance and Bonferroni’s multiple comparison test were used. The results were expressed as medians with ranges, and mean ± standard deviation of the mean in square brackets if required. In tables, the values indicate medians with ranges for quantitative variables and number of cases (rate) for qualitative variables.
Table 1
The characteristics of patients in the two groups are listed in Table 1. As they were matched for age, gender and ChildPugh score, these items did not differ between groups. The frequency of alcoholic cirrhosis was higher and that of viral cirrhosis was lower in the TIPS group. The frequency of HCC (pre-LT diagnosis) was higher in the TIPS group. The difference in waiting list time was not statistically significant between the two groups.
TIPS procedures Indications for TIPS (n = 72) included upper gastrointestinal bleeding in 28 patients (39%), refractory ascites in 41 (57%) and hepatorenal syndrome in 3 (4%). The median interval between TIPS and LT was 7.9 months (0.2—74.5). Before LT, 2 (3%) patients required repeat TIPS and 16 (22%) required TIPS revision (dilatation and intra-TIPS stenting). At the time of LT, 5 (7%) patients presented documented TIPS occlusion due to thrombosis. In all but one case of occlusion, revision attempts failed; as the patients were already listed for LT, a new TIPS insertion was not performed.
Liver transplantation Intra-operative findings are summarized in Table 2. Seven stents (10%) were non-functional due to clotting, including 5 detected before LT. Stent misplacement was observed in twenty-three patients (32%) with protrusion of the device into the suprahepatic segment of the inferior vena cava in 7 patients, protrusion below the portal vein bifurcation in 10, and protrusion at both sites in 6. Stent removal
Characteristics of patients.
Age (years) Male gender Cirrhosis etiology Alcohol Viral Hepatitis B or/and C Unknown origin Multiple origins Autoimmune cirrhosis Thesaurismosisa Hepatocellular carcinomab Child-Pugh score Waiting list duration (months)
TIPS group (n = 72)
Control group (n = 136)
P
51 (19—63) 55 (76%)
49 (15—64) 99 (73%)
NS NS
42 (58%) 14 (19%) 5 (7%) 7 (10%) 3 (4%) 1 (1%) 12 (17%) 10 (5—13) 4.3 (0.2—9.6)
56 (41%) 51 (38%) 6 (4%) 13 (10%) 3 (2%) 7 (5%) 9 (7%) 10 (5—14) 3.4 (0—17.1)
0.020 0.008 NS NS NS NS 0.029 NS NS
Indications for TIPS: before LT indication: n = 35 (49%); as a bridge to LT: n = 37 (51%): for refractory ascites (n = 25) and for gastrointestinal bleeding (n = 12); NS: not statistically significant. Significant results are in bold font. a Thesaurismosis: Wilson disease, hemochromatosis, glycogenesis. b HCC diagnosed before LT.
158 Table 2
L. Barbier et al. Intra-operative criteria: comparison between TIPS and control groups.
Ascites at opening of abdominal cavity (L) Venous Collateral Circulation None Moderate Severe Extensive Transfusion (units) Red blood cells Platelets Fresh frozen plasma Autotransfusion Surgery time Explant time (min) Total operative time (h) Intra-operative portocaval anastomosis
TIPS group (n = 72)
Control group (n = 136)
P
0 (0—14) [1.2 ± 2.6]
0 (0—11) [1.5 ± 2.4]
NS
21 (29%) 34 (47%) 11 (15%) 6 (8%)
12 46 39 39
< 0.001 NS 0.040 < 0.001
3 1 8 4
(0—12) (0—18) (0—25) (0—21)
119 (48—260) 5.3 (3.5—9) 18 (25%)
(9%) (33%) (29%) (29%)
3 (0—15) 1 (0—25) 10 (0—28) 5 (0—24)
NS NS NS NS
131 (55—384)
NS
5.5 (3—10) 15 (11%)
NS 0.016
NS: not statistically significant. Significant results are in bold font.
was difficult in 12 cases (17%) but complete extraction was achieved in all cases even in cases associated with extensive vein—wall encapsulation. In all cases with inferior vena cava involvement, TIPS removal was performed by total vena cava exclusion without venovenous shunt. Major venous collateral circulation (stages 2 and 3) was significantly less frequent in the TIPS group. There was no significant difference between the two groups with regard to either total procedure time or explant time. Requirement for blood-derived products was also statistically similar. Portocaval anastomoses were required more frequently in the TIPS group (25% vs 11%, P = 0.016). No TIPS-related surgical revision was required.
Postoperative recovery Postoperative outcomes are summarized in Table 3. No statistically significant difference was observed in any of the laboratory values measured. Total ascites volume during the first week was greater in the TIPS group. The median hospital stay was 20 days (range, 5—55) in the TIPS group and 25 days (range, 2—70) in the control group (P = 0.98). There was no difference between the two groups with respect to hemorrhage, acute renal failure, acute graft rejection, re-transplantation, and 1-year mortality. Incidental HCC on the liver specimens was discovered in 2 cases in TIPS group (3%) versus 11 cases in control group (9%), P = NS. Follow-up (excluding immediate postoperative deaths) was 30 months (range, 1—95).
Subgroups analyses According to TIPS patency status Results of comparison of TIPS group patients with occluded versus patent stents (n = 7 and 65, respectively) and versus
control group are shown in Table 4. Venous collateral circulation was less extensive in patients whose stents were patent at the time of LT. This difference was not observed for patients with occluded stents. The need for portocaval anastomosis was more frequent in the TIPS groups regardless of stent status (patent vs. occluded). Total ascites volume during the first week was greater only in patients with occluded TIPS. No difference in ascites volume was observed for patients with patent TIPS at the time of LT.
According to TIPS misplacement Patients with stent misplacement (all locations, n = 23) were compared to patients with normally placed TIPS (n = 49) and to patients in the control group (n = 136) with regard to transfusion requirements, operative times, ascites volume at the time of opening of the abdominal cavity and total ascites volume during the first week. No statistical significant difference was found with regard to any of these parameters. Performance of inferior vena cava clamping in patients with stent misplacement (n = 7) did not significantly modify any of these parameters.
According to TIPS indications We performed a comparison with regard to venous collateral circulation, ascites at opening and during the first week, creatinine at POD 7 and requirement for a portosystemic shunt between subgroups according to TIPS indications: TIPS for refractory ascites as a bridge for LT (n = 25), TIPS for gastrointestinal bleeding as a bridge for LT (n = 12), TIPS set up before LT indication (n = 35). There was no difference between groups, apart from the requirement for intraoperative portosystemic shunt, which was more frequent if the TIPS were placed as a bridge for refractory ascites or gastrointestinal bleeding.
TIPS before liver transplantation Table 3
159
Postoperative course: comparison between TIPS and control groups. TIPS group (n = 72)
Control group (n = 136)
P
AST peak (UI/mL), (N < 35) ALT peak (UI/mL), (N < 45)
456 (29—8437) 364 (49—8206)
NS NS
Creatinine on POD 7 (mol/L) Prothrombin time on POD 5 (%) Days necessary for factor V > 65% Overall ascites during first week (L)
96.5 (37—387) 70 (30—100) 3 (1—22) 7.6 (0—64) [10.9 ± 2.6] 5 (8%) 5 (7%) 1 (1%) 2 (3%) 4 (6%) 7 (10%) 2 (3%) 10% 5 (7%)
285 (11—7110) 294.5 (31—6203) 86 (44—362) 69 (2—100) 3 (0—15) 6.9 (0—28) [8.1 ± 2.4] 5 (4%) 4 (3%) 6 (4%) 3 (2%) 19 (14%) 17 (13%) 5 (4%) 13% 4 (3%)
Hemorrhage requiring transfusion Ascitis over 1 month Acute renal failure requirinq postoperative extra-renal epuration Surgical or radiological cavoplasty Acute graft rejection Infectious complications Thrombotic complications 1-year mortality rate Re-transplantation
NS NS NS 0.036 NS NS NS NS NS NS NS NS NS
POD: postoperative day; NS: not statistically significant. Significant results are in bold font.
Discussion This study shows that TIPS is a safe procedure for the treatment of portal hypertension in end-stage cirrhotic patients awaiting LT. Despite requiring intra-operative portocaval anastomosis more often, prior TIPS did not have a detrimental effect on intra-operative outcomes of LT, nor improved the conditions of the procedure. Also, TIPS had no impact either on postoperative hepatic and renal functions or on mortality rate. These results are in line with those reported previously (Table 5). Most studies have shown no difference between patients with and without prior TIPS with regard to postoperative complications and in-hospital stays. One exception was the study of Tripathi et al. [9] who reported a lower rate of pulmonary infection, a higher rate of extra-renal epuration, and a longer in-hospital stay (but not in ICU) in TIPS patients but who observed no difference regarding postoperative course. Valdivieso et al. [16] as well reported more transfusions and a longer operative time in the TIPS group. Similarly, the only difference noted in graft and survival rates was a better 1-year patient survival rate in the TIPS group as described by Guerrini et al. [7]. In the present study, we focused on the impact of TIPS occlusion or misplacement. The intra-operative assessment of venous collateral circulation was correlated with TIPS patency: this subjective criterion was part of a systematic checklist after opening and was performed by 3 experienced surgeons, decreasing inter-individual bias. Total ascites volume during the first week was greater in the TIPS group, but this is to be attributed only to occluded TIPS, as shown in the subgroups analyses. However, it should be noted that we did not routinely perform intra-operative hemodynamic measurements; therefore, the rate of shunt dysfunction might have been slightly underestimated.
A comparison between bare stents and PTFE-covered stents could not be performed, since there was very few PTFE-covered stents. However, if further studies confirm a benefit of covered stents on occlusion rate [5], this problem should less occur with the wider use of covered TIPS. Two major issues in the transplantation surgical technique may be influenced by the presence of a stent: • the need of a transient portocaval anastomosis [14,15]; • the interruption of the vena cava flow. If the TIPS is patent, there is less collateral venous circulation; and triad clamping can be made difficult by splanchnic hyperemia and hemodynamic instability. In this case, a portocaval anastomosis is performed during LT. In the literature, the reported need of temporary portocaval shunt placement has varied, up to 66% depending on the centre [9]. The rate of portocaval anastomosis is this series was 25% of the patients with TIPS, which is sharply lower than the 65% reported in our series previously [11]. If the TIPS is misplaced, a total inferior vena cava clamping may be necessary, whereas we usually perform LT with a lateral clamping in order to preserve the caval flow. In most cases, TIPS devices should be placed beyond the portal bifurcation proximal to the hepatic vein—caval junction, as proposed by Guerrini et al. [7]. Misplacement occurred in one third of the cases in this series. In the literature, the occurrence of stent misplacement, an albeit poorly defined parameter, has been ranged from 20% [10] to 66% [17] of the cases. In our series, stent misplacement was observed in 32% of the cases. As reported by Guerrini et al. [7], no complications were attributable to stent misplacement. As some patients’ general state will be greatly improved by TIPS insertion, their time on the waiting list can extend (mean waiting time 7.9 months [0.2—74.5]). HCC being one
160
Table 4
Intra-operative and postoperative main criteria: subgroups comparisons between occluded TIPS, patent TIPS, and control groups.
Venous collateral circulation None Moderate Severe Extensive Transfusion Red blood cells Platelets Plasma Autotransfusion Operative times Explant time (min) Total operative duration (h) Ascites at opening of abdominal cavity (L) Portosystemic shunt Creatinine at POD 7 (mol/L) Overall ascites during 1st week (L) Hemorrhage requiring transfusion Prolonged ascites (1 mo) Acute renal failure requiring extra-renal epuration
Occluded TIPS (1) (n = 7)
Patent TIPS (2) (n = 65)
Control group (3) (n = 136)
P between the 3 groups
P between (1) and (2)
P between (1) and (3)
P between (2) and (3)
2 1 1 3
(29%) (14%) (14%) (43%)
19 (29%) 33 (51%) 10 (15%) 3 (5%)
12 46 39 39
< 0.001 0.028 NS < 0.001
NS NS
NS NS
< 0.001 0.030
0.010
NS
< 0.001
5 0 8 5
(0—7) (0—6) (0—20) (0—13)
3 1 8 4
3 (0—15) 1 (0—25) 10 (0—28) 5 (0—24)
NS
0.043
0.034
NS
< 0.001
NS
105 (95—195) 5.7 (5—7.3) 0 (0—5) [1.3 ± 2.2] 3 (43%) 95 (69—342) 10.1 (0—63) [18.4 ± 22.2] 0 0 0
(0—12) (0—18) (0—25) (1—21)
120 (48—260) 5.2 (3.5—9.0) 0 (0—14) [1.2 ± 2.7] 15 (23%) 97 (37—387) 7.3 (0—64) [10.1 ± 11.9] 5 (8%) 5 (8%) 1 (2%)
(9%) (34%) (29%) (29%)
131 (55—384) 5.5 (3—10) 0 (0—11) [1.5 ± 2.4] 15 (11%) 86 (44—362) 6.9 (0—28) [8.1 ± 2.4] 5 (4%) 4 (3%) 6 (4%)
NS NS NS NS NS NS NS NS 0.013 NS 0.008 NS NS NS
POD: postoperative day; NS: not statistically significant. Significant results are in bold font.
L. Barbier et al.
Main studies comparing TIPS vs no TIPS before LT.
Authors
Period
Groups (n)
Complications of TIPS at time of LT
Portocaval shunt or bypass
Blood loss and operative time
Postoperative complications
Hospital stay
Other criteria
Survival
Guerrini et al., 2009 [7]
1993—2007
TIPS: 61 Cont: 591
28% misplaced
TIPS: 31% Cont: 8% (P = 0.01)
ND
ND
ND (ICU stay)
Patient survival better in TIPS group at 1 year ND in patient and graft survivals at 3 and 5 years
Moreno et al., 2003 [8] Tripathi et al., 2002 [9]
1996—2002
TIPS: 26 Cont: 50 TIPS: 29 Cont: 53
18% occluded 52% misplaced 18%: occluded 21%: technical complications due to TIPS
?
ND
ND
ND
If displacement: ND in intraand postoperative, except longer bypass time during LT —
TIPS: 66% Cont: 68% (P = NS)
ND
TIPS: ↓pulmonary infection, ↑dialysis
ND for ICU stay TIPS: ↑hospital stay (41 vs 26 days, P = 0.005)
Zhou et al., 2002 [10]
?
TIPS: 5 Cont: 54
?
ND
TIPS: no complications
?
Castellani et al., 2001 [11] Dell’Era et al., 2005 [21]
1993—1999
TIPS: 31 Cont: 55
20% (n = 1) misplaced 3%: occluded
More transfusion requirements if technical complication due to TIPS. TIPS did not affect graft function —
ND
ND
ND
—
?
1992—2000
? TIPS: 17 Cont: 45 Surgical shunts: 28
TIPS: 65% Cont: 36% (P = NS) ?
ND
ND
ND
ND in patient and graft survival
Chui et al., 2000 [17]
1994—1998
TIPS: 9 Cont: 178
?
ND
?
?
Surgical shunts affecting hepatic hilum have a negative impact on LT —
1993—1999
77%: 1 occluded 6 misplaced
TIPS before liver transplantation
Table 5
ND in patient survival 1-year patient and graft survivals identical
?
?
161
162
Table 5 (Continued) Authors
Period
Groups (n)
Complications of TIPS at time of LT
Portocaval shunt or bypass
Blood loss and operative time
Postoperative complications
Hospital stay
Other criteria
Survival
Valdivieso et al., 2012 [16]
1996— 2010
TIPS: 49 Cont: 776
33% misplaced 25% partially or totally occluded
No
ND
ND
—
ND
Present study
1996—2008
TIPS: 72 Cont: 136
32% misplaced 10% occluded
TIPS: 25% Cont: 11% (P = 0.016)
More transfusions and longer operative time in TIPS group ND
ND
ND
ND in case of migration In case of occlusion: more venous collateral circulation and postoperative ascites, ND in complications rate
ND in patient survival at 1 year
TIPS: transjugular intrahepatic portosystemic shunting; LT: liver transplantation; ND: not different; Cont: control group; ICU: intensive care unit; NS: not statistically significant.
L. Barbier et al.
TIPS before liver transplantation of the main causes of patient dropout from LT waiting lists [18], the question of a higher incidence of HCC in TIPS patients as rose by Banares et al. [19] becomes important. In our series, HCC was a contra-indication to TIPS insertion. In 2 cases, TIPS were set up in emergency for gastrointestinal bleeding and HCC was not known previously. For other patients with HCC in the TIPS group, the TIPS were inserted before HCC was diagnosed and LT indicated. However, in our experience, when considered independently from others known risk factors, TIPS insertion was not associated with an increased risk of HCC [20]. Alike, the recurrence rate of HCC after LT was not different between TIPS group and control group (P = 0.652). In any case, a careful screening for HCC should always be performed before TIPS set up. In conclusion, TIPS insertion can be proposed to patients with symptomatic portal hypertension awaiting liver transplantation. Shunt misplacement or occlusion is not associated with higher intra-operative or postoperative complication rates. In case of occlusion, TIPS revision should be proposed in order to keep the beneficial effect on portal hypertension.
Disclosure of interest
163
[8]
[9]
[10]
[11]
[12]
[13]
[14]
The authors declare that they have no conflicts of interest concerning this article. [15]
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