Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print March 24, 2004, 10.1148/radiol.2312021797
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2312021797v1
231/2/537    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ter Borg, P. C. J.
Right arrow Articles by Laméris, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ter Borg, P. C. J.
Right arrow Articles by Laméris, J. S.
(Radiology 2004;231:537-545.)
© RSNA, 2004

Vascular and Interventional Radiology

Transjugular Intrahepatic Portosystemic Shunts: Long-term Patency and Clinical Results in a Patient Cohort Observed for 3–9 Years

Pieter C. J. ter Borg, MD, Mirjam Hollemans, MD, Henk R. van Buuren, MD, PhD, Frank P. Vleggaar, MD, PhD, Michael Groeneweg, MD, PhD, Wim C. J. Hop, PhD and Johan S. Laméris, MD, PhD

1 From the Department of Gastroenterology and Hepatology (P.C.J.t.B., M.H., H.R.v.B., F.P.V., M.G.) and Department of Epidemiology and Biostatistics (W.C.J.H.), Erasmus MC, Dr. Molewaterplein 40, Room Ca 326, 3015 GD Rotterdam, the Netherlands; and Department of Radiology, Academic Medical Centre, Amsterdam, the Netherlands (J.S.L.). Received December 30, 2002; revision requested March 4, 2003; final revision received September 11; accepted October 21. Address correspondence to P.C.J.t.B. (e-mail: pterborg@zonnet.nl).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To retrospectively assess the outcome of transjugular intrahepatic portosystemic shunt (TIPS) placement in a nonselected group of consecutive patients.

MATERIALS AND METHODS: TIPS placement was attempted in 82 patients. Patients were followed up for at least 3 years according to a standard protocol that included repeated shunt evaluations. Fifty-four patients underwent TIPS placement for variceal bleeding, 24 for refractory ascites, and four for other indications. Recurrent bleeding, effect on ascites, long-term patency, development of encephalopathy, and survival and complication rates were evaluated with Kaplan-Meier survival analysis and Cox multivariate analysis.

RESULTS: TIPS placement was successful in 75 patients (91%). Mean follow-up lasted 29.4 months. Primary patency was 22% and 12%, primary-assisted patency was 67% and 46%, and secondary patency was 91% and 91% at 1- and 5-year follow-up, respectively. Nonalcoholic liver disease (P = .007) and increasing platelet counts (P = .006) independently predicted development of shunt insufficiency. The 1- and 5-year rates of recurrent variceal bleeding were 21% and 27%, respectively. In the majority of patients with refractory ascites, a beneficial effect of TIPS placement was observed. The risk for encephalopathy was 25% at 1-month follow-up and 52% at 3-year follow-up. The risk for chronic or severe intermittent encephalopathy was 15% at 1-year follow-up and 20% at 3-year follow-up. Serum creatinine levels (P = .001) and age (P = .02) were independent risk factors. Overall survival rate was 61%, 49%, and 42% at 1-, 3-, and 5-year follow-up, respectively. Age (P = .03), serum albumin level (P = .02), and serum creatinine level (P < .001) were independently related to mortality.

CONCLUSION: The risk for definitive loss of shunt function was 17% at 5-year follow-up, indicating that surveillance with shunt revision—when indicated—results in excellent long-term TIPS patency. TIPS placement effectively protects against recurrent bleeding.

© RSNA, 2004

Index terms: Hypertension, portal, 95.1268 • Liver, interventional procedures, 95.1268 • Shunts, protosystemic, 95.453 • Stents and prostheses, 95.1268


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
During the past decade, use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension increased. The clinical effectiveness of this approach has been documented extensively (1). In most studies, however, the duration of follow-up was relatively short, with mean or median follow-up times rarely exceeding 2 years (2,3).

Since TIPS placement was introduced into clinical practice in 1988 (4), it has been recognized that shunt dysfunction due to thrombosis or intimal hyperplasia is the Achilles’ heel of this procedure. Thus, the role of TIPS placement in the long-term management of complications of portal hypertension has been questioned (5,6). With regular follow-upand reintervention when indicated, however, excellent 2-year patency rates of up to 90% have been reported (7–10). With the exception of one study (11), however, the follow-up time in studies with Kaplan-Meier estimates of primary, primary-assisted, and secondary shunt patency did not exceed 18 months (7–10,12–17). Thus, the long-term patency of TIPS is not well defined, and it is not clear whether the development of shunt dysfunction is a chronic relentless problem or if its incidence decreases over time.

The aim of the present study was to retrospectively assess the outcome of TIPS placement in a nonselected group of consecutive patients who were followed up for at least 3 years according to a standard protocol that included repeated evaluations of shunt patency.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Nature of the Study
This was a retrospective study of patients who underwent treatment routinely and were observed according to a predefined protocol. Neither our institutional review board nor our national law required approval for this retrospective study. Informed consent was not required.

Study Population
From January 1992 until January 1998, TIPS placement was attempted in 82 patients. Follow-up data were recorded until January 2001. The cohort of patients in whom the procedure was technically successful was observed for a period of at least 3 years. Patient characteristics are presented in Table 1.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Patient Characteristics

 
TIPS Placement
The method used for TIPS placement has been described in detail elsewhere (18) and is only summarized here. Procedures were performed with general anesthesia. All patients received intravenous antibiotic prophylaxis (1.5 g of cefuroxime) 30 minutes before the procedure. During the first year we performed TIPS placement at our center, anticoagulation with intravenous heparin was started during the procedure and continued for 1 week. This policy was abandoned in June 1994 after we witnessed fatal gastric variceal bleeding during heparin administration in one patient who underwent TIPS placement for treatment of refractory ascites. Twenty-eight patients were routinely treated with heparin, whereas the remaining 54 patients were not.

Catheterization of the hepatic vein was performed through the right internal jugular vein. A needle was advanced through the liver parenchyma into a branch of the portal vein with ultrasonographic (US) and fluoroscopic guidance. A guide wire was then passed into the portal vein, and the parenchymatous tract was dilated with an angioplasty catheter. After balloon dilation, a balloon-expandable (Palmaz stent; Johnson & Johnson, Warren, NJ) or self-expandable (Wallstent; Schneider, Bulach, Switzerland) stent was introduced. Just before and after stent placement, pressure in the portal and caval veins at the level of the hepatic veins was recorded, and the pressure gradient was calculated. If necessary, additional balloon dilation was performed to reduce the pressure gradient to less than 12 mm Hg. In patients with variceal bleeding and persistent marked variceal perfusion after shunt placement, coil embolization was performed (J.S.L. and occasionally other interventional radiologists).

Follow-up Protocol
Assessment of stent function with Doppler US was performed 2, 7, and 30 days after TIPS placement, at 3-month intervals during the first year of follow-up, and every 6 months thereafter. Angiography was performed routinely at 6-month follow-up examinations and if stent dysfunction was suspected on the basis of clinical or US findings (J.S.L. and occasionally other interventional radiologists). US criteria for shunt dysfunction included the following: flow of less than 60 cm/sec, flow of more than 120 cm/sec along the entire stent, or absence of flow or reversal of intrahepatic portal flow direction in comparison with previous US images obtained after TIPS placement. Revision of the stent was performed when occlusion or stenosis was seen at angiography and when the portocaval pressure gradient was elevated, despite normal angiographic findings.

This protocol was modified in January 1997. From then on, patients underwent routine catheterization at 1- and 6-month follow-up. This change was made in an attempt to reduce the number of patients with shunt dysfunction at 6 months.

Clinical and Laboratory Data
Follow-up continued until January 2001 or until the patient died or underwent liver transplantation. Data for patients who were either lost to follow-up or who underwent orthotopic liver transplantation were censored (regarded as the end of follow-up) at the time of the last visit or at liver transplantation.

Definitions
Primary patency was defined as a patent stent without reintervention. Primary-assisted patency was defined as a patent stent after reintervention but without occlusion at any time. Secondary patency was defined as a patent stent after occlusion, with patency ending at the moment an untreated or untreatable occlusion was present (7). Shunt occlusion was defined as the absence of flow at US or angiography. Definitive shunt loss was defined as an untreated or untreatable shunt occlusion.

Complications were defined as clinical events observed within 30 days of TIPS placement that were certainly or possibly related to the procedure and required the adjustment of medical care (eg, prolonged stay in the intensive care unit or the hospital or treatment with antibiotics). Short-term complications occurred within 1 week of the procedure, whereas long-term complications occurred 1 week or more after the procedure. These complications did not include hepatic encephalopathy and shunt dysfunction, since these were recorded and analyzed separately. Variceal bleeding and recurrent bleeding were defined according to internationally accepted criteria (19,20). Only patients who underwent TIPS placement for treatment of variceal bleeding were analyzed for recurrent bleeding.

The effect of TIPS placement on ascites was assessed with US (J.S.L. and occasionally other radiologists) by using criteria suggested by Rossle et al (2). A complete response was defined as elimination of ascites, a partial response was defined as persisting ascites that did not require paracentesis, and an absence of response was defined as ascites that required paracentesis. Only patients who underwent TIPS placement for treatment of refractory ascites were assessed for its effect on ascites.

Hepatic encephalopathy was assessed according to criteria proposed by Opolon et al (21). Symptoms of grade I hepatic encephalopathy were lethargy, reversal of sleep pattern, and normal orientation. Symptoms of grade II hepatic encephalopathy were slurred speech, somnolence, inadequate behavior, difficult handwriting, and/or flapping tremor. Symptoms of grade III hepatic encephalopathy were disorientation in time, place, or person and/or precoma. Patients with grade IV hepatic encephalopathy were in a coma. Chronic encephalopathy was defined as clinical encephalopathy that did not respond to medical treatment and a protein-restricted diet. Severe intermittent encephalopathy was defined as disabling intermittent encephalopathy that persisted despite treatment.

Statistical Analysis
Data processing and analysis were performed by using SPSS version 9 software (SPSS, Chicago, Ill). The Student t test was used to analyze differences between groups. Encephalopathy, shunt patency, survival, and recurrent bleeding curves were created according to the Kaplan-Meier method and compared with results of the log-rank test. Cox regression analysis was performed to assess factors related to encephalopathy, shunt patency, and mortality. Logarithmic transformations of serum creatinine levels and platelet counts were used.

The following factors were included in a Cox univariate regression analysis of primary, primary-assisted, and secondary TIPS patency: age, sex, serum bilirubin and serum creatinine levels, platelet count, Child-Pugh score, presence of diabetes mellitus and/or ascites, alcoholic versus nonalcoholic cause, use of a self-expandable or balloon-expandable stent, portal pressure gradient, portal pressure and caval vein pressure before and after TIPS placement, and follow-up cohort (before or after the change in follow-up protocol).

The following factors were included in a Cox univariate analysis of encephalopathy: age, sex, indication (bleeding vs ascites), alcoholic versus nonalcoholic cause, serum bilirubin and serum creatinine levels, Child-Pugh score, presence of ascites, encephalopathy before and at TIPS placement, portal pressure gradient before and after TIPS placement, stent diameter, and follow-up cohort (before or after the change in follow-up protocol).

The following factors were included in a univariate regression analysis of survival: sex, age, presence of ascites, history of encephalopathy, indication (variceal bleeding vs other), platelet count, Child-Pugh score, follow-up cohort (before or after the change in follow-up protocol), and serum creatinine, serum albumin, and serum bilirubin levels.

The Cox proportional hazards model was applied to assess factors independently related to encephalopathy, patency, and mortality. We included factors that were significant or showed a trend toward statistical significance (P < .1) in the univariate analysis. Nonsignificant factors in the multivariate analysis were subsequently removed until factors with independent prognostic significance remained. A two-tailed P value less than or equal to .05 was considered to indicate a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Creation of a functional stent was achieved in 75 (92%) of the 82 patients.

Three unsuccessful procedures were performed in the 1st year, one in the 3rd year, one in the 4th year, and two in the 5th year after introduction of the technique. Reasons for failure were unsuccessful puncture of the portal venous system (n = 5), intraperitoneal bleeding due to perforation of the extrahepatic portal vein (n = 1), and stent occlusion during TIPS placement (n = 1). The mean duration of follow-up for all 75 patients with a successful procedure, including patients who died or underwent liver transplantation during follow-up, was 29.4 months ± 29.5 (range, 0.3–105.5 months). Patients (n = 22) still included in the study at the end of the follow-up period had been observed for a mean duration of 60.1 months ± 21.5. After 3 and 6 years, 32 and seven patients, respectively, were still being observed. Two patients were lost to follow-up at 1 and 32 months. Six patients underwent liver transplantation 1.3, 1.7, 3.3, 11.6, 26.5, and 73.5 months after TIPS placement, respectively.

Complications
Short-term complications occurred in 16 patients (Table 2) and were fatal in three. One patient died of heart failure, one of sepsis, and one of intraperitoneal bleeding. A long-term complication, sepsis, occurred 15 days after TIPS placement in one patient. Another potential complication, pulmonary hypertension, occurred 14 months after TIPS placement in one patient (22).


View this table:
[in this window]
[in a new window]

  		TABLE 2. Short-term Complications of TIPS Placement

 
Shunt Patency
The mean portocaval pressure gradient decreased from 15 mm Hg before TIPS placement to 7.3 mm Hg after TIPS placement (P < .001).

The median number of TIPS recatheterizations was one (range, 0–6), and the median number per patient follow-up year was one-half. Patency curves are shown in Figure 1. The primary patency rate was 22% at 1-year follow-up, 17% at 2-year follow-up, and 12% at 4- and 5-year follow-up. The primary-assisted patency rate was 67% at 1-year follow-up, 62% at 2-year follow-up, 51% at 4-year follow-up, and 46% at 5-year follow-up. The secondary patency rate was 91% at 1-year follow-up, 86% at 2-year follow-up, and 83% at 4- and 5-year follow-up. Angiographic confirmation of shunt occlusion was performed in six of nine patients with a definite occlusion.



View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Kaplan-Meier plot shows the primary (a), primary-assisted (b), and secondary (c) patency rates among 75 patients who underwent TIPS placement. In contrast to the low primary patency rate, the long-term secondary patency rate was 83% at 5-year follow-up.

 
The following factors were included in a Cox univariate regression analysis of patients with primary, primary-assisted, and secondary TIPS patency: age, sex, serum bilirubin and serum creatinine levels, platelet count, Child-Pugh score, diabetes mellitus and/or ascites, alcoholic versus nonalcoholic cause, use of a self-expandable or balloon-expandable stent, portal pressure gradient, portal pressure and caval vein pressure before and after TIPS placement, and follow-up cohort (before or after the change in follow-up protocol). Platelet count and alcoholic cause (P = .07) were found to be significant predictors of the primary patency rate. Multivariate analysis of these factors showed that both were independently related to shunt patency (Table 3). Thus, alcoholic cause and lower platelet count were predictive for the absence of shunt failure. No predictive factors were identified for the primary-assisted or secondary patency rate.


View this table:
[in this window]
[in a new window]

  		TABLE 3. Multivariate Analysis of Risk Factors

 
Additional angiography was performed 1 month after TIPS placement in all 18 patients included in the study who underwent TIPS placement in 1997. Five interventions were performed because angiography depicted shunt dysfunction.

Hepatic Encephalopathy
Fifteen (20%) patients experienced encephalopathy sometime before undergoing TIPS placement. At the time of TIPS placement, seven (9%) patients had clinical evidence of encephalopathy. In three of these patients, encephalopathy became a chronic problem, whereas it was transient in the others.

After TIPS placement, 37 (49%) patients developed a new episode of clinical encephalopathy. Of these 37 patients, grade I encephalopathy occurred in 12 (32%), grade II in 11 (30%), grade III in five (14%), and grade IV in five (14%). In four patients, the grade of encephalopathy was not recorded. In eight (22%) patients, no precipitating factor could be identified. Most patients were treated successfully with correction of the precipitating factors (eg, dehydration, infection, constipation, recurrent bleeding, and use of sleep medication) and administration of lactulose. Antibiotic treatment and/or a protein-restricted diet were instituted when symptoms persisted. Chronic or severe intermittent encephalopathy occurred in 12 patients (median age, 64 years). Of these 12 patients, nine died of hepatic failure, two died of infections, and one underwent liver transplantation.

The risk for encephalopathy was 25% at 1 month follow-up, 40% at 6-month follow-up, 44% at 1-year follow-up, 47% at 2-year follow-up, and 52% at 3-year follow-up (Fig 2, a). The risk for chronic or severe intermittent encephalopathy was 15% at 1-year follow-up, 18% at 2-year follow-up, and 20% at 3-year follow-up (Fig 2, b). There was no significant difference in shunt diameter between patients who developed encephalopathy after undergoing TIPS placement and those who did not (8.0 vs 9.5 mm, P = .25).



View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Kaplan-Meier plot shows the probability of developing hepatic encephalopathy (a) and chronic or severe intermittent hepatic encephalopathy (b) in 75 patients who underwent TIPS placement. Most cases of encephalopathy occurred within the first 6 months of follow-up.

 
The following factors were included in a Cox univariate analysis of encephalopathy: age, sex, indication (bleeding vs ascites), alcoholic versus nonalcoholic cause, serum bilirubin and serum creatinine levels, Child-Pugh score, presence of ascites, encephalopathy before and at TIPS placement, portal pressure gradient before and after TIPS placement, stent diameter, and follow-up cohort (before or after the change in follow-up protocol). Age, nonalcoholic cause, encephalopathy before and at TIPS placement, Child-Pugh score, and serum creatinine levels were found to be predictors of encephalopathy. Multivariate analysis showed that age, nonalcoholic cause, and encephalopathy at TIPS placement were independently related to development of encephalopathy after TIPS placement (Table 3). Alcoholic cause, younger age, and absence of hepatic encephalopathy before TIPS placement were predictive for remaining free of encephalopathy after TIPS placement.

Univariate analysis for chronic or severe intermittent encephalopathy showed that age, serum creatinine level, and encephalopathy prior to TIPS placement were predictive factors. Multivariate analysis revealed that age and serum creatinine level were independent predictors for the development of chronic or severe intermittent encephalopathy.

Recurrent Bleeding
Recurrent bleeding from varices and nonvariceal causes was observed in 10 (21%) and nine (19%) of the 48 patients, respectively, who successfully underwent TIPS placement for secondary prevention of variceal bleeding. In one patient, variceal recurrent bleeding occurred 48 months after the initial procedure; venography revealed total occlusion, and a new parallel TIPS was inserted. Variceal recurrent bleeding occurred within 6 months of TIPS placement (mean, 51 days; range, 1–173 days) in nine of 10 patients. In two of these patients, total shunt obstruction was due to thrombosis and intimal hyperplasia, respectively, and TIPS revision was performed. In another two patients, shunt stenosis without total obstruction was treated with balloon angioplasty.

In one patient with recurrent bleeding 1 day after TIPS placement, Doppler US showed normal TIPS function. TIPS catheterization was not performed, and the patient underwent endoscopic injection therapy. In the remaining four patients with variceal recurrent bleeding, portal venography showed no abnormalities, and portal-caval vein pressure gradients were below 12 mm Hg. Venography, however, showed the presence of patent collaterals—in particular, substantial persistent portal blood flow via the coronary vein in three patients and via the inferior mesenteric vein in one patient. The latter patient underwent TIPS placement for treatment of recurrent bleeding from anorectal varices. Embolization of the collaterals was performed in all four patients.

A second episode of recurrent gastroesophageal variceal bleeding occurred in two patients. In one patient, balloon dilation for shunt stenosis had been performed 6 days earlier after the first recurrence of hemorrhage. This patient was in very poor condition and died shortly afterward. In the other patient, TIPS function was normal, but portal venography showed persistent marked collateral blood flow. For technical reasons, embolization was unsuccessful. During the subsequent 5-year follow-up, this patient had no recurrences.

The 1-, 2-, and 5-year rates of recurrent bleeding from varices were 21%, 21%, and 27%, respectively (Fig 3). There was no significant difference in recurrent bleeding when analyzed according to the follow-up cohort either before or after the change in follow-up protocol. After the change in follow-up protocol, however, recurrent bleeding occurred in only one patient who refused further treatment after an early shunt occlusion.



View larger version (16K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3. Kaplan-Meier plot shows the probability of remaining free of recurrent bleeding in 48 patients who underwent TIPS placement for variceal bleeding. The majority of recurrent bleeding episodes occurred within 6 months of TIPS placement.

 
Ascites
TIPS were successfully introduced in all but one patient with refractory ascites. Table 4 shows the patient response to TIPS placement at 1-, 3-, 6-, 12-, and 36-month follow-up. At 6-month follow-up, 10 (43%) of 23 patients had died; at 36-month follow-up, 14 (61%) patients had died. Causes of death were liver failure (n = 7), renal failure that was apparent before TIPS placement (n = 2), variceal bleeding (n = 2), pneumonia (n = 2), and hepatocellular carcinoma (n = 1). Two patients underwent liver transplantation. Among the survivors, a complete or partial response was observed in the majority of patients. A complete or partial response was observed in nine of 11 patients and in seven of the nine surviving patients at 6- and 12-month follow-up, respectively. Diuretic therapy was reduced substantially in these patients.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Data on Clinical Course and Response to TIPS Placement for 23 Patients with Refractory Ascites

 
Survival
Two patients died within the first week after TIPS placement, one of hepatorenal syndrome and sepsis and the other—who was treated for refractory ascites—of massive gastric variceal bleeding while receiving intravenous heparin. During follow-up, 45 (60%) of 75 patients died. Causes of death were liver failure (n = 19, 42%), variceal bleeding (n = 4, 9%), and other causes (n = 22, 49%). The percentage of patients who survived TIPS placement was 88% at 1-month follow-up, 68% at 6-month follow-up, 61% at 1-year follow-up, 51% at 2-year follow-up, 49% at 3-year follow-up, and 42% at 5-year follow-up (Fig 4).



View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4. Kaplan-Meier plot shows the probability of survival after TIPS placement in 75 patients. Note the poor long-term prognosis, despite successful TIPS placement.

 
The following factors were included in a univariate regression analysis: sex, age, presence of ascites, history of encephalopathy, indication (variceal bleeding vs other), platelet count, Child-Pugh score, follow-up cohort (before or after the change in follow-up protocol), and serum creatinine, serum albumin, and serum bilirubin levels. Age, ascites, Child-Pugh score, and serum creatinine and serum albumin levels were all significant predictors of survival. Multivariate analysis of these factors with backward elimination showed that age and serum albumin and serum creatinine levels were related independently to mortality (Table 3).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
The results of the present study confirm that TIPS placement is not a single-step procedure and that repeated interventions are required to maintain function in the majority of patients. Our data also show, however, that efforts to maintain TIPS function can eventually result in good long-term patency and suggest that definitive shunt loss 3–4 years after placement is rare. We observed a 17% loss of shunt patency at 5-year follow-up. This may not be markedly different from the reported figures for surgical shunts, which ranged from 11% to 20% (23–28). Our data are compatible with earlier suggestions that in a subset of patients, pseudointimal proliferation may be a self-limiting process (10), and the necessity for shunt revisions may decrease over time (29).

To our knowledge, no generally accepted guidelines for shunt surveillance have emerged, and follow-up protocols differ from center to center (7,16,18). Most centers use both US and venography, but the optimal sequence and time intervals have yet to be established. In general, US is noninvasive, inexpensive, and simple, but it may have a lower sensitivity and specificity in the depiction of shunt dysfunction compared with angiography, which is an invasive and expensive procedure (30). Local experience and expertise are likely to be of decisive importance in the choice of the optimum protocol for a given center.

The follow-up protocol in the present study was changed in January 1997 to enable more frequent detection of shunt dysfunction at an early stage. Although there were no significant differences in survival rate, recurrent bleeding, shunt patency, and encephalopathy, follow-up for patients included in the study after the change in protocol was relatively short, and only 18 patients were observed after the change. In the period after January 1997, however, recurrent variceal bleeding occurred in only one patient with a known and untreated shunt occlusion, which suggests that the change in protocol might have been effective. Recent developments in US technology, such as contrast material–enhanced Doppler US and power Doppler US, might increase the value of this technique in the detection of shunt dysfunction (31,32).

When interpreting data on primary and secondary shunt patency, the influence of the type of surveillance method should be taken into account. It is conceivable that centers that use routine angiography are likely to perform more early reinterventions, resulting in lower primary patency rates. Thus, for the interpretation of the results of individual studies, reported secondary patency rates may be more informative.

Previous studies found a number of risk factors for developing shunt insufficiency, including diabetes mellitus (33), biliary venous fistulae (9,34), sex (33), age of more than 55–65 years (33), Child-Pugh score (35), low prothrombin time (18), high platelet count (18), portocaval pressure gradient greater than 18 mm Hg prior to TIPS placement (36), and portal venous pressure (37). We identified nonalcoholic liver disease and platelet count as risk factors for developing shunt dysfunction.

The role of platelets was not supported by the findings of a controlled trial in which the role of acetylsalicylic acid in the prevention of shunt occlusion was evaluated (38). In contrast, a marked reduction in the incidence of shunt stenosis was reportedly achieved with combined treatment with ticlopidine—a platelet aggregator inhibitor—and trapidil—a drug with antiplatelet-derived growth factor activity (39). Moderate consumption of alcohol, particularly red wine, has been reported to decrease the risk for peripheral (40), cardiovascular, and cerebrovascular arterial disease (41,42). Alcohol may also decrease the risk for venous thromboembolic events (43). One mechanism by which alcohol could have an effect on vascular disease is through inhibition of platelet reactivity (44).

Clearly, identification of risk factors for developing TIPS insufficiency has been far from consistent. The findings of this and other studies suggest that the absolute number of platelets (18) and platelet function (39) may be implicated. Further studies are needed to address the potential role of platelets and the medical modulation of platelet involvement. In addition, technical innovations, such as the introduction of less thrombogenic, covered, or drug-eluting stents, are important in attempting to find a solution to the critical problem of shunt obstruction (45–47).

Hepatic encephalopathy is an inherent problem of portosystemic shunt placement. Reported risk factors are age (18,48–50), bleeding (51), encephalopathy prior to the TIPS procedure (35,36,49), Child-Pugh score (35), nonalcoholic cause (51,52), sex (52), hypoalbuminemia (52), and portocaval pressure gradient of less than 10 mm Hg after TIPS placement (50). In the present study, risk factors for encephalopathy after TIPS placement were encephalopathy prior to TIPS placement, increased age, and nonalcoholic cause of the underlying liver disease. Increased age and encephalopathy prior to TIPS placement are well-recognized risk factors. The lower risk for encephalopathy in patients with alcoholic cirrhosis—which was also found by other researchers (52)—is difficult to explain, however, considering shunt patency in alcoholic patients was better and the incidence of subclinical encephalopathy in these patients may be higher (53). In approximately one-third of the patients with encephalopathy after TIPS placement, encephalopathy was chronic or present intermittently. Independent risk factors were increased serum creatinine levels and age older than 65 years. In patients older than 65 years and those with increased serum creatinine levels, indications for TIPS placement should be considered very carefully, and extra care should be taken to prevent, detect, and treat encephalopathy.

Our results for patients undergoing TIPS placement for treatment of refractory ascites are in agreement with previously reported data (54–59) and show that in a number of patients, TIPS may provide long-term control of previously refractory ascites. The general prognosis for patients with refractory ascites is grave, however, and reported 1-year survival rates after TIPS placement do not exceed 30%–50% (54–56,58). This emphasizes the fact that liver transplantation should always be the primary therapeutic approach for these patients. Two of our patients underwent TIPS placement while they had long-standing organic (eg, nonhepatorenal) kidney disease with renal insufficiency. TIPS placement was ineffective, and both patients died within 4 months. This experience is comparable to that reported by others (55,56,59) and confirms that in patients with chronic renal insufficiency (eg, those with a serum creatinine level higher than 200 µmol/L), TIPS placement is not a suitable treatment for refractory ascites.

Investigators in two studies (2,58) have compared TIPS placement with large-volume paracentesis, a procedure that is often regarded as the treatment of choice for refractory ascites. TIPS placement was found to have a beneficial effect on ascites. This was associated with an improvement in the rate of patients who survived without undergoing liver transplantation but was not associated with an increased risk for encephalopathy in the largest trial (2). Currently available data indicate that TIPS placement is a reasonable therapeutic option for patients with refractory ascites. Patients older than 60–65 years and those with chronic renal impairment are unlikely to benefit from TIPS placement, and repeated paracentesis seems to be a better treatment.

We found that 2-, 3- and 5-year survival rates were 51%, 49%, and 42%, respectively. Our data are highly comparable to the following data reported by other groups: 46%–60% survival rate at 2-year follow-up (11,16,60), 50% survival rate at 3-year follow-up (11), and 41% survival rate at 5-year follow-up (11). These findings emphasize the poor prognosis of patients with complications of advanced liver disease. On the other hand, it is rewarding that 40% of patients with otherwise difficult-to-treat or nonmanageable complications can be expected to survive for at least 5 years after TIPS placement.

The most important limitation of the present study may be the relatively small number of patients, especially those who survived for more than 3 years. The latter, however, is a characteristic of studies on the evaluation of therapeutic interventions in patients with advanced liver disease and complications of portal hypertension. Another weakness is the slight modification of the follow-up protocol during the study period.

In conclusion, after TIPS placement, regular surveillance with shunt revision when indicated can eventually result in excellent long-term patency. In our study, the risk for definitive shunt loss was 17% at 5-year follow-up. TIPS placement effectively protects against recurrent bleeding in the majority of patients with variceal bleeding. Recurrent variceal hemorrhage is usually due to shunt insufficiency, but persistent perfusion of portosystemic collaterals is another important cause. Severe encephalopathy can be expected to occur, particularly in patients older than 65 years and in those with renal impairment.


   FOOTNOTES
 
Abbreviation: TIPS = transjugular intrahepatic portosystemic shunt

Author contributions: Guarantors of integrity of entire study, all authors; study concepts and design, all authors; literature research, P.C.J.t.B., M.H., H.R.v.B.; clinical studies, all authors; data acquisition, P.C.J.t.B., M.H.; data analysis/interpretation, P.C.J.t.B., M.H., H.R.v.B., F.P.V., M.G.; statistical analysis, P.C.J.t.B., M.H., H.R.v.B., W.C.J.H.; manuscript preparation, P.C.J.t.B., M.H., H.R.v.B.; manuscript definition of intellectual content, editing, revision/review, and final version approval, all authors


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

  1. Rossle M, Siegerstetter V, Huber M, Ochs A. The first decade of the transjugular intrahepatic portosystemic shunt: state of the art. Liver 1998; 18:73-89.[Medline]
  2. Rossle M, Ochs A, Gulberg V, et al. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites. N Engl J Med 2000; 342:1701-1707.[Abstract/Free Full Text]
  3. Sanyal AJ, Freedman AM, Luketic VA, et al. The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts. Gastroenterology 1997; 112:889-898.[CrossRef][Medline]
  4. Richter GM, Palmaz JC, Noldge G, et al. The transjugular intrahepatic portosystemic stent-shunt: a new nonsurgical percutaneous method. Radiologe 1989; 29:406-411.[Medline]
  5. Casado M, Bosch J, Garcia-Pagan JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 1998; 114:1296-1303.[CrossRef][Medline]
  6. Meyer KM, Zibari GB, McMillan RW, et al. A retrospective study of the efficacy of transjugular intrahepatic portosystemic shunts. Am Surg 1996; 62:76-80.[Medline]
  7. LaBerge JM, Somberg KA, Lake JR, et al. Two-year outcome following transjugular intrahepatic portosystemic shunt for variceal bleeding: results in 90 patients. Gastroenterology 1995; 108:1143-1151.[CrossRef][Medline]
  8. Gschwantler M, Gebauer A, Rohrmoser M, et al. Clinical outcome 2 years after implantation of a transjugular intrahepatic portosystemic shunt for recurrent variceal bleeding. Eur J Gastroenterol Hepatol 1997; 9:15-20.[Medline]
  9. Saxon RS, Ross PL, Mendel-Hartvig J, et al. Transjugular intrahepatic portosystemic shunt patency and the importance of stenosis location in the development of recurrent symptoms. Radiology 1998; 207:683-693.[Abstract/Free Full Text]
  10. Sterling KM, Darcy MD. Stenosis of transjugular intrahepatic portosystemic shunts: presentation and management. AJR Am J Roentgenol 1997; 168:239-244.[Abstract/Free Full Text]
  11. Zhuang ZW, Teng GJ, Jeffery RF, Gemery JM, Janne d’Othee B, Bettmann MA. Long-term results and quality of life in patients treated with transjugular intrahepatic portosystemic shunts. AJR Am J Roentgenol 2002; 179:1597-1603.[Abstract/Free Full Text]
  12. Borsa JJ, Fontaine AB, Hoffer EK, et al. Retrospective comparison of the patency of Wallstents and Palmaz long-medium stents used for TIPS: transjugular intrahepatic portosystemic shunts. Cardiovasc Intervent Radiol 2000; 23:332-339.[CrossRef][Medline]
  13. Barange K, Peron JM, Imani K, et al. Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices. Hepatology 1999; 30:1139-1143.[CrossRef][Medline]
  14. Latimer J, Bawa SM, Rees CJ, Hudson M, Rose JD. Patency and reintervention rates during routine TIPSS surveillance. Cardiovasc Intervent Radiol 1998; 21:234-239.[CrossRef][Medline]
  15. Peron JM, Barange K, Otal P, et al. Transjugular intrahepatic portosystemic shunts in the treatment of refractory ascites: results in 48 consecutive patients. J Vasc Interv Radiol 2000; 11:1211-1216.[Medline]
  16. Stanley AJ, Jalan R, Forrest EH, Redhead DN, Hayes PC. Longterm follow up of transjugular intrahepatic portosystemic stent shunt (TIPSS) for the treatment of portal hypertension: results in 130 patients. Gut 1996; 39:479-485.[Abstract/Free Full Text]
  17. Textor HJ, Brensing KA, Wilhelm K, et al. TIPSS: Technische und klinische ergebnisse nach 4 jahren. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1998; 168:361-368.[Medline]
  18. Rossle M, Haag K, Ochs A, et al. The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding. N Engl J Med 1994; 330:165-171.[Abstract/Free Full Text]
  19. de Franchis R, Pascal JP, Ancona E, et al. Definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol 1992; 15:256-261.[CrossRef][Medline]
  20. de Franchis R. Developing consensus in portal hypertension. J Hepatol 1996; 25:390-394.[CrossRef][Medline]
  21. Opolon P, Rapin JR, Huguet C, et al. Hepatic failure coma (HFC) treated by polyacrylonitrile membrane (PAN) hemodialysis (HD). Trans Am Soc Artif Intern Organs 1976; 22:701-710.[Medline]
  22. van der Heijde RM, Lameris JS, van den Berg B, Wagenvoort CA, Hilvering C, van Buuren HR. Pulmonary hypertension after transjugular intrahepatic portosystemic shunt (TIPS). Eur Respir J 1996; 9:1562-1564.[Abstract]
  23. Mercado MA, Orozco H, Guillen-Navarro E, et al. Small-diameter mesocaval shunts: a 10-year evaluation. J Gastrointest Surg 2000; 4:453-457.[CrossRef][Medline]
  24. Rikkers LF, Burnett DA, Volentine GD, Buchi KN, Cormier RA. Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding: early results of a randomized trial. Ann Surg 1987; 206:261-271.[Medline]
  25. Kitano S, Iso Y, Hashizume M, et al. Sclerotherapy vs. esophageal transection vs. distal splenorenal shunt for the clinical management of esophageal varices in patients with child class A and B liver function: a prospective randomized trial. Hepatology 1992; 15:63-68.[CrossRef][Medline]
  26. Fischer JE, Bower RH, Atamian S, Welling R. Comparison of distal and proximal splenorenal shunts: a randomized prospective trial. Ann Surg 1981; 194:531-544.[CrossRef][Medline]
  27. Millikan WJ, Jr, Warren WD, Henderson JM, et al. The Emory prospective randomized trial: selective versus nonselective shunt to control variceal bleeding—ten year follow-up. Ann Surg 1985; 201:712-722.[Medline]
  28. Grace ND, Conn HO, Resnick RH, et al. Distal splenorenal vs. portal-systemic shunts after hemorrhage from varices: a randomized controlled trial. Hepatology 1988; 8:1475-1481.[Medline]
  29. Hidajat N, Vogl T, Stobbe H, et al. Transjugular intrahepatic portosystemic shunt: experiences at a liver transplantation center. Acta Radiol 2000; 41:474-478.[CrossRef][Medline]
  30. Owens CA, Bartolone C, Warner DL, et al. The inaccuracy of duplex ultrasonography in predicting patency of transjugular intrahepatic portosystemic shunts. Gastroenterology 1998; 114:975-980.[CrossRef][Medline]
  31. Furst G, Malms J, Heyer T, et al. Transjugular intrahepatic portosystemic shunts: improved evaluation with echo-enhanced color Doppler sonography, power Doppler sonography, and spectral duplex sonography. AJR Am J Roentgenol 1998; 170:1047-1054.[Abstract/Free Full Text]
  32. Uggowitzer MM, Kugler C, Machan L, et al. Value of echo-enhanced Doppler sonography in evaluation of transjugular intrahepatic portosystemic shunts. AJR Am J Roentgenol 1998; 170:1041-1046.[Abstract/Free Full Text]
  33. Shah SH, Lui HF, Helmy A, Redhead DN, Penny K, Hayes PC. Transjugular intrahepatic portosystemic stent-shunt insufficiency and the role of diabetes mellitus. Eur J Gastroenterol Hepatol 2001; 13:257-261.[CrossRef][Medline]
  34. Jalan R, Harrison DJ, Redhead DN, Hayes PC. Transjugular intrahepatic portosystemic stent-shunt (TIPSS) occlusion and the role of biliary venous fistulae. J Hepatol 1996; 24:169-176.[CrossRef][Medline]
  35. Sauer P, Theilmann L, Stremmel W, Benz C, Richter GM, Stiehl A. Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propranolol for variceal rebleeding. Gastroenterology 1997; 113:1623-1631.[CrossRef][Medline]
  36. Jalan R, Elton RA, Redhead DN, Finlayson ND, Hayes PC. Analysis of prognostic variables in the prediction of mortality, shunt failure, variceal rebleeding and encephalopathy following the transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage. J Hepatol 1995; 23:123-128.[CrossRef][Medline]
  37. Zuckerman DA, Darcy MD, Bocchini TP, Hildebolt CF. Encephalopathy after transjugular intrahepatic portosystemic shunting: analysis of incidence and potential risk factors. AJR Am J Roentgenol 1997; 169:1727-1731.[Abstract/Free Full Text]
  38. Theilmann L, Sauer P, Roeren T, et al. Acetylsalicylic acid in the prevention of early stenosis and occlusion of transjugular intrahepatic portal-systemic stent shunts: a controlled study. Hepatology 1994; 20:592-597.[CrossRef][Medline]
  39. Siegerstetter V, Huber M, Ochs A, Blum HE, Rossle M. Platelet aggregation and platelet-derived growth factor inhibition for prevention of insufficiency of the transjugular intrahepatic portosystemic shunt: a randomized study comparing trapidil plus ticlopidine with heparin treatment. Hepatology 1999; 29:33-38.[CrossRef][Medline]
  40. Vliegenthart R, Geleijnse JM, Hofman A, et al. Alcohol consumption and risk of peripheral arterial disease: the Rotterdam study. Am J Epidemiol 2002; 155:332-338.[Abstract/Free Full Text]
  41. Walsh CR, Larson MG, Evans JC, et al. Alcohol consumption and risk for congestive heart failure in the Framingham heart study. Ann Intern Med 2002; 136:181-191.[Abstract/Free Full Text]
  42. Gronbaek M, Deis A, Sorensen TI, Becker U, Schnohr P, Jensen G. Mortality associated with moderate intakes of wine, beer, or spirits. BMJ 1995; 310:1165-1169.[Abstract/Free Full Text]
  43. Pahor M, Guralnik JM, Havlik RJ, et al. Alcohol consumption and risk of deep venous thrombosis and pulmonary embolism in older patients. J Am Geriatr Soc 1996; 44:1030-1037.[Medline]
  44. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339:1523-1526.[CrossRef][Medline]
  45. Haskal ZJ, Davis A, McAllister A, Furth EE. PTFE-encapsulated endovascular stent-graft for transjugular intrahepatic portosystemic shunts: experimental evaluation. Radiology 1997; 205:682-688.[Abstract/Free Full Text]
  46. Nishimine K, Saxon RR, Kichikawa K, et al. Improved transjugular intrahepatic portosystemic shunt patency with PTFE-covered stent-grafts: experimental results in swine. Radiology 1995; 196:341-347.[Abstract/Free Full Text]
  47. Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346:1773-1780.[Abstract/Free Full Text]
  48. Cabrera J, Maynar M, Granados R, et al. Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage. Gastroenterology 1996; 110:832-839.[CrossRef][Medline]
  49. Sanyal AJ, Freedman AM, Shiffman ML, Purdum PP, 3rd, Luketic VA, Cheatham AK. Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study. Hepatology 1994; 20:46-55.[CrossRef][Medline]
  50. Riggio O, Merlli M, Pedretti G, et al. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: incidence and risk factors. Dig Dis Sci 1996; 41:578-584.[CrossRef][Medline]
  51. Rossle M, Deibert P, Haag K, et al. Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding. Lancet 1997; 349:1043-1049.[CrossRef][Medline]
  52. Somberg KA, Riegler JL, LaBerge JM, et al. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunts: incidence and risk factors. Am J Gastroenterol 1995; 90:549-555.[Medline]
  53. Groeneweg M, Quero JC, De Bruijn I, et al. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 1998; 28:45-49.[CrossRef][Medline]
  54. Forrest EH, Stanley AJ, Redhead DN, McGilchrist AJ, Hayes PC. Clinical response after transjugular intrahepatic portosystemic stent shunt insertion for refractory ascites in cirrhosis. Aliment Pharmacol Ther 1996; 10:801-806.[CrossRef][Medline]
  55. Ochs A, Rossle M, Haag K, et al. The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites. N Engl J Med 1995; 332:1192-1197.[Abstract/Free Full Text]
  56. Rees CJ, Rose JD, Record CO, et al. Transjugular intrahepatic portosystemic shunt: a limited role in refractory ascites. Eur J Gastroenterol Hepatol 1997; 9:969-973.[Medline]
  57. Quiroga J, Sangro B, Nunez M, et al. Transjugular intrahepatic portal-systemic shunt in the treatment of refractory ascites: effect on clinical, renal, humoral, and hemodynamic parameters. Hepatology 1995; 21:986-994.[CrossRef][Medline]
  58. Lebrec D, Giuily N, Hadengue A, et al. Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites—a randomized trial. French group of clinicians and a group of biologists. J Hepatol 1996; 25:135-144.
  59. Somberg KA, Lake JR, Tomlanovich SJ, LaBerge JM, Feldstein V, Bass NM. Transjugular intrahepatic portosystemic shunts for refractory ascites: assessment of clinical and hormonal response and renal function. Hepatology 1995; 21:709-716.[CrossRef][Medline]
  60. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000; 31:864- 871.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Arch SurgHome page
D. R. Elwood, J. J. Pomposelli, E. A. Pomfret, W. D. Lewis, and R. L. Jenkins
Distal Splenorenal Shunt: Preferred Treatment for Recurrent Variceal Hemorrhage in the Patient With Well-Compensated Cirrhosis
Arch Surg, April 1, 2006; 141(4): 385 - 388.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2312021797v1
231/2/537    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ter Borg, P. C. J.
Right arrow Articles by Laméris, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ter Borg, P. C. J.
Right arrow Articles by Laméris, J. S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
RADIOLOGY RADIOGRAPHICS RSNA JOURNALS ONLINE