Influence of transjugular intrahepatic portosystemic shunt in patients awaiting orthotopic liver transplant on post-transplant outcome

Abstract

Introduction

In patients with liver failure, orthotopic liver transplant (OLT) remains the only definitive treatment for end-stage disease.1 Currently, there are more than 15,000 patients awaiting liver transplant in the United States.2,3 From 2004 to 2008, the number of patients receiving transplants increased roughly 2% from 6171 to 6318, while new additions to the transplant list grew 4% from 10,170 to 10,608.2 While the demand for liver transplantation remains high, the number of available livers has remained fairly constant despite efforts to expand criteria for donations.3 The pre-transplant course is often accompanied by complications of decompensated liver disease and portal hypertension like ascites and gastrointestinal bleeding. Even though we attempt to optimize the use of the donor organ pool, we continue to have an absolute organ shortage with increased waiting times on the transplant list resulting in pre-transplant complications.2,4

Transjugular intrahepatic portal systemic shunt (TIPS) is currently the only nonsurgical method of creating a portal systemic shunt and is an effective tool in the symptomatic treatment of complications of advanced liver disease.5 TIPS have proven to be effective in controlling both variceal bleeding and refractory ascites.6,7 The creation of TIPS in patients awaiting OLT has been described by several research groups.8–14 It has been shown, in small case series and case controls studies, to decrease the symptomatology of patients awaiting liver transplant. In these patients, the TIPS procedure has been used as a bridging therapy to allow them to remain on the transplant list longer and reduce patient dropout.

Our goal was to evaluate the safety and efficacy of the TIPS in patients awaiting OLT and to identify factors affecting post-transplant survival. We present our 18-year case study of patients receiving TIPS before OLT.

Methods

Results

A total of 129 patients underwent TIPS followed by OLT and were included in our study. The mean age of the group was 54.67 years (SD, 11.45; range, 16–74 years). The mean duration of follow-up was 2.3 years (range, 1 day–15 years). The demographic, clinical, and laboratory data of the group area are described in Tables 1 and 2.

The mean duration between first TIPS placement and OLT was 1.5 years (range, 0.1–13.4 years). The post-transplant survival rates at 1 month,1 year, 3 years, 5 years, and 10 years were 98%, 82%, 75%, 69%, and 43%, respectively. The long-term median post-transplant survival in patients who underwent transplant after TIPS was 8.7 years (95% CI, 7.3–10.2). The technical success rate of the OLT was 100% in the patients who had undergone pre-transplant TIPS. The mean pre-TIPS portosystemic gradient was 17.56 (range, 6–70), and the mean drop in portosystemic gradient after TIPS was 11.73 (range, 0–57). The post-transplant survival was not influenced by pre-TIPS portosystemic gradient (P = 0.295) or the drop in pressure after TIPS (P = 0.423).

Factors affecting post-transplant survival were compared on univariate analysis (Table 3). Hepatitis C virus (HCV) positivity (P = 0.001) and high MELD scores (P = 0.018) were found to be associated with poorer post-transplant survival in patients who underwent TIPS (Figs. 1 and 2). The 1-year survival in HCV negative recipients was 84%, and in HCV positive recipients it was 75%. Age, sex, race, etiology of cirrhosis, indication for TIPS, and timing of TIPS were not statistical predictors of post-transplant survival. On multivariate analysis, both HCV positivity [P = 0.001; hazard ratio 2.50 (95% CI, 1.47–4.25)] and MELD score [P = 0.015; hazard ratio 2.45 (95% CI, 1.19–5.02)] were found to be significant predictors of post-transplant long-term survival.

In our study, we found that 23% of the patients developed stenosis of the TIPS and required restenting before OLT. The incidence of post-TIPS complications was 29.4% (38/129). The most common complication was procedure-related bleeding (8.5%) followed by hepatic encephalopathy (7.0%). The incidence of other complications was as follows: fever/infection 6.2%, pulmonary edema 4.7%, stent migration 1.6%; in-stent thrombosis 0.8%; and acute renal failure 0.8%.

Discussion

Our data on survival rates show adequate post-transplant survival with 1-, 3-, and 5-year rates of 82%, 75%, and 69%, respectively. This information was very consistent with nationally reported data on post-transplant survival.2 In a recent case control study by Guerrini et al,9 survival rates were similarly reported at 91.7%, 85%, and 81.7%, for 1, 3, and 5 years post-transplant, respectively, in patients who received pre-transplant TIPS. Although there was no long-term survival benefit, they reported seeing a decrease in early mortality in patients receiving TIPS compared to those not receiving TIPS. It has been hypothesized that the benefit of TIPS is related to the reduction of collateralization around the newly transplanted liver, increasing the available blood flow, and improving liver function, which may help increase short-term survival.9 However, multiple additional authors have consistently shown that TIPS does not affect either short- or long-term outcome8,11,15,16 So the proposed mechanism most likely has less of an effect on short-term survival and no effect on long-term survival. Additionally, it would follow that decreased gradient pressures lead to decreased collateralization. In our study, neither the initial nor the post-TIPS portosystemic gradient proved to have any prognostic value in determining the survival after OLT. If there was some benefit to decreasing collateralization of blood flow around the liver, one would expect that decreased gradient pressures would correlate with better outcomes, which we did not find. Together, these studies, including ours, suggest that TIPS does not increase or decrease mortality in the post-transplant period but most likely improves overall survival, as patients who would otherwise have fallen off the transplant list were effectively bridged to liver transplant.8,11,15,16

In our study, we found the main complication of the TIPS procedure to be refractory hepatic encephalopathy at 7.5%. Published literature reports an overall rate of post-shunt encephalopathy in 46% of cases5 with medically refractory cases at 5% of patients.17 The exact pathophysiology of post-shunt encephalopathy remains somewhat poorly understood but does seem to be related to the rate of change in portal-systemic flow which dramatically increases with shunt creation. It has been reported by Wroblewski et al that a two-stage TIPS procedure may be beneficial for patients who are encephalopathic pre-procedure and may decrease the development of post-shunt encephalopathy creating a more gradually change in the portal systemic blood flow.18 Prognostic indicators for encephalopathy development continue to remain poorly defined and need to be investigated.

Despite the successful use of TIPS in bridging patients to transplant, many authors have continued to suggest that TIPS may hinder the actual transplant procedure through misplacement of the shunt stents in either the suprahepatic inferior vena cava or the portal vein.14,19,20 In our study, all patients were successfully transplanted despite previous TIPS placement. In our experience, this tends to suggest that even slight misplacement of stent is easily corrected during the transplant surgery. However, it remains important that the TIPS stent is properly placed which does require the expertise of an experienced interventionalist.

In our study, one of the more significant prognostic factors was the presence of hepatitis C, which appears to be a strong indicator of poor survival post-transplant. In our population, we noted that 38% of our patients presented with hepatitis C as their underlying etiology of liver failure and had a 1-year survival rate of 75%. It has been previously shown that hepatitis C is indeed one of the largest etiologies of liver failure requiring transplant and also carries the highest mortality rates outside of fulminant failure and malignancy.1 This is most likely due to high rates of reinfection of the donor liver with the HCV, as reported in the literature.21 and it is not surprising that despite TIPS procedure, these patients still fare poorly.

The MELD score was designed in the late 1990s as a better predictor of short-term survival in the pre-transplant candidate.22 Since that time it has also been shown by Habib et al,23 in a study of 1472 patients, that MELD scores are also a predictor of post-transplant survival, but this remains a less powerful indicator than its primary use as an indicator of pre-transplant mortality. Although pre-transplant MELD score have been shown to be somewhat predictive of post-transplant survival,23 it remained to be seen whether MELD score has the same predictive power in patients who receive pre-transplant TIPS. We show that this is indeed the case as a patient’s pre-TIPS MELD score was predictive of outcome after transplant.

Another complication of the TIPS procedure is stent stenosis/ thrombosis and the need for restenting before transplant.24,25 In the literature, the frequency of patients undergoing TIPS revision within the first, second, and third years after TIPS placement was 67.5%, 38.0%, and 24.4%, respectively.24 In our study, we found that 23% of patient required restenting before OLT. Because in our population, patients were receiving TIPS as a bridge to definitive therapy, thrombosis rates overall were less common as the reduced time to definitive therapy limits thrombosis development.

In general, retrospective study designs suffer from numerous limitations. Of note, in our selection criteria we recorded patients who both received TIPS and had subsequent transplant; it is possible that by doing this we eliminated those with worse prognosis that were either removed from the transplant wait list or died before transplantation. However, our data still represent a large case series exploring the prognostic factors that affect post-transplant survival in patients receiving TIPS before transplant. Our data are consistent with previous reports on the success of TIPS in pre-transplant patients; however, there is need for prospective studies to conclusively determine the benefit of pre-transplant TIPS procedure on post-transplant survival.

To conclude, post-transplant survival in patients who undergo TIPS before OLT is excellent. Higher MELD scores and the presence of hepatitis C are associated with poor post-transplant survival. This study demonstrates the efficacy and safety utilizing the TIPS procedure in helping to ameliorate complications of portal hypertension in the pre-transplant period in large case series. With increasing utilization of liver for transplant and stagnation in growth of available livers, there are significant wait times until transplantation, and in those patients with refractory complications, TIPS serves a vital role in bridging patients until suitable organs become available.

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References