EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Although no longer a contraindication to liver transplant, portal vein thrombosis may lead to longer operative time and complexities in venous reconstruction. Strategies to maintain preoperative patency include systemic anticoagulation and/or transjugular intrahepatic portosystemic shunt placement. The former may not be ideal in cirrhotic patients prone to luminal gastrointestinal tract bleeding, and factors that predict improvements in portal vein thrombosis with the latter have not been well defined. Our goal was to evaluate the effectiveness of transjugular intrahepatic portosystemic shunt placement as monotherapy to improve and/or resolve portal vein thrombosis in otherwise eligible liver transplant candidates with partial or complete portal vein thrombosis and to identify factors predicting success.

Materials and Methods: We identified 30 patients from 2010 to 2015 who had transjugular intrahepatic portosystemic shunt placement for primary indication to maintain portal vein patency.

Results: The main portal vein was completely thrombosed in 5 of 30 (16.6%), nearly completely thrombosed in 9 of 30 (30%), and partially thrombosed in 16 patients (53.3%). Twenty-four patients (80%) had improvement and/or resolution of portal vein thrombosis after transjugular intrahepatic portosystemic shunt placement, with 18 of these (75%) having complete resolution. All 5 patients (20.8%) with complete thrombosis had improvement/resolution of portal vein thrombosis. Nine patients (30%) required hospitalization within 3 months for hepatic encephalopathy. There were 3 deaths (10%) not related to transjugular intrahepatic portosystemic shunt placement (10%). Nine patients underwent liver transplant after shunt placement (median 2.9 mo; range, 0.3-32 mo); all 9 received end-to-end anastomosis without need for intraoperative thrombectomy.

Conclusions: Transjugular intrahepatic portosystemic shunt placement may be effective as monotherapy for maintaining or restoring portal vein patency in selected liver transplant candidates, even in those with complete portal vein thrombosis. Further studies are needed to define potential responders to this approach.

Key words : Cirrhosis, Liver transplant, Portal vein thrombosis

The prevalence of portal vein thrombosis (PVT) in patients with cirrhosis at evaluation or at the time of liver transplant varies from 5%¹ to 26%.² Pathogenesis is multifactorial and related to several factors: altered balance of coagulation factors, increases in intrahepatic resistance to portal flow, and endothelial injury due to elevated portal pressure.^3,4 Liver transplant in a patient with PVT was first reported in Pittsburgh, Pennsylvania (USA).⁵ Since then, various surgical and medical strategies have been proposed to treat PVT, facilitating end-to-end portal inflow when feasible. Intraoperative methods are associated with significant complications, including prolonged operative times, increased postoperative complications, and higher in-hospital mortality rates.^3,5-8

The primary goal of management of PVT in patients on liver transplant wait lists is to achieve partial or complete recanalization to ensure portal flow to the allograft or to prevent propagation of thrombus, particularly into the confluence with the superior mesenteric vein. Two primary treatment strategies for patients with PVT on wait lists are anticoagulation therapy and transjugular intrahepatic portosystemic shunt (TIPS) placement. Complete recanalization rate with systemic anticoagulation agents has been reported to be as high as 40%³; however, studies are mixed with regard to optimal agents and the duration/intensity for this indication.^9,10 A major practical concern with the use of anticoagulant therapy is risk of inducing portal hypertensive-related bleeding and the need for repeated transfusion. Portal vein recanalization with TIPS placement has been reported in patients with PVT.¹¹ However, in most studies, TIPS was indicated to treat severe complications of portal hypertension, and PVT was identified incidentally during work-up prior to TIPS placement. To our knowledge, few studies have examined TIPS placement with primary intent to maintain/restore PVT patency for future liver transplant. In this study, we report the efficacy and intermediate-term follow-up of 30 consecutive patients receiving TIPS to maintain portal vein patency for future liver transplant.

Materials and Methods

Patient selection
After institutional review board approval, we conducted a retrospective review of 34 consecutive patients with cirrhosis who were on the transplant wait list and who had undergone TIPS placement at our institution (2010-2015) for primary indication to maintain portal vein patency. Four patients were excluded from our evaluation because of use of concomitant systemic anticoagulation agents.

Transjugular intrahepatic portosystemic shunt placement
Transjugular intrahepatic portosystemic shunt placement was performed utilizing the Ring Transjugular Intrahepatic Access Set with aColapinto needle (Cook Medical, Bloomington, IN, USA), with the procedure routinely performed from the right hepatic vein to the proximal right portal vein. Before 2012, this procedure was performed with fluoroscopic guidance with wedged CO2 portovenograms (Parallax, Waltham, MA, USA) and assisted by transabdominal ultrasonography and/or direct portal vein micropuncture access/wire placement to facilitate access.^12,13 After 2012, most of these procedures have been performed with intravascular ultrasonography guidance.^14,15

Transluminal angioplasty of the intrahepatic tract followed by deployment of a Viatorr (Gore Medical, Flagstaff, AZ, USA)-covered stent across the tract was carried out (nominal diameter of 10 mm). The appropriate stent length was determined by simultaneous portovenogram (utilizing a marker band flush catheter) and inferior venacavagram via a 10-French angle-tipped Ring set sheath. Stents were placed from the portal vein extending slightly into the inferior vena cava. Most stents were dilated initially to 8 mm, and pressures were measured. If the portosystemic gradient (PSG) was greater than 12 mm Hg, then the stents were further dilated to 9 or 10 mm to achieve a PSG of less than 12 mm Hg. A small number of patients with preexisting hepatic encephalopathy were only dilated initially to 6 mm. Repeat PSG, right atrial pressure, and a venogram were obtained after balloon dilation of the stent.

Techniques used in our center to clear the thrombus before placement of TIPS depend on thrombus acuity. For acute thromboses, we obtain dual right intrajugular access and utilize intravascular ultrasonography to guide access from the hepatic vein to the portal vein (usually the right hepatic vein to right portal vein) and place a Viatorr TIPS to secure access. Initially, the stent is not dilated to restrict the ability of thrombus to migrate and embolize. We then perform thrombolysis, thrombectomy, and angioplasty to clear the thrombus and establish good splenic and mesenteric venous inflow into the portal veins (Figures 1 to 6). This may be performed with or without main portal vein stent placement. Finally, the TIPS stent is dilated to achieve a right atrial PSG of 12 mm Hg or less to prevent thrombosis of the portovenous system after recanalization.

For cases of chronic thrombosis, we again obtain dual right intrajugular access and utilize intravascular ultrasonography to guide access from the hepatic vein to the portal vein (usually right hepatic vein to right portal vein). This also frequently requires recanalization of the splenic vein; mesenteric and portal veins may be assisted with trans-splenic and/or transhepatic access followed by angioplasty and stent placement to restore normal venous anatomy and flow.

Radiographic assessment and clinical variables
Improvement, resolution, or worsening of PVT was assessed by review of cross-sectional follow-up imaging at 6 months after TIPS placement based on assessment by United Network for Organ Sharing-certified abdominal radiologists. Our secondary objective included an analysis of baseline factors predicting response with TIPS monotherapy. Response with TIPS was operationally defined as improvement, resolution, or prevention of further extension of thrombus while on the liver transplant wait list as assessed with multiphasic cross-sectional imaging follow-up at 6 months after TIPS placement. Preplacement demographics included age, biologic sex, race, cause of cirrhosis, biologic Model for End-Stage Liver Disease (MELD), hemoglobin, creatinine, international normalized ratio, total bilirubin, albumin, thrombus extension, and history of hepatic encephalopathy.

Statistical analyses
Demographic results along with TIPS procedure variables were recorded and analyzed to assess baseline differences between those who did and those who did not respond to the procedure. Categorical variables were analyzed using the Fisher exact test. Continuous variables were compared using the Wilcoxon rank sum test. P < .05 was considered significant. Data were analyzed with STATA software version 14 (StataCorp, College Station, TX, USA)

Baseline demographics
Thirty patients underwent TIPS for primary indication to maintain or restore PVT patency (baseline characteristics are listed in Table 1). The main portal vein was completely thrombosed in 5 of 30 patients (16.6%), with near complete occlusion in 9 of 30 patients (30%) and partially thrombosed portal vein in 16 patients (53.3%). Mean MELD (± standard deviation) for the cohort was 13.2 ± 3.69, and average reduction in PSG with TIPS placement was 8.96 ± 3.81 mm Hg.

Efficacy of transjugular intrahepatic portosystemic shunt for portal vein thrombosis patency and predictors of response
Of 30 patients, 24 (80%) responded with improvement or resolution of PVT (Table 2). Of the 24 responders, 18 patients (75%) had complete resolution of PVT. All 5 patients (20.8%) with complete PVT had improvement/resolution.

The portal vein remained patent on the first cross-sectional image after TIPS placement in 17 patients (56%) (median of 1.4 mo after placement). The portal vein remained completely patent in 19 patients (63%) (median duration of 7.1 mo) during the available follow-up interval. Nine patients (30%) required hospitalization within 3 months for hepatic encephalopathy. There were 3 deaths (10%), which were not related to TIPS. Nine patients underwent liver transplant post-TIPS (median of 2.9 mo; range, 0.3-32 mo), and all 9 received end-to-end anastomoses (Table 3).

There were no differences in baseline demographics, TIPS procedural variables, or Yerdel grade of PVT between the responder and nonresponder groups (Table 2).

Portal vein thrombosis is increasingly recognized in patients with cirrhosis, especially in patients on the transplant wait list. Nonphysiologic techniques used to restore portal vein flow (hemitranspositions and cavoportal and renoportal anastomoses) are associated with significantly increased morbidity and mortality.^15,16 Furthermore, the use of anticoagulation agents for patients with chronic PVT is still controversial, and, in many candidates, systemic anticoagulation is relatively contraindicated due to high risk of luminal gastrointestinal tract bleeding.¹⁷ The use of TIPS for treatment of chronic PVT has been utilized by many transplant centers as a method to improve portal vein patency or prevent progression of the thrombus to maintain transition of the patient to liver transplant.

In this series, we found efficacy of TIPS monotherapy in maintaining and/or restoring PVT patency in liver transplant candidates. Interestingly, the grade of PVT and/or extension to superior mesenteric vein had no effect on the rate of response to TIPS for this indication. Our study has several limitations: principally, it is a retrospective analysis from a single center with a relatively small sample size and short follow-up duration. In this investigation, median MELD score was low (13), yet 30% of patients received a liver transplant within a median of 3 months; this is a notably higher rate of transplant for patients with MELD score of < 15. There are many regions in the United States and worldwide where a patient with a low MELD score would have to wait much longer for liver transplant, and a 63% 7-month patency rate may not be sufficient to justify TIPS placement. However, presented results call out the need for further prospective investigations to evaluate predictors of response to TIPS monotherapy for PVT patency and the long-term durability of this approach in liver transplant candidates.

Volume: 18 Issue: 7 December 2020

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