Portal Vein Recanalization–Transjugular Intrahepatic Portosystemic Shunt (PVR-TIPS) Facilitates Liver Transplantation in Cirrhotic Patients with Occlusive Portal Vein Thrombosis

Abstract

Portal vein thrombosis (PVT) is a heterogeneous condition with multiple possible etiologies and to varying degrees has historically limited candidacy for liver transplant (LT) in the cirrhotic patient population due to resultant difficulties in constructing a robust portal vein anastomosis. While intraoperative approaches to managing PVT are well-described, methods which approximate normal portal physiology are not always feasible depending on the extent of PVT, and other nonphysiologic techniques are linked with substantial morbidity and poor long-term outcomes. Portal vein recanalization–transjugular intrahepatic portosystemic shunt (PVR-TIPS) creation is an efficacious method of restoring physiologic portal flow in cirrhotic patients prior to LT allowing for end-to-end PV anastomosis, and is the product of decades-long institutional expertise in TIPS/LT and the support of a multidisciplinary liver tumor board. To follow is a review of the pertinent pathophysiology of PVT in cirrhosis, the rationale leading to the development and subsequent evolution of the PVR-TIPS procedure, technical lessons learned, and a summary of outcomes to date.

Portal vein thrombosis (PVT) is defined as complete or partial obstruction of the portal vein due to thrombus in the lumen and can result from local and systemic pathologies including malignancies, inflammatory disorders, trauma, and myeloproliferative/prothrombotic conditions. ¹ Here we review PVT in the cirrhotic patient population and its effect on liver transplant (LT) candidacy. In cirrhotic patients, PVT incidence increases from ∼1 to 30% as disease severity progresses from early-stage to late-stage cirrhosis at the time of LT candidacy. ^{2 3} In patients with hepatocellular carcinoma (HCC), a group heavily represented in our practice and those listed for LT, PVT incidence has been reported up to 40%. ⁴

Molecular and in vitro data suggest that cirrhosis stimulates a hypercoagulable state, though it has been suggested that the most important predictive variable for PVT development in cirrhotic patients is a reduced portal vein velocity. ^{5 6 7 8 9 10 11} Ensuing thrombus can further inhibit flow, and the liver compensates with numerous mechanisms, including “venous rescue,” in which extensive portal venous collateral networks form to bypass the obstruction, preserving flow to the liver (termed “portal cavernomatosis or cavernoma”). The original portal vein remains thrombosed and hypoperfused, ultimately becoming a scarred, thin fibrotic cord, which presents a challenging scenario for routine interventional recanalization techniques. ^{12 13 14} Subsequent anatomy is highly variable and can include the diversion of splanchnic blood flow into compliant vascular reservoirs, leading to large, competing varices and portosystemic shunts which portend additional morbidity and management complexity. When applicable, local factors such as the presence of HCC or exposure to locoregional tumor therapies also contribute to complexity. Thrombus itself can partially or completely occlude the main portal vein, and frequently extends into the superior mesenteric and splenic veins. The Yerdel classification is a commonly used grading system for PVT and ranges from grade 1 (partial PVT) to grade 4 (complete portomesenteric thrombosis). This system has been frequently cited to reflect anatomic PVT heterogeneity, though may be oversimplified when considering that Yerdel grade 2 PVT includes a range of partial PVT (50% occlusive) to total occlusive (100%) PVT, thus including clinically distinct scenarios. ¹⁵ When chronic PVT is untreated, it can worsen the sequela of portal hypertension and increase the risk of liver decompensation and life-threatening variceal hemorrhage.

LT is the ultimate treatment goal for cirrhotic patients, as it gives the best chance at long-term survival. ^{16 17 18 19} However, reestablishing portal venous flow is fundamental to the initial and long-term success of LT with or without PVT. Multiple studies have revealed that the presence of PVT in the graft recipient is associated with increased intraoperative and postoperative morbidity and is an independent risk factor for increased 1-year mortality posttransplant. ^{20 21} A study of the United Network for Organ Sharing (UNOS) registry data generated a pre-allocation score to predict survival outcomes following LT (P-SOFT) and found a significant negative impact of PVT on survival relative to other traditional risk factors. ²²

Transplant Surgeon's Dilemma

Physiologic techniques of surgical portal reconstruction include eversion thrombectomy, interposition grafts, and mesoportal jump grafts; however, depending on the extent of PVT, these may not be feasible. When an end-to-end anastomosis is achieved in a patient with PVT undergoing transplantation, survival is similar to patients without PVT. ^{23 24 25 26 27} If a physiologic reconstruction is not possible, then nonphysiologic techniques may be employed, including PV arterialization, caval transposition, and renoportal anastomosis. While these nonphysiologic reconstructions can be technically performed, there is little doubt that physiologic inflow is preferred as it is associated with improved outcomes and decreased morbidity and mortality following LT. ^{28 29 30 31} This was further validated in 2014 by the University of Miami group which demonstrated that 25% of its patients with complete PVT who underwent transplant received nonphysiologic portal venous reconstructions and ultimately had higher rates of gastrointestinal bleeding, PV rethrombosis, and worsened overall survival compared with patients who received physiologic reconstructions. ³²

For these reasons, chronic obliterative PVT remains a relative contraindication to LT at many centers. This has led to a multidisciplinary approach to the care of these patients at our center, often involving pretransplant portal vein recanalization and transjugular intrahepatic portosystemic shunt (TIPS) placement (PVR-TIPS) to facilitate a physiologic reconstruction at the time of transplant.

A Technical Solution

A complete technical description of the PVR-TIPS procedure has been previously published. ³³ It should again be emphasized that approach for a non-cirrhotic patient with PVT is clinically and technically distinct and worthy of separate procedural and periprocedural considerations. ³⁴ Prior to PVR-TIPS being performed before transplant, it is advisable that the patient has already completed the LT evaluation and workup and has been adequately prepared and listed for LT in the unlikely event of procedure-related decompensation.

Initial approach is akin to a standard TIPS and involves right internal jugular vein access for obtaining central venous pressures and for wedged hepatic venography in the right or middle hepatic vein with dilute nonionic contrast or carbon dioxide, which assesses the patency of intrahepatic portal venous branches. Initial PVR-TIPS procedures utilized transjugular and percutaneous transhepatic accesses for recanalization, but now the preferred method is via transsplenic approach, which since its adoption has simplified and expedited recanalization in most cases. Review of preprocedure imaging is fundamental, ideally with a triphasic computed tomography (CT) which will allow the operator to identify an intraparenchymal splenic vein branch leading directly to the main splenic vein. This target vessel can then be accessed under ultrasound guidance with a micropuncture needle within the splenic parenchyma. It is critical to access the vein within the parenchyma and not at the hilum to avoid causing perisplenic hematoma. It is also important to perform venography through the needle to ensure that the needle tip is within the splenic vein and not the splenic artery or the splenic parenchyma. If the needle tip is unknowingly in the splenic parenchyma, a wire can still easily advance, dissect through the soft splenic tissue, and track along the capsule without any tactile resistance. This may lead the operator to believe that the wire is in a collateral splenic venous branch, and if a sheath is placed in this situation a bleeding complication may occur. Once adequate intravenous position is confirmed, a mandril wire and AccuStick (Boston Scientific, Marlborough, MA) system can be used to exchange for a 5-Fr 35-cm radiopaque-tipped sheath, which can then be used to perform portal pressure measurements and splenoportography to further delineate portomesenteric anatomy and document the presence of varices or portosystemic shunts. Using an angled catheter–Glidewire combination such as the KMP (Cook, Bloomington, IN) and angled-tip Glidewire (Terumo, Somerset, NJ), the operator can probe for the thrombosed portal vein cord, typically found along the superior margin of the portal confluence and coursing superolaterally toward the liver hilum. However, the origin of the occluded portal vein can often be elusive due to the presence of cavernoma. Identifying a leftward coursing coronary vein can be helpful in marking the proximal aspect of the PV cord, and occasionally with diligent venography the presence of portal vein vasa vasorum can be distinguished from the cavernoma. An intrahepatic portal vein branch is then catheterized (occasionally with the aid of a microcatheter/wire system) and additional venography will identify a target for TIPS needle passage. A 10-mm snare such as an Amplatz gooseneck (Medtronic, Dublin, Ireland) is advanced through the catheter, and with the use of multiple fluoroscopic obliquities, a Colapinto TIPS needle (Cook) can be advanced through the hepatic parenchyma toward the snare. An initial longer parenchymal pass can be performed to approach the target, with more deliberate and incremental advancements closer to engagement with the snare. Through-and-through access is achieved with an exchange length stiff Glidewire through the TIPS needle, grasped by the snare and withdrawn through the splenic access sheath. It is imperative that there is equal effort pushing the wire by the IJ operator and pulling the wire by the splenic operator to avoid undue tension which can cause hepatic laceration via the exposed portion of the Guidewire. Others have reported success using a balloon in the portal vein as a fluoroscopic target. ³⁵ With this method, after puncture of the balloon with the TIPS needle, a wire is advanced primarily through the recanalized portal vein. If through-and-through access is desired, the wire can then be grasped in the patent splenic or superior mesenteric vein. A 100-cm 4-Fr is then used to exchange for an exchange-length working wire (Amplatz, Boston Scientific) to use for standard TIPS (VIATORR stent, Gore, Flagstaff, AZ) deployment and angioplasty (10 mm). It is important to maximize the length of the unstented main portal vein if the patient is eligible for LT. At our center, the transplant surgeons prefer to have at least 2 cm of unstented portal vein for the end-to-end anastomosis. Cranial extension of the stent into the inferior vena cava is not recommended unless it is deemed necessary for patency, as this may limit the transplant surgeon's ability to perform a caval piggyback anastomosis. ³⁶

After TIPS placement and angioplasty of the stent and chronically thrombosed PV, residual thrombus is only intervened upon (with further angioplasty or thrombectomy) if there is poor flow through the TIPS. Since low portal vein velocity has been shown to be the most important predictive variable in the formation of cirrhotic PVT, if there is brisk flow after PVR-TIPS, patency is likely to be maintained and any residual non–flow-limiting thrombus will resolve during the course of follow-up. This stands in contrast to noncirrhotic patients with PVT, who often have a prothrombotic disorder and require anticoagulation for long-term patency. After sufficient flow is established, pull-back venography and embolization of the splenic access tract is performed with 4 mm × 14 cm Nester coils (Cook) under ultrasound and fluoroscopic guidance.

If transsplenic recanalization is unsuccessful, transhepatic access and retrograde recanalization of the PV is a potential option, with the use of a 6-Fr sheath and a 0.018″ stiff working wire (positioned in the splenic or superior mesenteric vein to maintain access) alongside a KMP catheter, through which the snare can be advanced into the right or left portal vein and used as a fluoroscopic target, similar to transsplenic recanalization. A stiff Glidewire through the TIPS needle can then be advanced by pushing through the thrombosed PV with the snare and sheath as a unit over the 0.018″ wire. Once recanalized, the TIPS can be deployed. Safe, percutaneous transabdominal ultrasound-guided mesenteric (superior and inferior) venous access in those without accessible splenic veins has also been described. ³⁷ Following access, advancement of a snare into a portal vein branch can be used as a fluoroscopic target as in the other retrograde approaches. Gun-sight technique may be employed if necessary to achieve through-and-through access. Others have reported transmesenteric access utilizing a minilaparotomy incision to aid in gaining access to a peripheral mesenteric venous branch. ^{38 39}

Depending on the extent and location of varices/shunts, these may be treated at the time of recanalization or at 1-month follow-up splenoportography. If little or no residual thrombus is present at this initial follow-up, then further surveillance is pursued with ultrasound, CT, or magnetic resonance imaging.

Fig. 1 shows a procedure typically used for PVR-TIPS in a patient with PVT.

Fig. 1.

A 65-year-old woman with nonalcoholic steatohepatitis cirrhosis. Two years prior to undergoing liver transplantation, a contrast-enhanced CT ( a ) demonstrated a small portal vein (arrow) and a large gastrorenal shunt (circle) ( b ). Two years later, a pretransplant CT ( c ) demonstrated that in the interim the patient developed complete chronic thrombosis of the portal vein. Therefore, pretransplant PVR-TIPS was pursued. Using ultrasound guidance, an intraparenchymal splenic vein branch was accessed (arrow) ( d ) and splenic venography ( e ) demonstrated complete occlusion of the PV and opacification of a large gastrorenal shunt. The chronically occluded PV was crossed with a guidewire and catheter, through which a snare was placed as a fluoroscopic target (arrow) ( f ). After obtaining sheath access across the thrombosed PV, the TIPS stent was placed and the PV and TIPS were dilated with a 10-mm balloon ( g ). After plug embolization of the gastrorenal shunt, final venography ( h ) demonstrates flow through a patent portal vein and TIPS (arrows). Coil embolization of the splenic tract ( i ) was performed using ultrasound guidance (arrow). The patient then underwent liver transplantation 3 months later and follow-up CT ( j ) and ultrasound ( k ) 6 months posttransplant demonstrated patency of the end-to-end portal anastomosis (arrow).

Outcomes

In 2015 our group first reported technically successful recanalization PVR-TIPS in 43 out of 44 cirrhotic patients with PVT who were under consideration for LT but not deemed to be candidates at our center due to the presence of chronic PVT. ⁴⁰ In this study, 17 of 44 patients had complete occlusion of the PV (39%) and 27 of 44 had near-complete (>95%) occlusion of the PV. At the time of that publication, 50% of patients in the cohort had been transplanted, with an overall survival of 82% at 5 years. Also notable was that 1-month TIPS venogram demonstrated complete resolution of MPV thrombosis in 22 of 29 patients (76%) without anticoagulation. The transsplenic route was later presented separately in 11 patients with 100% technical success. ⁴¹

The patients from these studies were included in a final 2017 analysis of PVR-TIPS in 61 patients with technical success in 60 of 61. At a median follow-up of 19.2 months (range: 0–105.9 months), PV/TIPS patency was preserved in 55 of 61 patients (92%) and recurrent PV/TIPS thrombosis occurred in only 5 patients (8%) who all initially presented with complete PVT. TIPS stenosis occurred in 13 patients (22%) and transient encephalopathy was observed in 11 (18%). Twenty-four patients (39%) underwent successful LT with 23 of 24 receiving an end-to-end anastomosis and the lone other patient receiving an interposition graft due to a very short donor (living-related) PV. No posttransplant PVT was reported, with median imaging follow-up of 32.5%. Five-year overall survival rate in the cohort was 82%. ⁴²

In a recent analysis, 49 cirrhotic patients with PVT who were listed for transplant were split into two groups. One group of 35 patients underwent PVR-TIPS for chronic obliterative PVT (high risk for LT), and the other group of 14 patients with partial, expansile PVT (low risk for LT) proceeded directly to transplant. ⁴³ All patients received LT, and in the second group veno-veno bypass was required in a statistically significant greater number of cases (2 cases vs. 0 cases in the PVR-TIPS group). The second group also required significantly more intraoperative red blood cells. Despite no difference in overall survival between groups, the matched nature of this study highlights the efficacy of PVR-TIPS in resolving PVT and simplifying the surgical approach. The importance of this study was that it enhanced the survival of the high-risk group to match that of the low-risk group.

A recent study in 30 consecutive transplant-eligible patients demonstrated use of PVR-TIPS with resolution of PVT in 80% and LT with end-to-end anastomosis in 30%. ⁴⁴ Other small case series of PVR-TIPS often include the noncirrhotic patient population (again, worthy of separate considerations and analyses) or exclude patients with cavernoma or complete PV occlusion. ^{45 46 47}

Discussion

PVR-TIPS has been adopted as a first-line therapy for chronic PVT in transplant-bound patients at our center. Anticoagulation is an alternative therapy used for patients unable or unwilling to undergo PVR-TIPS, or as an adjunct following PVR-TIPS in cases of extensive PVT. The studies presented represent a sizable group of patients with PVT who have been bridged to LT with PVR-TIPS and exhibit favorable long-term patency, transplantation, and survival data.

Our observation has been that reestablishing PV flow after PVR-TIPS leads to a high rate of long-term patency, lysis of residual thrombus, and remodeling of the native, recanalized PV. This has been supported in a prospective, randomized trial which asserted the cirrhotic, post-TIPS patient does not benefit from anticoagulation. These studies support the premise that the predominant cause of thrombus resolution is flow-related and is relieved by TIPS placement. ⁴⁸

Cirrhotic patients with chronic PVT who successfully undergo pretransplant PVR-TIPS should be considered equivalent to a patient with no history of PVT in terms of transplant eligibility. The thrombosed fibrotic PV cord prior to PVR-TIPS becomes a patent vein suitable for an end-to-end physiologic surgical anastomosis and establishing PV patency should allow for transplantation to proceed uninhibited. As in the case of locoregional therapies for HCC, effective and maximized effort toward bridging to LT is what ultimately results in a desired long-term outcome for each patient. Thus, PVR-TIPS in the pretransplant setting is another example of the personalized impact of interventional radiology.

Future studies should include prospective assessment of PVR-TIPS versus surgical portal venous reconstruction at the time of LT. Some centers do not consider PVT a contraindication to LT, and therefore the application of PVR-TIPS will be subject to local practice patterns. However, regardless of practice patterns, a multidisciplinary approach to these complex patients is essential and has become a hallmark of our approach.

Conclusion

The goal of PVR-TIPS procedures in the pretransplant cirrhotic population is giving the surgeon the ability to treat the recanalized portal vein with familiarity and confidence to achieve physiologic reconstruction with end-to-end PV anastomosis. Routinely achieving this result by safely performing PVR-TIPS has effectively eliminated PVT, no matter the severity, as a relative contraindication for LT at our institution.