Chapter 23: The Transjugular Intrahepatic Portosystemic Shunt as a Prelude to and After Liver Transplantation Transjugular intrahepatic portosystemic shunt (TIPS) is an artificial conduit between the systemic and portal venous systems. This percutaneous procedure is commonly performed in patients with portal hypertension (PHT) for the management of variceal hemorrhage, refractory ascites, hepatic hydrothorax, and Budd-Chiari syndrome. TIPS creation has largely supplanted surgical portosystemic shunts for the decompression of PHT because it is less invasive and can be placed in patients with advanced hepatic failure.1 Although portosystemic shunts can mitigate the complications of PHT, they are not a definitive treatment of what is usually irreversible and progressive hepatic disease. Ultimately, liver transplantation, if the patient is an appropriate candidate, is generally the optimal long-term therapeutic option. With respect to liver transplantation, TIPS has an additional major advantage over surgical portosystemic shunts, namely its wholly intrahepatic location and potential for en bloc removal with the native liver at the time of recipient hepatectomy. In contradistinction, surgical portosystemic shunts such as the Warren shunt, Drapanas shunt, portocaval anastomosis, or splenorenal shunts and others all require additional surgery for their takedown or ligation.2 The demand for liver transplants has been consistent with approximately 15,000 patients on the waiting list at any particular time. Given a slowly worsening donor shortage, median pretransplant wait times increased from 12.9 months in 2009 to 18.5 months in 2011, which may also increase rates of drop-off from the transplant list.3 For these patients, TIPS routinely serves as “a bridge to transplantation,” ameliorating the symptoms and risk of PHT in the meantime. Aside from the accepted indications of TIPS placement, several studies have evaluated TIPS before transplantation, not as a temporizing measure for the management of portal hypertensive sequela but as a pretransplant prelude with the premise that decompression of the portal circulation would decrease portosystemic collateral engorgement, resulting in a reduction of intraoperative bleeding during liver transplantation.2,4–22 However, these studies, mostly in the transplant literature, have been equivocal from an intraoperative and posttransplant clinical outcome standpoint. Additionally, TIPS creation in liver transplant recipients is equally worthy of discussion because there has been a debate about whether liver transplantation increases the technical difficulty of the TIPS procedure. Several recent studies evaluating the outcomes of TIPS in liver transplant recipients are reviewed.23–30 This chapter discusses the results of TIPS as a preoperative prelude to liver transplantation and the technical and clinical outcomes of TIPS in liver transplant recipients. Careful selection of liver transplant candidates and medical optimization of those at higher risk has been found to reduce hospital resource utilization and improve outcomes.31–33 Specifically, intraoperative blood product administration serves as a surrogate marker directly related to hospital resource utilization and inversely related to clinical outcomes.2,31 Given that the typical liver transplant candidate has PHT, it follows that portal vein engorgement and increased portosystemic collateral flow are present. Redirecting portal venous flow through a shunt alters the pressure gradient across the portal system, thereby collapsing the portosystemic collaterals and presumably reducing the risk of intraoperative bleeding and use of blood products. Before the improvements in endoscopic therapeutics and the development of TIPS, the complications of PHT were managed surgically. As TIPS began to be performed more commonly than surgical shunts, comparisons between orthotopic liver transplants with surgical portosystemic shunts versus TIPS emerged. Patients with surgical portosystemic shunts have shunt reversal or take-down performed at the time of transplantation. However, because surgical shunts are often adhesed, discerning the surgical anatomy and performing the surgical dissection can be difficult. Ultimately, the higher operative complexity results in longer operative time, requiring more blood transfusions at transplantation and more hospital resources. In comparison, TIPS has the potential for complete in situ removal with the recipient’s hepatectomy adding little technical complexity to the transplant surgery. However, it is notable that TIPS malposition or migration can complicate liver transplantation. Multiple published cases have reported the presence of the TIPS stent in the inferior vena cava, right atrium, pulmonary artery, extrahepatic portal vein, and superior mesenteric vein with or without vascular incorporation.34–44 Although these reports have noted a malpositioned TIPS stent, all technical surgical difficulties that were encountered were overcome. While the exact incidence is not accurately known, improvements in stent technology have decreased stent migration, and medical centers with greater expertise and higher volume of TIPS likely have fewer problems with accurate and appropriate placement. Generally, the placement of TIPS has become safer and more routine over time and should not preclude transplant listing or complicate the transplantation, provided the availability of high quality preoperative imaging.45 Multiple comparative analyses between patients who have had a TIPS performed before liver transplant and patients who have not had a TIPS before liver transplant have been performed evaluating parameters such as intraoperative blood loss, recipient hepatectomy time, total operative time, patient survival, graft survival, postoperative complication rates, mean intensive care unit stay, and hospital stays.2,10,20–22,44,46–54 Across all parameters, in particular with respect to intraoperative transfusion of blood products, conflicting results have been published with no consistent difference emerging. Saad and coworkers published the only study comparing adult right lobe living related liver transplants with or without intentional TIPS 48 to 72 hours before transplant surgery.2 This case-controlled retrospective study also showed no significant value in performing TIPS before living related liver transplantation. However, the authors did conclude that TIPS may reduce the risk of poor outcomes in patients with high APACHE II (Acute Physiology and Chronic Health Evaluation II) scores and coagulopathy. Development of partial portal vein thrombosis is not uncommon in patients with liver failure and may herald full portal vein thrombosis, which develops in up to 26% of patients awaiting liver transplant. Similar to portal venous engorgement, portal vein thrombosis can technically complicate the transplant graft anastomosis and increase morbidity and mortality post-transplant.55,56 In most clinical scenarios, anticoagulation is the mainstay of therapy for venous thromboses. However, patients with PHT have an elevated risk of life-threatening bleeding on a background of intrinsic liver dysfunction, which typically precludes this as a long-term therapeutic strategy. TIPS creation has been used to prevent complete portal venous thrombosis and to improve portal vein recanalization in both patients with and without cirrhosis.57,58 Additionally, D’Avola et al59 and Gaba et al60 collectively documented 19 cases of partial portal vein thrombosis in patients who first underwent TIPS and then ultimately liver transplantation. None of the patients in these publications had residual thrombus at the time of transplant. In comparison, D’Avola et al noted that only 50% of the control group with partial portal vein thrombosis maintained portal patency until the time of transplant. Theoretically, clot resolution and portal patency may be attributable to the resultant improved anterograde flow dynamics. Although this has only been observed in a relatively small subset of patients, partial portal vein thrombosis may ultimately represent an evolving indication for TIPS in pretransplant candidates. The first human liver transplant was performed in 1963, but 1-year survival was not achieved until 1967. Cumulative improvements and evolution of surgical techniques and medications have made the practice of liver transplantation more successful. Liver transplant recipients are living longer, and because of sheer longevity, there is a higher likelihood of developing primary allograft failure or recurrence of the initial underlying cause of their liver disease, most commonly hepatitis C. These two etiologies are the leading cause of recurrent PHT in liver transplant recipients who undergo TIPS, but in reviewing the published literature, the cause varies among institutions.23,24 In the United Sates, TIPS is performed in 1% to 4% of the liver transplant recipient population.24,27,28 In three studies involving four institutions in the United States, a total of 81 liver transplant recipients underwent a TIPS procedure out of a total of 3785 liver transplant recipients (2.1%, n = 81 of 3785).24,27,28 Reversely, 5.5% of TIPS procedures performed at two of these institutions were found to be in transplant recipients.24 Reports by Nolte et al61 of 1 patient (1998), Lerut et al26 of 8 patients (1999), and Amesur et al25 of 12 patients (1999) were the initial publications on placement of TIPS after liver transplantation. In total, these reports comprised 21 patients in whom the etiology of recurrent PHT was recurrent hepatitis C in 76% (16 of 21 patients) and recurrent hepatitis B, recurrent primary biliary cirrhosis, hepatic veno-occlusive disease, and lymphoproliferative disease each in single cases. The etiology was not reported or was unknown in 1 patient. Refractory ascites or hepatic hydrothorax was the presenting symptom in 62% (13 of 21 patients), variceal hemorrhage in 33% (7 of 21 patients), and 1 case was performed in the setting of redo biliary surgery. In the years 2000 to 2009, six additional reports were published comprising an additional 57 patients with the three largest series by Kim et al27 of 11 patients, Choi et al30 of 18 patients, and Finkenstedt et al62 of 10 patients. Again, the predominant cause of recurrent PHT was recurrent hepatitis C in 53% (30 of 57 patients), acute or chronic rejection and delayed graft function in 16% (9 of 57 patients), hepatic veno-occlusive disease in 7% (4 of 57 patients), and various miscellaneous or unknown causes in the remainder. Of these patients, 49 of 57 (86%) patients presented with refractory ascites or hepatic hydrothorax, and only 8 of 57 (14%) presented with variceal hemorrhage.27,30,62–65 Since 2010, seven publications have presented an additional 121 patients with the largest by Saad et al24 presenting 38 cases, Feyssa et al28 presenting 26 cases, and King et al29 presenting 22 cases. Recurrent hepatitis C was responsible for recurrent PHT in 43% (52 of 121 patients), alcohol use alone or in combination with hepatitis B or C in 8% (10 of 121 patients), and vascular abnormalities or hepatic venous outflow obstruction in 10% (11 of 121 patients). Recurrent hepatitis B, hepatocellular carcinoma, cystic fibrosis, nonalcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, sarcoidosis, and cholangiopathy were all reported as well but in fewer than 10% of cases. The etiology was not reported or was unknown in 30 patients. Refractory ascites or hepatic hydrothorax continued to be the dominant reported indication for TIPS after transplant with 106 of 121 patients (87%) in this category. A total of 14 of 121 (12%) patients had a TIPS performed after transplant for variceal hemorrhage. A single case was reported for small-for-size syndrome (SFSS).23,24,28,29,66–68 There are two aspects for discussion regarding TIPS in liver transplant recipients: technical considerations and the actual clinical outcome of TIPS in this particular population. Early in the clinical practice of TIPS in the United States, there was a debate whether liver transplant anatomy adds to the technical difficulty of the procedure.22,25,69,70 Intuitively, knowledge of portal and hepatic venous anatomy and surgical anastomoses is paramount as was emphasized by Richard et al69 and supported by other subsequent authors. As transplant techniques have evolved, surgical anastomoses have changed as well. Traditionally, orthotopic liver transplantation involved caval reconstruction. In most modern centers, the piggyback anastomosis technique has supplanted caval reconstruction, avoiding veno-venous bypass and reducing the warm ischemic time of the graft, ultimately improving outcomes. Richard and coworkers69 raised the anatomic concern for piggyback anastomoses posing technical difficulty to the TIPS procedure. Although Saad and coworkers24
Introduction
TIPS as a Preoperative Prelude to Liver Transplantation
TIPS in Liver Transplant Recipients
Technical Aspects
Piggyback Anastomosis
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