Liver transplantation has come a long way over the past 50 years, becoming the mainstay definitive treatment of most types of liver failure. Advancements in both operative techniques for enhanced recovery and pharmacologic management have greatly increased survival rates in recipients1. The disparity between available donors and waitlisted patients is still a great challenge. Of the 317 patients on Mexico’s 2019 liver transplant waiting list, only 223 received a graft, accounting for just 70% of the patients in need2. This seemingly universal barrier is also present in the developed world. The United Kingdom reported that the discrepancy leads to the death of ∼9% of patients listed for transplant, before a donor organ becomes available. The United States reports that waitlist mortality varies geographically, ranging from 6.5 to 37.4 deaths per 100 waitlist-years3,4.

Medical therapy has evolved and been optimized for the treatment of patients with liver failure, as have procedures designed to aid and restore the physiologic baseline. Procedures, such as transjugular intrahepatic portosystemic shunt (TIPS) and portocaval shunt placement, aim to reduce the systemic vascular complications of portal hypertension5. Rapid normalization leads to mesenteric venous decongestion, increased effective arterial blood volume, and increased response to pharmacologic management6,7 that clinically translates to a lower incidence of variceal bleeding, decreased bacterial translocation, and improved renal function8. Current indications for TIPS placement include refractory esophageal varices or early interventions for patients with a high risk of treatment failure, Budd-Chiari syndrome, and treatment-refractory ascites, showing superior control, increased survival, and better glomerular filtration rates, when compared with paracentesis8,9. However, the benefits of TIPS placement come at the cost of worsening liver function. Decreased perfusion shows increased international normalized ratio and bilirubin values, reduced albumin, and an increased risk of developing pulmonary hypertension, due to cardiac overload, and higher rates of encephalopathy, due to the shunting of unfiltered blood10–12. Risks for complications are also associated with the procedure. They include vascular injuries to the carotid arteries or right atrium, bleeding, portal or caval perforations, and biliary duct injury. The incidence of those complications, along with TIPS infection, have been reported at less than 1%13. Thus, TIPS can be a safe “bridging” therapy that enables the treatment of refractory symptoms until transplantation becomes available14. The aim of the present study was to compare operative time, operative bleeding, transfusions, intensive care unit (ICU) stay, and short-term survival in patients with TIPS prior to orthotopic liver transplantation (OLT) versus patients that only underwent OLT (OLT-only group).

We performed our study at a low-volume TIPS and OLT center.

A retrospective review was conducted on patients that underwent liver transplantation at the Hospital San José Tec de Monterrey, since the program first began in 1999 until February 2020. Records for hospitalization, operative notes, and clinical data were reviewed for all patients. A total patient population of 92 was reviewed, of which 9 (9.8%) underwent TIPS prior to receiving the transplant. Clearance from the hospital ethics committee and patient consent were obtained for this study.

Transplants were distributed, according to the Mexican General Health Law, Article 336, which states that organ allocation is dependent on the receptor’s status, transplant opportunity, expected benefits, compatibility, and hospital location. Organs were recovered from donors after brain death in all cases and rapid extraction procurement with 4C in-situ portal and arterial preservation solution was carried out, followed by standard cold storage (Starzl). Wisconsin solution was used in the first 12 cases and histidine-tryptophan-ketoglutarate for all the remaining transplants. Whole liver transplantation was performed in all patients. The classic technique, with the aid of a venovenous bypass, was carried out in only one case, whereas a vena cava preservation technique was employed in the others. Biliary reconstruction was achieved via duct-to-duct anastomosis. All 9 TIPS placements were performed by the same interventional radiologist. Procedures were carried out under general anesthesia, with ultrasound-assisted right internal jugular vein puncture. Guidewires were navigated to achieve selective hepatic vein catheterization and pre-shunt measures were obtained for portal, hepatic, and inferior vena cava vessels. Portograms were analyzed for circulation aberrations. Balloon dilation was performed before stent placement, changes in portosystemic pressures were recorded, and shunt patency was verified.

After the initial analysis, 1:3 propensity score (PS) matching was performed through a multiple stepwise regression of age, smoking status, and Child-Pugh grade. The resulting PSs for complications and mortality were used to select control cases from the OLT-only patient pool, using a nearest neighbor algorithm with a .05 clamp.

TIPS decompression of portal circulation helps alleviate symptoms by normalizing portal pressure. It is not a definitive treatment but has long been used as a bridge to transplantation15. Its physiologic and anatomic effects have been thoroughly described, and prior studies have analyzed its impact on operative outcomes. The reduction in portal pressure is theorized to lead to reduced portosystemic collaterals and portal vein engorgement, which would translate into less operative risk, bleeding, and transfusions. The presence of those 3 factors have previously been associated with negative clinical outcomes by some authors, albeit with conflicting evidence16–19. Some of the complications described also result in higher resource use15. The intrahepatic nature of the shunt enables its removal in situ with the liver, with no additional maneuvers, but some studies describe extrahepatic migration of the stent or its creeping into the main portal vein, hepatic venous outflow, inferior vena cava, or mesenteric vein, resulting in intraoperative complications18,20. Thus, there are authors that categorize TIPS as a risk factor for surgical complications. The exact incidence of those complications and their actual impact has yet to be accurately described15.

Questions have been raised as to the extrahepatic benefits of TIPS, such as improvements in glomerular filtration rate and a consequent decrease in the MELD score, which could lead to inpatient classification inequality. Mumtaz et al. noted in their study that lower MELD scores associated with TIPS could lead to unequal transplant opportunities, with longer waiting times in equally decompensated patients8,21. Table 3 describes the waiting times for our cohort. Even with the benefits TIPS brings, the increased waiting time, the associated risk for infection, and failing liver function may prove to be counterproductive22. However, Casadaban et al. concluded that disease progression, even with TIPS, as reflected in the MELD score, is similar to patients without TIPS, suggesting that it does not significantly impact transplant candidacy23. In fact, Unger et al. noted there was no difference in 5-year survival between patients with TIPS without transplant and those that were transplanted. Both groups performed similarly, with respect to operating times and reinterventions24. In some studies, TIPS itself is suggested to be a high-mortality procedure, showing a 30-day mortality rate of up to 44%25. Further studies could dive deeper into waiting times in low volume settings and assess whether TIPS results in prolonged waiting times. A similar study in Vienna by Unger et al. found no impact on waiting times for patients that underwent pre-transplant TIPS in their setting24.

Other alternative therapies, such as surgical portosystemic shunts, achieve the same effect and prior studies have shown increased operative times due to adhesions, modified anatomy, and required TIPS reversal16,26. Our study found that vascular effects were insufficient for decreasing intraoperative transfusion requirements, but did not result in the previously described complications that lengthened operative times. The same was true for other associated variables, such as hospital stay and interventions, leading to the conclusion that TIPS can be safely undergone before transplant without positively or negatively affecting operative outcomes. In 2019, a total of 8,372 livers were transplanted in the United States27. Mexico, however, has a much lower transplantation volume. Official 2019 figures show that only 223 liver transplants were conducted nationwide, and of those, just 62 were performed at private institutions; 5 of them at our low-volume institution2.

To the best of our knowledge, our cohort is the first to describe outcomes in patients with TIPS + OLT, compared with patients that underwent OLT-only, at a low-volume center for both transplant and TIPS procedures in a developing country. While the information provided by our study might be useful for centers with similar scenarios, undoubtedly our study’s biggest limitation was the small size of the group of patients with TIPS. Further studies could include detailed reporting on both long-term and short-term complications, other than overall mortality.

In conclusion, TIPS placement continues to provide adequate bridge therapy for patients with recurrent ascites or refractory variceal bleeding, with safe operative results. In both developed and developing countries, the resources of surgeons, staff, and operating rooms are finite, and TIPS has no greater impact on their use than OLT-only procedures do. Its equal need for transfusion, operative time, and ICU stays shows it is an adequate tool, with no administrative costs during transplantation or effect on patient safety. Further studies on similar cohorts and in centers with similar volumes could further confirm such findings.

No financial support was received in relation to this article.

The authors declare that there is no conflict of interest.