Impact of Nonmalignant Portal Vein Thrombosis in Transplant Recipients With Nonalcoholic Steatohepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition and its more severe progressive state, nonalcoholic steatohepatitis (NASH), is currently the second most common indication for waitlisted adults in the United States. The association of portal vein thrombosis (PVT) prior to or at transplant and poor graft and patient outcomes is not well established, particularly among NASH patients who inherently have an increased hypercoagulable profile. Using the United Network for Organ Sharing dataset, we analyzed graft and patient outcomes of patients transplanted for the indication of NASH with and without PVT. Of 3,689 NASH transplant recipients, the prevalence of PVT was 12% (450 with PVT and 3,239 without PVT). NASH transplant recipients with PVT had inferior graft and patient survival compared to NASH transplant recipients without PVT, even after adjusting for recipient and donor demographic characteristics, body mass index (BMI), synthetic dysfunction, and presence of diabetes. In a multivariate Cox regression model, NASH transplant recipients with PVT had a 37% increased risk of graft failure (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.15-1.63; P < 0.001) and 31% increased risk of overall death (HR, 1.31; 95% CI, 1.09-1.58; P < 0.001) compared with NASH transplant recipients without PVT at transplant. This difference in graft and patient survival was most pronounced in the early post-transplant period. These results demonstrate NASH patients with PVT have decreased graft and patient survival independent of recipient and donor factors. This article is protected by copyright. All rights reserved.

Development of a Model to Predict Portal Vein Thrombosis in Liver Transplant Candidates: The Portal Vein Thrombosis Risk Index

“…PVT is a common complication in liver transplant candidates that is strongly associated with inferior outcomes in the perioperative transplant setting, including increased morbidity and mortality, which parallel lower health‐related quality of life . Consequently, the decision to proceed with liver transplantation listing, surveillance imaging, and treatment with either anticoagulation or transjugular intrahepatic portosystemic shunt (TIPS) in transplantation candidates with PVT remains one of much debate and uncertainty.…”

“…This is increasingly important given the worsening obesity and NASH epidemics that parallel the increasing demand for liver transplantation as evidenced by the fact that NASH is the leading indication for liver transplantation in women and simultaneous liver‐kidney transplantation for all sexes . Perhaps more importantly, recipients with NASH and PVT have inferior posttransplantation survival as demonstrated by Agbim et al, who found a 37% increased risk of graft failure and a 31% increased risk of overall death in NASH transplant recipients with PVT compared with NASH recipients without PVT at transplant. As more and more patients develop NASH cirrhosis, we would expect an increasing number of high‐risk patients to be identified by the PVT‐RI, further increasing its future clinical utility.…”

“…PVT is no longer considered to be an absolute contraindication to liver transplantation due to advances in liver transplantation techniques as well as better imaging modalities and classification systems to define the extent of clot burden . Despite newer approaches, patient‐centered outcomes remain inferior in candidates with PVT in both the pretransplant and posttransplant settings with greater rates of hepatic decompensation, decreased posttransplant survival, and lower health‐related quality of life . Risk factors for incident PVT include reduced portal vein blood flow, severity of liver disease, hepatocellular carcinoma (HCC), and also etiology of liver disease (eg, nonalcoholic steatohepatitis [NASH] and autoimmune hepatitis) .…”

“…(5,6) Despite newer approaches, patient-centered outcomes remain inferior in candidates with PVT in both the pretransplant and posttransplant settings with greater rates of hepatic decompensation, gaballa et al Abbreviations decreased posttransplant survival, and lower health-related quality of life. (7)(8)(9)(10) Risk factors for incident PVT include reduced portal vein blood flow, severity of liver disease, hepatocellular carcinoma (HCC), and also etiology of liver disease (eg, nonalcoholic steatohepatitis [NASH] and autoimmune hepatitis). (11)(12)(13)(14)(15)(16) Acquired hypercoagulability also plays a role in PVT development through elevated levels of prohemostatic factor VIII and decreased levels of the naturally occurring prohemostatic protein C, protein S, and antithrombin as well as heparin cofactor II.…”

Portal Vein Thrombosis Prediction: Rebalanced Coagulation and Rethinking Anticoagulation

“…Because the authors did not know if the presence of moderate‐to‐severe ascites predated the PVT, the data may show that more severe portal hypertension either predisposes patients to PVT or results from PVT; both are plausible but not distinguished in this study. In addition, NASH has previously been shown to be an independent risk factor for PVT in the UNOS data set, which is believed to be increased secondary to obesity and chronic inflammation . However, more work is needed to further detail the specific reasons for this finding.…”