Use Of Transjugular Intrahepatic Portosystemic Shunt Research Articles

The role of pre-emptive Transjugular Intrahepatic Portosystemic Shunt in acute variceal bleeding: a literature review.

The development of portal hypertension has serious implications in the natural history of liver cirrhosis, leading to complications such as ascites, hepatic encephalopathy and variceal bleeding. The management of acute variceal bleeding has improved in the last two decades, but despite the advances in endoscopic methods the overall prognosis remains poor, particularly within a subgroup of patients with more advanced disease. The role of Transjugular Intrahepatic Portosystemic Shunt (TIPSS) is a well-established method of achieving haemostasis by immediate portal decompression; however, its use in an emergency setting as a rescue strategy is still associated with high mortality. It has been shown that ‘early’ use of TIPSS as a pre-emptive strategy in a patient with acute variceal bleed in addition to the standard of care confers superior survival outcomes in a subgroup of patients at high risk of treatment failure and death. The purpose of this review is to appraise the literature around the indications, patient selection, utility, complications and economic considerations of pre-emptive TIPSS.

Transjugular intrahepatic portosystemic shunts in liver transplant recipients

The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive procedure used to relieve the signs and symptoms of portal hypertension in patients with liver disease. The most common indications for placement are refractory ascites and variceal hemorrhage. In properly selected candidates, TIPS placement can serve as a bridge to liver transplantation. Expertise in TIPS placement after transplantation has significantly increased, which has allowed the procedure to become a viable option for retransplant candidates suffering the consequences of recurrent portal hypertension due to portal vein thrombosis, recurrent liver disease, or hepatic venous outflow obstruction (HVOO). However, TIPSs in liver transplant recipients are associated with a lower clinical response rate and a higher rate of complications in comparison with patients with native liver disease, and they are, therefore, generally reserved for patients with a Model for End-Stage Liver Disease (MELD) score ≤ 15 and ≤ 12 in patients with HCV. The role of TIPS placement in nonliver transplant recipients has been well studied in large trials, and it translates well into clinical applicability to candidates for orthotopic liver transplantation (OLT). However, the experience with OLT recipients is heterogeneous and restricted to small series. Thus, we focus here on reviewing the current literature and discussing the proper use of TIPSs in liver transplant recipients.

Improved Outcomes of Budd-Chiari Syndrome in Paroxysmal Nocturnal Hemoglobinuria with Eculizumab Therapy

Abstract 3478Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of hematopoietic stem cells characterised by deficiency of cell membrane glycosylphosphatidylinositol-anchored proteins, rendering the cells susceptible to complement attack. Budd-Chiari syndrome (BCS) describes obstruction of the hepatic venous outflow tract. Complications such as ascites and varices often occur at the time of acute thrombosis. Conventional management includes anticoagulation, transjugular intrahepatic portosystemic shunt (TIPSS) placement, peripheral/local thrombolysis and orthotopic liver transplantation (OLT). The morbidity and mortality of PNH patients with BCS is particularly high: a new thrombotic event or thrombosis extension in anticoagulated patients is reported in 27%; a significant proportion of TIPSS fail due to recurrent thromboses; historically, mortality rates of 67% have been reported; hematopoietic stem cell transplantation and OLT have unacceptably high transplant-related mortalities. Eculizumab prevents cleavage of C5 and reduces risk of thrombosis in PNH. The role of this monoclonal antibody in the management of BCS with PNH has yet to be evaluated. Nineteen PNH patients (12 female, 7 male) with a BCS diagnosis who were subsequently given eculizumab, were identified from the Leeds PNH Service. Patients were diagnosed with PNH between 1991–2012 (median follow up from PNH diagnosis 7.5 yrs, range 2 mths – 21 yrs; from BCS diagnosis 3.5 yrs). Median age at PNH diagnosis was 30 yrs (range 19–87) and at BCS 32 yrs (range 19–87). The mean granulocyte clone size at PNH diagnosis (n=14) was 86.3% (range 59.7–99%) and at BCS (n=12) was 93.1% (range 80.9–99.6%). BCS was the presenting feature of PNH in 9 (47.4%). Six were diagnosed as part of diagnostic work-up during the acute BCS. In 3, a diagnosis of PNH was made 1, 6 and 26 months post BCS. Ten (52.6%) were already known PNH at the time of their BCS. None were receiving eculizumab. Median time from PNH to BCS was 30 mths, range 3–132. Seven were anticoagulated (5 primary prophylaxis) prior to BCS. Eight PNH patients (Group 1) developed BCS before the availability of eculizumab and remained alive long enough to receive therapy. Six in Group 1 (75%) developed BCS complications prior to commencing eculizumab including development of varices (n=1), progression of thrombus despite full anticoagulation (n=1), ascites necessitating TIPSS (n=2), hepatomegaly (n=3) and splenomegaly (n=3). Two did not endure BCS complications but suffered cerebral vein thrombotic events on anticoagulation. The median time to first dose of eculizumab therapy in Group 1 was 3 yrs (range 2 mths – 11 yrs). All patients remain on eculizumab (median follow-up 6.9 yrs, range 2.8 – 7.1); there have been no further thrombotic events in this cohort. Group 2 consists of 11 PNH patients in whom BCS was diagnosed during the availability of eculizumab. Four received this less than 14 days from onset of BCS without any subsequent complications. The remaining 7 started eculizumab 2 or more weeks from probable onset of BCS. Complications included ascites necessitating TIPSS and/or gastric/esophageal varices. TIPSS procedures were effective in all patients once on eculizumab with no occlusions. Importantly, 3 of the 19 patients have stopped secondary anticoagulation after starting eculizumab (due to thrombocytopenia, hemorrhage or perceived bleeding risk due to varices). There have been no further thrombotic episodes in these patients. This case series is the first to document 19 patients, managed with eculizumab with both PNH and BCS. Rapid intervention with eculizumab in addition to anticoagulation when safe to administer, appears to prevent the development of BCS associated complications. If complications are established at diagnosis, eculizumab can prevent progression and reoccurrence; it also facilitates successful use of TIPSS. We can conclude: a) primary prophylaxis is not sufficient to prevent BCS in patients with PNH b) prompt treatment with eculizumab may negate long-term complications of BCS and allows effective and safe use of TIPSS c) in selected cases, eculizumab therapy may facilitate the withdrawal of anticoagulation without increasing subsequent risk of thrombosis and d) survival for this cohort is currently 100%. The management of BCS in PNH with immediate commencement of eculizumab and, where appropriate, use of TIPSS, is associated with improved outcomes. Disclosures:Kelly:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Richards:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Arnold:Alexion Pharmaceuticals, Inc: Honoraria. Hillmen:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hill:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria.