Outcome of Budd-Chiari Syndrome Patients Treated With Direct Oral Anticoagulants: An Austrian Multicenter Study.

BACKGROUND AND AIMS: Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS. METHODS: The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers. RESULTS: Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n = 30) of patients had decompensated liver disease, and 87.2% (n = 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n = 16 of 22) of patients were switched from low-molecular-weight heparin (n = 12) or vitamin K antagonist (n = 4) to DOAC after disease stabilization or improvement, 27.3% (n = 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n = 2 upper gastrointestinal bleeding, n = 1 lower gastrointestinal bleeding, n = 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years. CONCLUSIONS: DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

Bevacizumab to Treat Cholangiopathy in Hereditary Hemorrhagic Telangiectasia: Be Cautious: A Case Report.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular dysplasia characterized by mucocutaneous telangiectasia and visceral arteriovenous malformations. Hepatic involvement with vascular malformations may lead to portal hypertension, biliary ischemia, and high-output cardiac failure. There is no curative treatment for the disease. Liver transplantation is indicated for life-threatening complications, but it carries significant risk due to surgery and immunosuppressive treatment. Some case reports or small open studies suggest that bevacizumab, a recombinant humanized anti-VEGF monoclonal antibody, should be efficient in limiting bleeding and in reducing liver disease in HHT.We report a case of a 63-year-old woman with HHT presenting with ischemic cholangiopathy. Liver transplant was indicated, but given a previous encouraging report showing a regression of biliary disease with bevacizumab in 3 patients with HHT this drug was proposed. No significant efficacy but a severe adverse effect was observed after 3 months: bilateral pulmonary embolisms, thrombosis in the right atrial cavity, and thrombosis of the right hepatic vein were evidenced. Bevacizumab was stopped; anticoagulant started. Four months later, the patient received a transplanted liver. She feels well 1 year later.This case report intends to provide the information for clinicians to consider the use of bevacizumab in HHT. Whereas several uncontrolled series and case reports have suggested the efficacy of this drug in reducing bleeding and liver disease, no severe side effects were mentioned to date. For the first time in HHT we report a life-threatening side effect of this drug and no efficacy. Moreover, systemic thrombosis, the observed complication, may preclude transplantation. To date, caution seems still indispensable when considering the use of bevacizumab in HHT.

Tamoxifen-associated Budd-Chiari syndrome complicated by heparin-induced thrombocytopenia and thrombosis: a case report and literature review.

We reported a rare case of Budd-Chiari syndrome (BCS) associated with tamoxifen use, which was later complicated by heparin-induced thrombocytopenia and thrombosis (HITT). The patient was a 44 year-old woman with a medical history of lobular carcinoma in situ, who had been on tamoxifen for 2 years, presented with abdominal pain and distention. Imaging studies followed by a liver biopsy confirmed the diagnosis of BCS. On extensive work-up, the patient was found to have an unclassified myeloproliferative disorder with positive JAK-2 V617 mutation. After discontinuing tamoxifen, the patient was started on intravenous heparin. However, later in the course, she developed HITT. Myeloproliferative disorder, in conjunction with tamoxifen, predisposed the patient to be highly thrombophilic resulting in BCS. HITT was found to be relatively common in BCS. Anticoagulation and blood count need to be carefully monitored, and the possibility of HITT emergence in these patients should always be kept in mind.

Heparin-induced thrombocytopenia associated with acute liver graft failure.

An orthotopic liver transplantation (OLT) is of a proven benefit in an acute liver failure (ALF). Heparin-induced thrombocytopenia (HIT) is strongly associated with thromboembolic complications. We present the case of a 56-year-old patient who underwent an OLT owing to an ALF of unknown aetiology. HIT type II with consecutive hepatic and portal vein thrombosis caused progressive graft failure. Total hepatectomy and porto-caval shunt were performed to reduce the toxic effects of liver cell necrosis such as multiorgan failure involving the respiratory, renal and cardiovascular systems. A suitable liver graft was allocated after an anhepatic bridging period of 56 h. Specific complications due to end-stage liver failure-such as acidosis, coagulopathy, decrease of vascular resistance, cerebral oedema, myocardial infarction and right heart failure-were treated. Following a re-OLT, the patient made a complete recovery. We present a rare case of HIT-associated early liver graft failure followed by a prolonged anhepatic phase and finally a successful re-OLT.

[Features of anesthesia in rats at abdominal operations].

Nowadays, in Russia, diethyl ether is the most popular narcosis for rodent and particular rats. We had tested the new methods based on Zoletil 100 + XylaVet (15 mg/kg and 15-10-5 mg/kg) respectively. 6 conventional female rats were treated with this narcosis. The rats, early have narcotized by diethyl ether were investigated as control group. All of 6 treated with new narcosis animals died in early post-operative time. Interestingly enough, that organ toxicity, except neurologic toxicity, was not described in literature and manuals. We assume that this new narcosis is the cause of portal thromboses.

[Budd-Chiari syndrome induced by hormonal oral contraception in the patient with congenital thrombophilia-factor V Leiden mutation--a case report]. / Zespól Budd-Chiari indukowany doustna antykoncepcja hormonalna u pacjentki z wrodzona trombofilia-mutacja czynnika V Leiden--opis przypadku.

The Budd-Chiari syndrome is a rare pathology resulting from various etiological factors which often contribute to its late diagnosis. Liver cirrhosis, malignant tumors and haematological disorders resulting in hypercoagulability, are the most common reasons of Budd-Chiari syndrome. The syndrome is characterized by portal hypertension and splanchnic congestion due to obstruction of hepatic venous outflow. The first symptoms include pain, ascites and hepatosplenomegaly. The diagnosis of Budd-Chiari syndrome can be achieved by Doppler ultrasonography, Computed Tomography scan, Magnetic Resonance or Single Photon Emission Computed Tomography. In the following article, a case report of a patient with diagnosed Budd-Chiari syndrome as a result of congenital thrombophilia-factor V Leiden gene mutation is presented. Clinical symptoms, diagnostic process, as well as treatment options, were shown in the article.

Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis.

Hepatic veno-occlusive disease (VOD) is a common complication of high-dose chemotherapy associated with bone marrow transplantation. While the pathogenesis of VOD is uncertain, plasminogen activator inhibitor-1 (PAI-1) has emerged as a diagnostic marker and predictor of VOD in humans. In this study, we investigated the role of PAI-1 in a murine model of VOD produced by long-term nitric oxide synthase inhibition using L-NAME. After 6 weeks, wild-type (WT) mice developed extensive fibrinoid hepatic venous thrombi and biochemical evidence of hepatic injury and dysfunction. In contrast, PAI-1-deficient mice were largely protected from the development of hepatic vein thrombosis. Furthermore, WT mice that received tiplaxtinin, an antagonist of PAI-1, were effectively protected from L-NAME-induced thrombosis. Taken together, these data indicate that NO and PAI-1 play pivotal and antagonistic roles in hepatic vein thrombosis and that PAI-1 is a potential target in the prevention and treatment of VOD in humans.

Possible association between Budd-Chiari Syndrome and gemtuzumab ozogamicin treatment in a patient with refractory acute myelogenous leukemia.

Gemtuzumab ozogamicin (GO; CMA-676; Mylotarg) is a chemotherapeutic agent approved for the treatment of CD33-positive acute myelogenous leukemia in patients of age 60 years or older after first relapse. Hepatic veno-occlusive disease has been reported to develop as a late complication of gemtuzumab ozogamicin treatment. A patient who developed Budd-Chiari Syndrome with hepatic vein thrombosis following treatment with GO is presented. This complication has not been previously reported, and it deserves to be considered as a possible adverse effect of gemtuzumab ozogamicin.

[Paroxysmal nocturnal hemoglobinuria revealed by hepatic vein thrombosis (Budd-Chiari syndrome) during Infliximab therapy]. / Thrombose des veines hépatiques au cours d'un traitement par infliximab (Remicade) révélant une hémoglobinurie paroxystique nocturne.

We report the case of a 41-Year-old man presenting with hepatic vein thrombosis (Budd-Chiari syndrome) during Infliximab therapy for ankylosing spondylitis. The systematic work-up revealed paroxysmal nocturnal hemoglobinuria. One Year later the patient was receiving anticoagulation therapy and was in good condition. The role of Infliximab in the development of thrombosis in this patient with rare underlying thrombophilia is discussed.

Extra hepatic portal vein thrombosis in a child associated with lupus anticoagulant.

The presence of lupus anticoagulant has been implicated in venous as well as arterial thrombosis. We report here a 10-year-old boy who presented to us with hematemesis, malaena and splenomegaly. An ultrasound showed a recanalized portal vein with collaterals suggestive of portal vein thrombosis. He had grade IV esophageal varices. The liver function tests were normal. Investigations for prothrombotic factors showed that tests for PNH and for APC resistance were negative. Levels of anti-thrombin II and protein C were normal. There was a prolonged activated partial thromboplastin time with a normal prothrombin time. Presence of lupus anticoagulant was confirmed with dilute Russell viper venom time and platelet neutralization test. Repeat tests after 10 weeks showed persistence of the lupus anticoagulant. ELISA test for anti-phospholipid antibody was negative. The association of lupus anticoagulant with portal vein thrombosis in the pediatric age group is very rare.

Budd-Chiari syndrome and Epstein-Barr virus (EBV) associated plasmacytoma in a patient with chronic active EBV infection.

A 42-year-old Japanese man with chronic active Epstein-Barr virus (EBV) infection initially responded to treatment with interleukin-2 (IL-2). Six months later he developed thrombosis in the hepatic veins, and Budd-Chiari syndrome associated with severe hepatic damage was diagnosed. He also developed a solitary EBV-positive plasmacytoma in the right femur. Since these rare complications occurred after long-term IL-2 therapy, the possibility that long-term IL-2 therapy might cause Budd-Chiari syndrome and liver damage as well as EBV-associated plasmacytoma is discussed.