Primary Budd-Chiari Syndrome (Hepatic Venous Outflow Tract Obstruction)
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1 Primary Budd-Chiari Syndrome (Hepatic Venous Outflow Tract Obstruction) Dominique-Charles Valla DHU UNITY Service d Hépatologie, Hôpital Beaujon (AP-HP), Clichy; CRI-UMR1149, Université Paris-Diderot and Inserm U1149, Paris, France
2 BCS Level of Obstruction in Europe 2% 49% 49% IVC Combined Hepatic veins EN-Vie BCS Cohort. Darwish Murad. Ann Intern Med 2009
3 Epidemiology of BCS France, 2010 Questionnaire survey Discharge code Incidence (per 10 6 per yr) Prevalence (per 10 6 ) Rare Romania: disease 100 = < cases per 10? 6 I. Ollivier and Réseau Français des Maladies Vasculaires du Foie. ILC Vienna 2015
4 Survival % Primary BCS Natural History Ascites with emaciation GI bleeding due to PHT Liver failure Adapted from Tavill. Gastroenterology years
5 Survival % Primary BCS Natural History Fulminant Acute Subacute Chronic Adapted from Tavill. Gastroenterology years
6 Primary Budd-Chiari Syndrome Etiology Diagnosis Treatment Challenges
7 Prothrombotic Conditions in Western Budd-Chiari Syndrome At least one condition 87% Multiple conditions 48% Local factor 5% A multifactorial systemic disorder EN-Vie BCS Cohort. Darwish Murad Ann Intern Med 2009
8 Western Budd-Chiari Syndrome Prevalence of Major Causes Myeloproliferative neoplasm 49% Paroxysmal nocturnal hemoglobinuria 10% Antiphospholipid syndrome 20% Factor V Leiden 12% An underlying blood disorder is the rule EN-Vie BCS Cohort. Darwish Murad Ann Intern Med 2009
9 Prothrombotic Disorders Diagnostic Pitfalls 1. Liver dysfunction decreases PC, PS and AT plasma levels Molecular analyses 2. Portal hypertension masks MPN. Hypersplenism decreases blood cell counts. V617F JAK2 & CALR mutations Clusters of dystrophic megacaryocytes (BMB)
10 JAK2 V617F CALR mutations Bone marrow biopsy No MPN? Pos ve Pos ve Pos ve MPN MPN MPN Turon, J Hepatol 2014, Rautou, ILC 2015
11 Prothrombotic Conditions in Western Budd-Chiari Syndrome At least one condition 87% Multiple conditions 48% Local factor 5% What is the local factor? EN-Vie BCS Cohort. Darwish Murad Ann Intern Med 2009
12 Site Specificity for Thrombosis in MPN V617F JAK2 Hepatic vein thrombosis 35-50% Portal vein thrombosis 20-35% Extra-splanchnic thrombosis 2% General population 0,2% Specificity of portal/hepatic venous endothelium? Mercier, NEJM Pardanani, Leukemia Plessier, Hepatology Kiladjian, Blood 2008, Dentali, Blood Qi, APT 2011.
13 Primary Budd-Chiari Syndrome Site Specificity in Prothrombotic Disorders Behcet s D. V Leiden Low SES MPD OC Valla J Hepatol 2009 PNH
14 Primary Budd-Chiari Syndrome Etiology Diagnosis Treatment Challenges
15 Diagnostic Strategy Any patient with acute or chronic, symptomatic or asymptomatic liver disease Copyright 2008 BMJ Publishing Group Ltd. Valla, D-C Gut 2008;57:
16 Primary Budd-Chiari Syndrome Etiology Diagnosis Treatment Challenges
17 EASL, Prague Baveno, 2005, 2010, 2015 Anticoagulation Medical therapy Angioplasty TIPS Transplantation
18 Budd-Chiari Syndrome - Survival 26% 13% LTx 39% TIPS 27% Tt méd. EN-Vie cohort. Seijo. Hepatology 2013
19 Primary Budd-Chiari Syndrome Etiology Diagnosis Treatment Challenges
20 Budd-Chiari Syndrome Current Challenges Complications of therapy Encephalopathy related to TIPS Bleeding related to anticoagulation therapy Prediction of treatment response Complications of blood disease Regenerative nodules and HCC Cazals-Hatem, Hepatology Chait, Br J Haematol Moucari, Gut Garcia-Pagan, Gastroenterology Rautou, J Hepatol Seijo, Hepatology 2013.
21 Budd-Chiari Syndrome Regenerative changes Macronodules T1 T2 Cazals-Hatem. Hepatology 2003
22 BCS complicated by HCC N Primary BCS 67 HCC 17 Pooled Prevalence 15.4% Ren, EJGH 2013 Park, WJG 2012.
23 BCS - HCC vs benign regenerative nodule Larger size (> 4cm) AFP > 20 ng/l Heterogeneous Hyperenhanced at arterial phase Wash-out at portal and/or late phase IVC obstruction Moucari. Gut Gwon, Radiology Liu, BMC Gastro Zhang Eur J Radiol 2012 Ren, EJGH 2013
24 Budd-Chiari syndrome - Conclusions A spontaneously fatal liver disease. Underlying blood disorder is the rule, with myeloproliferative neoplasm in the first place. BCS must be considered and assessed with Doppler-US in any patient with liver disease. Prognostication at baseline is not satisfactory.
25 Budd-Chiari syndrome - Conclusions Good results of a therapeutic strategy based on minimal invasiveness and stepwise approach. Severe treatment related complications Long-term outcome jeopardized by malignancy (underlying blood disease and HCC). Expert centers concentrating experience are needed.
26
27 BCS Level of Obstruction Country Year % IVC % IVC+HV % HV Europe Japan China India Korea Darwish Murad, Ann Intern Med Sakr, WJG Dilawari, Medicine Okuda, J Hepatol Uskudar WJS Park WJG Han Radiology 2012
28 V617F-JAK2 in Xi an, China Primary BCS 4/77 5.2% Primary portal vein thrombosis 15/ % Cirrhotic portal vein thrombosis 1/64 1.6% Qi. J Gastroenterol Hepatol 2012
29 Shresta J Gastroenterol Hepatol 1996
30 Meta-analysis - Thrombophilia and BCS OR 95% CI FV Leiden Prothrombin G20210A C677T MTHFR +/ Hyperhomocysteinemia Antithrombin deficiency Protein C deficiency Protein S deficiency Qi. J Gastroenterol Hepatol 2013, Hepatol Research 2014, Clin Gastroenterol Hepatol 2014
31 Vascular Liver Diseases N 254 DNA available N 206 Selective PC or PS deficiency N 35 PC deficiency (mean level 53%) N 18 Deleterious PROC mutation N 5 % 28 PS deficiency (mean level 44%) N 17 Deleterious PROS1 mutation N 4 % 24 Plessier, Alhenc-Gelas et al., AFEF 2014 BCS 74, PVT 150, OPV 30
32 Prognostic Scores for BCS Survival without LTx AUROC r 2 Child-Pugh MELD Clichy Rotterdam Rautou. Am J Gastro 2009
33 Prognostic Scores for BCS OLT-free survival BCS TIPS PI Score 0.08 x age x bilirubin x INR Garcia-Pagan, Gastroenterology 2008
34 BCS Level of Obstruction Country Year % IVC % IVC+HV % HV Europe Turkey Egypt Japan China India Korea Darwish Murad, Ann Intern Med Sakr, WJG Dilawari, Medicine Okuda, J Hepatol Uskudar WJS Park WJG Han Radiology 2012
35 Budd-Chiari Syndrome TIPS Hepatic Encephalopathy Total number of patients year probability % 21 Median time to 1 st episode months 1.2 Number transient 22 Number recurrent 4 Garcia-Pagan Gastroenterology 2008
36 BCS - Bleeding on Anticoagulation Therapy N N Death Prolonged Anticoagulation % Bleeding 24 17% 3 2% Portal hypertension 14 2 Intracranial 3 1 Other 7 0 Seijo. Hepatology 2013
37 Anticoagulation Medical therapy BCS TIPS PI Score 0.08 x age x bilirubin x INR Angioplasty TIPS Score >7 : PPV 99% NPV 96% Transplantation 1-yr OLT-free survival
38 Prognostic Scores for BCS Seijo. Hepatology 2013 Rotterdam score 1.27 x encephalopathy x ascites x prothrombin time x bilirubin BCS TIPS PI Score 0.08 x age x bilirubin x INR BCS Survival score 0.37 x age/ x ln creatinine x ln bilirubin AUC AUC AUC 0.767
39 HCC - BCS vs HBV Peripheral Pauci-nodular Well differentiated Portal venous invasion uncommon Selective TACE well tolerated? Shin Eur J Gastroenterol Hepatol Liu, BMC Gastro Gwon, Radiology 2010
40 BCS - Improved survival over 50 years ANTICOAGULATION Rx Copyright 2008 BMJ Publishing Group Ltd. Valla, D-C Gut 2008;57:
41 Primary Budd-Chiari Syndrome Site Specificity in Prothrombotic Disorders Behcet s D. V Leiden Low SES MPD OC Valla J Hepatol 2009 PNH
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