Budd chiari syndrome

Budd chiari syndrome

1. BUDD CHIARI SYNDROME DR ANANDO SENGUPTA DNB GASTRO 2 ND YR 10/4/18

2. Introduction Defined as obstruction of hepatic veins or terminal inferior vena cava (IVC) Synonymous with Hepatic venous outflow obstruction Obliterative hepatocavopathy

3. Epidemiology 0.2 and 2 per 1 million population in general population Incidence of BCS in Asia may be higher 4.9% of all portal hypertension patients- Japan 7-9% of all portal hypertension patients- India Primary BCS - venous anomaly (Thrombosis, Webs, Endophlebitis Secondary BCS - initial lesion outside the veins (Tumor, Abscess, Cysts)

4. Etiology Infections Aspergillosis Filariasis Hydatid cysts ( Echinococcus granulosus or E. multilocularis ) Liver abscess (amebic or pyogenic ) Pelvic cellulitis Schistosomiasis Syphilis TB Malignancies Adrenal carcinoma Hepatocellular carcinoma Leiomyosarcoma Leukemia Lung cancer Myxoma Renal carcinoma Rhabdomyosarcoma

5. Etiology Miscellaneous Behçet’s disease Celiac disease Dacarbazine therapy IBD Laparoscopic cholecystectomy Membranous obstruction of the vena cava Polycystic liver disease Sarcoidosis Trauma to abdomen or thorax

6. Membranous obstruction of the IVC Commoner in east Congenital or end result of acquired thrombosis (Recent Studies) Japan, China and other parts of Asia, South Africa India ( Khuroo & Datta , 1980 ) Chronic course : Most pts present with fibrosis, cirrhosis, PHTN Increased risk for HCC

7. Classification- Vessel involvement Type I- IVC with or without hepatic veins occlusion Type II- major hepatic veins Type III- small centrilobular veins

8. Pathophysiology

9. Pathophysiology ACUTE STAGE Portal vein becomes draining vein Increased hepatic arterial flow CHRONIC STAGE Necrotic areas replaced by fibrotic tissue Intrahepatic collateral vessels Heterogeneous enhancement with a reticular pattern at the periphery of liver

10. Pathophysiology Caudate lobe hypertrophy (50%) Portal vein obstruction - 10-20% Asynchronous obstruction of hepatic veins Hepatic veins – 66% (Usually two are blocked for disease to be clinically evident) Isolated occlusion of IVC – 10% Combined occlusion – 23% Horton et al Liver International ISSN 1478-3223 , 2007

11. Clinical features SYMPTOMS Abdominal pain & distention Anorexia Jaundice SIGNS Massive ascites (83- 100%) Hepatomegaly Collaterals Splenomegaly Jaundice Pedal edema Wasting Orloff et al Ann Surg 2000

12. Clinical suspicion Ascites , hepatomegaly and upper abdominal pain present simultaneously FHF with liver enlargement and ascites Liver disease in known case of prothrombotic disorder Patients with CLD, but intractable ascites contrasts with mildly altered LFT. May be few cases of idiopathic CLD.

13. Diagnosis Clinical findings Biochemical tests – LFT Imaging – ULTRASOUND ABDOMEN WITH DOPPLER : FIRST STEP – COMPUTED TOMOGRAPHY (CT) – MAGNETIC RESONANCE IMAGING (MRI) – HEPATIC VENOGRAPHY Infra and supra-hepatic caval pressure Hyper- coagulable profile, Bone marrow biopsy Liver Biopsy

14. LFT Bilirubin rise – varying extent Transaminase rise > 5 times - acute type ALP rise – varying extent Serum albumin decreases High SAAG ascites > 1.1gm/ dL

15. Doppler USG First investigation of choice Sensitivity & specificity > 85% CE-USG : superior to Gray scale & CD for detection/ characterisation of HV thrombosis HV patency and size/IVC Thrombosis Lack of visibility Reversal of flow Diffuse narrowing and irregularity Transformation into a cord-like remnant Collateral veins- hepatic/ extrahepatic

16. Limitations of sonography Restriction from body habitus , Intestinal gas or excessive ascites , Failure to detect fresh thrombus in veins, Failure to demonstrate patent veins within congested or shrunken cirrhotic liver Failure to demonstrate retroperitoneal collaterals Operator-dependency.

17. CECT Abdomen Venous anatomy – patent IVC, PV, HV and non visualisation of HV. Caudate lobe hypertrophy (Fan shaped enhancement) Collaterals, Ascites Liver- Necrotic areas Altered parenchymal perfusion pattern Early homogenous central enhancement Delayed patchy enhancement of periphery of liver Prolonged retention of contrast in the periphery Regenerative nodules Not useful in showing web in the IVC

18. MRI Particularly beneficial in non-diagnostic USG Liver morphology and regional perfusional disorders : similar to CECT. However, some parenchymal lesions such as Benign regeneration nodules (>10 in no,<4 cm & hypervascular ), Hemorrhagic necrosis and Perfusion disorders : MRI better than CECT Useful in differentiating regenerative nodules from HCC MR Angiography- before selecting a treatment modality

19. Angiography and Venography Conventional angiography Gold standard Pressure profile Anatomy of block IVC venography Infra-hepatic IVC To Right Atrium Pressure Gradient > 15mm Hg - Mesoatrial shunt Hepatic venography /SMA venography Occluded / narrow hepatic veins Spider web pattern of venous collaterals Wedge hepatic venous- IVC gradient >10mm Hg

20. Contemporary role of Venography TIPS placement, Catheter-directed thrombolysis , Mechanical thrombectomy Balloon angioplasty Recanalization of an occluded hepatic vein or vena cava with stent placement. Transjugular liver biopsy. Use of hepatic venography may be an essential guide and road map for surgical therapy in BCS Erdon , 2007 ; Kamath , 2006

21. Role of liver biopsy Parenchyma may be affected unevenly Exclusion of cirrhosis or severe fibrosis Feasibility of shunt Differentiates veno -occlusive disease & cirrhosis of other origin Trans-jugular biopsy Intense centrilobular & sinusoidal congestion, inflammation, cirrhosis and necrosis Extravasation of red cells in space of Disse . Limited value in assessment of severity and prognosis Tang T et al, J Hepatol 2001

22. Hyper Coagulable states : Workup CBC, prothrombin level, APTT , fibrinogen Red cell mass, plasma volume Bone marrow biopsy, cell culture, karyotype Anti-thrombin III assay Protein-C Assay S antigen assay Lupus anticoagulant Anticardiolipin antibodies Ham’s acid hemolysis test Activated protein –C (resistance and / or factor V Leiden mutation JAK2 mutations : marker is the gain-of-function mutation V617F of the JAK2 gene Plasma homocysteine level β- HCG pregnancy screen Endogenous erythroid colony assay Flow cytometry for blood cells deficient in CD55 and CD59 (PNH) Molecular test for G20210A Prothrombin gene mutation Anti– β 2 - glycoprotein-1 antibodies

23. Management Treatment depends on the cause, the anatomic characteristics and stage of liver disease, the pace of the disease Underlying disorder can be found in 70% cases & multiple disorders can be present in 25% Early relief of obstruction may reverse parenchymal abnormalities and improve survival Remove the cause Prevention of thrombosis extension Relieve the high pressure & congestion in liver Management of massive ascites

24. Management Medical therapy Minimal invasive interventions Surgery (Shunt and Non Shunt Surgeries) Liver transplantation

25. Medical Management Anticoagulants (Heparin/ warfarin ) Systemic thrombolytic therapy Management of ascites – Sodium restriction (<2gm/day) – Diuretic therapy – Therapeutic paracentesis Management of hematologic disorders

26. Anticoagulants – Recommended routinely – Underlying prothrombotic state – Heparin/ warfarin – INR 2.0-3.0 – Improvement in prognosis Zeitoun G et al, Hepatology 1999 – No reports of severe bleeding Janssen et al, J Hepatol 2003

27. Systemic thrombolytic therapy/Local Thrombolytic therapy No benefit Sharma et al, J Hepatol 2004 1/3rd of patients clinical response to treatment for periods of 2 months to 1 year. Recent series from China, 12 or 13 patients had patent hepatic veins without recurrent thrombosis after a mean follow-up of 24 months. The one initial treatment failure was salvaged by repeat angioplasty Zhang et al, 2013 Tissue plasminogen activator ( tPA ) is the direct thrombolytic of choice by catheter route

28. Medical therapy alone – Is it enough? 12/14 died within 6 months McCarthy PM et al, Arch Surg 1985 A complete response was achieved on medical therapy alone in 9 of 51 patients Plessier A et.al Hepatology 2006 8/20 significant improvement clinically and biochemically , 53% survival at 2 years Khuroo et al, J Gastroenterol Hepatol 2005

29. Minimal Invasive I nterventions Local thrombolytic therapy Transluminal angioplasty Endovascular stenting TIPS

30. Local thrombolytic therapy Catheter directed Delivered just proximal or within thrombus Overall success rate low Risk of bleeding Useful in patients with short history of thrombosis (acute disease) Sharma et al, J Hepatol 2004

31. Transluminal angioplasty alone Earlier studies : High re-occlusion rates 30 patients : Balloon angioplasty : successful in 28 ; restenosis occurred in 4. Kohli V, N undy S Lancet 1993 Long-term IVC patency has been achieved in more recent reports. ( particularly with using stents) Srinivas et al, 2012 Stents recommended with angioplasty Sharma et al, J Hepatol 2004

32. Angioplasty & S tenting Retrospective study from China 115 patients 57 % of the patients had membranous stenosis Success rate of stenting - 94 % in IVC and 87% in HV Patency : 90% at 45 months Zhang CQ et al, World J Gastroenterol 2003 Useful in- IVC webs, IVC stenosis , Focal HV stenosis , Post liver transplant patients

33. TIPS Decompresses portal system Covered stents- better results Indications- Bridge to transplant in fulminant BCS Acute form BCS Sub acute form BCS with Porta-caval pressure gradient < 10mmHg

34. Largest reported systematic review and metaanalysis 29 studies, 2255 patients Restenosis rate at 1 year in the TIPS group was 12 % 1 year survival in TIPS group : 87.3% 5 years survival in the TIPS group : 72.1% OS for any interventional strategy was 92% at 1 year and 76% at 5 years. Zhang et al, 2015 Complications of TIPS Procedure related mortality – 1-2% Worsening of encephalopathy- 13-44% Shunt dysfunction ( Portal pressure gradient > 12mm Hg, decreased luminal shunt diameter ) 18-78%

35. Surgical Management Decompressive surgical shunts Pre-requisite – Reversible liver injury Indication – Technically difficult TIPS (massive thrombosis) – Porta-caval pressure gradient > 10 mm Hg Radical membrane excision Surgical Removal of Venous Obstruction Liver Transplant

36. Quality of life after Surgical P ortal decompression Long-term shunt patency in 97-100%. Hepatic sinusoidal decompression was maintained. No ascites or need for diuretics. Liver function and size returned to normal. Variceal bleeding decreased Vascular thrombosis was prevented (anticoagulants). Encephalopathy did not occur when shunt was patent. 94-100% returned to work/housekeeping. 10 year survival was ≥ 91%. Quality of life was excellent when performed early in the course of disease Orloff MJ et al, Annals of Surg 2000

37. Liver transplantation Fulminant liver failure : rare C hronic and progressive liver disease (poor liver Synthetic function) Decompensated cirrhosis Decompensation after shunt procedures Shunt failure Unshuntable portal hypertension : Thrombosis of PV, SV, SMV Curative in protein C, S, antithrombin III deficiency and factor V leiden mutation Cruz E et al, Clin Transplant 2005 Tan HP et al, Liver Transpl 2000

38. Prognostic factors Age Severity of liver failure MELD/CTP score Presence of refractory ascites Serum creatinine Guy Zeitoun et al, Hepatology 1999 Valla DC et al, Semin Liv Dis 2002

39. Summary Difference in western and eastern literature Different sites and different pathology Shunt , TIPS and liver transplant- Complimentary modalities Treatment based on Presentation LFT Anatomy of block Available expertise

40. Eapen CE et al, Gut 2005