7. INTRODUCTION
Budd Chiari syndrome
■ First described by George Budd in 1845
■ Chiari presented details of 13 cases in 1899
■ Definition
■ Partial or complete Hepatic venous outflow obstruction at any level
from the small hepatic veins to the junction of inferior vena cava and
right atrium, regardless of the cause of obstruction.
■ Outflow obstruction caused by hepatic veno-occlusive disease and cardiac disorders is
excluded from this definition.
EASL 36th workshop, PragueJanssen et al, J Hepatol 2003
8. EPIDEMIOLOGY
• Incidence of BCS in Asia : app: 0.469per million Prevalence 5/million
• Incidence of BCS in Europe:2 /million Prevalence 1.4/million
• Pooled incidence : 1/million /year Prevalence 11/million
SEX PREDISPOSITION
• In West: F>M (2/3rd of the cases are F ): Median age: 35 to 50 years
• In Asia M=F : Median age is around 35 years
• 4.9% of all portal hypertension patients- Japan
• 7-9% of all portal hypertension patients- India
• Untreated cases :Progress to Hepatic congestion/Portal HTN/Ultimately Cirrhosis
• Fulminant cases: Acute liver failure
10. Primary vs Secondary
• Primary :- Hepatic venous outflow obstruction originating from
endoluminal venous lesion (thrombosis, webs, endophlebitis)
• Secondary :- Hepatic venous outflow obstruction originating from a
lesion outside the venous system (tumor, abscess, cysts).
• obstruct outflow by invading the lumen or by extrinsic compression.
11. PRIMARY BCS
■ At least one underlying inherited or acquired procoagulative disorder seen in 75%,
■ Multiple disorders in 25% of BCS patients
■ BCR ABL Negative Myeloproliferative disorders : MC Acquired cause 45-50%
■ 10-40% of above are associated with PCV
■ 30-50 % of above are associated with JAK2V617F mutation
■ Thrombophilic disorders are the next most frequent cause of BCS-
◻ MC being Factor V Leiden mutation.
Valla D et al. Primary myeloproliferative disorder and hepatic
vein thrombosis Ann Intern Med 1985
16. MEMBRANOUS OBSTRUCTION OF THE IVC
• As a cause of BCS m c in Asian than west population
• Affects predominantly the intra hepatic portion of IVC
• Bacterial Infection related
• Greater association with HCC
• Seen commonly in 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
19. 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
20. In 59 patients with HVOO, none had Factor V Leiden or G20210 PT gene mutation ---- SGPGI data- Indian Jr of gastroenterol 2005
21. Classification- Vessel involvement
• Type I- IVC with or without hepatic veins occlusion
• Type II- major hepatic veins
• Type III- small centrilobular veins
24. ACCORDING TO DURATION OF DISEASE
■ Fulminant <8 weeks
■ Acute 1 month- 6 months
■ Chronic >6 months
Dilawari JB, Medicine 1994
25. ACCORDING TO DURATION OF DISEASE
Fulminant - 7%
■ Present with encephalopathy, tender hepatomegaly, ascites, jaundice
■ Most common early puerperium
■ Highest mortality
Acute -28%
■ Present with tender hepatomegaly, ascites
Chronic- 65%
■ Present with signs & symptoms of portal hypertension
Dilawari JB, Medicine 1994
28. Association in BUDD CHIARY
• 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%
JOURAL OF HEPATOLOGY 2012
29.
30. DIAGNOSIS
Clinical findings/Manifestations
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
31. 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.
32. CLINICAL MANIFESTATIONS:
• Classical triad :Abdominal pain /Ascites/Hepatomegaly
• Presentation depends on extent/severity and rapidity of HVOTO and
presence of decompressing venous collaterals.
AT PRESENTATION:
• Ascitis:80% /Hepatomegaly:70%/Pain abdomen:60%
• Other manifestations: Fever/pedal edema/visible back veins
• Less common: Esophageal bleeding 5%
Hepatic encephalopathy 10%
Upto 20% are clinically asymptomatic
Upto 50% have clinically classified as acute have changes of chronicity
35. Liver function tests
• Bilirubin rise – varying extent
• Transaminase rise > 5 times - acute type
• ALP rise – varying extent
• Serum albumin decreases
• High SAAG ascites > 1.1gm/dL
• But total ascitic protein of >2.5-3 gm/dl
36.
37. DOPPLER ULTRASOUND
■ First investigation of choice
■ Sensitivity of > 75%
◻ Hepatic veins devoid of flow signal
◻ Hepatic venous collaterals, comma shaped
◻ Spider-web appearance usually located in the vicinity of the HV ostia
◻ Stagnant, reversed or turbulent flow( normal flow in HV is phasic in relation
to respiration and cardiac cycle).
Hyperchoic cord replaces the normal vein
38. LIMITATIONS
• 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.
39. CT /MRI:
• Inferior to doppler for intrahepatic collaterals
• Used to confirm the diagnosis
• Better appreciation of liver parenchyma demonstrating mosaic
pattern of enhancement indicating reduced perfusion with necrosis
• Concurrent PVT can be diagnosed
• Therapeutic planning owing to better spatial resolution
40. CECT
Acute Budd-Chiari syndrome
◻ The liver exhibits decreased peripheral enhancement caused by portal
and sinusoidal stasis and stronger enhancement of the central portion
of the liver parenchyma
◻ The thrombosed hepatic veins are hypo attenuating,
◻ Ascites and splenomegaly are usually present
41. Subacute or chronic BCS
◻ Portosystemic and intrahepatic collateral vessels
◻ Regions of hypoperfused liver parenchyma
◻ Inferior vena cava calcification
◻ Large (comma-shaped) intrahepatic collateral vessels
◻ Development of multiple regenerative nodules
◻ Characterestics of nodules in BCS:
Small<3 cm diameter
Multiple>10 lesions
Hypervascular
disseminated throughout the liver
Brancatelli etal -AJR: 2007
42. MRI
• T1-weighted MR image
shows straight demarcation
(arrows) between normally
perfused central portion of
liver and hypoperfused
periphery.
• T2-weighted fat-saturated MR
image shows hyperintensity
of liver periphery
Horton Liver Int. 2008
43. Doppler:
• Senstivity: 89%
• Specificity: 85%
• PPV: --
• NPV: --
CT venography:
• Senstivity: 86%
• Specificity: 97%
• PPV: 94%
• NPV: 94%
MR venography
• Senstivity: 100%
• Specificity: 67%
• PPV: 94%
• NPV: 100%
2020 The Authors. Published by the British Institute of Radiology
44. 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
45. ■ Hepatic venogram obtained
with selective catheterization
of hepatic vein shows
spiderweb pattern.
46. 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
47. ROLE OF LIVER BIOPSY
• Parenchyma may be affected unevenly
• Exclusion of cirrhosis or severe fibrosis
• Differentiates veno-occlusive disease & cirrhosis of other origin
Findings:
• Intense centrilobular & sinusoidal congestion, inflammation, cirrhosis
and necrosis
• Extravasation of red cells in space of Disse.
• Limited value in assessment of severity and prognosis
48. ASSESSMENT OF DIAGNOSIS
■ The diagnosis of Budd–Chiari syndrome should be suspected under the following
circumstances:
◻ ascites+ liver enlargement+ upper abdominal pain present simultaneously
◻ chronic liver disease with intractable ascites and only mildly altered liver
function tests
◻ liver disease in a patient known to have prothrombotic disorder
◻ fulminant hepatic failure is associated with liver enlargement and ascites
◻ chronic liver disease remains unexplained after acoholism, chronic viral
hepatitis B or C, autoimmunity, iron overload, Wilson’s disease and alpha-1
antitrypsin deficiency have been excluded.
49. Hyper Coagulable states : Workup
1) CBC, prothrombin level, APTT ,
2) Fibrinogen
3) Red cell mass, plasma volume
4) Bone marrow biopsy, cell culture
5) Anti-thrombin III assay
6) Protein-C Assay
7) S antigen assay
8) Lupus anticoagulant
9) Anticardiolipin antibodies
10) Ham’s acid hemolysis test
10) Activated protein –C (resistance and or
factor V Leiden mutation
11) JAK2 mutations : marker is the gain-of-
function mutation V617F of the JAK2 gene
12) Plasma homocysteine level
13) β-HCG pregnancy screen
14) Endogenous erythroid colony assay
15) Flow cytometry for blood cells deficient in
CD55 and CD59 (PNH)
16) Molecular test for G20210A Prothrombin
gene mutation
17) Anti–β 2 -glycoprotein-1 antibodies
50. PITFALLS OF HYPER COAGULABLE WORKUP
■ Acute thrombosis can result in transiently reduced levels of
antithrombin III , protein C and protein S
■ Heparin therapy produces 30% decline in plasma antithrombin III levels
■ Warfarin produces a marked drop in the functional activity of protein C
and protein S (but not heparin)
Hoffman: Hematology: Basic Principles and Practice, 4th ed.
51. Optimal timing of investigation
■ At least 2 weeks after the patient has completed the initial course of oral
anticoagulant therapy
■ If tested at the time of acute thrombosis or while on anticoagulation
◻ Normal levels - exclude the diagnosis of primary thrombophilia
◻ Low levels - will need to be confirmed by repeat testing after anticoagulation is
discontinued.
Hoffman: Hematology: Basic Principles and Practice, 4th ed.
52. The Impact of Liver Disease on the
Diagnosis of Prothrombotic Disorders
■ Antithrombin, protein C, and protein S are synthesized by hepatic cells
◻ a low level of a coagulation inhibitor can be interpreted as a primary defect only when the levels of coagulation factors are
entirely normal.
◻ Otherwise a familial deficiency has to be proved
■ Low levels of anticardiolipin antibodies are found in 20% of patients with chronic liver disease,
◻ diagnosis APLA syndrome is best established on the detection of lupus anticoagulant or antibeta-2 glycoprotein I
antibodies
◻ Indian data: ACL antibody levels were similar in BCS and cirrhosis( 30%)
Rakesh Aggarwal, Am J Gastroenterol 1998
Valla. D Thrombosis and Anticoagulation in Liver Disease: Hepatology 2008
53. The Impact of Liver Disease on the
Diagnosis of Prothrombotic Disorders
■ Myeloproliferative diseases (MPDs) can be easily overlooked in patients
with PHT
◻ Splenomegaly can be attributed to portal hypertension
◻ hemodilution and hypersplenism decrease peripheral blood cell counts and mask the
peripheral blood features of myeloproliferation.
◻ Conventional diagnostic criteria based on splenomegaly and peripheral blood cell
counts cannot be applied to patients with portal hypertension.
54. 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.
• TREATMENT TARGETS:
• Remove the cause
• Prevention of thrombosis extension
• Relieve the high pressure & congestion in liver
• Management of massive ascites
55. MANAGEMENT
• Medical therapy
• Minimal invasive interventions
• Surgery (Shunt and Non Shunt Surgeries)
• Liver transplantation
56. MEDICAL MANAGEMENT
• Anticoagulants (Heparin/ warfarin):Given in all BCS patients
• Systemic thrombolytic therapy
• Management of ascites
– Sodium restriction (<2gm/day)
– Diuretic therapy
– Therapeutic paracentesis
• Management of hematologic disorders
57. ANTICOAGULATION
■ Immediate and permanent anticoagulation as soon as diagnosis of BCS is made
■ Oral anticoagulants to be started on D 1 with overlap of heparin
◻ Warfarin intially causes a procoagulant effect due to rapid reduction in Protein-C
◻ Heparin to be continued for atleast 4 days or till INR is in therapeutic range ( 2.5)
for 2 days
■ Target INR 2.5:
◻ Inherited thrombophilia- 2.5
◻ Higher target 3.5 needed in APLA
■ Duration of therapy – life long
Guidelines on anticoagulation- British Journal of Hematology 1998
Valla etal Hepatology 2003
58. ■ INR to be monitored daily for first 4 days and then weekly until
stable INR is reached
■ Stopping anticoagulation prior to interventional procedure
◻ Warfarin to be stopped at least 3 D prior to procedure ( takes atleast 4
days for INR to reach 1.5)
◻ Once INR < 2 heparin can be instituted
59. • In India, a response rate of 60.5% was achieved with anticoagulant therapy
alone in patients with a CTP score up to 9.
Shukla A, Bhatia SJ.Indian J Gastroenterol 2010;29:8–11.
■ French study, 120 patients admitted from 1970 to 1992- routine
anticoagulaton asscoiated with increased survivival.
Zeitoun etal Hepatology1999
• In another multicentre study The use of anticoagulants did not yield a
significant beneficial effect on survival.
• Murad etal Hepatology 2004
Controls liver disease in approx. 15-20% only
Complications bleeding in: 20% patients (Pleisser et al. hepatology 2006)
60. RESPONSE TO MEDICAL THERAPY
• NEEDS PRESENCE OF ALL 6 criteria:
1) Absence of clinical ascites,normal Na and creatinine in the absence
of diuretic therapy or only low dose diuretics(spironolactone
75mg/d and furesemide 40mg/day with moderate Nacl intake.
2) Increase in factor v by >40% of normal value
3) Decrease conjugated bilirubin to below 0.8 mg/dl
4) Absence of 1st or recurrent GI Bleed with primary or secondary
prophylaxis
5) No occurance of SBP
6) BMI>20kg/m2 after removing ascites and edema
61. 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
62. THROMBOLYSIS
■ Thrombolysis more likely to
succeed if
◻ Thrombus is recent
◻ Thrombolytic agent was locally
infused
◻ Only partial occlusion is present
◻ Followed by angioplasty or
stenting done
Research lacunae:
■ First report of thrombolytic therapy in
the early 70s
Warren RL, et al.. Gastroenterology 1972
■ Currently, no level I data comparing
the efficacy of various drug regimes
■ (ie, streptokinase versus tissue
plasminogen activator).
■ Optimal drug delivery (systemic versus
local) / appropriate timing of
thrombolytic administration are
unknown.
Sharma S, et al. Pharmacological thrombolysis in Budd Chiari syndrome: a single centre experience
and review of the literature. J Hepatol 2016
63. Systemic thrombolytic therapy/Local
Thrombolytic therapy ( Acute BCS )
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
65. 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
66. ■ Those who do not improve or develop severe or recurrent complications
■ despite medical treatment should be considered for :
◻ Stenting,
◻ Transjugular intrahepatic portosystemic shunt (TIPS) or
◻ Surgical portosystemic shunting.
■ Liver transplantation should be considered when there is progression of
liver dysfunction
67. Transluminal angioplasty alone
• Earlier studies : High re-occlusion rates
• 30 patients : Balloon angioplasty : successful in 28 ; restenosis
occurred in 4.
Kohli V, Nundy 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
68. Angioplasty & Stenting
• 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
69. TIPS
• Long-term patency, despite routine anticoagulation therapy is only 50%,
with 36–72% of patients needing reintervention.
• 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
Senzolo etal Nat Clin Pract Gastroenterol Hepatol. 2005
70. ■ TIPS should be considered as first-line therapy
Those failing medical therapies and recanaliztion therapies before OLT
◻ Variceal bleeding occurs,
◻ For acute and chronic BCS, and
◻ Fulminant BCS if a liver donor is not available within 2–3 days.
71. • 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%
72. DIPS
• DIPS is an alternative to TIPS in which the caudate lobe is used to
create a side-to-side shunt.
• Employed in patients with subacute and chronic BCS with preserved
liver function.
• May be viable for patients when hepatic blood flow is further
compromised by portal vasculature thrombosis.
• Technical (100%) and clinical success (83.3%)
73. ADAM HATZIDAKIS1,*, NIKOLAOS GALANAKIS1 , Interventional Medicine & Applied Science, Vol. 9 (2),
pp. 86–93 (2017)
• six patients (three men and three women) with a mean age of 36.2
years.
• Technical success 100% with significant decrease in HVPG < 12
• In four out of five patients (who were followed up), ascites and
variceal bleeding resolved completely whereas in the other patient
ascites was slightly relieved.
75. SURGICAL SHUNT
■ The common shunts used are side to- side portocaval and mesocaval shunt
■ A differential of 10 mmHg or more between the portal vein and intra hepatic IVC
is considered essential.
■ Mesocaval shunt is often preferred
◻ Portocaval shunt is difficult in the presence of caudate lobe hypertrophy
◻ Mesocaval shunting can be achieved at some distance from the portal vein, thereby increasing the
feasibility of a subsequent liver transplantation.
◻ Associated with higher mortality rate in decompensated cirrhosis
◻ Currently, surgical shunts have been almost completely replaced by TIPS.
76.
77. Quality of life after Surgical Portal
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
78. LIVER TRANSPLANT
• Fulminant liver failure : rare
• Chronic 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
79. ■ There are seven major transplant series with more than 10
patients each, comprising 162 patients in total with survival
rates of 50–95%
■ Although almost all genetic thrombophilic disorders are cured
by transplantation, thrombosis still occurs and routine
anticoagulation therapy is necessary
82. HCC IN BCS
• Various study noted development of HCC in 2 to 6% of patient over 5
to 7 years of follow up.
• In one study from France, the cumulative incidence of HCC was 6% at
7 years of follow-up.
• Difficulties in diagnosis
• Nodular regenerative hyperplasia (NRH),
• Hepatocellular adenomas
• Benign lesions are usually multiple (>10 lesions), small in size (<4 cm),
hypervascular, and disseminated throughout the liver.
• LI-RADS criteria not applied.
• Histological evidence is must.
83. PROGNOSIS
■ The natural history of BCS is not well known, as most publications
report on treated patients
■ In the largest cohort of 237 patients, the severity of encephalopathy,
ascites, prothrombin time and serum levels of bilirubin were found
to be useful in predicting mortality.
■ Murad SD et al.. Hepatology 2004
■ In another study, the 5-year survival was 70% in patients with a
high Child or Pugh score, older age, ascites, and raised serum
creatinine, compared with 95% if all these factors were absent.
■ Zeitoun G et al.. Hepatology 1999
84.
85. SUMMARY
■ Anticoagulation started without delay.
■ Stable patients without symptoms—No interventional therapy to be given.
■ Portosystemic shunting or transplantation -not be proposed to patients
who improves rapidly on medical therapy
◻ Acute -in days
◻ Chronic- in weeks.
◻ TIPS insertion currently is preferred to surgical shunting.
◻ Transplant option should always be open- as patient can
deteriorate rapidly
