1. מחלות כלי דם של הכבד פרופ' ריפעת ספדי מנהל היחידה למחלות כבד
מרכז רפואי הדסה ע"כ, י"ם

2. אירועים טרומבוטיים בכבד
Hepatic Vein
Budd-Chiari Syndrome
Veno-occlusive Disease
Portal Vein Thrombosis
Heptic Artery Thrombosis
Peliosis Hepatis
Hepatic Artery Aneurysm
Hepatic Artery Atherosclerosis
Hepatic Artery
Gallbladder
Portal Vein
CBD

3. Budd-Chiari Syndrome

4. אירועים טרומבוטיים בכבד
Budd-Chiari Syndrome
Veno-occlusive Disease
Portal Vein Thrombosis
Heptic Artery Thrombosis
Peliosis Hepatis
Hepatic Artery Aneurysm
Hepatic Artery Atherosclerosis

5. Budd-Chiari Syndrome (BCS): Definition
Reductions in hepatic venous outflow:
From Rt. Atrium
To small hepatic venules
Including IVC
Results from thrombosis of ≥1 Hepatic Veins:
Increases sinusoidal pressure/ congestion
Portal hypertension
Reduced portal vein flow
Hepatomegally, ascites……

6. BCS, Etiology Hypercoagulable States: Infectious (10%): DILI:
Antiphospholipids Synd.
Antithrombin Def.
Factor V Leiden Mutation
Lupus anticoagulant
MTHFR
Myeloproliferative Disorders (PV & Eth) accounts ~50% (JAK2)
PNH
Postpartum thrombocytopenic Purpura
Pregnancy (10%)
Prot. S/C Def.
Prothrombin mutation G20210A
Sickle Cell Disease
Aspergillosis
Filariasis
Hydatid cyst
Liver Abscess
amebic
or pyogenic
Pelvic cellulitis
Schistosomiasis
Syphilis TB
In western countries, thrombosis oh hepatic veins is the most common presentation, wherease in Asia & Africa, membraneous obstruction of IVC accounts > 40%.
DILI:
OC’s, AZA, ChemoTx, HERBS

7. Spectrum of DILI , Amox-Clav)
MTX=methotrexate; AZA=azathioprine; OCP=oral contraceptives pills; chemo Tx=chemotherapy; SOS=sinusoidal obstruction syndrome (veno-occlusive disease; HCC=hepatocellular carcinoma

8. BCS, Etiology Malignancies (10%): Miscellaneous: Multiple factors:
Adrenal Carcinoma
Bronchogenic carcinoma
HCC
Leiomyosarcoma
Leukemia
Renal cell ca (RCC)
Rhabdomyosarcoma
Behcet’s Disease
Celiac Disease
Dacarbazin therapy
IBD
Lap. Cholecystectomy
Membraneous obstruction of vena cava (MOVC): ~70% in Asia & Africa
Polycystic Liver disease
Sarcoidosis
Trauma to hepatic veins
Living Related Liver Transplantation
Multiple factors:
Idiopathic:
Accounts 25%
Accounts 10%

9. Clinical Features of BCS
Usually:
Ages 20-40
Asymptomatic:
Thrombosis of one HV
Large veneous collaterals
Symptomatic
Affecting Factors:
Extent and Speed of obstruction
Extent and Speed of collateral formation

10. Clinical Features of BCS
Fulminant:
Rare
Preg. & complications
Acute 20-30%:
Tender Hepatomegally.
Ascites
Short term mortality 50%
Subacute to chronic:
Within > 6 months
Ascites
Develop cirrhosis
Hepatosplenomegaly
IVC may be occluded
Collaterals (flanks & back)
Edema
Mild LFT’s abnormalities

11. Pathology Zone 1 – most oxygenated; Zone 3 – least oxygenated
Hepatic Vein
Hepatic Artery
Portal Vein
CBD
Gallbladder

12. Zone 3 ischemia / centrilobular necrosis
Budd-Chiari Syndrome: Pathology
Zone 3 ischemia / centrilobular necrosis

13. BCS: Diagnosis Liver Function tests: Duppler US
Normal
Mild elevation
Marked elevation (cholestatic)
Duppler US
Sensitivity & Spec. > 80%
HV’s are not visualized
No flow signal in HV’s
Diagnostic accuracy low in:
Large body habitus.
Comma-shaped collaterals

14. 39-year-old woman with Budd-Chiari syndrome
Contrast-enhanced transverse CT scan obtained during portal phase
Brancatelli, G. et al. Am. J. Roentgenol. 2007;188:W168-W176
dilatation of azygos vein
Fig. 8A —39-year-old woman with Budd-Chiari syndrome. Contrast-enhanced transverse CT scan obtained during portal phase shows development of intrahepatic (black arrow) and extrahepatic (white arrow) subcutaneous collateral vessels after hepatic venous thrombosis. Ascites and dilatation of azygos vein (arrowhead) are evident.
intrahepatic & extrahepatic subcutaneous collateral vessels after hepatic venous thrombosis.
Copyright © 2007 by the American Roentgen Ray Society

15. MRI & CT MRI & CT do not add much to Dupplex US MRI > CT due to:
Provides more anatomic HV & IVC details
Less nephrotoxic (?)
US, CT & MRI are sufficient to diagnose BCS
Venography is almost not needed for diagnosis:
Pressure measurements
Biopsy
PTA
TIPS

16. 49-year-old woman with Budd-Chiari syndrome
Fig. 1A —49-year-old woman with Budd-Chiari syndrome. Unenhanced transverse CT scan shows dysmorphic liver with enlarged left lobe and caudate which has normal attenuation compared with other, low-density portions of liver. Ascites (a) is evident.
Brancatelli, G. et al. Am. J. Roentgenol. 2007;188:W168-W176
Copyright © 2007 by the American Roentgen Ray Society

17. 43-year-old woman with Budd-Chiari syndrome
Fig. 10A —43-year-old woman with Budd-Chiari syndrome. Contrast-enhanced transverse CT scan obtained during portal phase shows caudate lobe hypertrophy and left lobe atrophy. Central portion of liver is enhanced, and liver periphery is hypoperfused. More cephalic section (not shown) showed hepatic veins as areas of hypoattenuation due to thrombosis.
Brancatelli, G. et al. Am. J. Roentgenol. 2007;188:W168-W176
Copyright © 2007 by the American Roentgen Ray Society

18. 25-year-old woman with Budd-Chiari syndrome
Fig. 9 —25-year-old woman with Budd-Chiari syndrome. Contrast-enhanced coronal maximumintensity-projection CT scan obtained during portal phase shows patent inferior vena cava with extrinsic compression (arrow) of enlarged caudate lobe (C).
Brancatelli, G. et al. Am. J. Roentgenol. 2007;188:W168-W176
Copyright © 2007 by the American Roentgen Ray Society

19. Symptomatic BCS, Treatment
Diuretics:
Spironolactone
Furosemide
Diet Na+ restriction
Large Volume Paracentesis
Anticoaglation:
Heparin
Warfarin (INR 2-2.5)
Myeloproliferative DO:
Hydroxyurea
Aspirin

20. Symptomatic BCS, Treatment
Radiologic Intervention:
Angioplasty
TIPS
TIPS:
Low mortality
Usually successful
Intra hepatic VC to HV
Useful in HV & VC obstruction.
TIPS dysfunction in 70%
Covered stents improved patency from 19 to 67%.
Transplant complications if protruded to PV

21. BCS, Surgical Treatment
In MOVC cases:
Senning procedure:
Dorso-cranial liver resection.
&
Hepatico Atrial Anastomosis.
Fingure Fracture
Vena Cava Webs resection:
Direct Resection or
Trans-atrial
PS Shunt in classical BCS:
Effective Portal Hypertension relief
In successful cases:
PV became outflow.
Hepatomegaly resolves.
Histology improves
Prolonged survival 90%
Shunt thrombosis:
Mesocaval 33% in 5 yrs
Portocaval 3% over 13 yrs
CI in IVC occlusion
(Membraneous obstruction of vena cava)

22. Liver transplantation for Budd–Chiari
Fulminant BCS
Decompensated cirrhosis (CHILD B&C)
BCS recurrence 4-10%
Increase risk for HA & PV thrombosis
Overall 5 year survival 85%
Marco Senzolo et al. (2005) Update on the classification, assessment of prognosis and therapy of Budd–Chiari syndrome
Nat Clin Pract Gastroenterol Hepatol 2: 182–190 doi: /ncpgasthep0143

23. Veno-occlusive Disease

24. אירועים טרומבוטיים בכבד
Hepatic Vein
Hepatic Artery
Portal Vein
CBD
Gallbladder
Budd-Chiari Syndrome
Veno-occlusive Disease
Portal Vein Thrombosis
Heptic Artery Thrombosis
Peliosis Hepatis
Hepatic Artery Aneurysm
Hepatic Artery Atherosclerosis

25. Veno-Occlusive Disease Sinus Obstruction Disease
Pathology: Obstruction to HV outflow:
Subendothelial swelling
& Reticulated collagen
Central vein of lobule and branches
Endothelial oedema,
fibroblastic proliferation,
obstruction by fibrosis & thrombosis

26. Veno-Occlusive Disease Sinus Obstruction Disease
After bone marrow transplantation
25% incidence
Shortly post BMT
Due to toxic endothelial injury:
Chemotherapy
Radiation therapy
Azathioprin & 6MP
Plant alkaloids:
Senecio
Crotalaria

27. Veno-Occlusive Disease Sinus Obstruction Disease
Massive congestive & painful hepatomegaly
Ascites
Jaundiced, out of proportion.
Centrilobular necrosis leads to cirrhosis
Mortality 20% to 50% (100% in severe cases)

28. Veno-Occlusive Disease Sinus Obstruction Disease
Symptomatic treatment only for portal HTN
Inconclusive data:
Ursodeoxycholic acid
Heparin & LMWH
Prostaglandin E1
High doses of Glucocorticosteroids
N-acetylcysteine
Anti-Thrombin & Protein C
tPA
Defibrotide

29. Veno-Occlusive Disease Sinus Obstruction Disease
TIPS: 50% success, 10% long term survival.
Liver Transplantation!

30. Portal Vein Thrombosis

31. אירועים טרומבוטיים בכבד
Hepatic Vein
Hepatic Artery
Portal Vein
CBD
Gallbladder
Budd-Chiari Syndrome
Veno-occlusive Disease
Portal Vein Thrombosis
Heptic Artery Thrombosis
Peliosis Hepatis
Hepatic Artery Aneurysm
Hepatic Artery Atherosclerosis

32. Pathogenesis Cirrhosis (10-30%): Cancer:  Portal blood flow
 Liver synthetic activity of protein C, S & anti-Thr. III
High incidence of concomitant HCC
Cancer:
Tumor invasion
Compression or constriction effect from tumor mass
Prothrombogenic changes (cysteine protease)

33. Etiologies of PVT Local Factors 10-50% Thrombophilia 40-60%
Inflammatory
Surgical
Inherited
Acquired
Sepsis
Liver Transplant
FVL
Malignancy
Pancreatitis
Splenectomy
Prothrombin Mutation 20210G/A
APL syndrome
Diverticulitis
Colectomy
Anti-thrombin III
Anti-cardiolipin
Appendicitis
Umbilical Vein Catheters
Protein C/S deficiency
Elevated Homocysteine
Peptic Ulcer D.
Portocaval Shunt
OCPs
Blunt Trauma
Pregnancy
IBD
Simply stated many things have been known to cause PVT.
Above all, PVT is most common in liver disease and cirrhosis.
The quoted prevalence being approx 10-30% in all cirrhotics
The prevalence rate outside the realm of cirrhosis is unknown due to small numbers of cases reported.
The literature does try to categorize the etiologies of PVT into:
Local Factors such as surgeries and procedures of the abdomen, as well as inflammatory states of the GI tract.
And… Thrombophilic states including the genetically inherited states and other acquired processes that are known to be risk factors for thromboses
Local factors thought to attribute anywhere from 10-50% and thrombophillic states accounting for roughly half.
Our patient of course was found to have the prothrombin gene mutation
Which briefly is a new discovery (1996) by a gentleman named Poort
Is thought to raise thrombus risk by 2-4 fold with ethnic predominance in europeans
Concerning PVT this mutation is now thought to be a cause in many cases originally thought to be idiopathic
The green highlighted items are causes that are also common to many of our Family Medicine patients

34. Clinical manifestations
Acute PVT
No definitive time-frame distinguishes acute from chronic PVT (~ 60 days)
Abdominal pain, N/V (Mesenteric veins involved)
Few clinical consequences:
Immediate vasodilation of the hepatic arterial system
Rapid development of tortuous collateral veins bypassing (cavernous transformation)

35. Clinical manifestations
Chronic PVT
Portal hypertension
Hemorrhage of varices (30-70%),
Outcome of bleeding is better than with cirrhosis
Splenomegaly (50%) & hypersplenism
Ascites (10%),
Jaundice (<5%),
Encephalopathy
Abdominal pain when mesenteric veins involved
Normal to slightly increased LFT’s
10-year-survival was 81% without cirrhosis, cancer or mesenteric vein thrombosis (Janssen et al. Gut 2001)

36. Investigation Color doppler ultrasonography
Echogenic thrombus within portal vein lumen
Dilation proximal to the occlusion
Absence of an identifiable portal vein
Collateral vessels
(cavernous transformation)

37. Investigation CT scan MR angiography Portal venography
Filling defect in contrast-enhanced lumen
Train track appearance when totally occluded
MR angiography
Portal venography
Endoscopic ultrasound

38. Gadolinium-enhanced T1-weighted MR
22-year-old woman with chronic Budd-Chiari syndrome and portal vein occlusion
Gadolinium-enhanced T1-weighted MR
CT scan obtained during portal phase
CT scan obtained during portal phase
gallbladder varices
Fig. 7A —22-year-old woman with chronic Budd-Chiari syndrome and portal vein occlusion. Gadolinium-enhanced T1-weighted MR image (A) and contrast-enhanced transverse CT scan obtained during portal phase (B) show occlusion of vein (arrow, A and B) draining caudate lobe. Fig. 7C —22-year-old woman with chronic Budd-Chiari syndrome and portal vein occlusion. Contrast-enhanced transverse CT scan caudal in relation to B obtained during portal phase shows cavernous transformation of portal vein (arrow) and gallbladder varices (arrowhead). Ascites is evident. This case is unusual in that caudate lobe has impaired venous drainage with resulting heterogeneous enhancement.
occlusion of vein draining caudate lobe
cavernous transformation of PV
Brancatelli, G. et al. Am. J. Roentgenol. 2007;188:W168-W176
Copyright © 2007 by the American Roentgen Ray Society

39. Portal and hepatic vein thrombosus
Minimun intensity projections
Maximum intensity projection

40. Cavernous Transformation8

41. Treatment, General Treat complications:
Endoscopy with banding or sclerotherapy
Limited evidence for beta-blockers if non-cirrhotic
TIPS
PS Shunt
Mesocaval and splenorenal shunts
Sugiura Procedure (esophogastric de vascularization & transection)
Broad spectrum antibiotics if pylephlebitis

42. Acute/ recent-onset
Anticoagulation may result in recanalization in more than 80% of cases (Condat et al. Hepatology 2000)
High rates of recanalization with thrombolysis compared with conservative treatment (Malkowski et al. Hepatogastroenterology 2003)

43. Chronic PVT Vague Recommendations with Anticoagulation:
The risk of thrombosis is currently as clinically significant as the risk of bleeding.
The benefit-risk ratio favors anticoagulant therapy (Condat et al. Gastroenterology 2001)
Cohort study with 136 patients, 84 received anticoagulants, followed for median of 46 months.
Debate of anticoagulation use in non-cirrhotic PVT
- Condat & Sheen: 78-90% show resolution or
re-canalization of the thrombus

44. Anti coagulation PVT Anticoagulation for at least 3-6 months
Chronic anticoagulation if:
1) Hypercoagulable state
2) Surgical shunt
3) Concomitant mesenteric vein thrombus
Thrombolytics if mesenteric vein involvement or signs of ischemia
Broad spectrum antibiotics if pylephlebitis

45. Thank You