PVT In Patients With Chronic Liver Disease

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PVT In Patients With Chronic Liver Disease
Cooperation Bilharz-Beaujon Cairo - March 16-18,
2008

• Dominique-Charles Valla
• Hôpital Beaujon, APHP, Université Paris-7, Inserm
  CR3B

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PVT in Patients with Cirrhosis
Epidemiology Manifestations Causal factors Therapy
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Prevalence of Overt PVT in Cirrhosis
Screening for HCC 0.6 In-Hospital 7.0
Necropsy 8.0 Before LTx or PSS 15.0
Okuda et al. Gastroenterology 198589279-86.
Chang et al. J Pathol Bacteriol 196589473-80.
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Incidence of PVT in Patients with Cirrhosis
Amitrano, Endoscopy 2002. Francoz et al. Gut 2005
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Prevalence of Occult PVT in Cirrhosis Liver
explants
Veins involved
Small mural thrombus 64 Large veins (intimal
fibrosis) 25 Small veins (intimal fibrosis)
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Wanless et al. Hepatology 1995211238-47.
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Prevalence of Overt PVT in Schistosomiasis
Preoperative 5 Splenectomy/Devascularization
19 Distal splenorenal shunt 50
Widman. Hepatogastroenterology 2003
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PVT in Patients with Cirrhosis
Epidemiology Manifestations Causal factors Therapy
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PVT and Cirrhosis Associations

• Portal hypertensive bleeding
• Failure to control bleeding
• Ascites
• Hepatic encephalopathy
• Hyperdynamic circulation
• Intestinal ischemia or infarction

Nonami Hepatology 1992. Orloff J Gastrointest
Surg 1997. DAmico Hepatology 2003. Amitrano J
Hepatol 2004.
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PVT and Cirrhosis Associations
At LTx N Liver weight

• PVT 63 17 g/Kg
• No PVT 401 21 g/Kg

P lt .02
Nonami et al. Hepatology 1992161195-8
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PVT in Patients with Cirrhosis
Epidemiology Manifestations Causal factors Therapy
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Causes For Venous Thrombosis
Local factors
External Factors Environmental
THROMBOSIS
Internal Factors Prothrombotic Disorders
Inherited
Acquired
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Inherited Prothrombotic Disorders
Gain of function Factors (FV, FII) Common (gt
2.0) Moderate risk Dg DNA analysis
Loss of function Inhibitors (PC, PS,
AT) Uncommon (lt 0.1) High risk Dg Plasma level
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Acquired Prothrombotic Disorders
Common Moderate risk Inflammatory
states Malignancy Hyperhomocysteinemia
Uncommon High risk Myeloproliferative dis. APL
syndrome PNH Behcets disease
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Inherited Prothrombotic Disorders
Gain of function Factors (FV, FII) Common (gt
2.0) Moderate risk Dg DNA analysis
Loss of function Inhibitors (PC, PS,
AT) Uncommon (lt 0.1) High risk Dg Plasma level
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Coagulation Inhibitors in Cirrhosis
100
Child-Pugh
A
B
C
A
B
C
A
B
C
A
B
C
Protein C
Antithrombin
Protein S
Romero-Gomez. J Clin Gastroenterol 2000
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Acquired Prothrombotic Disorders
Common Moderate risk Inflammatory
states Malignancy Hyperhomocysteinemia
Uncommon High risk Myeloproliferative dis. APL
syndrome PNH Behcets disease
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PVT and Cirrhosis Antiphospholipid Ab

• ACL common in chronic liver diseases (20)
• Usually non specific (low fluctuating titer, no
  LA)

Mangia, Am J Gastroenterol 1999. Dalekos, Eur J
Gastro Hepato 2000. Munoz-Rodriguez, J Hepatol
1999. Prieto, Hepatology 1996. Quintarelli, J
Hepatol 1994. Violi, Hepatology 1997.
Romero-Gomez J Clin gastro 2000
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Risk Factors for Portal Vein Thrombosis. Cirrhosis
without HCC
Univariate Age, Child-Pugh class, Surgery
for portal hypertension Endoscopic
sclerotherapy Prothrombotic features
Mangia, Am J Gastroenterol 1999. Nonami,
Hepatology 1992. Davidson, Transplantation 1994.
Amitrano, J Hepatol 2004.
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PVT and Cirrhosis Prothrombotic Disorders
NS lt .05 lt .05 lt .01
7 2 5
F. V Leiden F. II gene mutation C677T MTHFR At
least one Two or more
13 35 43 70 22
14
0
Amitrano et al. Hepatology 200031345-8.
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Risk Factors for Portal Vein Thrombosis. Cirrhosis
without HCC
Univariate Age, Child-Pugh class, Surgery
for portal hypertension Endoscopic
sclerotherapy Prothrombotic features
Multivariate G20210A FII (OR 5.94)
Mangia, Am J Gastroenterol 1999. Nonami,
Hepatology 1992. Davidson, Transplantation 1994.
Amitrano, J Hepatol 2004.
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PVT in Patients with Cirrhosis
Epidemiology Manifestations Causal factors Therapy
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PVT and Cirrhosis Why to treat?

• To prevent aggravation ?
• To facilitate transplantation

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Portal Vein Thrombosis Clinical results of
anticoagulant therapy

• In patients without cirrhosis
• In patients with cirrhosis

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Acute PVT Complete Recanalization
Pts at risk

91 50 33 19 15 7 4
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Chronic Portal Vein Thrombosis
Anticoagulation
Anticoagulation
yes
yes
no
no
17
6.0
p 0.212
per 100 patients per year
p 0.015
7
1.2
Thrombosis
Bleeding
Condat et al. Gastroenterology 2001 120490
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Chronic portomesenteric venous thrombosis
Warfarine
yes
no
1.00
HR for Death
p0.038
0.10
Orr et al. Hepatology 2005 42 212A (AASLD San
Francisco 2005)
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Patients on the Waiting List for LTx
PVT before transplantation (n 29)
No anticoagulation (n 10)
Anticoagulation (n 19)
Recanalization (n 8)
Recanalization (n 0)
Francoz, Gut 2005
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TIPS for PVT in Cirrhosis

• Limited data
• Feasible and safe
• Risk of obstruction unclear
• Risk of encephalopathy unclear
• Benefit unclear

Senzolo Alim Pharmacol Therap 2006. Van Ha
Cardiovasc Intervent Radiol 2006. Bauer Liver
Transplant 2006
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PVT and Cirrhosis Summary

• Common in end-stage cirrhosis
• Uncommon in well-compensated cirrhosis
• Causal factors surgery, stasis, thrombophilias
• A marker for severity certainly
• A cause for aggravation uncertain
• A limitation for liver transplantation certainly

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PVT and Cirrhosis What we do in Beaujon
Objectives Recanalization (recent
thrombus) Prevention of thrombus
extension Indications ? Child A with
thrombophilia ? Patients listed for
LTx Monitoring Anti-Xa 0.5 U/ml Factor II
25 to 35
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Hemostasis in Cirrhosis

• Normal thrombin generation in platelet-poor
  plasma.
• Decreased thrombin generation in severely
  thrombocytopenic blood.
• Elevated levels of vWF support platelet adhesion
  despite reduced functional capacities.

Caldwell. Hepatology 2006
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INR in Patients with Cirrhosis

• Not related to prothrombin levels along the same
  regression line as for Vitamin K antagonists.
• Due to uncarboxylated metabolites of coagulation
  factors
• Interlaboratory variability.
• ? Adjustment based on Factor II level 25-35?

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Patients on the Waiting List for LTx
PVT before transplantation 24
Partial 21
Complete 3
Recanalization 0
Recanalization 15
No post-OLT PVT
Francoz, ILTS 2008
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Acute Portal Vein Thrombosis
Recanalisation
83
75
Thrombolysis (in situ, n 20)
Anticoagulation (alone, n 27)
Condat. Hepatology 2000
Holliingshead. J Vasc Interv Radiol 2005
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Acute Portal Vein Thrombosis
100
Major Bleeding


60
5
0
Thrombolysis (in situ, n 20)
Anticoagulation (alone, n 27)
Condat. Hepatology 2000
Holliingshead. J Vasc Interv Radiol 2005