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Cooperation Bilharz-Beaujon Cairo - March 16-18, 2008. PVT In Patients With Chronic Liver Disease. Dominique-Charles Valla Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B. PVT in Patients with Cirrhosis. Epidemiology Manifestations Causal factors Therapy.

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Pvt in patients with chronic liver disease

Cooperation Bilharz-Beaujon

Cairo - March 16-18, 2008

PVT In Patients With Chronic Liver Disease

Dominique-Charles Valla

Hôpital Beaujon, APHP, Université Paris-7, Inserm CR3B


PVT in Patients with Cirrhosis

Epidemiology

Manifestations

Causal factors

Therapy


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 1985;89:279-86.

Chang et al. J Pathol Bacteriol 1965;89:473-80.


18% pt/yr

Listed for liver transplantation

Sclerotherapy

12% pt/yr

Incidence of PVT in Patients with Cirrhosis

Amitrano, Endoscopy 2002. Francoz et al. Gut 2005


Prevalence of Occult PVT in Cirrhosis

Liver explants

% Veins involved

Small mural thrombus 64 %

Large veins (intimal fibrosis) 25 %

Small veins (intimal fibrosis) 36 %

Wanless et al. Hepatology 1995;21:1238-47.


Prevalence of Overt PVT in Schistosomiasis

Preoperative 5 %

Splenectomy/Devascularization 19 %

Distal splenorenal shunt 50 %

Widman. Hepatogastroenterology 2003


PVT in Patients with Cirrhosis

Epidemiology

Manifestations

Causal factors

Therapy


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.

D’Amico Hepatology 2003. Amitrano J Hepatol 2004.


PVT and Cirrhosis:

Associations

At LTx N Liver weight

  • PVT 63 17 g/Kg

  • No PVT 401 21 g/Kg

P < .02

Nonami et al. Hepatology 1992;16:1195-8


Advanced

Liver Disease

Thrombosis

Decreased Portal

Blood Inflow

Blood stasis

Wall changes (PHT)

Advanced

Liver Disease

Thrombosis


PVT in Patients with Cirrhosis

Epidemiology

Manifestations

Causal factors

Therapy


Causes For Venous Thrombosis

Local factors

External Factors Environmental

THROMBOSIS

Internal Factors Prothrombotic Disorders

Inherited

Acquired


Inherited prothrombotic disorders
Inherited Prothrombotic Disorders

Gain of function

Factors (FV, FII)

Common (> 2.0%)

Moderate risk

Dg: DNA analysis

Loss of function

Inhibitors (PC, PS, AT)

Uncommon (< 0.1%)

High risk

Dg: Plasma level


Acquired prothrombotic disorders
Acquired Prothrombotic Disorders

Common

Moderate risk

Inflammatory states

Malignancy

Hyperhomocysteinemia

Uncommon

High risk

Myeloproliferative dis.

APL syndrome

PNH

Behcet’s disease


Inherited prothrombotic disorders1
Inherited Prothrombotic Disorders

Gain of function

Factors (FV, FII)

Common (> 2.0%)

Moderate risk

Dg: DNA analysis

Loss of function

Inhibitors (PC, PS, AT)

Uncommon (< 0.1%)

High risk

Dg: Plasma level


Coagulation Inhibitors in Cirrhosis

75%

50%

0%

100%

Child-Pugh

B

A

C

A

B

C

B

C

B

C

A

A

Antithrombin

Protein C

Protein S

Romero-Gomez. J Clin Gastroenterol 2000


Acquired prothrombotic disorders1
Acquired Prothrombotic Disorders

Common

Moderate risk

Inflammatory states

Malignancy

Hyperhomocysteinemia

Uncommon

High risk

Myeloproliferative dis.

APL syndrome

PNH

Behcet’s disease


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


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.


p

With PVT

No PVT

PVT and Cirrhosis: Prothrombotic Disorders

NS

< .05

< .05

< .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 2000;31:345-8.


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.


PVT in Patients with Cirrhosis

Epidemiology

Manifestations

Causal factors

Therapy


PVT and Cirrhosis: Why to treat?

  • To prevent aggravation ?

  • To facilitate transplantation


Portal vein thrombosis clinical results of anticoagulant therapy

Portal Vein Thrombosis Clinical results of anticoagulant therapy

  • In patients without cirrhosis

  • In patients with cirrhosis


Acute pvt complete recanalization

60

40

Recanalization (%)

20

0

0

3

6

9

12

15

18

Time to recanalization (months)

Acute PVT: Complete Recanalization

Pts at risk:


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

Bleeding

Thrombosis

Condat et al. Gastroenterology 2001; 120:490


Chronic portomesenteric venous thrombosis

Warfarine

no

yes

1.00

HR for

Death

p=0.038

0.10

Orr et al. Hepatology 2005; 42: 212A (AASLD San Francisco 2005)


Patients on the waiting list for ltx
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


Tips for pvt in cirrhosis
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


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


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%


Hemostasis in cirrhosis
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


Inr in patients with cirrhosis
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%?


Patients on the waiting list for ltx1
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


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


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


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