vascular liver disease - filfoievascular liver disease dominique-charles valla dhu unity. service...
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Vascular Liver Disease
Dominique-Charles Valla
DHU UNITY. Service d’Hépatologie, Hôpital Beaujon (AP-HP), Clichy-la-Garenne;
and CRI, UMR U1149, Université Paris-Diderot and Inserm, Paris, France.
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Vascular liver diseases
Arteries
Hepatic venous system
Portal venous system
Sinusoids
Lymphatics
Obstruction
Dilatation
Fistula
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Vascular liver diseases
Arteries
Hepatic venous system
Portal venous system
Sinusoids
Lymphatics
Obstruction
Dilatation
Fistula
causing portal hypertension
Baveno 2005, 2010, 2015
EASL CPG, J HEP 2016
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Definition
Etiology
Diagnosis
Treatment
Outcome – Prognosis
Obstruction of the splanchnic venous systems
62 Baveno VI consensus statements. 1a;A to 5;D
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HVOTO Hepatic venous outflow tract obstruction
EHPVO Extrahepatic portal vein obstruction
IPH Idiopathic portal hypertension
Obstruction of the splanchnic venous systems
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HVOTO
• In the absence of malignancy
• In the absence of cirrhosis EHPVO
IPH
Obstruction of the splanchnic venous systems
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HVOTO Budd-Chiari syndrome
HV thrombosis, IVC thrombosis
Membranous obstruction of IVC
EHPVO Portal vein thrombosis
Portal cavernoma
IPH Hepatoportal sclerosis
Non cirrhotic portal fibrosis
Idiopathic non cirrhotic portal hypertension
Obliterative portal venopathy
Obstruction of the splanchnic venous systems
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Definition
Etiology
Diagnosis
Treatment
Outcome – Prognosis
Obstruction of the splanchnic venous systems
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HVOTO – EHPVO – IPH Etiology and Work-up : Baveno VI consensus
• Close collaboration with the hematologist
• Comprehensive work-up for prothrombotic conditions, systemic diseases, local factors
• V617F JAK2 and CALR mutations. Bone marrow biopsy if JAK2/CALR negative
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Risk Factors for Venous Thrombosis
• At least one 84% 67% 20%
• Multiple 46% 18% -
• Local factor 5% 21% -
HVOTO EHPVO IPH
Darwish Murad, Ann Intern Med 2009. Plessier, Hepatology 2010.
Siramolpiwat Hepatology 2014. Cazals Hatem, J Hepatol 2011
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Associated conditions
• MPN 49% 30% 8%
• APLS 25% 10% 1%
• FV or FII Leiden 15% 16% 7%
• Other systemic 25% 5% 38%
Darwish Murad, Ann Intern Med 2009. Plessier, Hepatology 2010.
Cazals-Hatem, J Hepatol 2011. Siramolpiwat Hepatology 2014.
HVOTO EHPVO IPH
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HVOTO – EHPVO – IPH Etiology and Work-up : Issues
• Diagnosis of primary deficiency in PC, PS or AT
• Diagnosis of primary antiphospholipid syndrome
• Exclusion of myeloproliferative neoplasm
• Other risk factors (obesity, poverty, etc.)
• Prothrombotic combinations (chips, scores?)
• Cause specific treatment and prognosis?
• Site of thrombosis: related to risk factor?
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Definition
Etiology
Diagnosis
Treatment
Outcome – Prognosis
Obstruction of the splanchnic venous systems
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HVOTO – EHPVO – IPH Diagnosis : Baveno VI consensus
Non-invasive vessel imaging Doppler US, MRI, CT
→ To demonstrate HVOTO and EHPVO
→ To rule out HVOTO and EHVPO for IPH
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Budd-Chiari syndrome
Collateral circulation
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Recent* Portal Vein Thrombosis
* “Acute”
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Portal cavernoma
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HVOTO – EHPVO – IPH Diagnosis : Baveno VI consensus
Liver biopsy
• HVOTO : Unnecessary
• EHPVO : Helpful
• IPH : Crucial to rule out cirrhosis
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IPH – Diagnosis : Issues
• From a vague syndrome to discrete entities
• Non-invasive tools for diagnosis
• Idiopathic portal hypertension without PHT but typical vascular changes at biopsy?
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IPH and related entities
- Obliterative portal venopathy
- Hepatoportal sclerosis
- Nodular regenerative hyperplasia
Pathology
Idiopathic portal hypertension
Noncirrhotic intrahepatic portal hypertension
Clinics &
Pathology
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Definition
Etiology
Diagnosis
Treatment
Outcome – Prognosis
Obstruction of the splanchnic venous systems
• HVOTO
• EHPVO
• IPH
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Anticoagulation Medical therapy
TIPS
Transplantation
Angioplasty
EASL, Prague 2001. Baveno, 2005, 2010, 2015
BCS/HVOTO
†
LTx
TIPS
Med. Rx.
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BCS/HVOTO Treatment and outcome issues
• Complications of therapy
– Encephalopathy related to TIPS
– Bleeding related to anticoagulation therapy
• Prediction of treatment response
• Underlying blood disease
• Regenerative nodules and HCC
Cazals-Hatem, Hepatology 2003. Chait, Br J Haematol 2005. Moucari, Gut 2008.
Garcia-Pagan, Gastroenterology 2008. Rautou, J Hepatol 2011. Seijo, Hepatology 2013.
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Definition
Etiology
Diagnosis
Treatment
Outcome – Prognosis
Obstruction of the splanchnic venous systems
• HVOTO
• EHPVO
• IPH
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Noncirrhotic Splanchnic Vein Thrombosis
From Ageno, JAMA Intern Med 2015
Major Thrombotic Events
Major Bleeding Events
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EHPVO – Therapy : Baveno consensus
• Recent PVT → Immediate anticoagulation
• Chronic EHPVO → long-term anticoagulation
after prophylaxis of bleeding related to PHT
If - documented prothrombotic state or
- recurrent thrombosis or
- intestinal infarction
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Recent Portal Vein Thrombosis
Portal
Splenic
Sup. mesenteric
EN-Vie Cohort: 95 anticoagulated patients
Plessier. Hepatology 2010
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EHPVO – Therapy : Baveno consensus
• Recent PVT → Immediate anticoagulation
• Chronic EHPVO → long-term anticoagulation
after prophylaxis of bleeding related to PHT
If - documented prothrombotic state or
- recurrent thrombosis or
- intestinal infarction
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EHPVO – Therapy : Baveno consensus
Management of portal hypertension
•NSBB and endoscopic variceal banding as recommended for cirrhosis
•Meso-Rex shunt in children
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EHPVO – Therapy : Issues
• Adapting anticoagulation to risk factors
• Adding antiplatelet agents on
• Anticoagulation when causes controlled ?
• New oral anticoagulants
• Role of TIPS and Meso-Rex in adults
Improving efficacy and safety
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Definition – Nosology
Etiology – Work-up for causes
Manifestations – Diagnosis
Treatment
Outcome – Prognosis
Obstruction of the splanchnic venous systems
causing portal hypertension
• BCS/HVOTO
• EHPVO
• IPH
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IPH – Therapy : Baveno consensus
• Manage portal hypertension as in patients
with cirrhosis
• Screen for portal vein thrombosis q. 6 mos.
• Anticoagulation for portal vein thrombosis
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Survival in patients with IPH
Siramolpiwat, Hepatology 2014 Schouten, APT 2012
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IPH – Therapy : Issues
• Mechanisms of disease(s)
• Anticoagulation for blocking disease
progression and preventing complications
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HVOTO
• In patients with cirrhosis EHPVO
IPH
Obstruction of the splanchnic venous systems
Partial PVT Occlusive PVT
10% (5-16) 3% (1-4)
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PVT in cirrhosis: Baveno consensus
• Screening q. 6 mos in LT candidates
• Anticoagulation in LT candidates with PVT
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Advanced
Cirrhosis
Nery. Hepatology 2014
Portal vein Thrombosis
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Advanced
Cirrhosis
Portal vein Thrombosis
?
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Advanced Cirrhosis
Portal Vein Thrombosis
?
Villa, E. et al. Gastroenterology 2012
Nery, F. et al Hepatology 2014
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PVT in cirrhosis: Issues
• How to anticoagulate/monitor anticoagulation
• Benefit/risk ratio of anticoagulation therapy
for preventing or treating PVT in cirrhosis
• New oral anticoagulants
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Impact of PVT before LTx
Englesbe. Liver Transplant 2010. SRTR 22,291 listed candidates. Occlusive PVT 4.02%
Hazard Ratio (95% CI)