Massimo Primignani U.O. Gastroenterologia 1 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano 19th AISF Pre-Meeting Course “Vascular Diseases of the Liver” Roma, 22 Febbraio 2017
Massimo Primignani
U.O. Gastroenterologia 1
Fondazione IRCCS Cà Granda
Ospedale Maggiore Policlinico
Milano
19th AISF Pre-Meeting Course
“Vascular Diseases of the Liver”
Roma, 22 Febbraio 2017
Massimo Primignani
U.O. Gastroenterologia 1
Fondazione IRCCS Cà Granda
Ospedale Maggiore Policlinico
Milano
Natural history and management of
complications of chronic extrahepatic
portal vein obstruction
Massimo PrimignaniU.O. Gastroenterologia 1
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano
Il sottoscritto dichiara di non aver avuto negli ultimi 12 mesi conflitto d’interesse in relazione a questa presentazione
e che la presentazione non contiene/contiene discussione
di farmaci in studio o ad uso off-label
Baveno VI
SESSION 6 – Vascular diseases of the liver in cirrhotic and non-cirrhotic portal
hypertension: coagulation, anti-coagulation, anti-platelet drugs
CONSENSUS STATEMENTS
EXTRA-HEPATIC PORTAL VEIN OBSTRUCTION (EHPVO) – DEFINITION
• EHPVO is the obstruction of the extra-hepatic portalvein, with or without involvement of the intra-hepaticportal veins or other segments of the splanchnicvenous axis. It does not include isolated thrombosisof splenic vein or superior mesenteric vein (SMV).
• EHPVO is characterized by features of recentthrombosis or of portal hypertension with portalcavernoma as a sequel of portal vein obstruction.
Baveno VI
SESSION 6 – Vascular diseases of the liver in cirrhotic and non-cirrhotic portal
hypertension: coagulation, anti-coagulation, anti-platelet drugs
CONSENSUS STATEMENTS
EXTRA-HEPATIC PORTAL VEIN OBSTRUCTION (EHPVO) – DEFINITION (II)
• Presence of cirrhosis, other underlying liver diseases(i.e. non-cirrhotic portal hypertension) and/ormalignancy should be ruled out.
• EHPVO in those situations should be considered asdifferent entities.
Portal Cavernoma
Porto-porto
collateral circulation
Dilated hepatic
artery
Bile Ducts
Venous Drainage
of CBD
Adapted from D. Lebrec
PV
CEMRI image of a portal vein cavernoma
Chronic EHPVO-Clinical Features
Well tolerated variceal bleed
Splenomegaly
Hypersplenism
Growth retardation in children
Jaundice, ascites rare
Webb and Sherlock 1979, Mitra 1987, Yachha 1997, Kato 2002, Sarin 2002, Condat and Valla, 2003, Rangari 2003,
EHPVO: Natural History
Esophageal variceal bleed, repeated, well tolerated
Gastric and anorectal varices - bleed
Slow liver dysfunction in some
Ascites – spontaneous (5-10%)
Portal biliopathy - jaundice
Growth retardation, delayed sexual characters
Webb and Sherlock 1979, Chawla 1990, Yachha, 1997, Mishra 1997, Kato 2002, Sarin 2002, Condat and Valla, 2003, Rangari 2003,
EHPVO- Management of complications
I. Prophylaxis bleeding/rebleeding
II. Portal Biliopathy
III. Prevention of thrombosis extention and relapse: Anticoagulant therapy
IV. Chronic EHPVO in children
EHPVO- Management of complications
I. Prophylaxis of bleeding/rebleeding
II. Portal Biliopathy
III. Prevention of thrombosis extentionand relapse: Anticoagulant therapy
IV. Chronic EHPVO in children
Primary prevention of bleeding
• No RCTs compared non-selective beta-blockers vs.endoscopic band ligation in EPVHO.
• In this scenario, as well as in the context of the acutebleeding and of secondary prophylaxis, Baveno VIrecommends to follow the guidelines regarding PH incirrhosis.
Baveno VI
SESSION 6 – Vascular diseases of the liver in cirrhotic and non-cirrhotic portal
hypertension: coagulation, anti-coagulation, anti-platelet drugs
CONSENSUS STATEMENTS
TREATMENT OF PORTAL HYPERTENSION IN EHPVO
•There is insufficient data on whether beta-blockersor endoscopic therapy should be preferred forprimary prophylaxis. Thus, guidelines for cirrhosisshould be applied (5;D).
Noronha Ferreira Hepatology 2016
• 178 patients with chronic PVT.
• Median follow-up : 49 (1-598) months.
• Variceal bleeding : initial manifestation in 15%
• Initial endoscopy in the remaining 151 :
no varices in 34%
small esophageal varices in 19%
large esophageal varices in 40%
gastric varices without LEVs in 7%
Actuarial probability of development of varices
probability of developing them was
2%, 22%, and 22% at 1, 3, and 5
years
2%, 22%, and 22% at 1, 3, and 5 years
Noronha Ferreira Hepatology 2016
Actuarial probability of enlargement of varices
13%, 40%, and 54% at 1, 3, and 5 years
Noronha Ferreira Hepatology 2016
Has the patient developed PVT-related complications?
• In chronic EHPVO more than two third of the subjects have gastro-esophageal varices at screening endoscopy.
• In patients without varices at baseline, varices developin 22% after 3 years
perform follow-up endoscopy
Noronha Ferreira Hepatology 2016, Condat B Gastroenterology. 2001
Actuarial probability of bleeding in patients on
primary prophylaxis
9%, 20%, and 32% at 1, 3, and 5 years
Noronha Ferreira Hepatology 2016
Median dose of NSBB: 100 mg (10-240)
Actuarial probability of rebleeding
9%, 20%, and 32% at 1, 3, and 5
Noronha Ferreira Hepatology 2016
Course of varices in chronic noncirrhotic, nontumoral PVT is similar to that in cirrhosis
Using the same therapeutic approach as for cirrhosis is associated with a low risk of bleeding and death
• baseline endoscopy at diagnosis of PV
• subsequent endoscopies at 2-year or 3-year intervals in patients with no EVs or small EVs at baseline
• beta-blockers or endoscopic band ligation (EBL) as a primary prophylaxis
• drug plus EBL to treat variceal bleeding and prevent rebleeding
Noronha Ferreira Hepatology 2016, Condat B Gastroenterology. 2001
Portal venogram following transjugular
puncture of the portal vein shows varices
and contrast accumulation within the
portal cavernoma
Following TIPS placement variceal filling is
reduced and contrast accumulation within the
cavernoma is no longer seen
Alimentary Pharmacology and Therapeutics, 2006
EHPVO- Management of complications
I. Prophylaxis variceal bleeding
II. Portal Biliopathy
III. Prevention of thrombosis extention and relapse: Anticoagulant therapy
IV. Chronic EHPVO in children
Portal cholangiopathy
• Abnormalities of the biliary system and gallbladder due
to ischemia at the time of portal vein thrombosis and
local ischemia due to local wall compression by the
peribiliary collaterals.
• >80% of patients with portal cavernoma develop some
degree of portal cholangiopathy, but just a minority
develops symptoms during the follow up:
- right abdominal pain
- pruritus, jaundice
- gallbladder stones
- cholangitis
Dhiman RK et al. Gut. 2007
Portal cholangiopathy – clinical presentation
Asymptomatic: no biliary symptoms despite
the presence of biliary abnormalities on ERC or
MRC
With symptoms:
- Chronic cholestasis, likely to be caused by
biliary stricture
- Biliary pain or acute cholangitis, likely to be
caused by biliary stones (5-8%)
- Secondary Biliary Cirrhosis
MRCP classification of biliary tree abnormality with clinical correlates
I. Minimal irregularities or angulation of the biliary tree
II. Indentations or strictures without dilatation of the biliary
tree;
III. Strictures with dilatation (intrahepatic duct >4 mm or
extrahepatic duct >7 mm)
MRCP classification of biliary tree abnormality with clinical correlates
I. Minimal irregularities or angulation of the biliary tree
II. Indentations or strictures without dilatation of the biliary
tree;
III. Strictures with dilatation (intrahepatic duct >4 mm or
extrahepatic duct >7 mm)
ERC in a patient with
EHPVO showing
irregular intrahepatic
ducts and indentations
of common hepatic and
bile duct
I. Minimal irregularities or angulation of the biliary tree
MRCP classification of biliary tree abnormality with clinical correlates
I. Minimal irregularities or angulation of the biliary tree
II. Indentations or strictures without dilatation of the biliary
tree;
III. Strictures with dilatation (intrahepatic duct >4 mm or
extrahepatic duct >7 mm)
ERC and MR cholangiography in EHPVO: strictures on common hepatic and
intrahepatic bile ducts with smooth narrowing of middle common bile duct
II. Indentations or strictures without dilatation of the biliary tree
MRCP classification of biliary tree abnormality with clinical correlates
I. Minimal irregularities or angulation of the biliary tree
II. Indentations or strictures without dilatation of the biliary
tree;
III. Strictures with dilatation (intrahepatic duct >4 mm or
extrahepatic duct >7 mm)
ERC: defects in the CBD suggestive
of stones, along with dilatation of
intrahepatic biliary ducts
MRC in the same patient : multiple filling
defects, due to choledochal varices in the
intrahepatic and extrahepatic biliary system.
III. Biliary strictures with dilatation
MR cholangiography and portography
• MR cholangiography and portography is non-invasive and can demonstrate bile duct changes and portal collaterals simultaneously
• MR cholangiography with MR portography is superior to ERC in delineating changes in intrahepatic biliary ducts and in differentiating choledochal varices from CBD stones
• MR portography delineates the entire splenoportal axis and portal collaterals, which helps to assess the possibility of shunt surgery.
Treatment of Portal Colangiopathy
• Asymptomatic patients do not require any treatment
• Treatment of symptoms is focused on the management of portal hypertension and relief of obstructive jaundice
Endoscopic treatment
• endoscopic sphincterotomy
• stone extraction
• mechanical lithotripsy
• biliary stricture dilatation with/ without stent
or nasobiliary drain placement.
Adverse events of endoscopic treatment
• Bleeding from bile duct varices (haemobilia) during
biliary dilatation.
• Bleeding at sphincterotomy, due to venous collaterals in
ampullary and juxtapapillary region.
• Filling defects within the biliary system could be due to
stones or choledochal varices:
(varices do not move with the balloon catheter at ERC)
Prefer balloon catheter over Dormia basket for removing CBD stones after sphincterotomy to minimise
the risk of haemobilia.
Surgical treatment - 1
• High morbidity/mortality of bilioenteric anastomosis as the collateral vessels around the bile ducts make the surgical dissection difficult
• Patients should undergo portosystemic shunt surgery before any bilioenteric anastomosis is planned.
• Most patients improve with shunt surgery and may not require further surgery
Surgical treatment - 2
• Shunt surgery may be indicated in patients with
previous bleeding and hypersplenism resulting
in significant anaemia and/or thrombocytopenia.
• TIPS also reverses the biliary changes in these
patients: useful in selected patients.
• OLT is the only option in patients with
intractable disease, when both endoscopic and
surgical treatments have failed or are not
feasible.
Endoscopy or surgery?
• Surgical treatment is preferred for dominant biliary
strictures with a shuntable vein as it provides long-
lasting relief of symptoms.
• Endoscopic treatment is preferred for patients with CBD
stones, cholangitis or for patients with dominant biliary
stricture, but without a shuntable vein.
- risk of secondary biliary cirrhosis (recurrent stent blockage,
cholangitis)
- scheduled biliary stent exchange every 4–6 months
EHPVO- Management of complications
I. Prophylaxis variceal bleeding
II. Portal Biliopathy
III. Prevention of thrombosis extention and relapse: Anticoagulant therapy
IV. Chronic EHPVO in children
Baveno VI
SESSION 6 – Vascular diseases of the liver in cirrhotic and non-cirrhotic portal
hypertension: coagulation, anti-coagulation, anti-platelet drugs
CONSENSUS STATEMENTS
ANTICOAGULATION IN CHRONIC EHPVO• In patients without underlying prothrombotic disease,
there is scarce information to recommend anticoagulant therapy (5;D).
• In patients with a persistent documented prothrombotic state, recurrent thrombosis or intestinal infarction long-term anticoagulant therapy is recommended (3b;B).
• Anticoagulation should be started after adequate portal hypertensive bleeding prophylaxis has been initiated (5;D).
Algorithm of the use of anticoagulation in the management of EHPVO
EHPVO- Management of complications
I. Prophylaxis variceal bleeding
II. Portal Biliopathy
III. Prevention of thrombosis extention and relapse: Anticoagulant therapy
IV. Chronic EHPVO in children
Pediatric EHPVO
EHPVO is the commonest cause of varices and upper gastrointestinal bleeding in children
Umbilical vein catheterization or omphalitis are the most frequently reported causes of pediatric EHPVO
Meso-Rex bypass is a surgery option in children with complication of chronic EHPVO
Embryologic origins of the Rex Recessus
Meso-Rex Bypass
Classification of patency of the intrahepatic portal vein in children with portal vein cavernoma
Partial obstruction
of the left liver
thrombosis of the
left liver
thrombosis of
the right liver
extensive thrombosis
of the intrahepatic
portal veins
Complete patency
of the intrahepatic
portal veins
including the RR
Transjugular retrograde wedged
portography indicating complete
patency
Intraoperative portal venography
showing complete patency
Highest sensitivity and specificity
Meso-Rex Bypass, when feasible, is the primary approach in children with EHPVO with evidence of cavernoma
Criteria for ensuring a success rate of>90%.
• “A” type anatomy confirmed by wedge two dimensional portography
• Normal HVPG determined at the time of portography and/or liver
biopsy revealing no fibrosis or underlying liver disease that would
impact portal flow
• Patent superior mesenteric vein and splenic vein without thrombosis
• Bilateral internal jugular vein patency
• Hematological evaluation excluding an intrinsic prothrombotic
condition that would not be reversed by MRB
• Body weight >8 kg
• Echocardiography excluding significant cardiovascular abnormalities
and significant pulmonary hypertension
Resolution of biliopathy after reconstitution of
portal blood flow by MRB
Increase in liver mass and decrease in spleen
size after MRB
Resolution of hepatic nodules after
Meso-Rex Bypass
Baveno VI
SESSION 6 – Vascular diseases of the liver in cirrhotic and non-cirrhotic portal
hypertension: coagulation, anti-coagulation, anti-platelet drugs
CONSENSUS STATEMENTS
TREATMENT OF PORTAL HYPERTENSION IN EHPVO
Meso-Rex by-pass should be considered in all childrenwith complications of chronic EHPVO, who should bereferred to centers with experience in treating thiscondition (5;D).
Alternatives to Meso-Rex Bypass
• Endoscopic Variceal Ligation
• Endoscopic variceal sclerotherapy (dictated by patient size restrictions)
• Distal splenorenal shunt