Francesco Vizzutti
Azienda Ospedaliero Universitaria Careggi, Firenze
Il sottoscritto dichiara di non aver avuto negli ul timi dodici mesi conflitto d’interesse in relazione a questa pre sentazione e che la presentazione non contiene discussione di f armaci in
studio o ad uso off-label
HEPATIC VENOUS PRESSURE GRADIENT
PORTAL HYPERTENSION
Complicanza ineluttabile della cirrosi epatica carat terizzata dall’aumento patologico del gradiente di pressione portale o
HVPG (>5 mmHg)
Complicanze:
Sanguinamento da rottura di varici
Ascite, HRS e SBP
PHG e colopatia dell’ipertensione portale
HPS, PPH
Spillover porto-sistemico & HE
25
12
10
5
0
HVPG (mmHg)
Varices
Bleeding
HE Ascites
SBP
HPSPHG
HRS
PPH
SUBclinical Portal Hypertension
DIRECT METHODS USED TO MEASURE PORTAL PRESSURE
Transhepatic portal vein catheterization
Intra-operative mesenteric vein catheterization
Splenic pulp pressure measurement
Umbilical vein catheterization
Pre-Sinusoidal Portal Hypertension
…. avoid spitting
HVC IS PERFORMED UNDER STRICTLYSTERILE CONDITION …….
VENOUS ACCESS SITES FOR HEPATICVEIN CATHETERIZATION
FHVP
WHVP
Portal PHVPG=WHVP-FHVP
PCG=portal P- cava P
HEPATIC VEIN CATHETERIZATION
Balloon catheter
HVPG MEASUREMENT
Portal vein
Hepatic vein
NORMAL
Portal vein
Hepatic vein
CIRRHOTIC
x
xxx
RATIONALE FOR HVC
WHVP (mmHg)
Por
tal P
ress
ure
(mm
Hg)
00
10 20 30 40
10
20
30
40Agreement RI
Overall series 0.99
• HCV 0.94
• Alcool 0.93
• HCV + Alcool 0.97
RI - interclass correlation coefficient
Perelló, Hepatology 1999
HVPG MEASUREMENTS AT HEPATIC VEIN CATHETERIZATION
Complications: puncture site, supraventricular arrhythmias
Contraindications: plt<20x10 9/PT<30% (call repl.)allergic reaction
THREE IN ONE
1. HVPG
1
3. CO2 Portography
3
2. TJLB
2
Ascites ±
Varices
6.6%
4.4%
4%
DEATH
1%
3.4%
20%
57%
Stage 3
De
com
pe
nsa
ted
No varices
No ascitesStage 1
Co
mp
en
sate
d
Varices
No ascites
7%
Stage 2
Bleeding ±
Ascites
7.6%
Stage 4
THE NATURAL HISTORY AND PROGNOSIS OF CHIRROSIS
J Hep 2006, D’Amico et al
≈ 50% within 6 w.
from BOV
INTERNATIONAL CONSENSUS WORKSHOP AND POSTGRADUATE COURSE:current consensus and future directions in the diagnosis and treatment of portal hypertension
20thANNIVERSARYBaveno V
PRE-PRIMARY PROPHYLAXIS
BACKGROUND:
Baveno III:
Portal Pressure is predicting of varices formation.
More data are needed.
Baveno IV:
De novo formation of varices: 4-6% per year
HVPG is predictive of varices formation
Stratify: HVPG: 6-10 and no varices
HVPG>10 and no varices
Small Varices
NSBB are ineffective in preventing EV formation.
(Groszmann RJ et al. NEJM 2005)
Pts with small varices respond to BB because
haemodynamic changes have developed yet.
PROPOSED STATEMENTS:
Prevention of the development of complications of portal
hypertension is an important area of research. (5;D)
Pre-primary prophylaxis should only include patients
without gastro-esophageal varices. (5;D)
Hepatic venous pressure gradient (HVPG) ≥ 10 mmHg is
predictive of varices formation and decompensation. (1b;A)
Treatment of underlying liver disease may reduce portal
hypertension and prevent its clinical complications. (1b;A)
There is no indication, at this time, to use beta-blockers to
prevent the formation of varices. (1b;A)
HVPG measurement in pre-primary prophylaxis may be
recommended only in the context of clinical trials. (5; D)
Ascites ±
Varices
6.6%
4.4%
4%
DEATH
1%
3.4%
20%
57%
Stage 3
De
com
pe
nsa
ted
No varices
No ascitesStage 1
Co
mp
en
sate
d
Varices
No ascites
7%
Stage 2
Bleeding ±
Ascites
7.6%
Stage 4
THE NATURAL HISTORY AND PROGNOSIS OF CHIRROSIS
J Hep 2006, D’Amico et al
≈ 50% within 6 w.
from BOV
INTERNATIONAL CONSENSUS WORKSHOP AND POSTGRADUATE COURSE:current consensus and future directions in the diagnosis and treatment of portal hypertension
20thANNIVERSARYBaveno V
PRIMARY PROPHYLAXIS
PROPOSED STATEMENTS HVPG
- In centers where adequate resources and expertise are available, HVPG measurement should be
routinely used for prognostic and therapeutic indications (5;D)
-Controlled trials using pharmacological therapy in primary prophylaxis should include HVPG
measurements (5;D)
- A decrease in HVPG of at least 20% from baseline or to ≤12 mmHg after chronic treatment with
NSBB is clinically relevant in the setting of primary prophylaxis (1a;A)
- Acute HVPG response to intravenous propranolol may be used to identify responders to beta-
blockers, specifically a decrease in HVPG of 10% or to ≤≤≤≤12 mmHg may be relevant in this setting
(1b;A)
BAVENO IV: A la carte treatment using HVPG-response in primary prophylaxis needs to be evaluated, especially in
high-risk patients. Until then, routine use of HVPG cannot be recommended (5;D)
Ascites ±
Varices
6.6%
4.4%
4%
DEATH
1%
3.4%
20%
57%
Stage 3
De
com
pe
nsa
ted
No varices
No ascitesStage 1
Co
mp
en
sate
d
Varices
No ascites
7%
Stage 2
Bleeding ±
Ascites
7.6%
Stage 4
THE NATURAL HISTORY AND PROGNOSIS OF CHIRROSIS
J Hep 2006, D’Amico et al
≈ 50% within 6 w.
from BOV
SECONDARY PROPHYLAXIS
BACKGROUND:
Baveno IV:
Patients with cirrhosis who have not received primary
prophylaxis:
•NSBB (1a;A), EVL (1a;A) or both (1b;A) should be used
for prevention of recurrent bleeding
•Combination of NSBB and EVL is probably the best
treatment (1a;A) but more trial are needed
•Assessment of haemodynamic response to drug
therapy provides prognostic information about
rebleeding risk (2b B)
Patients with cirrhosis who are on NSBB for PP and
bleed:
•EVL should be added (5D)
PROPOSED STATEMENTS:
Patients with Cirrhosis
•Combination of beta-blockers and band ligation is the
preferred therapy as it results in lower rebleeding
compared to either therapy alone. (1a;A)
•Hemodynamic response to drug therapy provides
information about rebleeding risk and survival (1a;A)
•The addition of ISMN to beta-blockers may improve the
efficacy of treatment in hemodynamic non-responders (2;A
Check)
Cirrhotics unable/unwilling to VBL
•NSBB + ISMN is the preferred option (1a;A)
Cirrhotics and contraindication/intolerance to NSBB
•EVL is the preferred treatment (5D)
Time to start secondary prophylaxis
Secondary prophylaxis should start as soon as possible from day 6 of the index variceal episode (5, D)
The start time of secondary prohylaxis should be documented
(Baveno IV) (Baveno V: No Changes)
INTERNATIONAL CONSENSUS WORKSHOP AND POSTGRADUATE COURSE:current consensus and future directions in the diagnosis and treatment of portal hypertension
20thANNIVERSARYBaveno V
INTERNATIONAL CONSENSUS WORKSHOP AND POSTGRADUATE COURSE:current consensus and future directions in the diagnosis and treatment of portal hypertension
20thANNIVERSARYBaveno V
TREATMENT OF ACUTE BLEEDING
BACKGROUND:
Baveno IV:
No adequate prognostic model has been developed to
predict outcomes (2b;B)
No individual characteristics sufficiently predict
prognosis (2b;B)
Child-Pugh class, active bleeding at endoscopy, hepatic
venous pressure gradient (HVPG), infection, renal
failure, severity of initial bleeding, presence of portal
vein thrombosis or of hepatocellular carcinoma and ALT
have been identified as indicators of poor prognosis
(2b;B)
POST BAVENO IV:
HVPG 20 independent predictor of 5-day failure in AVB
(Abrdaldes JG et al 2008)
Role for early TIPS in HVPG>20? (Thabut 2007)
PROPOSED STATEMENTS:
HVPG >20 mmHg, Child-Pugh Class C, and active bleeding at
endoscopy are the variables most consistently found to
predict 5-day treatment failure. (2b;B)
Child-Pugh class C, MELD score > 18, and failure to control
bleeding or early rebleeding are the variables most
consistently found to predict 6-week mortality. (2b;B)
Patients with GI bleeding and features suggesting cirrhosis
should have upper endoscopy as soon as possible after
admission (within 12 hours) (5d)
In suspected variceal bleeding, vasoactive drugs should be
started as soon as possible, before diagnostic endoscopy.
(1B)
Endoscopic therapy is recommended in any patient who
presents with documented upper GI bleeding and in whom
esophageal varices are the cause of bleeding (1a;A)
APPLICATIONS OF HVPG MEASUREMENT
Diagnosis of portal hypertension
Presinusoidal: normal WHVP and FHVP
Sinusoidal: increased WHVP and normal FHVP
Postsinusoidal: both WHVP and FHVP increased
Classification of portal hypertension
Assessment of disease severity
Response to therapy for portal hypertension
CHRONIC LIVER DISEASE
COMPENSATED CIRRHOSIS
DECOMPENSATED CIRRHOSIS
DEATH
≥6 mmHg risk of disease progression post OLT HCV
≥10 mmHg clinicaly significant PH
≥12 mmHg variceal rupture
≥16 mmHg increased
risk of mortality
≥20 mmHg treatment failure and mortality in VB
≥22 mmHg risk of mortality in AAHSINGLE HVPG MEASUREMENT
CHANGES IN HVPG
reduction of ≥20%
reduction to <12 mmHg
reduction of ≥10%
reduction of ≥20%
reduction of ≥10-12% at acute propranolol
APPLICATIONS OF HVPG MEASUREMENT
Diagnosis of portal hypertension
Classification of portal hypertension
Assessment of new therapeutic agents
Assessment of disease severity
Response to therapy for portal hypertension
Changes in HVPG and guidance of therapy
Identification of high-risck populations