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