Emorragie digestive superiori varicose:

dalla legatura al TIPS

Francesco Vizzutti

Dipartimento di Medicina Clinica e Sperimentale

Università degli Studi di Firenze

Azienda Ospedaliero Universitaria Careggi

SOD Medicina Interna ed Epatologia

Il sottoscritto dichiara di non aver avuto negli ultimi

dodici mesi conflitto d’interesse in relazione a

questa presentazione e che la presentazione non

contiene discussione di farmaci in studio o ad uso

off-label.

Chronic liver disease

Compensated cirrhosis

Decompensated cirrhosis

Death

• Hepatitis B/C • Alcohol • NASH • Cholestatic • Autoimmune

• Variceal hemorrhage • Ascites • Encephalopathy • Jaundice

Increasing liver fibrosis and neo-angiogenesis

Development of HCC

THE NATURAL HISTORY OF CHRONIC LIVER DISEASE

Ascites ±

Varices

6.6%

4.4%

4%

DEATH

1%

3.4%

20%

57%

Stage 3

De

com

pe

nsa

ted

No varices

No ascites Stage 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

D’Amico J Hep 2006

≈ 50% within 6 w. from BOV

HC

C (

3%

ye

ar)

wo

rse

ou

tco

me

in

wh

ate

ve

r

sta

tus

it

de

ve

lop

s.

SANGUINAMENTO Valutazione iniziale (Anamnesi, esame obbiettivo,

esami ematochimici, colture)

Rianimazione

iniziare farmaci vasoattivi

profilassi antibiotica

Endoscopia

Emorragia

non da IP

EMORRAGIA DA IP

Trattare secondo la causa dell’emorragia

EVL o Scleroterapia,

farmaci vasoattivi fino a 5 giorni

Successo Fallim.

TIPS

Iniziare profilassi

del risanguinamento Shunt chirurg.

d’urgenza

FAILURE TO CONTROL BLEEDING

OR EARLY REBLEEDING 10 TO 20%

TREATMENT OF ACUTE BLEEDING

HVPG >20 mmHg, Child-Pugh Class C, and active bleeding at endoscopy are the variables most consistently found to predict 5-day treatment failure

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

Failure to control AVH

Early Rebleeding 6-month Mortality

0%

20%

40%

60%

23%

52%

0

5

10

15

20

Transfusions (UU) Days in ICU Days in Hospital

9.0 7

40%

19

p<0.004

0%

4.7 4

14

12% 7%

p<0.001 p<0.007

p<0.007 p<0.02 p<0.02

HVPG ≥ 20 mmHg

HVPG < 20 mmHg

Moitinho E Gastroenterology 1999

PROGNOSTIC VALUE OF EARLY MEASUREMENTS OF PORTAL PRESSURE IN ACUTE VARICEAL BLEEDING

Clinical variables:

Systolic blood pressure ≤100 mmHg - 1 point

Non-alcoholic cirrhosis – 1 point

CP B – 1 point

CP C – 2 point

Abraldes J Hep 2008

Risk Point % of 5-day failure

Low 0-1 2

Intermediate 2 12

High 3-4 40

20th ANNIVERSARY

TREATMENT OF ACUTE BLEEDING In suspected variceal bleeding, vasoactive drugs should be started as soon as possible, before diagnostic endoscopy

Endoscopic therapy is recommended in any patient who presents with documented upper GI bleeding and in whom esophageal varices are the cause of bleeding

Patients with GI bleeding and features suggesting cirrhosis should have upper endoscopy as soon as possible after admission (within 12 hours)

Ligation is the recommended form of endoscopic therapy for acute esophageal variceal bleeding, although sclerotherapy may be used in the acute setting if ligation is technically difficult

Vasoactive drugs (terlipressin, somatostatin, octreotide, vapreotide) should be used in combination with endoscopic therapy and continued for up to 5 days

Endoscopic therapy with tissue adhesive (e.g. N-butyl-cyanoacrylate) is recommended for acute bleeding from isolated gastric varices (IGV) and those gastro-esophageal varices type 2 that extend beyond the cardia

EVL or tissue adhesive can be used in bleeding from gastroesophageal varices type 1 (GOV1)

Uncontrolled data suggest that self-expanding covered esophageal metal stent may be an option in refractory esophageal variceal bleeding, although further evaluation is needed

Persistent bleeding despite combined pharmacological and endoscopic therapy is best managed by TIPS with PTFE-covered stents

Rebleeding during the first 5 days may be managed by a second attempt at endoscopic therapy. If rebleeding is severe, PTFE-covered TIPS is likely the best option

TREATMENT OF ACUTE BLEEDING

TIPS AS A RESCUE THERAPY IN FAILURES OF MEDICAL AND ENDOSCOPIC TREATMENT

Patients CP (A/B/C) Initial control Mortality

Mc Cormick

20

1/7/12

100%

55%

Jalan 19 3/3/13 100% 42%

Sanyal 30 1/7/22 100% 40%

Chau 112 5/27/80 98% 37%

Gerbes 11 1/3/7 100% 27%

Bañares 56 11/22/23 96% 28%

Azoulay 58 3/8/47 93% 30%

SIRS

Sepsis

Infection

Alcoholic

hepatitis

Viral

hepatitis

Drugs and

hepatotoxins

Fungemia

Bacterial

infection

PI related

bleeding

Surgery

SIRS

Sepsis

Infection

Alcoholic

hepatitis

Viral

hepatitis

Drugs and

hepatotoxins

Fungemia

Bacterial

infection

PI related

bleeding

Surgery

PI related

bleeding

Surgery

AoCLF

Bernard B, Gastroenterology 1995

Distribution of the date of occurrence of the first bacterial infection

0

20

40

60

1 2 4 5 6 7 hospitalization day

% o

f to

tal in

fect

ions

3

OCCURRENCE OF BACTERIAL INFECTION IN BLEEDING CIRRHOTIC PATIENTS

Bernard B Gastroenterology 1995

P < 0.01 P < 0.01

Rebleeding and mortality in patients with and without infection

0

10

20

30

40

50

60

Rebleeding Mortality

% patients

With infection

Without infection

PROGNOSTIC SIGNIFICANCE OF BACTERIAL INFECTION IN BLEEDING CIRRHOTIC PATIENTS

AVH IN CIRRHOSIS

TREATMENT OF ACUTE BLEEDING

An early TIPS within 72 hours (ideally < 24 hours) should be considered in patients at high-risk of treatment failure (e.g. Child-Pugh class C <14 points or Child class B with active bleeding) after initial pharmacological and endoscopic therapy

Balloon tamponade should only be used in massive bleeding as a temporary “bridge” until definitive treatment can be instituted (for a maximum of 24 h, preferably in an intensive care facility)

F. Vizzutti 2011

Hep 2005, Boyer and Haskal

TIPS CONTRAINDICATIONS

RCT OF PTFE-COVERED VS. BARE STENTS

Bureau C Gastroenterology 2004

600 400 200 0

PTFE (n=39)

Bare stents (n=41)

Days

1,0

0,8

0,6

0,4

0,2

p=0.001

Free of TIPS Dysfunction

• Trend for decreased mortality and encephalopathy rate favoring PTFE stents.

0

10

20

30

40

50

Treatment Failure 6 Weeks Mortality

HVPG < 20 mmHg

HVPG > 20 mmHg VE

HVPG > 20 mmHg TIPS

%

4% 50% 0% 4% 38% 15%

Moneschillo A Hepatology 2004

NS

Monescillo A Hepatology 2004

In 9 European centers, 63 high-risk patients with acute variceal bleeding i.e.

Child C or B + active bleeding

PTFE-TIPS (10mm)

(n=32) (within 24h:19; 48h:10; 72h:3)

Continue on standard therapy for 5 days followed by secondary

prophylaxis with BB+IsMn + EBL

(n=31)

PTFE-TIPS as rescue Rx

Acute Rx: Vasoactive drugs + endoscopic Rx + antibiotics

EARLY PTFE-TIPS vs. DRUG+EBL

Garcia-Pagan JC NEJM 2010

97%

50%

Garcia-Pagan JC NEJM 2010

96%

67%

6-week

86%

60%

1-year

85%

62%

69%

35%

Garcia-Pagan JC NEJM 2010

EARLY TIPS VS STANDARD TREATMENT: SURVIVAL METANALYSIS

Number of patients need to be treated to save a life: 3.3

Study RD (fixed) RD (fixed) 95% CI 95% CI

Monescillo 2004 -0.35 [-0.60, -0.09]

Garcia-Pagan 2008 -0.26 [-0.47, -0.06]

Total (95% CI) -0.30 [-0.46, -0.14]

Test for overall effect: Z = 3.65 (P = 0.0003)

-1 -0.5 0 0.5 1

Favours treatment Favours control

Early TIPS/Control

26 / 26

32 / 31

58 / 57

EARLY TIPS

SECONDARY PROPHYLAXIS

Patients who fail endoscopic and pharmacological treatment for the prevention of rebleeding:

- Covered TIPS is effective and is the preferred option. Surgical shunt in

Child-Pugh A and B patients is an alternative if TIPS is unavailable.

- Transplantation provides good long-term outcomes in appropriate

candidates and should be considered. TIPS may be used as a bridge to

transplantation

Patients who have bled for IGV type I or GOV-2:

- N-butyl-cyanoacrylate or TIPS are recommended

NON RESPONDER

PCG 27 mmHg PCG 6 mmHg

Garcia Pagan JC GUT 2009

46-65% (Bosch J Lancet 2003)

BCS

RAP 3 mmHg

PP 28 mmHg

Porto-caval gradient 25 mmHg

PP 23 mmHg

RAP 12 mmHg

Porto-caval gradient 11 mmHg

PVT

IVCP 11 mmHg

PP 41 mmHg

PCG 30 mmHg PCG 14 mmHg

IVCP 15,5 mmHg

PP 29,5 mmHg

ISOLATED RECTAL VARICES

PCG 22 mmHg

PCG 10 mmHg

Registro Italiano sull’utilizzo del TIPS

Coordinatori AISF:

Filippo Schepis (MO)

Oliviero Riggio (Roma)

Francesco Salerno (MI)

Francesco Vizzutti (FI)

Coordinatori SIGE:

M. Grosso (CN)

R. Cioni (PI)

TIPS VS. ENDOSCOPIC THERAPY

As Initial Treatment to Prevent Rebleeding

Encephalopathy

Variceal rebleeding

Death

Death from rebleeding

TIPS better Endoscopic Rx better

Zheng J Clin Gastroenterol 2008

12 RCT included

Bambha Gut 2008

AVH: MELD AND 5-DAY REBLEEDING

Hep 2005, Boyer and Haskal

…….. incidence of fatal complications (intra-abdominal hemorrhage, laceration of the hepatic artery or portal vein, and right heart failure) was 1.7% (range, 0.6%-4.3%). Interestingly, the risk of fatal complications was 3% in institutions that had performed fewer than 150 TIPS total compared with 1.4% in those that had performed a greater number. These data suggest that there is a learning curve associated with the safe creation of a TIPS. Major procedural complications are expected in no more than 3% of cases; if rates exceed these levels, internal quality assessment should be considered.

BLEEDING FROM ECTOPIC VARICES:

TREATMENT WITH TIPS AND EMBOLISATION

Ectopic variceal bleeding 5% cause of bleeding in cirrhotics

Endoscopic treatment is ineffective (especially for rectal varices)

Patients Rebleeding Further successful

embolisation

Total TIPS 19*

TIPS alone 12 42% (48h) 80%

TIPS +

Embolisation 6 28% 100%

* 2 technical failure

Vangeli M J Hepatol 2004