Transcript Nessun titolo diapositiva

Management of patients with cirrhosis and
refractory ascites
P. Angeli
Dept. of Clinical and
Experimental Medicine
University of Padova
Treviso 4 Giugno 2009
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Subtypes of refractory ascites
• Diuretic-resistant ascites: ascites that cannot be
mobilized or he early recurrence of which cannot be
prevented because od a lack of response to dietary
sodium restriction and intensive diuretic therapy.
• Diuretic-intractable ascites: ascites that cannot be
mobilized or the early recurrence of which cannot be
prevented because of the development of diureticinduced complications that preclude the use of an
effective diuretic regimen.
V. Arroyo et al. Hepatology 1996 ; 23 : 165-176.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Plasma renin concentration (pg/ml) in cirrhotic patients
with responsive or refractory ascites
300
P < 0.05
200
100
0
Responsive ascites
Refractory ascites
I. Colle et al. Eur. J. Gastroenterol. Hepatol. 2001 ; 13 : 251-256.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Factors that may affect the efficacy of diuretics
•
•
•
•
Inadequate sodium intake
Excessive physical activity
Drugs (NSAIDs, vasodilators)
Bacterial infections
V. Arroyo et al. Hepatology 1996 ; 23 : 165-176.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Prevalence of no compliance to reduced sodium intake
among cirrhotic patients with asccites according to the
response to diuretic therapy
100
(%)
80
P < 0.05
60
40
20
0
Responsive ascites
Refractory ascites
P. Angeli et al. 2005
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Acute effects of Ibuprofen on renal blood flow
in cirrhotic patients with ascites
Renal blood flow (ml/min)
1000
N = 5 ; P < 0.05
800
600
400
200
0
Basal
After Ibuprofen
G. Laffi et al. Gastroenterology 1986 ; 90 : 182-187.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Sites of infections in cirrhotic patients
(%)
100
75
50
25
0
Urinary tract
Ascites
Blood
Respiratory
tract
M. Borzio et al. Digest. Liver Dis. 2001 ; 33 : 41-48.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of survival in cirrhotic patients
with ascites
1
%
Responsive ascites
0,75
P < 0.001
0,5
0,25
Refractory ascites
0
12
24
36
48
60
months
F. Salerno et al. Am. J. Gastroenterol. 1993 ; 88 : 514-519
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Independent predictors of death in patients with
refractory ascites
•
•
•
•
Older age
Hepatocellular carcinoma
Diabetes
No abstinence from alcohol
beverage
R. Moreau et al. Liver Int. 2004 ; 24 : 457-464.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Plasma renin concentration (pg/ml) in cirrhotic
patients with responsive or refractory ascites
300,00
P < 0.05
200,00
100,00
0,00
Responsive ascites
Refractory ascites
I. Colle et al. Eur. J. Gastroenterol. Hepatol. 2001 ; 13 : 251-256.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Therapeutic options for refractory ascites
•
•
•
•
Paracentesis
Peritoneovenous shunting
TIPS
Liver transplantation
K. Moore et al. Hepatology 2003 ; 38 : 258-266.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Postparacentesis circulatory dysfunction (PPCD):
plasma renin activity
(ng/ml/h)
50
* = P < 0.05
40
*
30
20
10
0
Before paracentesis
1 hour after
paracentesis
With PPCD
6th day after
paracentesis
Without PPCD
L. Ruiz-Del-Arbol et al. Gastroenterology 1997 ; 113 : 579-586.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Percent decrease in systemic vascular resistance in
patients with and without postparacentesis circulatory
dysfunction (PPCD)
0
%
-5
-10
-15
-20
P < 0.05
with PPCD
without PPCD
L. Ruiz-Del-Arbol et al. Gastroenterology 1997 ; 113 : 579-586.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Plasma renin activity in patients without and with
postparacentesis circulatory dysfunction (PPCD)
(ng/ml/h)
20
16
* = P < 0.0025; ** = P < 0.001
**
**
*
12
8
4
0
B 48 h 1 d 1 mo 6 mos
without PPCD
B 48 h 1 d 1 mo 6 mos
with PPCD
A. Gines et al. Gastroenterology 1996 ; 11 : 1002-1010.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of survival in patients with and without
postparacentesis circulatory dysfunction (PPCD)
1
%
without PPCD
0,8
0,6
0,4
P = 0.01
with PPCD
0,2
0
2
4
6
8
10
12
14
16
18
A. Gines et al. Gastroenterology 1996 ; 11 : 1002-1010.
months
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Postparacentesis circulatory dysfunction: plasma
renin activity
(ng/ml/h)
15
*
12
* = P < 0.001
9
6
3
0
Before paracentesis
With Albumin
After paracentesis
Without Albumin
P. Gines et al. Gastroenterology 1988 ; 94 : 1493-1502.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Prevalence of postparacentesis circulatory
dysfunction
60
%
P < 0.05
P < 0.025
40
20
0
< 5 liters
Albumin
5-9 liters
> 9 liters
Dextran 70 and polygeline
A. Gines et al. Gastroenterology 1996 ; 11 : 1002-1010.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of survival in patients treated
with paracentesis with or without intravenous albumin
1
%
without albumin
0,8
0,6
with albumin
P = N.S.
0,4
0,2
0
5
10
15
20
25
30
35
P. Gines et al. Gastroenterology 1988 ; 94 : 1493-1502.
weeks
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Prevalence of postparacentesis circulatory
dysfunction: plasma renin activity (ng/ml/h)
15
12
P = N.S.
9
6
3
0
Before paracentesis
With Albumin
After paracentesis
With Terlipressin
R. Moreau et al. Gut 2002 ; 50 : 90-94.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Ascites recurrence after therapeutic
paracentesis versus diuretics
(%)
100
80
P < 0.001
60
40
20
0
Diuretics
No Diuretics
G. Fernandez-Esparrach et al. J. Hepatol. 1997 ; 26 : 614-620.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Large volume paracentesis
• Paracentesis should be total.
• Volume expansion after paracentesis is necessary. Synthetic
plasma substitutes may be used if the volume of ascitic fluid
removed is < 5 l. For patients in whom the volume removed is > 5 l.
albumin should be used.
• Albumin should be used at a dose of 8 gr per liter of ascitic fluid
removed.
• To reduce the frequency of paracentesis patients may continue to
receive diuretics as tolerated.
K. Moore, et al. Hepatology 2003 ; 38 : 258-266.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of survival in cirrhotic patients
with refractory ascites: paracentesis vs Le Veen shunt
1
%
Le Veen shunt
0,8
0,6
0,4
P = N.S.
0,2
Paracentesis
0
6
12
18
A. Ginès et al. Hepatology 1995 ; 22 : 124-131.
months
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of readmission to the hospital for ascites
in cirrhotic patients with refractory ascites:
paracentesis vs Le Veen shunt
1
Paracentesis
%
0,8
0,6
P <0.001
0,4
Le Veen shunt
0,2
0
6
12
18
A. Ginès et al. Hepatology 1995 ; 22 : 124-131.
months
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Readmission to the hospital in patients with refractory ascites:
paracentesis vs Le Veen shunt
Mean hospital stay
Paracentesis
Le Veen shunt
P
Total
6
16
< 0.01
For ascites
3
13
< 0.01
For other reasons
15
17
N.S.
A. Ginès et al. Hepatology 1995 ; 22 : 124-131.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Potential adverse effects of peritoneovenous shunt
• Symptomatic disseminated intravascular
coagulation
• Severe bacterial infections
• Thrombotic obstruction of the venous limb
of the prothesis
• Intraperitoneal fibrosis
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of developing renal impairment in cirrhotic
patients with refractory ascites:
paracentesis vs Le Veen shunt
1
Le Veen shunt
%
0,8
P = N.S.
0,6
0,4
0,2
Paracentesis
0
6
12
18
A. Ginès et al. Hepatology 1995 ; 22 : 124-131.
months
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Conclusions (1)
• In candidates to liver transplantation the first
line treatment for refractory ascites is total
paracentesis.
• PVS is contraindicated in candidates to liver
transplantation.
• In non transplant candidates PVS may be
considered after failure of paracentesis (need
of 3 or more paracentesis per month) in
presence of contraindications to TIPS.
K. Moore et al. Hepatology 2003 ; 38 : 258-266.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Published controlled clinical trials: paracentesis
versus TIPS
• Lebrec D.J. et al. Hepatol. 1996 ; 25 : 135 144
• Rossle M. et al. N. Engl. J. Med. 2000 ; 342 :
1701-1707.
• Gines P. et al. Gastroenterology 2002 ; 123 :
1839-1847.
• Sanyal AJ. et al. Gastroenterology 2003 ; 124
: 634-641.
• Salerno F. et al. Hepatology 2004 ; 40 : 629635.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Mobilization of ascites in patients with refractory ascites:
paracentesis vs TIPS
AT 3 MONTHS
TIPS
PARACENTESIS
Complete
14 (51%)
4 (18%)
Partial
6 (26%)
3 (14%)
Complete
15 (79%)
5 (24%)
Partial
1 (5%)
4 (19%)
P
< 0.01
AT 6 MONTHS
< 0.01
M. Rossle et al. N. Engl. J. Med. 2000 ; 342 : 1701-1707.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Changes of urine sodium excretion at 3 months
after paracentesis or TIPS
150
P < 0.005
125
100
75
50
25
0
Baseline
At 3 months
Paracentesis
TIPS
F. Salerno et al. Hepatology 2004 ; 40 : 629-635.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Clinical outcome in patients with refractory ascites
according to the assigned treatment
Events
TIPS
(n° = 35)
Paracentesis
(n° = 35)
P value
27 (77%)
23 (66%)
N.S.
2.2±0.4
1.1±0.2
<0.01
Moderate (I-II grade)
Patients n°
18 (51%)
14 (40%)
N.S.
Moderate (I-II grade)
Episodes/patient
1.1±0.3
0.6±0.1
N.S.
Severe (III-IV grade)
Patient n°
21(60%)
12(34%)
<0.05
Severe (III-IV grade):
epidodes/patient
1.1±0.2
0.5±0.02
<0.025
Hepatic encephalopathy
Patients n°
Episodes/patient
P. Gines et al. Gastroenterology 2002 ; 123 : 1839-1847.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of development of de novo HRS or progression
from type 2 to type 1 HRS in patients with refractory ascites
1
%
P < 0.025
With TIPS
0,8
With paracentesis plus albumin
0,6
0,4
0,2
0
6
12
18
P. Gines et al. Gastroenterology 2002 ; 123 : 1839-1847.
24
mo
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of survival in patients with refractory or
recurrent ascites: paracentesis vs TIPS
1
%
TIPS
0,8
P = N.S.
0,6
0,4
paracentesis
0,2
0
500
1000
1500
AJ. Sanyal et al. Gastroenterology 2003 ; 124 : 634-641.
days
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of survival in patients with refractory or
recurrent ascites: paracentesis vs TIPS
1
%
TIPS
0,8
P < 0.025
0,6
0,4
paracentesis
0,2
0
12
24
36
48
F. Salerno et al. Hepatology 2004 ; 40 : 629-635.
months
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Contraindications to TIPS
•
•
•
•
•
•
•
•
•
•
Child-Pugh score > 11
serum bilirubin > 6 mg/dl
serum creatinine > 3 mg/dl
history of recurrent grade 2 hepatic encephalopathy
age greater than 72
serious cardiac or pulmonary dysfunction
complete portal vein thrombosis
HCC
recent gastrointestinal bleeding
ongoing bacterial infection
F. Salerno et al. Hepatology 2004 ; 40 : 629-635.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
A meta-analysis of TIPS versus paracentesis in patients with
refractory ascites
Recurrence of ascites
Lebrec 1996
Rossle 2000
Gines 2002
Sanyal 2003
Salerno 2004
TOTAL
Lower with
TIPS
0.2
0.4
0.6
0.8
1
A. Albillos et al. J. Hepatol. 2005 ; XX : 1-7.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
A meta-analysis of TIPS versus paracentesis in patients with
refractory ascites
Encephalopaty
Lebrec 1996
Rossle 2000
Gines 2002
Sanyal 2003
Salerno 2004
Lower with
paracentesis
TOTAL
1
20
40
A. Albillos et al. J. Hepatol. 2005 ; XX : 1-7.
100
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
A meta-analysis of TIPS versus paracentesis in patients with
refractory ascites
Mortality
Lebrec 1996
Rossle 2000
Gines 2002
Sanyal 2003
Salerno 2004
TOTAL
Lower with
TIPS
0.5
Lower with
paracentesis
1
2
3
4
5
A. Albillos et al. J. Hepatol. 2005 ; XX : 1-7.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Quality of life in cirrhotic patients after paracentesis or
TIPS
Main outcomes
TIPS
(n=33)
Paracentesis
(n=33)
P
Rehospitalization
28 (84%)
30 (91%)
N.S.
Rehospitalization
per patient
2.10.3
1.60.2
N.S.
F. Salerno et al. Hepatology 2004 ; 40 : 629-635.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Quality of life in cirrhotic patients after paracentesis or TIPS
Baseline
6 Months
12 Months
28.48.4
7.08.4
5.010.5
P
PCS
TIPS
N.S.
Paracentesis
26.89.3
6.39.3
2.011.7
44.712.6
3.78.3
3.312.6
MCS
TIPS
0.06
Paracentesis
41.010.3
3.412.7
0.511.9
MS. Campbell et al. Hepatology 2005 ; 42 : 635-640.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Control of ascites according to the assigned treatment
Main outcomes
TIPS
(n=33)
Paracentesis
(n=33)
P
Treatment failure
7 (21%)
19 (57%)
<0.0025
Ascites recurrence
13 (39%)
20 (61%)
<0.001
1.40.4
5.10.7
<0.001
Paracentesis per
patient per year
F. Salerno et al. Hepatology 2004 ; 40 : 629-635.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Probability of remaining free of shunt dysfunction
after TIPS procedure
1
%
Coated Stent
0,8
P < 0.001
0,6
0,4
Uncoated Stent
0,2
0
6
12
18
24
months
C. Bureau et al. Gastroenterology 2004 ; 126 : 469-475.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Peritoneal port for treatment of refractory ascites
MA. Savin et al. J. Vasc. Interv. Radiol. 2005 ; 16 : 363-368.
MANAGEMENT OF PATIENTS WITH CIRRHOSIS
Conclusions (2)
• Paracentesis is the first line treatment of refractory
ascites in patients with cirrhosis.
• TIPS is recommended in patients who did not tolerate
recurrent total paracentesis, also in those waiting for
liver transplantation.
• TIPS is also indicated if paracentesis fails to
adequately remove ascitic fluid (e.g. loculated ascites).
K. Moore et al. Hepatology 2003 ; 38 : 258-266.