Management of Cirrhotic Complications › files › slide17.09.00- 09.20... · TIPS in Refractory...
Transcript of Management of Cirrhotic Complications › files › slide17.09.00- 09.20... · TIPS in Refractory...
Management of Cirrhotic
Complications
“Uncontrolled Ascites”
Siwaporn Chainuvati, MD
Siriraj Hospital
Mahidol University
Topic
Definition, pathogenesis
Current therapeutic options
Experimental treatments
Clinical approach
Probability of Survival in
Patients with Cirrhosis and
Refractory Ascites
Gines P et al. NEJM 2004:1646-54
Non-refractory
ascites
Diagnostic Criteria
Lack of response to maximal doses of diuretic for at least 1 week
Persistent ascites despite sodium restriction
Mean weight loss < 0.8 kg over 4 days
Urinary sodium excretion less than sodium intake
Early recurrence of ascites within 4 weeks of fluid mobilization
Diuretic-induced complications in the absence of other precipitating factors
Runyon B et al. Hepatology 2009:2087-2107, EASL Journal of Hepatology 2010:397-417
Conditions Leading to Transient
Refractoriness to Diuretic
Therapy
Inappropriate dose of diuretics
Iatrogenic causes of renal failure: NSAIDs, ACEI, aminoglycosides
Pre-renal failure precipitated by diarrhea, vomiting, SBP
Non-compliance with low sodium diet
Salerno F et al. Liver Int 2010:937-947
Refractory Ascites
Diuretic-resistant ascites (20%)
• Lack of response to sodium restriction and high-dose diuretic (furosemide 160 mg, spironolactone 400 mg)
Diuretic-intractable ascites (80%)
• Development of diuretic-induced complications
Runyon B et al. Hepatology 2009:20872107
EASL Journal of Hepatology 2010:397-417
Clinical Impact of
Refractory Ascites
Dilutional Hyponatremia
Hepatorenal Syndrome
Hepatic Hydrothorax
Spontaneous Bacterial
Peritonitis
Spontaneous Bacterial Empyema
Umbilical Hernia
Siqueira F et al Gastroenterol Hepatol 2009
Dilutional Hyponatremia
• 30% of patients with
ascites
• Increase mortality if
Na< 125 mEq/L
• Fluid restriction if Na<
120mEq
Umbilical Hernia
• 20% of patients with
ascites
• At risk of inguinal
hernia development
• Paracentesis
• Avoid surgery due to
high risk of fluid
leakage, infection,
bleeding
• Incarceration,
strangulation, SBP
Siqueira F et al Gastroenterol Hepatol 2009
CIRRHOSIS
Treatment of Refractory Ascites
Liver transplantation
Large volume paracentesis (LVP) + albumin
Transjugular intrahepatic portosystemic shunt (TIPS)
Continue diuretics if no complication and Ur Na excretion > 30 mEq/L
Wong F Journal of Gastroenterol and Hapatol 2012:11-20
Runyon B et al. Hepatology 2004:1-16
Complications of Paracentesis
Bleeding < 1%
Leakage of ascitic fluid
Paracentesis-induced circulatory dysfunction (PICD) or post-paracentesis circulatory dysfunction (PPCD)
• Increase cardiac output, decline of peripheral and splanchnic vascular resistance, activation of RAAS, increase HVPG
PICD
70% occurs after LVP with no expander
15-50% after LVP with plasma expander
Shorter time to ascites recurrence
20% HRS and/or hyponatremia
Reduced survival
PRA level> 50% of pretreatment value to > 4 ng/ml*hr at 6th d
PRA
Ruiz-Del-Arbol L et al.
Gastroenterology 1997:579-586
PICD Depends on the Type of Plasma Volume Expander and the Amount of Ascites Removed
De
ve
lop
me
nt
of
PC
D
%
Ascites removed
Overall <5-6 L >5-6 L
70
60
50
40
30
20
10
0
No expander
Saline
Synthetic expander
Albumin
Gines et al., Gastroenterology 1988; 94:1493;
Gines et al., Gastroenterology 1996; 111:1002;
Sola-Vera et al., Hepatology 2003; 37:1147
Albumin Infusion in Patients Undergoing
Large-Volume Paracentesis: A Meta-Analysis of Randomized Trials
Trials (1988-2010) 1225 patients
Albumin
(6-8 g/L)
Control
(Dextran-70,
3.5% gelatin, 6% HES,
3.5% saline,
Norepinephrine, Midodrine, Terlipressin)
PICD (13 Trials:N= 857)
15% 30%
Mortality (11 trials:N= 927)
12% 14.4%
Bernardi M et al. Hepatology 2012:1172-1181
Albumin reduces morbidity and mortality among cirrhotic patients, tense ascites, LVP
Transjugular Intrahepatic
Portosystemic Shunt (TIPS)
Side-side porto caval shunt
Decrease portal pressure
Improvement of circulatory dysfunction
Improvement on renal blood flow, urine Na-excretion, serum Cr
Colombo L J Clin gastroenterol 2007:S344-351
Rosle M et al. Gut 2010:988-1000
Bhogal H et al. Clin Gastroenterol Hepatol 2011:936-946
Contraindications for TIPS
Absolute
Contraindication
Relative
Contraindication
• Congestive heart failure • Age > 70
• Severe pulmonary
hypertension > 50
mmHg
• Portal vein thrombosis
• Child-Pugh > 12 • HCC
• Multiple hepatic cysts • INR > 5
• Uncontrolled
encephalopathy
• Platelets < 20,000 mm3
• Unrelieved biliary
obstruction
Meta-Analyses of TIPS and LVP
on Refractory Ascites
n TIPS,
%
LVP,% P TIPS,
%
LVP,% P TIPS,
%
LVP,% P
Lebrec
1996
25 38 0 - 23 0 - 29 56 <.05
Rossle
2000
60 84 43 - 58 48 NS 69 52 NS
Gines
2002
70 51 17 .003 77 66 NS* 41 35 NS
Sanyal
2003
109 58 16 <.001 42 23 NS* 19 mo 12 mo NS
Salerno
2004
66 79 42 .012 61 39 NS* 77 52 .021
Narahara
2011
60 87 20 <.001 67 17 <.001 80 49 <.005
Ascites control Encephalopathy Survival at 1 yr
Bhogal H et al. Clin Gastroenterol Hepatol 2011:936-946
TIPS in Refractory Ascites
Improved transplant-free survival, better control of ascites
Lower PHTN related complications (GIB, SBP, HRS)
HE (30%) more severe HE in TIPS group (OR 2.26)
(Age, CPT >11, MELD >18)
Can cause cardiac failure, liver failure, endotipsitis, intravascular hemolysis
Patient’s selection: Age, bilirubin level < 5 mg/dl, Na > 130 mEq/L
Salerno et al. Liver Int 2010:1137-1342
Rosle M et al. Gut 2010:988-1000
Vasoconstrictors, Albumin Control PCD% Ascites control
Terlipressin
(2006)
Albumin 23 vs 10
Midodrine (2006) Albumin 60 vs 30
Octreotide+
Midodrine (2012)
Albumin 25 vs 18 Time to LVP 10 d
vs 8 d
Albumin 4 g
(2011)
Albumin 8 g 14 vs 20 Time to LVP 98 d
vs 112 d
SMT+ Midodrine
SMT+ Clonidine
SMT+Midodrine+
Clonidine
Diuretic+ LVP
(SMT)
Better control of
ascites in
SMT+ midodrine,
SMT+M+C
Future options
• No recommendation
to use Vasopressin
V2 receptor
antagonists
• Automated Low-
Flow Ascites pump
system (peritoneo-
vesical)
Wong F Journal of Gastroenterol and Hapatol 2012:11-20
Automated Low Flow Pump
System for the Treatment of
Refractory Ascites
Bellot P et al. Journal of Hepatology 2013 in press
Nutritional Support in Patients with
Refractory Ascites Main outcome Parenteral-
nutrition-
support,
balanced diet
and BCAA
(n=40)
Balanced diet
and BCAA (n=40)
Low sodium diet
(n=40) P- value
Death at 12 mo 18 (45%) 24 (60%) 33 (82.5%) A:B=0.048
A:C=<0.01
B:C= 0.046
LVP per mo 1.1 (0.8-2.5) 1.3 (1-2.9) 2.1 (1.5-4) A:B= NS
A:C=<0.01
B:C= 0.034
Encephalopathy 18 (45%) 15 (37.5%) 31 (77.5%) A:B= NS
A:C=<0.01
B:C= <0.01
GI bleeding 10 (25%) 13 (32.5%) 21 (52%) A:B= NS
A:C=<0.01
B:C= <0.01
HRS 6 (15%) 9 (22.5%) 15 (37.5%) A:B= NS
A:C=<0.01
B:C= <0.01
SBP 7 (17.5%) 9 (22.5%) 15 (37.5%) A:B= NS
A:C=<0.01
B:C= <0.01
Liver
transplantation
3 (7.5%) 4 (10%) 3 (7.5%) NS
Sorrentino P et al. Journal of Gastroenterol and Hapatol 2012
Recommendation
Cirrhotic with ascites not responsive to diuretics
Exclude infection,
malignancy, NSAIDS use
Refractory ascites (meet
criteria)
Dietary noncompliance (urine Na 24 hr)
LVP with albumin (6-8 g/L if >5L of
fluid removal)
Liver Transplant evaluation
Liver not yet available or
frequent paracentesis
Consider TIPS
Not responsive Responsive No TIPS: Bilirubin > 5 mg/dl,
CPT >11, PSE grade >2
Thank You
Post-paracentesis Renin Levels Correlate Inversely with Systemic
Vascular Resistance
Ruiz-Del-Arbol L et al. Gastroenterology 1997:579-586
Study Drugs PCD (%) PCD in
albumin
(%)
Ascites
recurrence (d)
Moreau 2006 Terlipressin 27 23
Singh 2006 Terlipressin 23 10
Appenrodt
2008
Midodrine 61 31
Bari 2012 Midodrine+
octreotide+
albumin
18 25 Albumin 10
Vaso 8
Alessandria
2011
(tense
ascites)
Albumin 4g/L
(half-dose)
14 20 ½ Albumin 98
Albumin 112
Vasocontrictors + albumin
Odds Ratio (CI)
Albumin Control
Event Control Event Control
PCD in trials comparing albumin
vs alternative treatment
Bernardi M et al. Hepatology 2012
Cumulative probability of transplant
free survival according to TIPS and
Paracentesis
P= 0.035 by
Log-rank
TIPS
Salerno et al. Gastroenterology 2007
Cirrhosis:
obstruction to flow Portal
Hypertension
Sheer
stress,
Vasodilator
Splanchnic
vasodilatation
Portosystemic
shunting of
vasodilators
Systemic
arterial
vasodilation
EABV
Activation of
RAAS &SNS
&AVP
Sensitivity of
renal
circulation to
vasoconstrictor GFR, RBF,
Na retention ASCITES