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CIRRHOTIC ASCITES
DR SADIK MEMONFCPS (MEDICINE), FCPS (GASTROENTEROLOGY), AGA-M
ISRA UNIVERSITY HYDERABAD.
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Development of Complications inCompensated Cirrhosis
AscitesJaundice
EncephalopathyGI hemorrhage
Probability
of
developing
event
0
20
60
80
100
0 60
40
20 40 80 100 120 140 160
MonthsGines et. al., Hepatology 1987; 7:122
NATURAL HISTORY OF CIRRHOSIS
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Case 1
Dr. Muhammad Sadik
MemonAssociate Professor / GastroenterologistHead Section of Gastroenterology &
Hepatology
Department of Medicine
Isra University Hospital
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A 35 year old gentleman came to
you, with progressive abdominal
distension.Palmer erythna
Wasting
AnemiaShifting dullness positive
Splenomegaly
Pedal edema
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What is your probable diagnosis?
How will treat?
1) RE-assurance
2) Salt- restriction, alternative to salt
restriction
3) Water restriction
4) Diuretics.
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HVPG > 12 mmHg is Necessary for Ascites toDevelop and is Associated with Low Sodium
Excretion
Urinarysodium
(mEq/L)
No ascites
Ascites
HVPG
(mmHg
)
0
20
50
60
30
40
10
0 5 10 15 20 2512
Morali et al., J Hepatol 1992; 16:249
HVPG > 12 mmHg IS NECESSARY FOR ASCITES TO DEVELOP AND IS ASSOCIATED WITH LOW SODIUM EXCRETION
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0
20
40
100Urinary
sodium
excretion(mmol/day
)
60
80
120
140
4
Noascites
Moderateascites
Tenseascites
Eisenmenger et al, J Clin Invest 1950; 29:1491
Urinary Sodium Excretion is Decreased inCirrhotic Patients with Ascites
URINARY SODIUM EXCRETION IS DECREASED IN CIRRHOTIC PATIENTS WITH ASCITES
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Cirrhosis
Activation ofneurohumoral
systems (renin,angiotensin,aldosterone)
Effectivearterial blood
volume
Hepaticvenous
outflow block
Ascites
Sinusoidalpressure
(HVPG 10-12mmHg)
Sodium andwater
retention
Arteriolarresistance(vasodilation)
PATHOGENESIS OF ASCITES
ULTRASOUND IS THE MOST SENSITIVE METHOD TO DETECT ASCITES
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Ultrasound is the Most SensitiveMethod to Detect Ascites
Liver
Ascites
ULTRASOUND IS THE MOST SENSITIVE METHOD TO DETECT ASCITES
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Activation ofneurohumora
l systems
Site of Action of Different Therapies for Ascites
Cirrhosis
Intrahepaticresistance
Arteriolarresistance(vasodilation)
Sinusoidalpressure
Ascites Sodium andwaterretention
TIPSTIPS
Diuretics
PVS
PVS
Albumin
LVP
Effectivearterial blood
volume
MECHANISM OF ACTION OF THE DIFFERENT THERAPIES FOR ASCITES
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Treatment of Ascites
Portal HypertensionNo ascites
Uncomplicatedascites
Refractory
ascites
Hepatorenalsyndrome
No specific therapy
Consider salt restriction
PREVENTION OF ASCITES
TREATMENT OF UNCOMPLICATED ASCITES
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Treatment of Ascites
Uncomplicatedascites
Refractory
ascites
Hepatorenalsyndrome
Portal HypertensionNo ascites
TREATMENT OF UNCOMPLICATED ASCITES
MECHANISMS OF ACTION OF SODIUM RESTRICTION AND DIURETICS IN THE MANAGEMENT OF ASCITES
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Sodium andwater
retention
Activation ofneurohumora
l systems
Effectivearterial blood
volume
Cirrhosis
Intrahepaticresistance
Arteriolarresistance(vasodilation)
Sinusoidalpressure
Ascites Sodium andwaterretention
Na restrictiionDiuretics
MECHANISMS OF ACTION OF SODIUM RESTRICTION AND DIURETICS IN THE MANAGEMENT OF ASCITES
SPIRONOLACTONE IS MORE EFFECTIVE THAN FUROSEMIDE IN CIRRHOTIC PATIENTS WITH ASCITES
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Spironolactone is More Effective ThanFurosemide in Cirrhotic Patients with
AscitesResponse No response Total
Furosemide 11 10 21(80-160 mg/d)
Spironolactone 18 1 19
(150-300 mg/d)
Perez-Ayuso et al. Gastroenterology 1983; 84:961
SPIRONOLACTONE IS MORE EFFECTIVE THAN FUROSEMIDE IN CIRRHOTIC PATIENTS WITH ASCITES
DIFFERENT DIURETIC REGIMENS IN PATIENTS WITH CIRRHOTIC ASCITES
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Different Diuretic Regimens in Patientswith Cirrhotic Ascites
Combination Schedule(n=50)
SP 100mg/d +
FUR 40mg/d
SP 200mg/d +
FUR 80mg/d
SP 400mg/d +
FUR 160mg/d
Progressive Schedule(n=50)
Spironolactone (SP)
100 200 400mg/d
SP 400mg/d +
Furosemide (FUR)
40 60 80 160mg/d
4days
4days
Santos et al., J Hepatol 2003; 39:187
DIFFERENT DIURETIC REGIMENS IN PATIENTS WITH CIRRHOTIC ASCITES
DIFFERENT DIURETIC REGIMENS IN PATIENTS WITH CIRRHOTIC ASCITES
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Different Diuretic Regimens in Patientswith Cirrhotic Ascites
Combination Schedule(n=50)
SP 100mg/d +
FUR 40mg/d
SP 200mg/d +
FUR 80mg/d
SP 400mg/d +
FUR 160mg/d
Progressive Schedule(n=50)
Spironolactone (SP)
100 200 400mg/d
SP 400mg/d +
Furosemide (FUR)
40 60 80 160mg/d
4days
4days
Santos et al., J Hepatol 2003; 39:187
TREATMENT OF PATIENTS WITH UNCOMPLICATED ASCITES
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Treatment of Ascites
Portal HypertensionNo ascites
Uncomplicatedascites
Refractory
ascites
Hepatorenalsyndrome
1) Salt restriction + diuretics2) Large volume
paracentesis (LVP) inhospitalized patients withtense ascites
TREATMENT OF PATIENTS WITH UNCOMPLICATED ASCITES
MANAGEMENT OF UNCOMPLICATED ASCITES
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Management of Uncomplicated
Ascites
Definition: Ascites responsive to diureticsin the absence of infection and
renal dysfunction
Sodium restriction Effective in 10-20% of cases
Predictors of response: mild or moderateascites, Urine Na excretion > 50 mEq/day
Diuretics
Should be spironolactone-based
A progressive schedule (spironolactonefurosemide) requires fewer dose adjustmentsthan a combined therapy (spironolactone +
furosemide)
MANAGEMENT OF UNCOMPLICATED ASCITES
MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION
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Sodium Restriction
2 g (or 5.2 g of dietary salt) a day
Fluid restriction is not necessary unless thereis hyponatremia (
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Diuretic TherapyDosageSpironolactone 100-400 mg/day
Furosemide (40-160 mg/d) for inadequate weight lossor if hyperkalemia develops
Increase diuretics if weight loss 0.5 kg/day in patientswithout edema and >1 kg/day in those with edema
Side effects
Renal dysfunction, hyponatremia, hyperkalemia,encephalopathy, gynecomastia
Management of Uncomplicated Ascites
MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY
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Case
A 45 years old gentleman came to you withaltered sleep pattern. His son furtheradded that he is not good at business(Accounting).
He does not remember the prices of variousgoods since 4 days. He is known case ofcirrhosis of liver and on diuretics(Furosemide40mg/day and spironolectone100mg / day). He responded very well andhis tummy size decreased very much.
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Questions????
Q1. What is the new problems
arises in this patient?
Q2. Will you continue diuretics?
Q3. What laboratory test you will
perform?
TREATMENT OF REFRACTORY ASCITES
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Treatment of Ascites
Portal HypertensionNo ascites
Uncomplicatedascites
Refractory
ascites
Hepatorenalsyndrome
DEFINITION AND TYPES OF REFRACTORY ASCITES
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Definition and Types of Refractory
Ascites
Occurs in ~10% of cirrhotic patients
Diuretic-intractable ascites
Therapeutic doses of diuretics cannot be achievedbecause of diuretic-induced complications
Diuretic-resistant ascites
No response to maximal diuretic therapy (400 mg
spironolactone + 160 mg furosemide/day)
20%
80%
Arroyo et al. Hepatology 1996; 23:164
PATIENTS WITH REFRACTORY ASCITES HAVE A WORSE SURVIVAL THAN PATIENTS WITH DIURETIC-RESPONSIVE ASCITES
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Patients with Refractory Ascites Have AWorse Survival than Patients with Diuretic-
Responsive Ascites
Survival
probability
1.0
.8
.6
.4
.2
0120 24 4836 60 8472
Refractory ascites
Non refractory ascites
p
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Ascites
Albumin
Activation ofneurohumora
l systems
Effectivearterial blood
volume
Cirrhosis
Intrahepaticresistance
Arteriolarresistance(vasodilation)
Sinusoidalpressure
Sodium andwater
retention
LVP+
Effectivearterial blood
volume
Ascites
MECHANISMS OF ACTION OF THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT IN THE MANAGEMENT OF ASCITES
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Effectivearterial blood
volume
Sinusoidalpressure
Activation ofneurohumora
l systems
Cirrhosis
Intrahepaticresistance
Arteriolarresistance(vasodilation)
Ascites Sodium andwaterretention
TIPSSinusoidalpressure
Effectivearterial blood
volume
COMPARED TO LVP, TIPS IS ASSOCIATED WITH LESS ASCITES RECURRENCE BUT MORE ENCEPHALOPATHY
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Compared to LVP, TIPS Reduces AscitesRecurrence But Increases Risk of
Encephalopathy
* Episodes/patient
LVP TIPS
p
(n=35) (n=35)
Recurrent ascites 11.7 2.7* 3.6 1.7
0.003
TIPS obstruction - 40%-
Grade 3-4 PSE 0.5 0.02 1.1 0.02
0.02Gines et al., Gastroenterology 2002; 123:1839
SURVIVAL IS NOT DIFFERENT BETWEEN PATIENTS TREATED WITH LARGE-VOLUME PARACENTESIS (LVP) OR TRANSJUGULAR
INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS)
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0 3 6 9 12 18 21 2415
Months
1
0.2
0.4
0.6
0.8
Probabilit
y of
survival
0
Paracentesis and albumin
TIPS
p = 0.51
Survival is Not Different BetweenPatients Treated With LVP or TIPS
Gines et al., Gastroenterology 2002; 123:1839
INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS)
META-ANALYSIS OF TIPS VS. LVP+ALBUMIN FOR REFRACTORY ASCITES
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Survival (month 12)
Encephalopathy
Meta-Analysis of TIPS vs. LVP +Albumin for Refractory Ascites
Deltenre et al., Liver International 2005; 25:349
Ascites control (month 4)
Ascites control (month 12)
0 More with TIPSMore with LVP
RiskDifference
PERITONEO-VENOUS SHUNT (PVS) IS USEFUL IN THE TREATMENT OF REFRACTORY ASCITES
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Peritoneo-Venous Shunt (PVS) isUseful in the Treatment of Refractory
Ascites
Use of jugular
vein will hinder
TIPS placement
Intraabdominal
adhesions may
complicate liver
transplant surgery
One-way
valve
LARGE VOLUME PARACENTESIS (LVP) VS. PERITONEOVENOUS SHUNT (PVS) IN REFRACTORY ASCITES
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Large Volume Paracentesis (LVP) vsPeritoneovenous Shunt (PVS) in
Refractory Ascites
LVP PVS p value
Episodes of recurrent ascites 125 38
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Treatment of Ascites
HepatorenalSyndrome
RefractoryAscites
Uncomplicat
edAscites
PortalHypertension
No Ascites
1) LVP + albumin
2) TIPS
3) PVS (in non-TIPS, non-
transplant candidates)
LVP = large volume paracentesis
TIPS = transjugular intrahepatic portosystemic shu
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ASCITES II
A 56 years old lady admitted to the hospital
with increasing abdominal pain and fever for
three days. She is K/C of HCV cirrhosis
decompensated with ascites. On
examination she has stigmata of chronic
liver disease and tender abdomen. She is
vitally stable and febrile.
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1. What complication has this patient
developed? What is the mechanism?
3. How will you diagnose this
complication?
5. What is the treatment of this
(immediate and long term)?
SPONTANEOUS BACTERIAL PERITONITIS (SBP) COMPLICATES ASCITES AND CAN LEAD TO RENAL DYSFUNCTION
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Spontaneous Bacterial Peritonitis (SBP)Complicates Ascites and Can Lead to Renal
Dysfunction
SBP
HVPG >10 mmHgExtremeVasodilation
HVPG >10 mmHg
Severe Vasodilation
HVPG >10 mmHgModerate Vasodilation
HVPG
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Bacterial Infections Are More Frequent inSevere Liver Disease
Author n Child A Child B Child C
Bleichner 149 3% 23% 48%(1986) *
Kuo 2589 1% 5% 17%(1991)
Yoshida 1140 3% 10% 27%
(1993)
* patients with GI hemorrhage
S t B t i l P it iti (SBP) iSPONTANEOUS BACTERIAL PERITONITIS (SBP) IS THE MOST COMMON INFECTION IN CIRRHOTIC PATIENTS
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Spontaneous Bacterial Peritonitis (SBP) isthe Most Common Infection in Cirrhotic
Patients
0
25
50
75
100
125
150
UTI PneumoniaSBP
Bacteremia
Procedure-related
Spontaneous
#Hospitalize
d cirrhotic
patients
Fernndez et al., Hepatology 2002; 35:140
TYPES OF BACTERIA ISOLATED FROM HOSPITALIZED CIRRHOTIC PATIENTS
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Types of Bacteria Isolated fromHospitalized Cirrhotic Patients
0
20
40
60
80
100Culture positive
Gram (-) bacteria
Gram (+) bacteria
Both
SBP UTI Pneumoni
a
Overall
%
Fernndez et al., Hepatology 2002; 35:140
CLINICAL CHARACTERISTICS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)
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Clinical Characteristics of SpontaneousBacterial Peritonitis
Fever
Jaundice
Confusion
Hypotension
Abdominal pain
Abdominal tenderness
No signs or symptoms
%
0 20 40 60 80 100
MORTALITY ASSOCIATED WITH SBP HAS BEEN DECREASING BY EARLY DIAGNOSIS AND TREATMENT
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Mortality Associated with SBP has beenDecreasing by Early Diagnosis and Treatment
%Mortality
100
80
40
20
0
60
1970s 1980s Early 90s Late 90s 2000s
EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)
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Early Diagnosis of SBP
Diagnostic paracentesis:
If symptoms / signs of SBP occur
Unexplained encephalopathy and / orrenal dysfunction
At any hospital admission
Diagnosis based on ascitic fluid
PMN count >250/mm3
Rimola et al., J Hepatol 2000; 32:142
TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)
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Treatment ofSpontaneous BacterialPeritonitis
Recommended antibiotics for initial empirictherapy
i.v. cefotaxime , ceftrioxone, amoxicillin-clavulanic acid
oral ofloxacin (uncomplicated SBP) avoid aminoglycosides
Minimum duration: 5 days
Re-evaluation if ascitic fluid PMN count hasnot decreased by at least 25% after 2 days oftreatment
Rimola et al., J Hepatol 2000; 32:142
RENAL DYSFUNCTION IS A POOR PROGNOSTIC SIGN IN SPONTANEOUS BACTERIAL PERITONITIS (SBP)
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Renal Dysfunction is a Poor PrognosticSign in Spontaneous Bacterial Peritonitis
Renal status N
DeathsNo renal insufficiency 166 12 (7%)
Renal insufficiency 65 27 (42%)
Transient 21 1 (5%)
Stable 26 8 (31%)
Progressive 18 18 (100%)
Follo et al. Hepatology 1994; 20:1945
ALBUMIN DECREASES RENAL DYSFUNCTION AND SHORT-TERM MORTALITY IN SPONTANEOUS BACTERIAL PERITONITIS (SBP)
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Antibiotics Antibiotics +
alone (n=63) albumin(n=63)
p
Resolution of SBP 93% 98%
ns
Renal dysfunction 32% 10%
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Spontaneous Bacterial PeritonitisUse of Intravenous Albumin
Albumin (plus antibiotics) is indicated if: BUN > 30 mg/dL
creatinine > 1.0 mg/dL
bilirubin > 4 mg/dL
Albumin is not indicated in patients with apredicted 100% cure and survival:
community-acquired SBP no GI hemorrhage
no encephalopathy
normal renal function
SURVIVAL AFTER DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)
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Survival After Development ofSpontaneous Bacterial Peritonitis
Probability
of survival
(%)
Months0
1.0
.8
.4
.2
.6
3 6 12 24 36
0