CIRRHOTIC ASCITES

DR SADIK MEMON
FCPS (MEDICINE), FCPS (GASTROENTEROLOGY), AGA-M
ISRA UNIVERSITY HYDERABAD.
 NATURAL HISTORY OF CIRRHOSIS

Development of Complications in
Compensated Cirrhosis
100

80

Probability 60 Ascites
Jaundice
of
developing 40 Encephalopathy
GI hemorrhage
event
20

0
0 20 40 60 80 100 120 140 160

Months
Gines et. al., Hepatology 1987; 7:122
 Case 1
Dr. Muhammad Sadik
Memon
Associate Professor / Gastroenterologist
Head Section of Gastroenterology &
Hepatology
Department of Medicine
Isra University Hospital
A 35 year old gentleman came to
you, with progressive abdominal
distension.
Palmer erythna
Wasting
Anemia
Shifting dullness positive
Splenomegaly
Pedal edema
 What is your probable diagnosis?

How will treat?

1) RE-assurance
2) Salt- restriction, alternative to salt
restriction
3) Water restriction
4) Diuretics.
 HVPG > 12 mmHg IS NECESSARY FOR ASCITES TO DEVELOP AND IS ASSOCIATED WITH LOW SODIUM EXCRETION

HVPG > 12 mmHg is Necessary for Ascites to

Develop and is Associated with Low Sodium
Excretion
60 No ascites
Ascites
50

40
Urinary
sodium 30
(mEq/L)
20

10

0
0 5 10 12 15 20 25
HVPG
(mmHg
)
Morali et al., J Hepatol 1992; 16:249
 URINARY SODIUM EXCRETION IS DECREASED IN CIRRHOTIC PATIENTS WITH ASCITES

Urinary Sodium Excretion is Decreased in

Cirrhotic Patients with Ascites
140
120

100
Urinary
sodium 80
excretion
60
(mmol/day
) 40
20

0
No Moderate Tense
ascites ascites ascites
Eisenmenger et al, J Clin Invest 1950; 29:1491
 PATHOGENESIS OF ASCITES

Cirrhosis
Hepatic Arteriolar
venous resistance
outflow block (vasodilation)

Sinusoidal Effective
pressure arterial blood
(HVPG ≥ 10-12 volume
mmHg)

Activation of
Sodium and
Ascites water
neurohumoral
systems (renin,
angiotensin,
retention aldosterone)
 ULTRASOUND IS THE MOST SENSITIVE METHOD TO DETECT ASCITES

Ultrasound is the Most Sensitive

Method to Detect Ascites

Ascites

Liver
 MECHANISM OF ACTION OF THE DIFFERENT THERAPIES FOR ASCITES

Site of Action of Different Therapies for Ascites

Cirrhosis
Arteriolar
Intrahepatic resistance
resistance (vasodilation)

Albumin Effective
Sinusoidal TIPS TIPS
pressure PVS arterial blood
volume
PVS
LVP Diuretics
Activation of
Sodium and
Ascites water
neurohumora
l systems
retention
 PREVENTION OF ASCITES

Treatment of Ascites

Portal Hypertension No specific therapy

No ascites Consider salt restriction

Uncomplicated
ascites

Refractory
ascites

Hepatorenal
syndrome
 TREATMENT OF UNCOMPLICATED ASCITES

Treatment of Ascites

Portal Hypertension
No ascites

Uncomplicated
ascites

Refractory
ascites

Hepatorenal
syndrome
 MECHANISMS OF ACTION OF SODIUM RESTRICTION AND DIURETICS IN THE MANAGEMENT OF ASCITES

Cirrhosis
Arteriolar
Intrahepatic resistance
resistance (vasodilation)

Diuretics Effective
Sinusoidal Na restrictiion arterial blood
pressure
volume

Activation of
Sodium
Ascites Sodiumand
and neurohumora
water
water l systems
retention
retention
 SPIRONOLACTONE IS MORE EFFECTIVE THAN FUROSEMIDE IN CIRRHOTIC PATIENTS WITH ASCITES

Spironolactone is More Effective Than

Furosemide in Cirrhotic Patients with
Ascites
Response 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

 DIFFERENT DIURETIC REGIMENS IN PATIENTS WITH CIRRHOTIC ASCITES

Different Diuretic Regimens in Patients

with Cirrhotic Ascites
Progressive Schedule Combination Schedule
(n=50) (n=50)
Spironolactone (SP) SP 100mg/d +
100 → 200 → 400 FUR 40mg/d
mg/d
4days

SP 400mg/d + SP 200mg/d +
Furosemide (FUR) FUR 80mg/d
40 → 60 → 80 → 160
mg/d 4days

SP 400mg/d +
FUR 160mg/d

Santos et al., J Hepatol 2003; 39:187

 DIFFERENT DIURETIC REGIMENS IN PATIENTS WITH CIRRHOTIC ASCITES

Different Diuretic Regimens in Patients

with Cirrhotic Ascites
Progressive Schedule Combination Schedule
(n=50) (n=50)
Spironolactone (SP) SP 100mg/d +
100 → 200 → 400 FUR 40mg/d
mg/d
4days

SP 400mg/d + SP 200mg/d +
Furosemide (FUR) FUR 80mg/d
40 → 60 → 80 → 160
mg/d 4days

SP 400mg/d +
FUR 160mg/d

Santos et al., J Hepatol 2003; 39:187

 TREATMENT OF PATIENTS WITH UNCOMPLICATED ASCITES

Treatment of Ascites

Portal Hypertension
No ascites

Uncomplicated 1) Salt restriction + diuretics

ascites 2) Large volume
paracentesis (LVP) in
hospitalized patients with
Refractory tense ascites
ascites

Hepatorenal
syndrome
 MANAGEMENT OF UNCOMPLICATED ASCITES

Management of Uncomplicated
Ascites
Definition: Ascites responsive to diuretics
in the absence of infection and
renal dysfunction
Sodium restriction
• Effective in 10-20% of cases
• Predictors of response: mild or moderate
ascites, Urine Na excretion > 50 mEq/day
Diuretics
• Should be spironolactone-based
• A progressive schedule (spironolactone 
furosemide) requires fewer dose adjustments
than a combined therapy (spironolactone +
furosemide)
 MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION

Management of Uncomplicated Ascites

Sodium Restriction

• 2 g (or 5.2 g of dietary salt) a day

• Fluid restriction is not necessary unless there

is hyponatremia (<125 mmol/L)

• Goal: negative sodium balance

• Side effect: unpalatability may compromise

nutritional status
 MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY

Management of Uncomplicated Ascites

Diuretic Therapy
Dosage
• Spironolactone 100-400 mg/day
• Furosemide (40-160 mg/d) for inadequate weight loss
or if hyperkalemia develops
• Increase diuretics if weight loss <1 kg in the first week
and < 2 kg/week thereafter
• Decrease diuretics if weight loss >0.5 kg/day in patients
without edema and >1 kg/day in those with edema

• Side effects
• Renal dysfunction, hyponatremia, hyperkalemia,
encephalopathy, gynecomastia
 Case

A 45 years old gentleman came to you with

altered sleep pattern. His son further
added that he is not good at business
(Accounting).
He does not remember the prices of various
goods since 4 days. He is known case of
cirrhosis of liver and on diuretics
(Furosemide40mg/day and spironolectone
100mg / day). He responded very well and
his tummy size decreased very much.
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

Treatment of Ascites

Portal Hypertension
No ascites

Uncomplicated
ascites

Refractory
ascites

Hepatorenal
syndrome
 DEFINITION AND TYPES OF REFRACTORY ASCITES

Definition and Types of Refractory

Ascites
Occurs in ~10% of cirrhotic patients

• Diuretic-intractable ascites
80%
Therapeutic doses of diuretics cannot be achieved
because of diuretic-induced complications

• Diuretic-resistant ascites
20%
No response to maximal diuretic therapy (400 mg
spironolactone + 160 mg furosemide/day)

Arroyo et al. Hepatology 1996; 23:164

 PATIENTS WITH REFRACTORY ASCITES HAVE A WORSE SURVIVAL THAN PATIENTS WITH DIURETIC-RESPONSIVE ASCITES

Patients with Refractory Ascites Have A

Worse Survival than Patients with Diuretic-
Responsive Ascites
1.0

.8
Non refractory ascites
.6
Survival
probability
.4 p<0.001

.2
Refractory ascites
0
0 12 24 36 48 60 72 84
Months
Salerno et al., Am J Gastroenterol 1993; 88:514
 MECHANISMS OF ACTION OF LARGE VOLUME PARACENTESIS IN THE MANAGEMENT OF

Cirrhosis
Arteriolar
Intrahepatic resistance
resistance (vasodilation)

LVP
Effective
Sinusoidal + arterial blood
pressure
Albumin volume

Activation of
Sodium and
neurohumora
Ascites
Ascites water
l systems
retention
 MECHANISMS OF ACTION OF THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT IN THE MANAGEMENT OF ASCITES

Cirrhosis
Arteriolar
Intrahepatic resistance
resistance (vasodilation)

Sinusoidal Effective
Sinusoidal TIPS
pressure arterial blood
pressure
volume

Activation of
Sodium and
Ascites water
neurohumora
l systems
retention
 COMPARED TO LVP, TIPS IS ASSOCIATED WITH LESS ASCITES RECURRENCE BUT MORE ENCEPHALOPATHY

Compared to LVP, TIPS Reduces Ascites

Recurrence But Increases Risk of
Encephalopathy

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

* Episodes/patient
0.02
Gines et al., Gastroenterology 2002; 123:1839
 SURVIVAL IS NOT DIFFERENT BETWEEN PATIENTS TREATED WITH LARGE-VOLUME PARACENTESIS (LVP) OR TRANSJUGULAR
INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS)

Survival is Not Different Between

Patients Treated With LVP or TIPS
1
Paracentesis and albumin

0.8
TIPS
p = 0.51

0.6
Probabilit
y of
0.4
survival

0.2

0
0 3 6 9 12 15 18 21 24
Months
Gines et al., Gastroenterology 2002; 123:1839
 META-ANALYSIS OF TIPS VS. LVP+ALBUMIN FOR REFRACTORY ASCITES

Meta-Analysis of TIPS vs. LVP +

Albumin for Refractory Ascites

Ascites control (month 4)

Ascites control (month 12)

Survival (month 12)

Encephalopathy
Risk
Differenc
More with LVP 0 More with TIPS e

Deltenre et al., Liver International 2005; 25:349

 PERITONEO-VENOUS SHUNT (PVS) IS USEFUL IN THE TREATMENT OF REFRACTORY ASCITES

Peritoneo-Venous Shunt (PVS) is

Useful in the Treatment of Refractory
Ascites
Use of jugular
vein will hinder
TIPS placement

One-way
valve
Intraabdominal
adhesions may
complicate liver
transplant surgery
 LARGE VOLUME PARACENTESIS (LVP) VS. PERITONEOVENOUS SHUNT (PVS) IN REFRACTORY ASCITES

Large Volume Paracentesis (LVP) vs

Peritoneovenous Shunt (PVS) in
Refractory Ascites

LVP PVS p value

Episodes of recurrent ascites 125 38 <0.001

PVS obstruction - 40% -

Hospital stay 48 ± 8 44 ± 6 ns

Survival 57% 44% ns

Gines et al., N Engl J Med 1991; 325:829

 TREATMENT OF REFRACTORY ASCITES

Treatment of Ascites

Portal
Hypertension
No Ascites

Uncomplicat
ed
Ascites
1) LVP + albumin
Refractory 2) TIPS
Ascites 3) PVS (in non-TIPS, non-
transplant candidates)

Hepatorenal
Syndrome
LVP = large volume paracentesis
TIPS = transjugular intrahepatic portosystemic shun
 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.
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

Spontaneous Bacterial Peritonitis (SBP)

Complicates Ascites and Can Lead to Renal
Dysfunction
Portal HVPG <10 mmHg
Hypertension Mild Vasodilation
No Ascites

Uncomplicate HVPG >10 mmHg

d Moderate Vasodilation
Ascites

SBP Refractory HVPG >10 mmHg

Ascites Severe Vasodilation

Hepatorenal HVPG >10 mmHg

Syndrome Extreme
Vasodilation
 BACTERIAL INFECTIONS ARE MORE FREQUENT IN SEVERE LIVER DISEASE

Bacterial Infections Are More Frequent in

Severe 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
 SPONTANEOUS BACTERIAL PERITONITIS (SBP) IS THE MOST COMMON INFECTION IN CIRRHOTIC PATIENTS

Spontaneous Bacterial Peritonitis (SBP) is

the Most Common Infection in Cirrhotic
Patients
150

125

100
#
Hospitalize
75
d cirrhotic
patients
50

25

0
SBP UTI Pneumonia Procedure- Spontaneous
related

Bacteremia
Fernández et al., Hepatology 2002; 35:140
 TYPES OF BACTERIA ISOLATED FROM HOSPITALIZED CIRRHOTIC PATIENTS

Types of Bacteria Isolated from

Hospitalized Cirrhotic Patients

100
Culture positive
80 Gram (-) bacteria
Gram (+) bacteria
60 Both

%
40

20

0
SBP UTI Pneumoni Overall
a

Fernández et al., Hepatology 2002; 35:140

 CLINICAL CHARACTERISTICS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Clinical Characteristics of Spontaneous

Bacterial Peritonitis

Fever

Jaundice

Abdominal pain

Confusion

Abdominal tenderness

Hypotension

No signs or symptoms

0 20 40 60 80 100
%
 MORTALITY ASSOCIATED WITH SBP HAS BEEN DECREASING BY EARLY DIAGNOSIS AND TREATMENT

Mortality Associated with SBP has been

Decreasing by Early Diagnosis and Treatment

100

80

60
%
Mortality
40

20

0
1970’s 1980’s Early 90’s Late 90’s 2000’s
 EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Early Diagnosis of SBP

• Diagnostic paracentesis:
• If symptoms / signs of SBP occur
• Unexplained encephalopathy and / or
renal 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)

Treatment of Spontaneous Bacterial

Peritonitis
• Recommended antibiotics for initial empiric
therapy
• i.v. cefotaxime , ceftrioxone, amoxicillin-
clavulanic acid
• oral ofloxacin (uncomplicated SBP)
• avoid aminoglycosides

• Minimum duration: 5 days

• Re-evaluation if ascitic fluid PMN count has

not decreased by at least 25% after 2 days of
treatment
Rimola et al., J Hepatol 2000; 32:142
 RENAL DYSFUNCTION IS A POOR PROGNOSTIC SIGN IN SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Renal Dysfunction is a Poor Prognostic

Sign in Spontaneous Bacterial Peritonitis

Renal status N
Deaths
No 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)

Albumin Decreases Renal Dysfunction and Short-

term Mortality in Spontaneous Bacterial Peritonitis

Antibiotics Antibiotics +

alone (n=63) albumin (n=63)

p

Resolution of SBP 93% 98%

ns

Renal dysfunction 32% 10%

<0.001

Hospital mortality 27% 10%

<0.001
Sort et al., N Engl J Med 1999; 341:403
 SPONTANEOUS BACTERIAL PERITONITIS (SBP): USE OF INTRAVENOUS ALBUMIN

Spontaneous Bacterial Peritonitis

Use 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 a

predicted 100% cure and survival:
• community-acquired SBP
• no GI hemorrhage
• no encephalopathy
• normal renal function
 SURVIVAL AFTER DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Survival After Development of

Spontaneous Bacterial Peritonitis
1.0

.8

.6
Probability
of survival .4
(%)
.2

0
0 3 6 12 24 36
Months

Tito et al., Hepatology 1988; 8:27