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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


Sinusoidalpressure

Ascites Sodium andwaterretention

TIPSTIPS

Diuretics

PVS

PVS

Albumin

LVP


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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Refractory

ascites

Hepatorenalsyndrome


TREATMENT OF UNCOMPLICATED ASCITES

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

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Sodium andwater

retention


l systems


volume

Cirrhosis



Sinusoidalpressure


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



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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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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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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


l systems


volume

Cirrhosis



Sinusoidalpressure

Sodium andwater

retention

LVP+


volume

Ascites

MECHANISMS OF ACTION OF THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT IN THE MANAGEMENT OF ASCITES

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volume

Sinusoidalpressure


l systems

Cirrhosis




TIPSSinusoidalpressure


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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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

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