Liver Blood Supply

04/20/2304/20/23 22

Management of Adult Patients With Management of Adult Patients With Ascites Due to CirrhosisAscites Due to Cirrhosis AASLD 2004 GuidelineAASLD 2004 Guideline

Ahmed Mayet, Pharm.DAhmed Mayet, Pharm.D

04/20/2304/20/23 33

Liver Blood SupplyLiver Blood Supply

75% blood 75% blood supply by portal supply by portal and hepatic and hepatic veinsveins

25% by hepatic 25% by hepatic arteriesarteries

04/20/2304/20/23 55

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Hepatocytes Hepatocytes

functionfunction

as as detoxificationdetoxification

of toxicof toxic

substances substances

and and synthesizersynthesizer

of proteins,of proteins,

carbohydrates,carbohydrates,

hormones andhormones and

related related

materials materials

Kupffer Cell act Kupffer Cell act

as as phagocyticphagocytic cell cell

04/20/2304/20/23 77

04/20/2304/20/23 88

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ClassificationClassification

Pre-Sinusoidal Sinusoidal

Post-Hepatic

Pre-Hepatic

Post-Sinusoidal

04/20/2304/20/23 1515

Healthy LiverHealthy Liver

04/20/2304/20/23 1616

Definition:Definition:

CCirrhosisirrhosis of the liver is the result of the liver is the result of various disease processes and of various disease processes and is characterized by diffuse fibrosis is characterized by diffuse fibrosis and conversion of the normal liver and conversion of the normal liver architecture into structurally architecture into structurally abnormal nodules. abnormal nodules.

04/20/2304/20/23 1717

DefinitionsDefinitions

FibrosisFibrosis – Excess deposition of the Excess deposition of the

components of extracellular components of extracellular matrix (collagens, matrix (collagens, glycoproteins, proteoglycans) glycoproteins, proteoglycans) within the liver within the liver

– Reversible process Reversible process

CirrhosisCirrhosis – Diffuse hepatic process Diffuse hepatic process

characterized by fibrosis and characterized by fibrosis and conversion of normal liver conversion of normal liver architecture into structurally architecture into structurally abnormal nodules abnormal nodules

– Irreversible process Irreversible process

04/20/2304/20/23 1919

EtiologyEtiology Most common causesMost common causes

– Hepatitis (26%)Hepatitis (26%)– Alcoholic liver Alcoholic liver

disease (21%) disease (21%) – Hepatitis C+ alcoholic Hepatitis C+ alcoholic

disease (15%)disease (15%)– Cryptogenic Cryptogenic

causes(18%)causes(18%)– Hepatitis B(15%) Hepatitis B(15%) – Miscellaneous (5%)Miscellaneous (5%)

Miscellaneous (5%)Miscellaneous (5%)– Autoimmune hepatitisAutoimmune hepatitis– Primary billiary cirrhosisPrimary billiary cirrhosis– Secondary billiary Secondary billiary

cirrhosiscirrhosis– Primary sclerosing Primary sclerosing

cholangitis cholangitis – Hemochromatosis Hemochromatosis – Wilson disease Wilson disease – Alpha-1 antitrypsin Alpha-1 antitrypsin

deficiency deficiency – Drug inducedDrug induced– Venous outflow Venous outflow

obstruction (budd-chiari obstruction (budd-chiari syndrome)syndrome)

– Chronic right side heart Chronic right side heart failure failure

04/20/2304/20/23 2121

Sign and Symptoms and Sign and Symptoms and clinical finding of Liver clinical finding of Liver

CirrhosisCirrhosis Anorexia, nausea, abdominal discomfort, Anorexia, nausea, abdominal discomfort,

weight loss, and malaiseweight loss, and malaise Ascites, peripheral edema, jaundice, spider Ascites, peripheral edema, jaundice, spider

nevi, palmar erythemanevi, palmar erythema Gynecomastia, testicle atrophy, Gynecomastia, testicle atrophy,

amenorrhea, pubical hair lostamenorrhea, pubical hair lost Hepatomegaly, spleenomegaly, Hepatomegaly, spleenomegaly,

encephalopathy, and bleedingencephalopathy, and bleeding

04/20/2304/20/23 2222

Laboratory FindingsLaboratory Findings

Initially elevated ALT and AST level but Initially elevated ALT and AST level but at the end stage they can be normal or at the end stage they can be normal or below normalbelow normal

Elevated bilrubin most of the timeElevated bilrubin most of the time Low albumin levelLow albumin level Prolong prothrombin time (PT) and Prolong prothrombin time (PT) and

APTTAPTT Elevated serum creatinine and blood Elevated serum creatinine and blood

urea nitrogen (BUN)urea nitrogen (BUN)

04/20/2304/20/23 2323

ClassificationClassification Parameters Points assigned to laboratory values and signs*

11 22 33

laboratory valuelaboratory value Total serum

bilirubin level

<2 mg per dL (34 µmol per L)

2 to 3 mg per dL(34 to 51 µmol per L)

>3 mg per dL

Serum albumin level >3.5 g per dL (35 g per L)

2.8 to 3.5 g per dL

(28 to 35 g per L)

<2.8 g per dL

International Normalized Ratio

< 1.70 1.71 to 2.20 >2.20

Signs

Ascites

Encephalopathy

Non

None

Controlled

medically

Poorly

controlled

Based on total points, a patient with cirrhosis is assigned to one of three classes: Child class A = 5 to 6 points; Child class B = 7 to 9 points; Child class C = 10 to 15 points. Gastroenterology 2001;120:727

04/20/2304/20/23 2525

ComplicationsComplications

Portal hypertension Portal hypertension Variceal Hemorrhage Variceal Hemorrhage Ascites Ascites Spontaneous Bacterial PeritonitisSpontaneous Bacterial Peritonitis Hepatic Encephalopathy Hepatic Encephalopathy Hepatorenal SyndromeHepatorenal Syndrome

04/20/2304/20/23 2727

Risks of Complications of Cirrhosis

Cirrhosis

VaricealBleeding

HCC

Ascites

Encephalopathy

Bennett WG et al, Ann Intern Med 1997;127:855

0.4%

1.5%

2.5%

1.1%

percent per year

Death

Liver Transplant

11%

?20+%

?30+%

04/20/2304/20/23 2828

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Portal HypertensionPortal Hypertension

Portal pressure increases to 5 mmHg more than the Portal pressure increases to 5 mmHg more than the pressure in the inferior vena cavapressure in the inferior vena cava

Development of varices and alternative routes of blood Development of varices and alternative routes of blood flowflow

Risk of varices when portal pressure exceed the vena Risk of varices when portal pressure exceed the vena cava pressure by cava pressure by > > 12 mmHg12 mmHg

Hemorrhage from varices occurs in 25-40% of cirrhotic Hemorrhage from varices occurs in 25-40% of cirrhotic patientspatients

Each episode of bleeding carries a 30% risk of death Each episode of bleeding carries a 30% risk of death

04/20/2304/20/23 3232

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Target for Therapy

Cirrhosis

Resistance to portal flow

Portal Pressure

Varices/Variceal Hemorrhage

Splanchnic arteriolarresistance

Portal bloodflow

Venodilators

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Prevention of First Variceal Hemorrhage

Non-selective Beta-blockers prevent first variceal hemorrhage:

Bleeding rate

1-2 yr

Control Beta-Blockers

All Varices

(11 trials)

25%

(n=600)

15%

(n=590)

Large Varices

(8 trials)

30%

(n=411)

14%

(n=400)

Small Varices

(3 trials)

7%

(n=100)

2%

(n=91)

D’Amico et al, Sem Liv Dis. 1999

04/20/23 35

Treatment of Varices/Variceal Hemorrhage

VaricesNo hemorrhage

Small VaricesNo hemorrhage

Prevention of variceal growth?

Medium/large varices

No hemorrhage

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Preventing Growth of Small Varices

Nadolol may prevent the growth of small varices:

Merkel et al, Gastroentrology 2004

04/20/23 37



Small VaricesNo hemorrhage

1) Beta-Blockers (propranolol or

nadolol) indefinitely2) Endoscopic variceal

ligation in patients intolerant or

contraindicated to beta-blockers

Medium/large varices

No hemorrhage

04/20/2304/20/23 3838

ESOPHAGEAL VARICEAL ESOPHAGEAL VARICEAL BLEEDINGBLEEDING

Primary prophylaxisPrimary prophylaxis– Pharmacotherapy:Pharmacotherapy:– Non selective Non selective ββ-Blocker (Propranolol)-Blocker (Propranolol)

↓↓Portal pressure by ↓CO → ↓ Blood flow.Portal pressure by ↓CO → ↓ Blood flow. Long acting BB (Nadolol) or propanolol Long acting BB (Nadolol) or propanolol Average dose of (60 mg/d), preferred in the Average dose of (60 mg/d), preferred in the

evening, mean dose 160 mg/devening, mean dose 160 mg/d HR not less than 55 beats/min & SBP not less than HR not less than 55 beats/min & SBP not less than

90 mm Hg.90 mm Hg. Adverse effects in 27% of patients. Adverse effects in 27% of patients. What are they?What are they?

04/20/23 40

Target for Therapy

Cirrhosis

Resistance to portal flow

Portal Pressure

VaricealObliteration

Splanchnic arteriolarresistance

Portal bloodflow

Variceal bandligation/

sclerotherapy

04/20/23 41

Endoscopic varicieal band ligation

Endoscopic varicieal band ligation:

Bleeding controlled in 90%

Rebleeding rate 30%

Compared with sclerotherapy:

Less rebleeding

Less mortality

Fewer complications

Fewer treatment sessionsLaine and Cook. Ann Intern Med 1995

04/20/2304/20/23 4242

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Prevention of First Variceal Hemorrhage

Variceal Band Ligation (VBL) vs. beta-blockers:

Khuroo et al, Aliment Pharmacol Ther 2005

04/20/2304/20/23 4444

ESOPHAGEAL ESOPHAGEAL VARICEAL BLEEDING, VARICEAL BLEEDING, Cont’dCont’d Endoscopic therapy:Endoscopic therapy:

– Endoscopic variceal sclerotherapy is not Endoscopic variceal sclerotherapy is not recommended in the primary recommended in the primary prophylaxis of variceal bleeding.prophylaxis of variceal bleeding.

– Endoscopic variceal band ligation (EVL) Endoscopic variceal band ligation (EVL) was shown to be safe and more effective was shown to be safe and more effective than propranolol in the primary than propranolol in the primary prophylaxis of variceal bleeding.prophylaxis of variceal bleeding.

– Further confirmation is needed.Further confirmation is needed.

04/20/23 45

Prophylaxis of Variceal Hemorrhage

Diagnosis of Cirrhosis

Endoscopy

No varives Small varives Medium/large varives

Follow-up endoscopy in 2-3 years

Beta-blocker therapyNo CIStepwise increase until

maximum tolerated doseContinue beta-blockers life-long

CI or intolerance

Endoscopic variceal band ligation

04/20/23 46


No Varices


Varicealhemorrhage

Recurrenthemorrhage

Control hemorrhage

04/20/23 47

Treatment of Acute Variceal Hemorrhage

General management:

IV access & fluid resuscitation

Do not over transfuse (Hgb about 8)

Fresh frozen plasma, Vit K

Antibiotic prophylaxis

Specific therapy:

Pharmacological therapy

terlipressin, somatostatin, Octreotide, vasopressin + NG

Endoscopic therapy (ligation or sclerotherapy)

Shunt therapy: TIPS or surgical shunt

04/20/2304/20/23 5050

Acute variceal Bleeding, Acute variceal Bleeding, Cont’dCont’d

Pharmacotherapy:Pharmacotherapy:– While a waiting for endoscopyWhile a waiting for endoscopy– Give Give Vasopressin: 0.2-0.9 IU/min IV infusion for Vasopressin: 0.2-0.9 IU/min IV infusion for

maximum of 24 to 48 hoursmaximum of 24 to 48 hours

Associated with major complications such as Associated with major complications such as angina, arrhythmia, MI, bowel, liver and spleen angina, arrhythmia, MI, bowel, liver and spleen infarction and local tissue necrosis and CVAinfarction and local tissue necrosis and CVA

No longer recommendedNo longer recommended The combination of vasopressin with The combination of vasopressin with

nitroglycerin nitroglycerin more effective & reduced the more effective & reduced the cardiac complicationscardiac complications. .

04/20/2304/20/23 5151

Acute variceal Acute variceal Bleeding, Cont’dBleeding, Cont’d

Pharmacotherapy, Cont’dPharmacotherapy, Cont’d2.2. Terlipressin:Terlipressin:

Analogue of vasopressin.Analogue of vasopressin. Has a longer half-life than vasopressin Has a longer half-life than vasopressin

and can be given as a bolus infusion q4h.and can be given as a bolus infusion q4h. As effective as vasopressin with less SE.As effective as vasopressin with less SE. Dose: 2 mg IV 6 hourly till bleeding stops Dose: 2 mg IV 6 hourly till bleeding stops

and then 1 mg IV 6 hourly for further 24 and then 1 mg IV 6 hourly for further 24 hours.hours.

04/20/2304/20/23 5353

Acute variceal Acute variceal Bleeding, Cont’dBleeding, Cont’d Pharmacotherapy, Cont’dPharmacotherapy, Cont’d4.4. Octreotide:Octreotide:

A synthetic analogue of somatostatin.A synthetic analogue of somatostatin. Widely used to control acute variceal Widely used to control acute variceal

hemorrhage hemorrhage Has been shown to be effective in Has been shown to be effective in

controlling bleeding and in decreasing controlling bleeding and in decreasing bleeding related mortality.bleeding related mortality.

Bolus dose of 50 mcg and continuous IV Bolus dose of 50 mcg and continuous IV infusion of 50 mcg/h for 5 days.infusion of 50 mcg/h for 5 days.

04/20/23 54

Pharmacological TreatmentOctreotide

Dosing Recommendations:

Given initially as a 50-mg intravenous bolus then as a constant infusion at 50 mg/h for 3 to 5 days

Main Side Effects:

Dizziness, fatigue, headache, diarrhea, abdominal pain, bradycardia, dysrhythmias, blurred vision & nausea

04/20/2304/20/23 5555

Acute variceal Bleeding, Acute variceal Bleeding, Cont’dCont’d

Endoscopic TherapyEndoscopic Therapy– Endoscopic injection of hypertonic solution Endoscopic injection of hypertonic solution

(sclerotherapy) controls active hemorrhage from (sclerotherapy) controls active hemorrhage from esophageal varices in about 90% of patients.esophageal varices in about 90% of patients.

– Endoscopic variceal band ligation (EVL) was shown Endoscopic variceal band ligation (EVL) was shown to be comparable to endoscopic sclerotherapy with to be comparable to endoscopic sclerotherapy with less complications.less complications.

– EVL is currently the initial procedure of choice.EVL is currently the initial procedure of choice.– Complications of EVL includeComplications of EVL include

Superfacial ulceration and dysphagiaSuperfacial ulceration and dysphagia Transient chest discomfort and rarely esophageal Transient chest discomfort and rarely esophageal

stricturesstrictures

04/20/2304/20/23 5959

Acute variceal Acute variceal Bleeding, Cont’dBleeding, Cont’d Other modalitiesOther modalities

– Balloon tamponadeBalloon tamponade– Cold ice water lavageCold ice water lavage– SurgerySurgery– Transjugular intrahepatic Transjugular intrahepatic

portosystemic shunt (TIPS)portosystemic shunt (TIPS)

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Prophylaxis antibiotics improves outcome in cirrhotic patients with GI hemorrhage:

Control

N =270

Antibiotic

N=264

Infection 45% 14%

SBP

Bacteremia

27% 8%

Death 24% 15%

Bernard B, et al. hepatology 1999

04/20/23 61


Probability of remaining free of recurrent variceal hemorrhage:

Hou MC, et al. hepatology 2004

04/20/23 62


Vasoactive drugs are as effective as sclerotherapy in acute variceal hemorrhage:

D’Amico G, et al. gastroentrology 2003

04/20/23 63


Combination of pharmacological therapy/endoscopic therapy is more effective than endoscopy alone:

Banares R et al. hepatology 2002

04/20/23 64


Endoscopic varicieal band ligation:

Bleeding controlled in 90%

Rebleeding rate 30%

Compared with sclerotherapy:

Less rebleeding

Less mortality

Fewer complications

Fewer treatment sessionsLaine and Cook. Ann Intern Med 1995

04/20/23 65


Transjugular intrahepatic portsystemic shunt (TIPS)

04/20/23 67


Transjugular intrahepatic portsystemic shunt (TIPS): TIPS in rescue therapy for recurrent variceal hemorrhage: (at second rebreeding for esophageal varices)

TIPS is indicated in patients who rebleed on combination endoscopic plus pharmacological therapy

In patients with Child A/B cirrhosis, the distal spleno-renal shunt is as effective as TIPS

Henderson et al. Hepatology 2004

04/20/23 68


No Varices


Varicealhemorrhage

Recurrenthemorrhage

Safe vasoactive drug + endoscopic therapy +

antibiotic therapyTIPS/shunt (rescue

therapy)

04/20/23 69


No Varices


Varicealhemorrhage

Recurrenthemorrhage

Preventing recurrent hemorrhage

04/20/23 70

Secondary Prophylaxis

Lowest rebleeding rates are obtained in HVPG responders & with ligation + beta-blockers:

Bosch J, and Garcia-Pagan JC, Lancet 2003. Lo GH, et al. hepatology 2000. De la pena J, et al. hepatology 2005

04/20/23 71

Pharmacological TreatmentBeta-Blockers

Dosing Recommendations:

The most commonly used is propranolol & nadolol

The initial dose of nadolol is between 40-80 mg & propranolol is 20-40 given at bedtime and titrated every 4 to 5 days to reduce heart rate by 25% from baseline or to a heart rate of 55 beats per minute

04/20/23 72

Pharmacological TreatmentBeta-Blockers

Relative Contraindications:

Patients with type 1 diabetes mellitus, severe obstructive lung disease, asthma, & congestive heart failure

Main Side Effects:

Cardiac failure, bradycardia, bronchospasm, impotence, hypotension, & fatigue

04/20/2304/20/23 7373

Prevention of Prevention of Rebleeding:Rebleeding: Occurs in about 75% of pts. within 6 Occurs in about 75% of pts. within 6

weeks of the initial episode.weeks of the initial episode. EVL is the preferred therapeutic EVL is the preferred therapeutic

method at weekly or twice weekly method at weekly or twice weekly intervals until the esophageal varices intervals until the esophageal varices are obliterated.are obliterated.

Then endoscopy is performed at 3 Then endoscopy is performed at 3 months and then every 6 to 12 months and then every 6 to 12 months thereaftermonths thereafter

The addition of propranolol may The addition of propranolol may enhance benefit enhance benefit

04/20/2304/20/23 7474

04/20/2304/20/23 7575

ASCITESASCITES

04/20/2304/20/23 7676

Ascites Ascites

Accumulation of excessive fluid within the Accumulation of excessive fluid within the peritoneal cavity peritoneal cavity

Ascites is the most common of the major Ascites is the most common of the major complications of cirrhosis.complications of cirrhosis.

50% of patients with compensated cirrhosis will 50% of patients with compensated cirrhosis will develop ascites during 10 years of observationdevelop ascites during 10 years of observation

Two year mortality is 50%Two year mortality is 50% Six months mortality is 50% in patient with Six months mortality is 50% in patient with

diuretics resistant ascitesdiuretics resistant ascites Treatment of ascites doesn't improve mortalityTreatment of ascites doesn't improve mortality

04/20/2304/20/23 7777

ASCITES, Cont’dASCITES, Cont’d

..

04/20/2304/20/23 7878

Effectivearterial bloodvolume

Portal bloodinflow

SINUSODIALPRESSURE

PORTALPRESSUREGRADIENT

CIRRHOSIS

Intrahepaticresistance toportal flow

Arteriolarresistance

ASCITESCOLLATERALS

(VARICES)

?

Splanchnic Systemic

Activation ofneurohumoral

systems

Sodium andwater retention

Gastroenterology 2001;120:727

Pathogenesis

04/20/2304/20/23 7979

AscitesAscites Ascites results from renal retention of Ascites results from renal retention of

salt and water with localization of this salt and water with localization of this excess fluid into the peritoneal cavity excess fluid into the peritoneal cavity due to portal hypertension.due to portal hypertension.

Treatment of ascites is therefore aimed Treatment of ascites is therefore aimed at creating a –ve sodium and water at creating a –ve sodium and water balance and, if this strategy is balance and, if this strategy is inadequate, at decreasing portal inadequate, at decreasing portal pressure by portosystemic shuntingpressure by portosystemic shunting

04/20/2304/20/23 8383

Management

Goals of therapy To mobilize ascitic fluid To diminish abdominal discomfort,

back pain, and difficulty in ambulation

To prevent major complications

04/20/2304/20/23 8484

Management Cont,

Pharmacological management – Diuretics

Aldactone (Aldosterone antagonist)

Furosemide (Loop diuretic

Nonpharmacological management – Na+ Restriction– Therapuetic

paracentesis– Peritoneovenous

shunt– TIPS

04/20/2304/20/23 8585

Non-diuretics Therapy Sodium and water restriction

– Sodium output must exceed sodium intake – Eliminate ascites in 10-20% of patients with

– Urinary sodium excretion > 50 mmol/d– Mild to moderate ascites

– No complications associated with dietary Na restriction

– Dietary sodium intake is restricted to 88 mmol/day

– The goal of treatment to increase urinary sodium excretion to > 78 mmol/day

– Only 10–15% of patients spontaneously excrete > 78 mmol/day.

04/20/2304/20/23 8686


General measures:General measures:– Bed rest is advisable for patients with a Bed rest is advisable for patients with a

large amount of ascites.large amount of ascites.– Dietary sodium is restricted to 2 gm/d if Dietary sodium is restricted to 2 gm/d if

necessary.necessary.– Fluids are restricted to 1500 mL/d but in Fluids are restricted to 1500 mL/d but in

the presence of dilutional hyponatremia the presence of dilutional hyponatremia (serum sodium level <120 mEq/L) fluids (serum sodium level <120 mEq/L) fluids are limited to less than 1000 mL/dare limited to less than 1000 mL/d

04/20/2304/20/23 8787

Diuretics Therapy

Choice of agent – High level of circulating aldosterone

Decrease execration and increase production Activation of RAS hepatic impairment prolongs the half life of aldosterone Low concentration of albumin

– Spironolactone is rational choice

– Dose 100 mg to 200 mg up to 400 mg

– Combination with other diuretics

– Spironolactone to furosemide ratio (100-40 mg)

04/20/2304/20/23 8888

ASCITES, Cont’dASCITES, Cont’d Diuretic therapy:Diuretic therapy:

– The choice of diuretic therapy depends on the The choice of diuretic therapy depends on the urinary sodium levels.urinary sodium levels.

– Urinary Na level >50 mEq/L, use spironolactone Urinary Na level >50 mEq/L, use spironolactone alone (100-400 mg/d)alone (100-400 mg/d)

– Urinary Na level is 10-30 mEq/L, use a combination Urinary Na level is 10-30 mEq/L, use a combination of furosemide and spironolactone in a ratio of 40 mg of furosemide and spironolactone in a ratio of 40 mg and 100 mgand 100 mg

– Common complications of diuretic therapy include Common complications of diuretic therapy include electrolyte imbalances (hyponatremia, hypo and electrolyte imbalances (hyponatremia, hypo and hyperkalemia), hepatic encephalopathy, renal hyperkalemia), hepatic encephalopathy, renal impairment, gynecomastia, and muscle cramps.impairment, gynecomastia, and muscle cramps.

04/20/2304/20/23 8989

Diuretics Therapy

Monitoring – Clinical response

Body Weight, urine output, and abdominal girth Goal Weight loss of 0.5-2 kg/day (0.5-2L/day) Urine output exceeds input by 300 to 1000 ml/day Aggressive dieresis if peripheral edema presents (2kg/day)

– Laboratory parameters Serum Cr Urinary chemistries (Na and K ratio)

Complications Hypokalemic-hypochloremic metabolic alkalosis and hyponatremia Prerenal azotemia

04/20/2304/20/23 9090


Diuretic therapy, Cont’dDiuretic therapy, Cont’d– If the patient is suffering from If the patient is suffering from

respiratory distress, then large-volume respiratory distress, then large-volume paracentesis is needed in addition to paracentesis is needed in addition to diuretic therapy or for quick relieve.diuretic therapy or for quick relieve.

– Target weight loss should be 1 kg/d in Target weight loss should be 1 kg/d in patients with peripheral edema and 0.5 patients with peripheral edema and 0.5 kg/d in those without peripheral kg/d in those without peripheral edema.edema.

04/20/2304/20/23 9292

Large Volume Paracentesis

Indications – Patients with cirrhosis experiencing respiratory or cardiac

symptoms

Procedure Removal of ascitic fluid from the abdominal cavity with a

needle or a catheter

It is not a definitive treatment Complications

– Hypotension, oliguria, shock, encephalopathy, hepatorenal syndrome

– Hemorrhage, perforation, infection protein depletion

04/20/2304/20/23 9393

Large Volume ParacentesisUse of Albumin

Rational – High incidence of paracentesis induced

circulatory dysfunction

– Reduction of CO worsening renal functions Dose

– 50 ml of a 25% albumin solution per liter of ascites removed (8 grams per every liter remove)

04/20/2304/20/23 9494

04/20/2304/20/23 9595

04/20/2304/20/23 9696

Stop here Stop here

04/20/2304/20/23 9797

Refractory Ascites

– Failure to lose 200g of weight in a patient despite

– Severe Na restriction (50 meq/day)

– Maximal doses of diuretic

– 50% 6-month mortality

04/20/2304/20/23 9898

Refractory AscitesRefractory Ascites

DefinitionDefinition International Ascites Club defined International Ascites Club defined

it as:it as: ‘ ‘ascites that cannot be mobilized, ascites that cannot be mobilized,

or early recurrence of ascites or early recurrence of ascites which cannot be satisfactorily which cannot be satisfactorily prevented by medical therapy’.prevented by medical therapy’.

04/20/2304/20/23 9999

Refractory Ascites Refractory Ascites SubtypesSubtypes Diuretic-resistance ascites: Diuretic-resistance ascites: Ascites that cannot be Ascites that cannot be

mobilized, or early mobilized, or early recurrence of ascites recurrence of ascites which cannot be which cannot be prevented because of prevented because of a lack of response to a lack of response to dietary sodium dietary sodium restriction and intense restriction and intense diuretic therapy.diuretic therapy.

Diuretic-intractable Diuretic-intractable ascites:ascites:

Ascites that cannot Ascites that cannot be mobilized or the be mobilized or the early recurrence of early recurrence of which cannot be which cannot be prevented because prevented because of the development of the development of diuretic-inducedof diuretic-induced

complications that complications that preclude the use of preclude the use of an effective diuretic an effective diuretic dosage.dosage.

04/20/2304/20/23 100100

Diagnostic CriteriaDiagnostic Criteria

1.Treatment duration: patients 1.Treatment duration: patients must be on intensive diuretic must be on intensive diuretic therapy for at least one week.therapy for at least one week.

2.Intensive diuretic therapy: 2.Intensive diuretic therapy: spironolactone 400 mg and spironolactone 400 mg and frusemide 160 mg per dayfrusemide 160 mg per day

3. Dietary sodium restriction: 3. Dietary sodium restriction: sodium intake <50mEq per day.sodium intake <50mEq per day.

04/20/2304/20/23 101101

Diagnostic CriteriaDiagnostic Criteria(cont)(cont)

4. Lack of response: weight loss <200 4. Lack of response: weight loss <200 g/day during the last four days and g/day during the last four days and urinary sodium excretion <50 mEq/day.urinary sodium excretion <50 mEq/day.

5. Early ascites recurrence: reappearance 5. Early ascites recurrence: reappearance of moderate to massive or tense ascites of moderate to massive or tense ascites within 4 weeks of initial mobilization. within 4 weeks of initial mobilization.

(Re-accumulation of ascites within 2–3 (Re-accumulation of ascites within 2–3 days of paracentesis should not be days of paracentesis should not be considered as early ascites).considered as early ascites).

04/20/2304/20/23 102102

Diagnostic CriteriaDiagnostic Criteria (cont) (cont)

6. Diuretic-induced complications-6. Diuretic-induced complications- hepatic encephalopathy; hepatic encephalopathy; renal failure: an increase in Srcr renal failure: an increase in Srcr

conc by more than 100%,to >2 conc by more than 100%,to >2 mg/dL (176 mmol/L);mg/dL (176 mmol/L);

Hyponatremia: decrease Sr Na Hyponatremia: decrease Sr Na conc by more than 10 mEq/L, to conc by more than 10 mEq/L, to <125 mEq/L;<125 mEq/L;

hypokalemia: less than 3 mEq/L;hypokalemia: less than 3 mEq/L; hyperkalemia more than 6 mEq/L,hyperkalemia more than 6 mEq/L,

04/20/2304/20/23 104104

MANAGEMENT OFMANAGEMENT OFREFRACTORY ASCITESREFRACTORY ASCITES

The current acceptable treatments The current acceptable treatments for refractory ascites are:for refractory ascites are:

1.Large volume paracentesis (LVP) plus 1.Large volume paracentesis (LVP) plus albumin infusion.albumin infusion.

2.Transjugular intrahepatic portosystemic 2.Transjugular intrahepatic portosystemic shunt (TIPS).shunt (TIPS).

3.Peritoneovenous shunt.3.Peritoneovenous shunt.

4.Liver transplantation.4.Liver transplantation.

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Large Volume Large Volume ParacentesisParacentesis(LVP)(LVP) LVP is a ‘symptomatic therapy’. LVP is a ‘symptomatic therapy’. Patients treated with LVP should Patients treated with LVP should

receive I.V albumin infusion at a receive I.V albumin infusion at a dose of 6-8g for each liter of dose of 6-8g for each liter of ascitic fluid removed.ascitic fluid removed.

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Large Volume Large Volume ParacentesisParacentesis(LVP)(LVP)(cont)(cont)

Complications:Complications: LVP can lead to postparacentesis LVP can lead to postparacentesis

circulatory dysfunction (PCD), a circulatory dysfunction (PCD), a vasculatory state characterized by an vasculatory state characterized by an increase in plasma renin activity that increase in plasma renin activity that reaches a peak 6 days after LVP.reaches a peak 6 days after LVP.

These patients experience poorer These patients experience poorer outcome.outcome.

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Transjugular intrahepatic Transjugular intrahepatic portosystemic shunt (TIPS)portosystemic shunt (TIPS)

Reduces ascites formation by:Reduces ascites formation by: Decreasing portal pressure.Decreasing portal pressure. Improving renal perfusion and GFR.Improving renal perfusion and GFR. TIPS decompresses both the TIPS decompresses both the

splanchnic and hepatic splanchnic and hepatic microcirculation, causing decreased microcirculation, causing decreased lymphatic formation in both the liver lymphatic formation in both the liver and splanchnic organs.and splanchnic organs.

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Transjugular intrahepatic Transjugular intrahepatic portosystemic shunt (TIPS)portosystemic shunt (TIPS)

Transjugular intrahepatic Transjugular intrahepatic portosystemic shunt canportosystemic shunt can

ameliorate the ascites problem in ameliorate the ascites problem in patients awaiting (or not suitable patients awaiting (or not suitable for) liver transplant.for) liver transplant.

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Transjugular intrahepatic Transjugular intrahepatic portosystemic shunt portosystemic shunt (TIPS)(TIPS)contcont

Complications:Complications: Hepatic encephalopathy (46%, Hepatic encephalopathy (46%,

most within 1most within 1stst month) month) Shunt dysfunction (8% within 1Shunt dysfunction (8% within 1stst

month, 27% late shunt dysfxn)month, 27% late shunt dysfxn) Only 8% had a liver transplant.Only 8% had a liver transplant.

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Hepatorenal syndrome Hepatorenal syndrome (HRS)(HRS)

Definition:Definition: Hepatorenal syndrome (HRS) is a Hepatorenal syndrome (HRS) is a

functional renal impairment which functional renal impairment which occurs either in acute or chronic liver occurs either in acute or chronic liver disease with advanced hepatic failure disease with advanced hepatic failure and portal hypertension.and portal hypertension.

The probability of patients with ascites The probability of patients with ascites developing HRS is approximately 20% developing HRS is approximately 20% at 1 year and 40% at 5 years.at 1 year and 40% at 5 years.

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Hepatorenal syndrome Hepatorenal syndrome (HRS)(HRS)(Cont)(Cont)

HRS represents the underfilling of HRS represents the underfilling of the arterial circulation from the arterial circulation from vasodilatation that is located vasodilatation that is located mainly in the splanchnic vascular mainly in the splanchnic vascular bed, and that is secondary to bed, and that is secondary to severe portal hypertension. severe portal hypertension.

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Hepatorenal syndrome Hepatorenal syndrome (HRS)(HRS) (Cont)(Cont) Diagnostic CriteriaDiagnostic Criteria Srcr of 132 Srcr of 132 µmol/Lµmol/L and CL and CLCRCR of 40 mL/min, of 40 mL/min, Serum sodium < 130 mEq/L.Serum sodium < 130 mEq/L. Proteinuria less than 500 mg/dL and no Proteinuria less than 500 mg/dL and no

ultrasonographic evidence of obstructive ultrasonographic evidence of obstructive uropathy or parenchymal renal diseases.uropathy or parenchymal renal diseases.

urine volume < 500 mL/day, urine volume < 500 mL/day, urine sodium < 10 mEq/L,urine sodium < 10 mEq/L, urine osmolarity higher than plasma urine osmolarity higher than plasma

osmolarity, osmolarity, Red blood cells in urine < 50 per high-power Red blood cells in urine < 50 per high-power

field field

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Hepatorenal syndrome Hepatorenal syndrome (HRS)(HRS) (Cont)(Cont)

Diagnostic CriteriaDiagnostic Criteria There must be no evidence of:There must be no evidence of: Shock, ongoing bacterial infection Shock, ongoing bacterial infection current or recent treatment with current or recent treatment with

nephrotoxic drugs. nephrotoxic drugs. There shouldn’t be an excess of There shouldn’t be an excess of

gastrointestinal fluid lossgastrointestinal fluid loss

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Hepatorenal syndrome Hepatorenal syndrome (HRS)(HRS) (Cont)(Cont)

Diagnostic CriteriaDiagnostic Criteria There must be no sustained There must be no sustained

improvement in renal function improvement in renal function (decrease in serum creatinine to (decrease in serum creatinine to ≤ 132 ≤ 132 µmol/Lµmol/L or increase in CL or increase in CLCRCR to to ≥ 40 mL/min).≥ 40 mL/min).

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Hepatorenal syndrome Hepatorenal syndrome (HRS)(HRS) Subtypes Subtypes Type I HRS:Type I HRS: Rapidly progressiveRapidly progressive renal failure with a renal failure with a

doubling of srcr to doubling of srcr to >220 >220 mmol/Lmmol/L, or a , or a CLCLCRCR of <20 mL/min of <20 mL/min in < 2 weeks. in < 2 weeks.

Prognosis is very Prognosis is very poor; 80% of poor; 80% of patients die within patients die within 2weeks, and 10% 2weeks, and 10% survive for > 3 survive for > 3 months.months.

Type II HRS:Type II HRS: Is defined by a Is defined by a

serum creatinine serum creatinine level > 132 mmol/L level > 132 mmol/L and/or CLand/or CLCRCR <40 <40 mL/min, but renal mL/min, but renal function slowly function slowly deteriorates anddeteriorates and

it has a better it has a better prognosis.prognosis.

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Management of Management of hepatorenal syndromehepatorenal syndrome

The currently available The currently available treatments for HRS include:treatments for HRS include:

1. Medical therapy.1. Medical therapy. 2. Transjugular intrahepatic 2. Transjugular intrahepatic

portocaval shunt.portocaval shunt. 3. Liver transplantation3. Liver transplantation..

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Medical Therapy:Medical Therapy:

The aims of medical therapy are The aims of medical therapy are to increase peripheral vascular to increase peripheral vascular resistance in order to:resistance in order to:

Correct intravascular volume Correct intravascular volume depletiondepletion

Decrease renal cortical Decrease renal cortical constriction.constriction.

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Medical Therapy:Medical Therapy:ContCont

Ornipressin (ornithine-8-vasopressin) Ornipressin (ornithine-8-vasopressin) has been used to treat eight patients has been used to treat eight patients with cirrhosis complicated by the HRS with cirrhosis complicated by the HRS for 15 days.for 15 days.

It was used at the dose 2 IU/hr, It was used at the dose 2 IU/hr, together with albumin 1 g/kg during together with albumin 1 g/kg during the first day and a maintenance dose the first day and a maintenance dose of 20–60 g/day. of 20–60 g/day.

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These patients showed a and These patients showed a and sustained improvement in renal sustained improvement in renal function. function.

Treatment using terlipressin with Treatment using terlipressin with and without albumin in the and without albumin in the patients with HRS type I also patients with HRS type I also demonstrated the improvement demonstrated the improvement in renal function without ischemic in renal function without ischemic complication.complication.

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Midodrine plus albumin 10–20 g/day Midodrine plus albumin 10–20 g/day and octreotide: Five patients with HRS and octreotide: Five patients with HRS type I without serious side effects.type I without serious side effects.

NN-acetylcysteine (150 mg/kg -acetylcysteine (150 mg/kg intravenously over 2 h, followed by intravenously over 2 h, followed by continuous infusion of 100 mg/kg per continuous infusion of 100 mg/kg per day for 5 days). This led to day for 5 days). This led to improvement of renal function despite improvement of renal function despite a lack of hepatic or hemodynamic a lack of hepatic or hemodynamic changes. changes.

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Renal venodilators,, have been used in an Renal venodilators,, have been used in an attempt to reduce intrarenal vascular attempt to reduce intrarenal vascular resistance.resistance.

However, there was no obvious benefit.However, there was no obvious benefit. The combination of peripheral The combination of peripheral

vasoconstrictors and renal vasodilators has vasoconstrictors and renal vasodilators has also failed to improve renal function in cases also failed to improve renal function in cases of HRS.of HRS.

More studies are required to assessMore studies are required to assess which is the most suitable regimen.which is the most suitable regimen.

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Liver transplantationLiver transplantation

Liver transplantation is the ideal treatment Liver transplantation is the ideal treatment because it can replace the cirrhotic liver, the because it can replace the cirrhotic liver, the primary cause of the Pathophysiology of a primary cause of the Pathophysiology of a normally functioning organ. normally functioning organ.

Patients with HRS who undergo liver Patients with HRS who undergo liver transplantation have a higher requirement of transplantation have a higher requirement of post-transplant hemodialysis, and higher post-transplant hemodialysis, and higher morbidity and in-hospital mortalitymorbidity and in-hospital mortality

rates than those without HRS who receive a rates than those without HRS who receive a liver transplant.liver transplant.

However, the long-term survival is still However, the long-term survival is still excellent.excellent.

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ConclusionConclusion

Many treatment modalities can Many treatment modalities can act as a bridge to improve the act as a bridge to improve the condition of patients suffering condition of patients suffering from refractory ascites and from refractory ascites and hepatorenal syndrome. hepatorenal syndrome.

However, liver transplantation, However, liver transplantation, remains the only therapy that remains the only therapy that improves long-term survival.improves long-term survival.

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SPONTANEOUS SPONTANEOUS BACTERIAL BACTERIAL PERITONITIS (SBP)PERITONITIS (SBP) In hospitalized patients the In hospitalized patients the

prevalence of SBP range between prevalence of SBP range between 10% and 30%10% and 30%

A neutrophil count greater than A neutrophil count greater than 250/mm in the absence of an intra-250/mm in the absence of an intra-abdominal source of infection in the abdominal source of infection in the ascitic fluid is suggestive of SBP and ascitic fluid is suggestive of SBP and should prompt administration of an should prompt administration of an antibiotic.antibiotic.

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SPONTANEOUS BACTERIAL SPONTANEOUS BACTERIAL PERITONITIS (SBP), Cont’dPERITONITIS (SBP), Cont’d

>92% of all cases of SBP are monomicrobial, >92% of all cases of SBP are monomicrobial, withwith– Escheria coli (the most common isolate)Escheria coli (the most common isolate)– Klebsiella speciesKlebsiella species– Other G-ve bacteriaOther G-ve bacteria– G+ve organisms, Streptococcal (25%)G+ve organisms, Streptococcal (25%)– Anaerobic infection (rare <5%)Anaerobic infection (rare <5%)

As with polymicrobial bacteria or fungi, As with polymicrobial bacteria or fungi, consider secondary bacterial peritonitis.consider secondary bacterial peritonitis.

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Cefotaxime (2 g IV 8 hourly for 5-7 days) or Cefotaxime (2 g IV 8 hourly for 5-7 days) or Ceftriaxone (1-2 gm IV once daily for 5-7 days)Ceftriaxone (1-2 gm IV once daily for 5-7 days)

Oral Ofloxacin (400 mg PO 12 hourly) has Oral Ofloxacin (400 mg PO 12 hourly) has shown to be as effective as Cefotaxime in the shown to be as effective as Cefotaxime in the treatment of uncomplicated SBP.treatment of uncomplicated SBP.

Antibiotic therapy should be further modified Antibiotic therapy should be further modified based on the results of ascitic fluid C/S and based on the results of ascitic fluid C/S and antibiotic sensitivities of the isolated organismsantibiotic sensitivities of the isolated organisms

Secondary prophylaxis with oral Norfloxacin Secondary prophylaxis with oral Norfloxacin (400 mg/d) may be indicated in patients after (400 mg/d) may be indicated in patients after more than a few episode of SBP.more than a few episode of SBP.

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Secondary peritonitis from gut Secondary peritonitis from gut perforation should be considered perforation should be considered in ay patient with neutrocytic in ay patient with neutrocytic ascites with polymicrobial ascites with polymicrobial bacteriabacteria

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3 Criteria for secondary peritonitis:3 Criteria for secondary peritonitis:– The initial ascitic fluid is neutrocytic and The initial ascitic fluid is neutrocytic and

fulfils 2 of the following criteria:fulfils 2 of the following criteria:

i.i. Total protein > 1 g/dlTotal protein > 1 g/dl

ii.ii. Glucose < 50 mg/dlGlucose < 50 mg/dl

iii.iii. Lactate dehydrogenase > the upper limit Lactate dehydrogenase > the upper limit of normal for serum. of normal for serum.

In addition, a leukocyte > 10 x 10/L and In addition, a leukocyte > 10 x 10/L and the presence of multiple organismsthe presence of multiple organisms

9

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HEPATIC HEPATIC ENCEPHALOPATHY ENCEPHALOPATHY (HE)(HE) Hepatic encephalopathy is a Hepatic encephalopathy is a

neuropsychiatry syndrome neuropsychiatry syndrome caused by liver disease.caused by liver disease.

It occurs most often in patients It occurs most often in patients with cirrhosis but is seen in acute with cirrhosis but is seen in acute form in acute hepatic failure.form in acute hepatic failure.

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In the World Congress of Gastroenterology they classified hepatic encephalopathy to:

Type A (=acute) describes HE associated with ALF Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease Type C (=cirrhosis) occurs in patients with cirrhosis and portal hypertension with portal-systemic shunt

Nomenclature

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HEPATIC HEPATIC ENCEPHALOPATHY, ENCEPHALOPATHY, Cont’dCont’d Factors precipitating HE:Factors precipitating HE: UremiaUremia

Spontaneous, diuretic inducedSpontaneous, diuretic induced DrugsDrugs

Sedatives, antidepressants, hypnoticsSedatives, antidepressants, hypnotics Gastrointestinal bleedingGastrointestinal bleeding Excess dietary proteinExcess dietary protein ConstipationConstipation Electrolytes imbalanceElectrolytes imbalance

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HEPATIC HEPATIC ENCEPHALOPATHYENCEPHALOPATHY Factors precipitating HE, Cont’dFactors precipitating HE, Cont’d Paracentesis (volumes > 3-5 liters)Paracentesis (volumes > 3-5 liters) HypokalaemiaHypokalaemia InfectionsInfections Trauma (including surgery)Trauma (including surgery) Portalsystemic shuntsPortalsystemic shunts

Surgical, spontaneous (large)Surgical, spontaneous (large)

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HEPATIC HEPATIC ENCEPHALOPATHY, ENCEPHALOPATHY, Cont’dCont’d Differential diagnosis of HE:Differential diagnosis of HE: Subdural haematomaSubdural haematoma Drug or alcohol intoxicationDrug or alcohol intoxication Delirium tremensDelirium tremens Wernicke’s encephalopathyWernicke’s encephalopathy Primary psychiatric disordersPrimary psychiatric disorders HypoglycemiaHypoglycemia Neurological Wilson’s diseaseNeurological Wilson’s disease

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HEPATIC ENCEPHALOPATHY, HEPATIC ENCEPHALOPATHY, Cont’dCont’d

Management:Management: Episodes of encephalopathy are Episodes of encephalopathy are

common in cirrhosis.common in cirrhosis. The principles areThe principles are

To treat or remove precipitating causesTo treat or remove precipitating causesTo reduce or eliminate protein intake andTo reduce or eliminate protein intake andTo suppress production of neurotoxins by To suppress production of neurotoxins by

bacteria in the bowelbacteria in the bowel

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HEPATIC HEPATIC ENCEPHALOPATHY, ENCEPHALOPATHY, Cont’dCont’d Management, Cont’dManagement, Cont’d Dietary protein is eliminated or Dietary protein is eliminated or

reduced below 20 g/dreduced below 20 g/d Glucose (300 g/d) is given orally or Glucose (300 g/d) is given orally or

parenterally in severe casesparenterally in severe cases As encephalopathy improves, dietary As encephalopathy improves, dietary

protein is increased by 10-20 g/d protein is increased by 10-20 g/d every 48 hours to an intake of 40-60 every 48 hours to an intake of 40-60 g/dg/d

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HEPATIC HEPATIC ENCEPHALOPATHY, ENCEPHALOPATHY, Cont’dCont’d Management, Cont’dManagement, Cont’d Lactulose (15-30 ml 8-hourly)Lactulose (15-30 ml 8-hourly)

Disaccharide which is taken orally and Disaccharide which is taken orally and reach the colon intactreach the colon intact

Metabolized by colonic bacteriaMetabolized by colonic bacteria It produce an osmotic laxative effectIt produce an osmotic laxative effect It ↓ the pH of the colonic contentsIt ↓ the pH of the colonic contentsLimits colonic ammonia absorption andLimits colonic ammonia absorption andPrevent the incorporation of nitrogen Prevent the incorporation of nitrogen

into bacteriainto bacteria

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HEPATIC ENCEPHALOPATHY, HEPATIC ENCEPHALOPATHY, Cont’dCont’d

Management, Cont’dManagement, Cont’d LactitolLactitol

A rather alternative to lactuloseA rather alternative to lactulose With less explosive action on bowel functionWith less explosive action on bowel function

Neomycin (1-4 g 4-6-hourly)Neomycin (1-4 g 4-6-hourly) An antibiotic which acts by reducing the An antibiotic which acts by reducing the

bacterial flora content of the bowelbacterial flora content of the bowel Alternative to lactulose in case of diarrheaAlternative to lactulose in case of diarrhea Poorly absorbed antibioticPoorly absorbed antibiotic Can cause ototoxicity, Can cause ototoxicity, Not used very oftenNot used very often

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PULMONARY PULMONARY MANIFESTATIONSMANIFESTATIONS Hepatic hydrothoraxHepatic hydrothorax

– In about 13% of patients with cirrhosisIn about 13% of patients with cirrhosis– Fluid in the pleural space can be detected on Fluid in the pleural space can be detected on

chest radiograph (usually Rt sided 66%)chest radiograph (usually Rt sided 66%)– Management options include:Management options include:

Medical control of ascitesMedical control of ascites Therapeutic thoracentesis for relieve of dyspneaTherapeutic thoracentesis for relieve of dyspnea TIPSTIPS

– Chest tube drainage is not advised unless the Chest tube drainage is not advised unless the pleural fluid becomes infected (SBEmpyema)pleural fluid becomes infected (SBEmpyema)

– Definitive treatment of refractory hydrothorax in Definitive treatment of refractory hydrothorax in the setting of CLD is liver transplantation.the setting of CLD is liver transplantation.

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PULMONARY PULMONARY MANIFESTATIONS, Cont’dMANIFESTATIONS, Cont’d

Hepatopulmonary Syndrome:Hepatopulmonary Syndrome:– Characterized by pulmonary vascular Characterized by pulmonary vascular

dilatation and hypoxemia (Pao2 <70 mm dilatation and hypoxemia (Pao2 <70 mm Hg) in the setting of advanced liver diseaseHg) in the setting of advanced liver disease

– Orthodeoxia (worsening hypoxemia when Orthodeoxia (worsening hypoxemia when the patient stand) is characteristically seenthe patient stand) is characteristically seen

– Therapeutic options are limited, and only Therapeutic options are limited, and only successful liver transplantation has been successful liver transplantation has been shown to reverse the hypoxemia in these shown to reverse the hypoxemia in these patients.patients.

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PULMONARY PULMONARY MANIFESTATIONS, MANIFESTATIONS, Cont’dCont’d Portopulmonary hypertension:Portopulmonary hypertension:

– An increase in pulmonary artery pressures An increase in pulmonary artery pressures occurs in 20% of patients with advanced occurs in 20% of patients with advanced liver disease.liver disease.

– Intravenous prostacyclin has been shown Intravenous prostacyclin has been shown to improve pulmonary hemodynamics in to improve pulmonary hemodynamics in some patients.some patients.

– Liver transplantation has been successful Liver transplantation has been successful in patients with mild pulmonary in patients with mild pulmonary hypertension, but mortality rates are high hypertension, but mortality rates are high in moderate to severe casesin moderate to severe cases

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NUTRITIONAL DISORDERSNUTRITIONAL DISORDERS Protein-energy malnutrition is highly prevalent Protein-energy malnutrition is highly prevalent

in hospitalized patients with advanced in hospitalized patients with advanced cirrhosis.cirrhosis.

Other nutritional deficiencies of dietary Other nutritional deficiencies of dietary components such ascomponents such as– VitaminsVitamins– Trace elementsTrace elements– Polyunsaturated fatty acidsPolyunsaturated fatty acids

Nutritional therapy should be considered in the Nutritional therapy should be considered in the management of patients with cirrhosis, and management of patients with cirrhosis, and some data suggest that enteral nutrition may some data suggest that enteral nutrition may favorably influence short-term survival.favorably influence short-term survival.

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ENDOCRINE ENDOCRINE ABNORMALITIESABNORMALITIES Thyroid disorders:Thyroid disorders:

– Low thyroxine levels tend to be seen Low thyroxine levels tend to be seen only in the later stages of the illness.only in the later stages of the illness.

– Patients with primary biliary Patients with primary biliary cirrhosis and autoimmune hepatitis cirrhosis and autoimmune hepatitis should be carefully monitored for should be carefully monitored for the development of hypothyroidism the development of hypothyroidism due to Hashimoto thyroiditisdue to Hashimoto thyroiditis

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ENDOCRINE ENDOCRINE ABNORMALITIES, ABNORMALITIES, Cont’dCont’d

Sexual dysfunction:Sexual dysfunction:– Gonadal dysfunction commonly Gonadal dysfunction commonly

accompanies end-stage liver disease.accompanies end-stage liver disease.– Manifestations may include sexual Manifestations may include sexual

dysfunction and abnormalities of the dysfunction and abnormalities of the hypothalmic-pituitary-gonadal axishypothalmic-pituitary-gonadal axis

– Management of sexual dysfunction is Management of sexual dysfunction is challenging, and no treatment has been challenging, and no treatment has been shown to be of benefit thus farshown to be of benefit thus far

– Studies have shown an improvement in Studies have shown an improvement in sexual function after liver transplantation, sexual function after liver transplantation, but the exact mechanism for this remains but the exact mechanism for this remains un clearun clear

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CONCLUSIONCONCLUSION

Although effective therapy is Although effective therapy is available for most of the available for most of the complications of cirrhosis, liver complications of cirrhosis, liver transplantation is the only transplantation is the only treatment modality.treatment modality.

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THANKSTHANKS

Liver Blood Supply

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