Management of adult patients with ascites due to cirrhosis aasld 2004 guideline ahmed mayet pharm d
This presentation is the property of its rightful owner.
Sponsored Links
1 / 123

Liver Blood Supply PowerPoint PPT Presentation


  • 212 Views
  • Uploaded on
  • Presentation posted in: General

Management of Adult Patients With Ascites Due to Cirrhosis AASLD 2004 Guideline Ahmed Mayet, Pharm.D. Liver Blood Supply. 75% blood supply by portal and hepatic veins 25% by hepatic arteries. Hepatocytes function as detoxification of toxic substances and synthesizer of proteins,

Download Presentation

Liver Blood Supply

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Management of adult patients with ascites due to cirrhosis aasld 2004 guideline ahmed mayet pharm d

Management of Adult Patients With Ascites Due to CirrhosisAASLD 2004 GuidelineAhmed Mayet, Pharm.D


Liver blood supply

Liver Blood Supply

  • 75% blood supply by portal and hepatic veins

  • 25% by hepatic arteries


Liver blood supply

Hepatocytes

function

as detoxification

of toxic

substances

and synthesizer

of proteins,

carbohydrates,

hormones and

related

materials

Kupffer Cell act

as phagocytic cell


Classification

Pre-Hepatic

Sinusoidal

Pre-Sinusoidal

Post-

Sinusoidal

Classification

Post-

Hepatic


Healthy liver

Healthy Liver


Definition

Definition:

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


Definitions

Definitions

Fibrosis

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

  • Reversible process

    Cirrhosis

  • Diffuse hepatic process characterized by fibrosis and conversion of normal liver architecture into structurally abnormal nodules

  • Irreversible process


Etiology

Most common causes

Hepatitis (26%)

Alcoholic liver disease (21%)

Hepatitis C+ alcoholic disease (15%)

Cryptogenic causes(18%)

Hepatitis B(15%)

Miscellaneous (5%)

Miscellaneous (5%)

Autoimmune hepatitis

Primary billiary cirrhosis

Secondary billiary cirrhosis

Primary sclerosing cholangitis

Hemochromatosis

Wilson disease

Alpha-1 antitrypsin deficiency

Drug induced

Venous outflow obstruction (budd-chiari syndrome)

Chronic right side heart failure

Etiology


Sign and symptoms and clinical finding of liver cirrhosis

Sign and Symptoms and clinical finding of Liver Cirrhosis

  • Anorexia, nausea, abdominal discomfort, weight loss, and malaise

  • Ascites, peripheral edema, jaundice, spider nevi, palmar erythema

  • Gynecomastia, testicle atrophy, amenorrhea, pubical hair lost

  • Hepatomegaly, spleenomegaly, encephalopathy, and bleeding


Laboratory findings

Laboratory Findings

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

  • Elevated bilrubin most of the time

  • Low albumin level

  • Prolong prothrombin time (PT) and APTT

  • Elevated serum creatinine and blood urea nitrogen (BUN)


Classification1

Classification

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


Complications

Complications

  • Portal hypertension

  • Variceal Hemorrhage

  • Ascites

  • Spontaneous Bacterial Peritonitis

  • Hepatic Encephalopathy

  • Hepatorenal Syndrome


Risks of complications of cirrhosis

Risks of Complications of Cirrhosis

?30+%

HCC

Death

1.5%

11%

2.5%

Ascites

Cirrhosis

?20+%

1.1%

Variceal

Bleeding

0.4%

Liver

Transplant

percent per year

Encephalopathy

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


Portal hypertension

Portal Hypertension

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

  • Development of varices and alternative routes of blood flow

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

  • Hemorrhage from varices occurs in 25-40% of cirrhotic patients

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


Target for therapy

Target for Therapy

Cirrhosis

Splanchnic arteriolar

resistance

Resistance to portal flow

Venodilators

Portal Pressure

Portal blood

flow

Varices/Variceal Hemorrhage


Prevention of first variceal hemorrhage

Prevention of First Variceal Hemorrhage

Non-selective Beta-blockers prevent first variceal hemorrhage:

D’Amico et al, Sem Liv Dis. 1999


Treatment of varices variceal hemorrhage

Treatment of Varices/Variceal Hemorrhage

Varices

No hemorrhage

Small Varices

No hemorrhage

Prevention of variceal growth?

Medium/large varices

No hemorrhage


Preventing growth of small varices

Preventing Growth of Small Varices

Nadolol may prevent the growth of small varices:

Merkel et al, Gastroentrology 2004


Treatment of varices variceal hemorrhage1

Treatment of Varices/Variceal Hemorrhage

Varices

No hemorrhage

  • Beta-Blockers (propranolol or nadolol) indefinitely

  • Endoscopic variceal ligation in patients intolerant or contraindicated to beta-blockers

Small Varices

No hemorrhage

Medium/large varices

No hemorrhage


Esophageal variceal bleeding

ESOPHAGEAL VARICEAL BLEEDING

  • Primary prophylaxis

    • Pharmacotherapy:

    • Non selective β-Blocker (Propranolol)

      • ↓Portal pressure by ↓CO → ↓ Blood flow.

      • Long acting BB (Nadolol) or propanolol

      • Average dose of (60 mg/d), preferred in the evening, mean dose 160 mg/d

      • HR not less than 55 beats/min & SBP not less than 90 mm Hg.

      • Adverse effects in 27% of patients.

      • What are they?


Target for therapy1

Target for Therapy

Cirrhosis

Splanchnic arteriolar

resistance

Resistance to portal flow

Portal Pressure

Variceal band

ligation/

sclerotherapy

Portal blood

flow

Variceal

Obliteration


Endoscopic varicieal band ligation

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 sessions

Laine and Cook. Ann Intern Med 1995


Prevention of first variceal hemorrhage1

Prevention of First Variceal Hemorrhage

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

Khuroo et al, Aliment Pharmacol Ther 2005


Esophageal variceal bleeding cont d

ESOPHAGEAL VARICEAL BLEEDING, Cont’d

  • Endoscopic therapy:

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

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

    • Further confirmation is needed.


Prophylaxis of variceal hemorrhage

Prophylaxis of Variceal Hemorrhage

Diagnosis of Cirrhosis

Endoscopy

No varives

Small varives

Medium/large varives

Follow-up endoscopy in 2-3 years

Beta-blocker therapy

No CI

  • Stepwise increase until maximum tolerated dose

  • Continue beta-blockers life-long

CI or intolerance

Endoscopic variceal band ligation


Treatment of varices variceal hemorrhage2

Treatment of Varices/Variceal Hemorrhage

No Varices

Varices

No hemorrhage

Variceal

hemorrhage

Control hemorrhage

Recurrent

hemorrhage


Treatment of acute variceal hemorrhage

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


Acute variceal bleeding cont d

Acute variceal Bleeding, Cont’d

  • Pharmacotherapy:

    • While a waiting for endoscopy

    • Give Vasopressin: 0.2-0.9 IU/min IV infusion for maximum of 24 to 48 hours

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

    • No longer recommended

    • The combination of vasopressin with nitroglycerin  more effective & reduced the cardiac complications.


Acute variceal bleeding cont d1

Acute variceal Bleeding, Cont’d

  • Pharmacotherapy, Cont’d

  • Terlipressin:

    • Analogue of vasopressin.

    • Has a longer half-life than vasopressin and can be given as a bolus infusion q4h.

    • As effective as vasopressin with less SE.

    • Dose: 2 mg IV 6 hourly till bleeding stops and then 1 mg IV 6 hourly for further 24 hours.


Acute variceal bleeding cont d2

Acute variceal Bleeding, Cont’d

  • Pharmacotherapy, Cont’d

  • Octreotide:

    • A synthetic analogue of somatostatin.

    • Widely used to control acute variceal hemorrhage

    • Has been shown to be effective in controlling bleeding and in decreasing bleeding related mortality.

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


Pharmacological treatment octreotide

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


Acute variceal bleeding cont d3

Acute variceal Bleeding, Cont’d

  • Endoscopic Therapy

    • Endoscopic injection of hypertonic solution (sclerotherapy) controls active hemorrhage from esophageal varices in about 90% of patients.

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

    • EVL is currently the initial procedure of choice.

    • Complications of EVL include

      • Superfacial ulceration and dysphagia

      • Transient chest discomfort and rarely esophageal strictures


Acute variceal bleeding cont d4

Acute variceal Bleeding, Cont’d

  • Other modalities

    • Balloon tamponade

    • Cold ice water lavage

    • Surgery

    • Transjugular intrahepatic portosystemic shunt (TIPS)


Treatment of acute variceal hemorrhage1

Treatment of Acute Variceal Hemorrhage

Prophylaxis antibiotics improves outcome in cirrhotic patients with GI hemorrhage:

Bernard B, et al. hepatology 1999


Treatment of acute variceal hemorrhage2

Treatment of Acute Variceal Hemorrhage

Probability of remaining free of recurrent variceal hemorrhage:

Hou MC, et al. hepatology 2004


Treatment of acute variceal hemorrhage3

Treatment of Acute Variceal Hemorrhage

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

D’Amico G, et al. gastroentrology 2003


Treatment of acute variceal hemorrhage4

Treatment of Acute Variceal Hemorrhage

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

Banares R et al. hepatology 2002


Treatment of acute variceal hemorrhage5

Treatment of Acute Variceal Hemorrhage

Endoscopic varicieal band ligation:

Bleeding controlled in 90%

Rebleeding rate 30%

Compared with sclerotherapy:

Less rebleeding

Less mortality

Fewer complications

Fewer treatment sessions

Laine and Cook. Ann Intern Med 1995


Treatment of acute variceal hemorrhage6

Treatment of Acute Variceal Hemorrhage

Transjugular intrahepatic portsystemic shunt (TIPS)


Treatment of acute variceal hemorrhage7

Treatment of Acute Variceal Hemorrhage

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


Treatment of varices variceal hemorrhage3

Treatment of Varices/Variceal Hemorrhage

No Varices

Varices

No hemorrhage

  • Safe vasoactive drug + endoscopic therapy + antibiotic therapy

  • TIPS/shunt (rescue therapy)

Variceal

hemorrhage

Recurrent

hemorrhage


Treatment of varices variceal hemorrhage4

Treatment of Varices/Variceal Hemorrhage

No Varices

Varices

No hemorrhage

Variceal

hemorrhage

Preventing recurrent hemorrhage

Recurrent

hemorrhage


Secondary prophylaxis

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


Pharmacological treatment beta blockers

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


Pharmacological treatment beta blockers1

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


Prevention of rebleeding

Prevention of Rebleeding:

  • Occurs in about 75% of pts. within 6 weeks of the initial episode.

  • EVL is the preferred therapeutic method at weekly or twice weekly intervals until the esophageal varices are obliterated.

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

  • The addition of propranolol may enhance benefit


Ascites

ASCITES


Ascites1

Ascites

  • Accumulation of excessive fluid within the peritoneal cavity

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

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

  • Two year mortality is 50%

  • Six months mortality is 50% in patient with diuretics resistant ascites

  • Treatment of ascites doesn't improve mortality


Ascites cont d

ASCITES, Cont’d

  • .


Liver blood supply

Pathogenesis

CIRRHOSIS

Intrahepatic

resistance to

portal flow

Arteriolar

resistance

?

Systemic

Splanchnic

SINUSODIAL

PRESSURE

PORTAL

PRESSURE

GRADIENT

Effective

arterial blood

volume

Portal blood

inflow

Activation of

neurohumoral

systems

COLLATERALS

(VARICES)

ASCITES

Sodium and

water retention

Gastroenterology 2001;120:727


Ascites2

Ascites

  • Ascites results from renal retention of salt and water with localization of this excess fluid into the peritoneal cavity due to portal hypertension.

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


Management

Management

  • Goals of therapy

    • To mobilize ascitic fluid

    • To diminish abdominal discomfort, back pain, and difficulty in ambulation

    • To prevent major complications


Management cont

Pharmacological management

Diuretics

Aldactone (Aldosterone antagonist)

Furosemide (Loop diuretic

Nonpharmacological management

Na+ Restriction

Therapuetic paracentesis

Peritoneovenous shunt

TIPS

Management Cont,


Non diuretics therapy

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.


Ascites cont d1

ASCITES, Cont’d

  • General measures:

    • Bed rest is advisable for patients with a large amount of ascites.

    • Dietary sodium is restricted to 2 gm/d if necessary.

    • Fluids are restricted to 1500 mL/d but in the presence of dilutional hyponatremia (serum sodium level <120 mEq/L) fluids are limited to less than 1000 mL/d


Diuretics therapy

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)


Ascites cont d2

ASCITES, Cont’d

  • Diuretic therapy:

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

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

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

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


Diuretics therapy1

Diuretics Therapy

  • Monitoring

    • Clinicalresponse

      • 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


Ascites cont d3

ASCITES, Cont’d

  • Diuretic therapy, Cont’d

    • If the patient is suffering from respiratory distress, then large-volume paracentesis is needed in addition to diuretic therapy or for quick relieve.

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


Large volume paracentesis

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


Large volume paracentesis use of albumin

Large Volume ParacentesisUseofAlbumin

  • 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)


Stop here

Stop here


Refractory ascites

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


  • Refractory ascites1

    Refractory Ascites

    • Definition

    • International Ascites Club defined it as:

      ‘ascites that cannot be mobilized, or early recurrence of ascites which cannot be satisfactorily prevented by medical therapy’.


    Refractory ascites subtypes

    Diuretic-resistance ascites:

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

    Diuretic-intractable ascites:

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

    complications that preclude the use of an effective diuretic dosage.

    Refractory Ascites Subtypes


    Diagnostic criteria

    Diagnostic Criteria

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

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

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


    Diagnostic criteria cont

    Diagnostic Criteria(cont)

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

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

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


    Diagnostic criteria cont1

    Diagnostic Criteria (cont)

    6. Diuretic-induced complications-

    • hepatic encephalopathy;

    • renal failure: an increase in Srcr conc by more than 100%,to >2 mg/dL (176 mmol/L);

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

    • hypokalemia: less than 3 mEq/L;

    • hyperkalemia more than 6 mEq/L,


    Management of refractory ascites

    MANAGEMENT OFREFRACTORY ASCITES

    • The current acceptable treatments for refractory ascites are:

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

      2.Transjugular intrahepatic portosystemic shunt (TIPS).

      3.Peritoneovenous shunt.

      4.Liver transplantation.


    Large volume paracentesis lvp

    Large Volume Paracentesis(LVP)

    • LVP is a ‘symptomatic therapy’.

    • Patients treated with LVP should receive I.V albumin infusion at a dose of 6-8g for each liter of ascitic fluid removed.


    Large volume paracentesis lvp cont

    Large Volume Paracentesis(LVP)(cont)

    • Complications:

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

    • These patients experience poorer outcome.


    Transjugular intrahepatic portosystemic shunt tips

    Transjugular intrahepatic portosystemic shunt (TIPS)

    • Reduces ascites formation by:

    • Decreasing portal pressure.

    • Improving renal perfusion and GFR.

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


    Transjugular intrahepatic portosystemic shunt tips1

    Transjugular intrahepatic portosystemic shunt (TIPS)

    • Transjugular intrahepatic portosystemic shunt can

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


    Transjugular intrahepatic portosystemic shunt tips cont

    Transjugular intrahepatic portosystemic shunt (TIPS)cont

    • Complications:

    • Hepatic encephalopathy (46%, most within 1st month)

    • Shunt dysfunction (8% within 1st month, 27% late shunt dysfxn)

    • Only 8% had a liver transplant.


    Hepatorenal syndrome hrs

    Hepatorenal syndrome (HRS)

    • Definition:

    • Hepatorenal syndrome (HRS) is a functional renal impairment which occurs either in acute or chronic liver disease with advanced hepatic failure and portal hypertension.

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


    Hepatorenal syndrome hrs cont

    Hepatorenal syndrome (HRS)(Cont)

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


    Hepatorenal syndrome hrs cont1

    Hepatorenal syndrome (HRS)(Cont)

    • Diagnostic Criteria

    • Srcr of 132 µmol/L and CLCR of 40 mL/min,

    • Serum sodium < 130 mEq/L.

    • Proteinuria less than 500 mg/dL and no ultrasonographic evidence of obstructive uropathy or parenchymal renal diseases.

    • urine volume < 500 mL/day,

    • urine sodium < 10 mEq/L,

    • urine osmolarity higher than plasma osmolarity,

    • Red blood cells in urine < 50 per high-power field


    Hepatorenal syndrome hrs cont2

    Hepatorenal syndrome (HRS)(Cont)

    • Diagnostic Criteria

    • There must be no evidence of:

    • Shock, ongoing bacterial infection

    • current or recent treatment with nephrotoxic drugs.

    • There shouldn’t be an excess of gastrointestinal fluid loss


    Hepatorenal syndrome hrs cont3

    Hepatorenal syndrome (HRS)(Cont)

    • Diagnostic Criteria

    • There must be no sustained improvement in renal function (decrease in serum creatinine to ≤ 132 µmol/L or increase in CLCR to ≥ 40 mL/min).


    Hepatorenal syndrome hrs subtypes

    Type I HRS:

    Rapidly progressive

    renal failure with a doubling of srcr to >220 mmol/L, or a CLCR of <20 mL/min in < 2 weeks.

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

    Type II HRS:

    Is defined by a serum creatinine level > 132 mmol/L and/or CLCR <40 mL/min, but renal function slowly deteriorates and

    it has a better prognosis.

    Hepatorenal syndrome (HRS) Subtypes


    Management of hepatorenal syndrome

    Management of hepatorenal syndrome

    • The currently available treatments for HRS include:

    • 1. Medical therapy.

    • 2. Transjugular intrahepatic portocaval shunt.

    • 3. Liver transplantation.


    Medical therapy

    Medical Therapy:

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

    • Correct intravascular volume depletion

    • Decrease renal cortical constriction.


    Medical therapy cont

    Medical Therapy:Cont

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

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


    Medical therapy cont1

    Medical Therapy:Cont

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

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


    Medical therapy cont2

    Medical Therapy:Cont

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

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


    Medical therapy cont3

    Medical Therapy:Cont

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

    • However, there was no obvious benefit.

    • The combination of peripheral vasoconstrictors and renal vasodilators has also failed to improve renal function in cases of HRS.

    • More studies are required to assess

      which is the most suitable regimen.


    Liver transplantation

    Liver transplantation

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

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

      rates than those without HRS who receive a liver transplant.

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


    Conclusion

    Conclusion

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

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


    Spontaneous bacterial peritonitis sbp

    SPONTANEOUS BACTERIAL PERITONITIS (SBP)

    • In hospitalized patients the prevalence of SBP range between 10% and 30%

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


    Spontaneous bacterial peritonitis sbp cont d

    SPONTANEOUS BACTERIAL PERITONITIS (SBP), Cont’d

    • >92% of all cases of SBP are monomicrobial, with

      • Escheria coli (the most common isolate)

      • Klebsiella species

      • Other G-ve bacteria

      • G+ve organisms, Streptococcal (25%)

      • Anaerobic infection (rare <5%)

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


    Spontaneous bacterial peritonitis sbp cont d1

    SPONTANEOUS BACTERIAL PERITONITIS (SBP), Cont’d

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

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

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

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


    Spontaneous bacterial peritonitis sbp cont d2

    SPONTANEOUS BACTERIAL PERITONITIS (SBP), Cont’d

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


    Spontaneous bacterial peritonitis sbp cont d3

    SPONTANEOUS BACTERIAL PERITONITIS (SBP), Cont’d

    • 3 Criteria for secondary peritonitis:

      • The initial ascitic fluid is neutrocytic and fulfils 2 of the following criteria:

      • Total protein > 1 g/dl

      • Glucose < 50 mg/dl

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

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

    9


    Hepatic encephalopathy he

    HEPATIC ENCEPHALOPATHY (HE)

    • Hepatic encephalopathy is a neuropsychiatry syndrome caused by liver disease.

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


    Liver blood supply

    Nomenclature

    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


    Hepatic encephalopathy cont d

    HEPATIC ENCEPHALOPATHY, Cont’d

    • Factors precipitating HE:

    • Uremia

      • Spontaneous, diuretic induced

    • Drugs

      • Sedatives, antidepressants, hypnotics

    • Gastrointestinal bleeding

    • Excess dietary protein

    • Constipation

    • Electrolytes imbalance


    Hepatic encephalopathy

    HEPATIC ENCEPHALOPATHY

    • Factors precipitating HE, Cont’d

    • Paracentesis (volumes > 3-5 liters)

    • Hypokalaemia

    • Infections

    • Trauma (including surgery)

    • Portalsystemic shunts

      • Surgical, spontaneous (large)


    Hepatic encephalopathy cont d1

    HEPATIC ENCEPHALOPATHY, Cont’d

    • Differential diagnosis of HE:

    • Subdural haematoma

    • Drug or alcohol intoxication

    • Delirium tremens

    • Wernicke’s encephalopathy

    • Primary psychiatric disorders

    • Hypoglycemia

    • Neurological Wilson’s disease


    Hepatic encephalopathy cont d2

    HEPATIC ENCEPHALOPATHY, Cont’d

    • Management:

    • Episodes of encephalopathy are common in cirrhosis.

    • The principles are

      • To treat or remove precipitating causes

      • To reduce or eliminate protein intake and

      • To suppress production of neurotoxins by bacteria in the bowel


    Hepatic encephalopathy cont d3

    HEPATIC ENCEPHALOPATHY, Cont’d

    • Management, Cont’d

    • Dietary protein is eliminated or reduced below 20 g/d

    • Glucose (300 g/d) is given orally or parenterally in severe cases

    • As encephalopathy improves, dietary protein is increased by 10-20 g/d every 48 hours to an intake of 40-60 g/d


    Hepatic encephalopathy cont d4

    HEPATIC ENCEPHALOPATHY, Cont’d

    • Management, Cont’d

    • Lactulose (15-30 ml 8-hourly)

      • Disaccharide which is taken orally and reach the colon intact

      • Metabolized by colonic bacteria

      • It produce an osmotic laxative effect

      • It ↓ the pH of the colonic contents

      • Limits colonic ammonia absorption and

      • Prevent the incorporation of nitrogen into bacteria


    Hepatic encephalopathy cont d5

    HEPATIC ENCEPHALOPATHY, Cont’d

    • Management, Cont’d

    • Lactitol

      • A rather alternative to lactulose

      • With less explosive action on bowel function

    • Neomycin (1-4 g 4-6-hourly)

      • An antibiotic which acts by reducing the bacterial flora content of the bowel

      • Alternative to lactulose in case of diarrhea

      • Poorly absorbed antibiotic

      • Can cause ototoxicity,

      • Not used very often


    Pulmonary manifestations

    PULMONARY MANIFESTATIONS

    • Hepatic hydrothorax

      • In about 13% of patients with cirrhosis

      • Fluid in the pleural space can be detected on chest radiograph (usually Rt sided 66%)

      • Management options include:

        • Medical control of ascites

        • Therapeutic thoracentesis for relieve of dyspnea

        • TIPS

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

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


    Pulmonary manifestations cont d

    PULMONARY MANIFESTATIONS, Cont’d

    • Hepatopulmonary Syndrome:

      • Characterized by pulmonary vascular dilatation and hypoxemia (Pao2 <70 mm Hg) in the setting of advanced liver disease

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

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


    Pulmonary manifestations cont d1

    PULMONARY MANIFESTATIONS, Cont’d

    • Portopulmonary hypertension:

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

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

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


    Nutritional disorders

    NUTRITIONAL DISORDERS

    • Protein-energy malnutrition is highly prevalent in hospitalized patients with advanced cirrhosis.

    • Other nutritional deficiencies of dietary components such as

      • Vitamins

      • Trace elements

      • Polyunsaturated fatty acids

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


    Endocrine abnormalities

    ENDOCRINE ABNORMALITIES

    • Thyroid disorders:

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

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


    Endocrine abnormalities cont d

    ENDOCRINE ABNORMALITIES, Cont’d

    • Sexual dysfunction:

      • Gonadal dysfunction commonly accompanies end-stage liver disease.

      • Manifestations may include sexual dysfunction and abnormalities of the hypothalmic-pituitary-gonadal axis

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

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


    Conclusion1

    CONCLUSION

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


    Thanks

    THANKS


  • Login