Treatment of Treatment of chronic liver chronic liver

diseasedisease

Treatment Treatment

Cause ( Etiology)Cause ( Etiology) Complication Complication

Etiology Etiology

InfectionInfection AlcoholAlcohol AutoimmuneAutoimmune CholestaticCholestatic InfiltrativeInfiltrative MetabolicMetabolic VascularVascular DrugsDrugs

Complications Complications

AscitesAscites GI bleedGI bleed SBPSBP EdemaEdema Hepatoma Hepatoma EncephalopathyEncephalopathy Hepatorenal syndromeHepatorenal syndrome

Viral hepatitisViral hepatitis

Hepatitis BHepatitis B Nucleoside Nucleoside

analoguesanalogues LamivudineLamivudine AdefovirAdefovir Telbivudine Telbivudine EntecavirEntecavir TenofovirTenofovir Interferon Interferon

Hepatitis CHepatitis C Alfa interferonAlfa interferon Pegylated Pegylated

interferoninterferon Ribavirin Ribavirin

Autoimmune Autoimmune hepatitishepatitis

PrednisonePrednisone AzathioprineAzathioprine New drugsNew drugs• BudesonideBudesonide• CyclosporineCyclosporine• TacrolimusTacrolimus• RapamycinRapamycin• Mycophenolate Mycophenolate

mofetilmofetil

NAFLDNAFLD Weight lossWeight loss Underlying diseaseUnderlying disease Silymarin/Silymarin/

metforminmetformin Bariatric surgeryBariatric surgery

AlcoholAlcohol AbstinenceAbstinence Fatty liverFatty liver Liver transplantLiver transplant

Wilson diseaseWilson disease PenicillaminePenicillamine TrientineTrientine Zinc acetateZinc acetate TetrathiomolybdatTetrathiomolybdat

e e • Family screeningFamily screening

PBCPBC Ursodeoxycholic Ursodeoxycholic

acidacid SymptomaticSymptomatic• Cholestyramine/Cholestyramine/

RifampicinRifampicin• Calcium/vitamin DCalcium/vitamin D PSCPSC ERCPERCP Liver transplantLiver transplant

HemochromatosisHemochromatosis PhlebotomyPhlebotomy Family screeningFamily screening Alpa1 antitrypsinAlpa1 antitrypsin

deficiencydeficiency 4-phenylbutyric 4-phenylbutyric

acidacid Liver transplantLiver transplant Genetic counselingGenetic counseling

Liver insufficiency

Liver insufficiency

Variceal hemorrhageVariceal hemorrhage

Complications of Cirrhosis Complications of Cirrhosis Result from Portal Result from Portal

Hypertension or Liver Hypertension or Liver InsufficiencyInsufficiency

Complications of Cirrhosis Complications of Cirrhosis Result from Portal Result from Portal

Hypertension or Liver Hypertension or Liver InsufficiencyInsufficiency

CirrhosisCirrhosisAscitesAscites

EncephalopathyEncephalopathy

JaundiceJaundice

Portal hypertension

Portal hypertension Spontaneous

bacterial peritonitis

Spontaneous bacterial peritonitis

Hepatorenal syndromeHepatorenal syndrome

COMPLICATIONS OF CIRRHOSISCOMPLICATIONS OF CIRRHOSIS

Varices/Variceal

Hemorrhage

Varices/Variceal

Hemorrhage

Varicealobliteration

Varicealobliteration

Portal pressure

Portal pressure

Resistance to portal flowResistance

to portal flow

CirrhosisCirrhosis

Resistance to portal flowResistance

to portal flowSplanchnic arteriolar

resistance

Splanchnic arteriolar

resistance

Portal blood inflow

Portal blood inflow

Variceal Band Ligation or

Sclerotherapy

Variceal Band Ligation or

Sclerotherapy

MECHANISM OF ACTION OF ENDOSCOPIC THERAPY IN PORTAL HYPERTENSIONMECHANISM OF ACTION OF ENDOSCOPIC THERAPY IN PORTAL HYPERTENSION

Predictors of hemorrhage: Variceal size Red signs Child B/C

Predictors of hemorrhage: Variceal size Red signs Child B/C

NIEC. N Engl J Med 1988; 319:983NIEC. N Engl J Med 1988; 319:983

Variceal hemorrhageVariceal hemorrhage Varix with red signsVarix with red signs

PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGEPROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE

Treatment of Varices / Treatment of Varices / Variceal HemorrhageVariceal HemorrhageTreatment of Varices / Treatment of Varices / Variceal HemorrhageVariceal Hemorrhage

RecurrenthemorrhageRecurrent

hemorrhage

Varicealhemorrhage

Varicealhemorrhage

VaricesNo hemorrhage

VaricesNo hemorrhage

No varicesNo varices

Management depends on the size of varicesManagement depends on the size of varices

MANAGEMENT OF PATIENTS WITH VARICES WHO HAVE NEVER BLEDMANAGEMENT OF PATIENTS WITH VARICES WHO HAVE NEVER BLED

Treatment of Varices / Treatment of Varices / Variceal HemorrhageVariceal HemorrhageTreatment of Varices / Treatment of Varices / Variceal HemorrhageVariceal Hemorrhage

RecurrenthemorrhageRecurrent

hemorrhage

Varicealhemorrhage

Varicealhemorrhage

Medium/ large varicesNo hemorrhage

Medium/ large varicesNo hemorrhage

Small varicesNo hemorrhage

Small varicesNo hemorrhage

No varicesNo varices

1) -blockers (propranolol, nadolol) indefinitely

2) Endoscopic Variceal Ligation in patients intolerant to -blockers

1) -blockers (propranolol, nadolol) indefinitely

2) Endoscopic Variceal Ligation in patients intolerant to -blockers

MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGEHEMORRHAGE

Treatment of Varices / Treatment of Varices / Variceal HemorrhageVariceal HemorrhageTreatment of Varices / Treatment of Varices / Variceal HemorrhageVariceal Hemorrhage

Control of hemorrhageControl of hemorrhage

RecurrenthemorrhageRecurrent

hemorrhage

Varicealhemorrhage

Varicealhemorrhage

Medium/ large varicesNo hemorrhage

Medium/ large varicesNo hemorrhage

Small varicesNo hemorrhage

Small varicesNo hemorrhage

No varicesNo varices

CONTROL OF ACUTE VARICEAL HEMORRHAGECONTROL OF ACUTE VARICEAL HEMORRHAGE

Treatment of Acute Treatment of Acute Variceal HemorrhageVariceal HemorrhageTreatment of Acute Treatment of Acute

Variceal HemorrhageVariceal HemorrhageGeneral Management: General Management:

IV access and fluid resuscitationIV access and fluid resuscitation Do not over transfuse (hemoglobin ~ 8 Do not over transfuse (hemoglobin ~ 8

g/dL)g/dL) Antibiotic prophylaxisAntibiotic prophylaxis

Specific therapy:Specific therapy: Pharmacological therapy: Terlipressin, Pharmacological therapy: Terlipressin,

Somatostatin and analogues, Vasopressin Somatostatin and analogues, Vasopressin + Nitroglycerin+ Nitroglycerin

Endoscopic therapy: Ligation, Endoscopic therapy: Ligation, SclerotherapySclerotherapy

Shunt therapy: TIPS, surgical shuntShunt therapy: TIPS, surgical shunt

General Management: General Management: IV access and fluid resuscitationIV access and fluid resuscitation Do not over transfuse (hemoglobin ~ 8 Do not over transfuse (hemoglobin ~ 8

g/dL)g/dL) Antibiotic prophylaxisAntibiotic prophylaxis

Specific therapy:Specific therapy: Pharmacological therapy: Terlipressin, Pharmacological therapy: Terlipressin,

Somatostatin and analogues, Vasopressin Somatostatin and analogues, Vasopressin + Nitroglycerin+ Nitroglycerin

Endoscopic therapy: Ligation, Endoscopic therapy: Ligation, SclerotherapySclerotherapy

Shunt therapy: TIPS, surgical shuntShunt therapy: TIPS, surgical shunt

TREATMENT OF ACUTE VARICEAL HEMORRHAGETREATMENT OF ACUTE VARICEAL HEMORRHAGE

Endoscopic Variceal Endoscopic Variceal Band LigationBand Ligation

Endoscopic Variceal Endoscopic Variceal Band LigationBand Ligation

Bleeding controlled in 90%Bleeding controlled in 90%

Rebleeding rate 30%Rebleeding rate 30%

Compared with Sclerotherapy:Compared with Sclerotherapy:Less rebleedingLess rebleedingLower mortalityLower mortalityFewer complicationsFewer complicationsFewer treatment sessionsFewer treatment sessions

Bleeding controlled in 90%Bleeding controlled in 90%

Rebleeding rate 30%Rebleeding rate 30%

Compared with Sclerotherapy:Compared with Sclerotherapy:Less rebleedingLess rebleedingLower mortalityLower mortalityFewer complicationsFewer complicationsFewer treatment sessionsFewer treatment sessions

ENDOSCOPIC VARICEAL BAND LIGATIONENDOSCOPIC VARICEAL BAND LIGATION

Transjugular Intrahepatic Transjugular Intrahepatic Porto systemic ShuntPorto systemic Shunt

Transjugular Intrahepatic Transjugular Intrahepatic Porto systemic ShuntPorto systemic Shunt

Hepatic Hepatic veinveinHepatic Hepatic veinvein

Portal veinPortal veinPortal veinPortal veinSplenic Splenic veinveinSplenic Splenic veinvein

Superior Superior mesenteric veinmesenteric veinSuperior Superior mesenteric veinmesenteric vein

TIPSTIPSTIPSTIPS

THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNTTHE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT

Gastric VaricesGastric VaricesGastric VaricesGastric Varices

Pretreatment cyanoacrylatePretreatment cyanoacrylatePretreatment cyanoacrylatePretreatment cyanoacrylate Post-treatment cyanoacrylatePost-treatment cyanoacrylatePost-treatment cyanoacrylatePost-treatment cyanoacrylate

ENDOSCOPIC IMAGES OF GASTRIC VARICESENDOSCOPIC IMAGES OF GASTRIC VARICES

MildMild

Mild and Severe Portal Hypertensive GastropathyMild and Severe Portal Hypertensive Gastropathy

SevereSevere

Mosaic patternMosaic pattern Mosaic pattern + red spotsMosaic pattern + red spots

Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533

ENDOSCOPIC IMAGES OF MILD ENDOSCOPIC IMAGES OF MILD AND SEVERE PORTAL AND SEVERE PORTAL

HYPERTENSIVE GASTROPATHYHYPERTENSIVE GASTROPATHY

Ascites and Hepatorenal SyndromeAscites and Hepatorenal Syndrome

ASCITES AND HEPATORENAL SYNDROMEASCITES AND HEPATORENAL SYNDROME

Natural History of AscitesNatural History of AscitesNatural History of AscitesNatural History of Ascites

HVPG >10 mmHgExtreme Vasodilation

HVPG >10 mmHgExtreme Vasodilation

HVPG >10 mmHgSevere Vasodilation

HVPG >10 mmHgSevere Vasodilation

HVPG >10 mmHgModerate Vasodilation

HVPG >10 mmHgModerate Vasodilation

HVPG <10 mmHgMild VasodilationHVPG <10 mmHgMild Vasodilation

HepatorenalSyndrome

HepatorenalSyndrome

RefractoryAscites

RefractoryAscites

Uncomplicated

Ascites

Uncomplicated

Ascites

Portal Hypertension

No Ascites

Portal Hypertension

No Ascites

NATURAL HISTORY OF ASCITESNATURAL HISTORY OF ASCITES

Diagnostic Diagnostic ParacentesisParacentesisDiagnostic Diagnostic

ParacentesisParacentesisIndicationsIndicationsIndicationsIndications

ContraindicationsContraindicationsContraindicationsContraindications

New-onset ascitesNew-onset ascites

Admission to hospitalAdmission to hospital

Symptoms/signs of SBPSymptoms/signs of SBP

Renal dysfunctionRenal dysfunction

Unexplained encephalopathyUnexplained encephalopathy

New-onset ascitesNew-onset ascites

Admission to hospitalAdmission to hospital

Symptoms/signs of SBPSymptoms/signs of SBP

Renal dysfunctionRenal dysfunction

Unexplained encephalopathyUnexplained encephalopathy

NoneNone NoneNone

DIAGNOSTIC PARACENTESISDIAGNOSTIC PARACENTESIS

Management of Management of Uncomplicated AscitesUncomplicated Ascites

Management of Management of Uncomplicated AscitesUncomplicated AscitesDefinition:Definition: Ascites responsive to Ascites responsive to diuretics in the absence of infection and diuretics in the absence of infection and renal dysfunctionrenal dysfunction

Definition:Definition: Ascites responsive to Ascites responsive to diuretics in the absence of infection and diuretics in the absence of infection and renal dysfunctionrenal dysfunction

Sodium restrictionSodium restriction Effective in 10-20% of casesEffective in 10-20% of cases Predictors of response: mild or moderate Predictors of response: mild or moderate

ascites, Urine Na excretion > 50 mEq/dayascites, Urine Na excretion > 50 mEq/day

DiureticsDiuretics Should be spironolactone-basedShould be spironolactone-based A progressive schedule (spironolactone A progressive schedule (spironolactone

furosemide) requires fewer dose furosemide) requires fewer dose adjustments than a combined therapy adjustments than a combined therapy (spironolactone + furosemide)(spironolactone + furosemide)

Sodium restrictionSodium restriction Effective in 10-20% of casesEffective in 10-20% of cases Predictors of response: mild or moderate Predictors of response: mild or moderate

ascites, Urine Na excretion > 50 mEq/dayascites, Urine Na excretion > 50 mEq/day

DiureticsDiuretics Should be spironolactone-basedShould be spironolactone-based A progressive schedule (spironolactone A progressive schedule (spironolactone

furosemide) requires fewer dose furosemide) requires fewer dose adjustments than a combined therapy adjustments than a combined therapy (spironolactone + furosemide)(spironolactone + furosemide)

MANAGEMENT OF UNCOMPLICATED ASCITESMANAGEMENT OF UNCOMPLICATED ASCITES

Sodium RestrictionSodium Restriction

2 g (or 5.2 g of dietary salt) a day2 g (or 5.2 g of dietary salt) a day

Fluid restriction is not necessary unless Fluid restriction is not necessary unless there is hyponatremia (<125 mmol/L)there is hyponatremia (<125 mmol/L)

Goal: negative sodium balanceGoal: negative sodium balance

Sodium RestrictionSodium Restriction

2 g (or 5.2 g of dietary salt) a day2 g (or 5.2 g of dietary salt) a day

Fluid restriction is not necessary unless Fluid restriction is not necessary unless there is hyponatremia (<125 mmol/L)there is hyponatremia (<125 mmol/L)

Goal: negative sodium balanceGoal: negative sodium balance

Management of Management of Uncomplicated AscitesUncomplicated Ascites

MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTIONMANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION

Diuretic TherapyDiuretic TherapyDosageDosage

Spironolactone 100-400 mg/day Spironolactone 100-400 mg/day Furosemide (40-160 mg/d) for inadequate Furosemide (40-160 mg/d) for inadequate weight loss or if hyperkalemia developsweight loss or if hyperkalemia develops

Increase diuretics if weight loss <1 kg in the Increase diuretics if weight loss <1 kg in the first week and < 2 kg/week thereafterfirst week and < 2 kg/week thereafter

Decrease diuretics if weight loss >0.5 kg/day in Decrease diuretics if weight loss >0.5 kg/day in patients without edema and >1 kg/day in those patients without edema and >1 kg/day in those with edemawith edema

Side effectsSide effectsRenal dysfunction, hyponatremia, Renal dysfunction, hyponatremia, hyperkalemia, encephalopathy, gynecomastiahyperkalemia, encephalopathy, gynecomastia

Diuretic TherapyDiuretic TherapyDosageDosage

Spironolactone 100-400 mg/day Spironolactone 100-400 mg/day Furosemide (40-160 mg/d) for inadequate Furosemide (40-160 mg/d) for inadequate weight loss or if hyperkalemia developsweight loss or if hyperkalemia develops

Increase diuretics if weight loss <1 kg in the Increase diuretics if weight loss <1 kg in the first week and < 2 kg/week thereafterfirst week and < 2 kg/week thereafter

Decrease diuretics if weight loss >0.5 kg/day in Decrease diuretics if weight loss >0.5 kg/day in patients without edema and >1 kg/day in those patients without edema and >1 kg/day in those with edemawith edema

Side effectsSide effectsRenal dysfunction, hyponatremia, Renal dysfunction, hyponatremia, hyperkalemia, encephalopathy, gynecomastiahyperkalemia, encephalopathy, gynecomastia

Management of Uncomplicated Management of Uncomplicated AscitesAscites

MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPYMANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY

Definition and Types of Definition and Types of Refractory AscitesRefractory Ascites

Definition and Types of Definition and Types of Refractory AscitesRefractory Ascites

Occurs in ~10% of cirrhotic patientsOccurs in ~10% of cirrhotic patientsOccurs in ~10% of cirrhotic patientsOccurs in ~10% of cirrhotic patients

Diuretic-intractable ascitesDiuretic-intractable ascites

Therapeutic doses of diuretics cannot be Therapeutic doses of diuretics cannot be achieved achieved because of diuretic-induced because of diuretic-induced complicationscomplications

Diuretic-resistant ascitesDiuretic-resistant ascites

No response to maximal diuretic therapy (400 mg No response to maximal diuretic therapy (400 mg spironolactone + 160 mg furosemide/day)spironolactone + 160 mg furosemide/day)

Diuretic-intractable ascitesDiuretic-intractable ascites

Therapeutic doses of diuretics cannot be Therapeutic doses of diuretics cannot be achieved achieved because of diuretic-induced because of diuretic-induced complicationscomplications

Diuretic-resistant ascitesDiuretic-resistant ascites

No response to maximal diuretic therapy (400 mg No response to maximal diuretic therapy (400 mg spironolactone + 160 mg furosemide/day)spironolactone + 160 mg furosemide/day)

20%20%

80%80%

DEFINITION AND TYPES OF REFRACTORY ASCITESDEFINITION AND TYPES OF REFRACTORY ASCITES

Spontaneous Bacterial Peritonitis Spontaneous Bacterial Peritonitis (SBP) Complicates Ascites and Can (SBP) Complicates Ascites and Can

Lead to Renal DysfunctionLead to Renal Dysfunction

Spontaneous Bacterial Peritonitis Spontaneous Bacterial Peritonitis (SBP) Complicates Ascites and Can (SBP) Complicates Ascites and Can

Lead to Renal DysfunctionLead to Renal Dysfunction

SBPSBP

HVPG >10 mmHgExtreme VasodilationHVPG >10 mmHgExtreme Vasodilation

HVPG >10 mmHgSevere VasodilationHVPG >10 mmHgSevere Vasodilation

HVPG >10 mmHgModerate VasodilationHVPG >10 mmHgModerate Vasodilation

HVPG <10 mmHgMild VasodilationHVPG <10 mmHgMild Vasodilation

HepatorenalSyndrome

HepatorenalSyndrome

RefractoryAscites

RefractoryAscites

UncomplicatedAscites

UncomplicatedAscites

Portal Hypertension

No Ascites

Portal Hypertension

No Ascites

SPONTANEOUS BACTERIAL PERITONITIS (SBP) COMPLICATES ASCITES AND CAN LEAD TO SPONTANEOUS BACTERIAL PERITONITIS (SBP) COMPLICATES ASCITES AND CAN LEAD TO RENAL DYSFUNCTIONRENAL DYSFUNCTION

Early Diagnosis of Early Diagnosis of SBPSBP

Early Diagnosis of Early Diagnosis of SBPSBP

Diagnostic paracentesisDiagnostic paracentesis:: If symptoms / signs of SBP occurIf symptoms / signs of SBP occur Unexplained encephalopathy and / or Unexplained encephalopathy and / or

renal dysfunctionrenal dysfunction At any hospital admissionAt any hospital admission

Diagnosis based on ascitic fluidDiagnosis based on ascitic fluidPMN count >250/mmPMN count >250/mm33

Diagnostic paracentesisDiagnostic paracentesis:: If symptoms / signs of SBP occurIf symptoms / signs of SBP occur Unexplained encephalopathy and / or Unexplained encephalopathy and / or

renal dysfunctionrenal dysfunction At any hospital admissionAt any hospital admission

Diagnosis based on ascitic fluidDiagnosis based on ascitic fluidPMN count >250/mmPMN count >250/mm33

EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Microorganisms Isolated in Spontaneous Microorganisms Isolated in Spontaneous Bacterial Peritonitis Bacterial Peritonitis

Microorganisms Isolated in Spontaneous Microorganisms Isolated in Spontaneous Bacterial Peritonitis Bacterial Peritonitis

MicroorganismMicroorganism % of % of CasesCases

Gram-negative bacilliGram-negative bacilli 7272

Gram-positive cocciGram-positive cocci 2929

MicroorganismMicroorganism % of % of CasesCases

Gram-negative bacilliGram-negative bacilli 7272

Gram-positive cocciGram-positive cocci 2929

MICROORGANISMS ISOLATED IN SPONTANEOUS BACTERIAL PERITONITIS (SBP)MICROORGANISMS ISOLATED IN SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Treatment ofTreatment of Spontaneous Spontaneous Bacterial PeritonitisBacterial Peritonitis

Treatment ofTreatment of Spontaneous Spontaneous Bacterial PeritonitisBacterial Peritonitis

Recommended antibiotics for initial Recommended antibiotics for initial empiric therapyempiric therapy

i.vi.v. cefotaxime,. cefotaxime, i.v. amoxicillin-clavulanic acidi.v. amoxicillin-clavulanic acid avoid aminoglycosidesavoid aminoglycosides

Minimum duration: 5 daysMinimum duration: 5 days

Recommended antibiotics for initial Recommended antibiotics for initial empiric therapyempiric therapy

i.vi.v. cefotaxime,. cefotaxime, i.v. amoxicillin-clavulanic acidi.v. amoxicillin-clavulanic acid avoid aminoglycosidesavoid aminoglycosides

Minimum duration: 5 daysMinimum duration: 5 days

TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Indications for Prophylactic Indications for Prophylactic Antibiotics to Prevent Antibiotics to Prevent Spontaneous Bacterial Spontaneous Bacterial

Peritonitis Peritonitis

Indications for Prophylactic Indications for Prophylactic Antibiotics to Prevent Antibiotics to Prevent Spontaneous Bacterial Spontaneous Bacterial

Peritonitis Peritonitis

Patients who have recovered from SBP Patients who have recovered from SBP (long-term)(long-term)

Norfloxacin 400 mg p.o. daily, indefinitelyNorfloxacin 400 mg p.o. daily, indefinitely

Weekly Quinolones Weekly Quinolones

Patients who have recovered from SBP Patients who have recovered from SBP (long-term)(long-term)

Norfloxacin 400 mg p.o. daily, indefinitelyNorfloxacin 400 mg p.o. daily, indefinitely

Weekly Quinolones Weekly Quinolones

INDICATIONS FOR PROPHYLACTIC ANTIBIOTICS TO PREVENT SPONTANEOUS BACTERIAL INDICATIONS FOR PROPHYLACTIC ANTIBIOTICS TO PREVENT SPONTANEOUS BACTERIAL PERITONITIS (SBP)PERITONITIS (SBP)

Characteristics of Characteristics of Hepatorenal SyndromeHepatorenal Syndrome

Characteristics of Characteristics of Hepatorenal SyndromeHepatorenal Syndrome Renal failure in patients with cirrhosis, Renal failure in patients with cirrhosis,

advanced liver failure and severe sinusoidal advanced liver failure and severe sinusoidal portal hypertensionportal hypertension

Absence of significant histological changes Absence of significant histological changes in the kidney (“functional” renal failure)in the kidney (“functional” renal failure)

Marked arteriolar vasodilation in the extra-Marked arteriolar vasodilation in the extra-renal circulationrenal circulation

Marked renal vasoconstriction leading to Marked renal vasoconstriction leading to reduced glomerular filtration ratereduced glomerular filtration rate

Renal failure in patients with cirrhosis, Renal failure in patients with cirrhosis, advanced liver failure and severe sinusoidal advanced liver failure and severe sinusoidal portal hypertensionportal hypertension

Absence of significant histological changes Absence of significant histological changes in the kidney (“functional” renal failure)in the kidney (“functional” renal failure)

Marked arteriolar vasodilation in the extra-Marked arteriolar vasodilation in the extra-renal circulationrenal circulation

Marked renal vasoconstriction leading to Marked renal vasoconstriction leading to reduced glomerular filtration ratereduced glomerular filtration rate

CHARACTERISTICS OF HEPATORENAL SYNDROME (HRS)CHARACTERISTICS OF HEPATORENAL SYNDROME (HRS)

Two Types of Two Types of Hepatorenal SyndromeHepatorenal Syndrome

Two Types of Two Types of Hepatorenal SyndromeHepatorenal Syndrome

Type 1Type 1 Rapidly progressive renal failure (2 Rapidly progressive renal failure (2

weeks)weeks) Doubling of creatinine to >2.5 Doubling of creatinine to >2.5

Type 2Type 2 More slowly progressiveMore slowly progressive Creatinine >1.5 mg/dL or Creatinine Creatinine >1.5 mg/dL or Creatinine

Clearance < 40 ml/minClearance < 40 ml/min Associated with refractory ascitesAssociated with refractory ascites

Type 1Type 1 Rapidly progressive renal failure (2 Rapidly progressive renal failure (2

weeks)weeks) Doubling of creatinine to >2.5 Doubling of creatinine to >2.5

Type 2Type 2 More slowly progressiveMore slowly progressive Creatinine >1.5 mg/dL or Creatinine Creatinine >1.5 mg/dL or Creatinine

Clearance < 40 ml/minClearance < 40 ml/min Associated with refractory ascitesAssociated with refractory ascites

TYPES OF HEPATORENAL SYNDROME (HRS)TYPES OF HEPATORENAL SYNDROME (HRS)

Management of Hepatorenal SyndromeManagement of Hepatorenal Syndrome

Proven efficacy Liver transplantation

Under investigation Vasoconstrictor + albumin Transjugular intrahepatic portosystemic shunt

(TIPS) Vasoconstrictor + TIPS Extracorporeal albumin dialysis (ECAD)

Ineffective Renal vasodilators (prostaglandin, dopamine) Hemodialysis

Proven efficacy Liver transplantation

Under investigation Vasoconstrictor + albumin Transjugular intrahepatic portosystemic shunt

(TIPS) Vasoconstrictor + TIPS Extracorporeal albumin dialysis (ECAD)

Ineffective Renal vasodilators (prostaglandin, dopamine) Hemodialysis

MANAGEMENT OF HEPATORENAL SYNDROMEMANAGEMENT OF HEPATORENAL SYNDROME

Hepatic EncephalopathyHepatic Encephalopathy

Pathophysiology of Hepatic Pathophysiology of Hepatic EncephalopathyEncephalopathy

AmmoniaAmmonia

Upregulation of astrocytic peripheral Upregulation of astrocytic peripheral

benzodiazepine receptors (PBR)benzodiazepine receptors (PBR)

Neurosteroid productionNeurosteroid production

Modulation of GABA receptorModulation of GABA receptor

Hepatic encephalopathyHepatic encephalopathy

AmmoniaAmmonia

Upregulation of astrocytic peripheral Upregulation of astrocytic peripheral

benzodiazepine receptors (PBR)benzodiazepine receptors (PBR)

Neurosteroid productionNeurosteroid production

Modulation of GABA receptorModulation of GABA receptor

Hepatic encephalopathyHepatic encephalopathy

PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHYPATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY

Hepatic Hepatic Encephalopathy is a Encephalopathy is a Clinical DiagnosisClinical Diagnosis

Hepatic Hepatic Encephalopathy is a Encephalopathy is a Clinical DiagnosisClinical Diagnosis

Clinical findings and history importantClinical findings and history important

Ammonia levels are unreliableAmmonia levels are unreliable

Ammonia has poor correlation with Ammonia has poor correlation with diagnosisdiagnosis

Measurement of ammonia Measurement of ammonia notnot necessarynecessary

Number connection testNumber connection test

Slow dominant rhythm on EEGSlow dominant rhythm on EEG

Clinical findings and history importantClinical findings and history important

Ammonia levels are unreliableAmmonia levels are unreliable

Ammonia has poor correlation with Ammonia has poor correlation with diagnosisdiagnosis

Measurement of ammonia Measurement of ammonia notnot necessarynecessary

Number connection testNumber connection test

Slow dominant rhythm on EEGSlow dominant rhythm on EEG

HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSISHEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS

STAGES OF HEPATIC ENCEPHALOPATHYSTAGES OF HEPATIC ENCEPHALOPATHY

ConfusionConfusion

DrowsinessDrowsiness

SomnolenceSomnolence

ComaComa

11 22 33 44StageStage

Stages of Hepatic EncephalopathyStages of Hepatic Encephalopathy

Treatment of Hepatic Treatment of Hepatic EncephalopathyEncephalopathy

Treatment of Hepatic Treatment of Hepatic EncephalopathyEncephalopathy

Identify and treat precipitating factorIdentify and treat precipitating factor InfectionInfection GI hemorrhageGI hemorrhage Prerenal azotemiaPrerenal azotemia SedativesSedatives ConstipationConstipation

Lactulose (adjust to 2-3 bowel Lactulose (adjust to 2-3 bowel movements/day)movements/day)

Protein restriction, short-term (if at all)Protein restriction, short-term (if at all)

Identify and treat precipitating factorIdentify and treat precipitating factor InfectionInfection GI hemorrhageGI hemorrhage Prerenal azotemiaPrerenal azotemia SedativesSedatives ConstipationConstipation

Lactulose (adjust to 2-3 bowel Lactulose (adjust to 2-3 bowel movements/day)movements/day)

Protein restriction, short-term (if at all)Protein restriction, short-term (if at all)

TREATMENT OF HEPATIC ENCEPHALOPATHYTREATMENT OF HEPATIC ENCEPHALOPATHY

Liver transplantLiver transplant

All patients with end stage liver All patients with end stage liver disease should be assessed for liver disease should be assessed for liver transplant when ever is proven to transplant when ever is proven to significantly prolong survival and significantly prolong survival and improve quality of life in a coast improve quality of life in a coast effective manner over natural effective manner over natural history of the liver disease and other history of the liver disease and other medical and non transplant surgical medical and non transplant surgical intervention.intervention.