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.