上海交通大学医学院内科学livercirrhosis.pptx

ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCEHepatic cirrhosisMa Xiong,M.D.,Associate ProfessorShanghai Institute of Digestive Disease,Renji HospitalShanghai Jiao Tong University School of MedicineHepatic CirrhosisHepatic Cirrhosis End stage of any chronic liver diseaseEnd stage of any chronic liver disease Characterized Characterized histologicallyhistologically by by regenerative nodules surrounded by regenerative nodules surrounded by fibrous tissuefibrous tissue ClinicallyClinically there are two types of cirrhosis:there are two types of cirrhosis:CompensatedCompensated DecompensatedDecompensatedDEFINITION OF CIRRHOSISDEFINITION OF CIRRHOSISCirrhosisCirrhosisNormalNormalNodulesNodulesIrregular surfaceIrregular surfaceGROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVERGROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVERCirrhotic liverCirrhotic liverNodular,irregular surfaceNodular,irregular surfaceNodulesNodulesGROSS IMAGE OF A CIRRHOTIC LIVERCirrhosisCirrhosisNormalNormalNodules surrounded by Nodules surrounded by fibrous tissuefibrous tissueHISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVERHISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVERHISTOLOGICAL IMAGE OF CIRRHOSISHISTOLOGICAL IMAGE OF CIRRHOSISFibrosisFibrosisRegenerative Regenerative nodulenodulePATHOGENESIS OF LIVER FIBROSISHepatocytesHepatocytesSpace of DisseSpace of DisseSinusoidal Sinusoidal endothelial cellendothelial cellHepatic Hepatic stellate cellstellate cellFenestraeFenestraeNormal Hepatic SInusoidNormal Hepatic SInusoidRetinoid Retinoid dropletsdropletsPATHOGENESIS OF LIVER FIBROSISAlterations in Microvasculature in CirrhosisAlterations in Microvasculature in Cirrhosis Activation of stellate cellsActivation of stellate cells Collagen deposition in space of DisseCollagen deposition in space of Disse Constriction of sinusoidsConstriction of sinusoids Defenestration of sinusoidsDefenestration of sinusoidsCompensatedCompensatedcirrhosiscirrhosisDecompensatedDecompensatedcirrhosiscirrhosisDeathDeathChronic Chronic liver liver diseasediseaseNatural History of Chronic Liver DiseaseDevelopment of Development of complications:complications:Variceal hemorrhageVariceal hemorrhage Ascites Ascites Encephalopathy Encephalopathy Jaundice JaundiceNATURAL HISTORY OF CHRONIC LIVER DISEASE606040408080100100120120140140160160004040606080802020202000100100MonthsMonthsProbability of Probability of survivalsurvivalAll patients All patients with cirrhosiswith cirrhosisDecompensated Decompensated cirrhosiscirrhosis180180Decompensation Shortens SurvivalDecompensation Shortens SurvivalGines et.al.,Hepatology 1987;7:122Gines et.al.,Hepatology 1987;7:122Median survivalMedian survival 9 years 9 yearsMedian survivalMedian survival 1.6 years 1.6 yearsSURVIVAL TIMES IN CIRRHOSIS10Liver Liver insufficiencyinsufficiencyVariceal hemorrhageVariceal hemorrhageComplications of Cirrhosis Result from Portal Complications of Cirrhosis Result from Portal Hypertension or Liver InsufficiencyHypertension or Liver InsufficiencyCirrhosisCirrhosisAscitesAscitesEncephalopathyEncephalopathyJaundiceJaundicePortal Portal hypertensionhypertensionSpontaneous Spontaneous bacterial bacterial peritonitisperitonitisHepatorenal Hepatorenal syndromesyndromeCOMPLICATIONS OF CIRRHOSISCirrhosis-DiagnosisCirrhosis-Diagnosis Cirrhosis is a histological diagnosisCirrhosis is a histological diagnosis However,in patients with chronic However,in patients with chronic liver disease the presence of various liver disease the presence of various clinical features suggests cirrhosisclinical features suggests cirrhosis The presence of these clinical The presence of these clinical features can be followed by non-features can be followed by non-invasive testing,prior to liver biopsyinvasive testing,prior to liver biopsyDIAGNOSIS OF CIRRHOSISIn Whom Should We Suspect Cirrhosis?In Whom Should We Suspect Cirrhosis?Any patient with chronic liver diseaseAny patient with chronic liver disease Chronic abnormal aminotransferases and/or Chronic abnormal aminotransferases and/or alkaline phosphatasealkaline phosphatase Physical exam findingsPhysical exam findings Stigmata of chronic liver disease(muscle wasting,Stigmata of chronic liver disease(muscle wasting,vascular spiders,palmar erythema)vascular spiders,palmar erythema)Palpable left lobe of the liverPalpable left lobe of the liver Small liver spanSmall liver span SplenomegalySplenomegaly Signs of decompensation(jaundice,ascites,Signs of decompensation(jaundice,ascites,asterixis)asterixis)DIAGNOSIS OF CIRRHOSIS CLINICAL FINDINGSLaboratoryLaboratory Liver insufficiencyLiver insufficiency Low albumin(3.8 g/dL)Low albumin(1.3)Prolonged prothrombin time(INR 1.3)High bilirubin(1.5 mg/dL)High bilirubin(1.5 mg/dL)Portal hypertensionPortal hypertension Low platelet count(175 x1000/Low platelet count(1AST/ALT ratio 1In Whom Should We Suspect Cirrhosis?In Whom Should We Suspect Cirrhosis?DIAGNOSIS OF CIRRHOSIS LABORATORY STUDIESCT Scan in CirrhosisCT Scan in CirrhosisLiver with an irregular surfaceLiver with an irregular surfaceSplenomegalySplenomegalyCollateralsCollateralsDIAGNOSIS OF CIRRHOSIS CAT SCANNoNoYesYesDiagnostic AlgorithmDiagnostic AlgorithmPatient with chronic liver disease and any of the following:Patient with chronic liver disease and any of the following:Variceal hemorrhageVariceal hemorrhageAscitesAscitesHepatic encephalopathyHepatic encephalopathyLiver biopsy not Liver biopsy not necessary for the necessary for the diagnosis of cirrhosisdiagnosis of cirrhosisPhysical findings:Physical findings:Enlarged left hepatic lobeEnlarged left hepatic lobeSplenomegalySplenomegalyStigmata of chronic liver diseaseStigmata of chronic liver diseaseLaboratory findings:Laboratory findings:ThrombocytopeniaThrombocytopeniaImpaired hepatic synthetic functionImpaired hepatic synthetic functionRadiological findings:Radiological findings:Small nodular liverSmall nodular liverIntra-abdominal collateralsIntra-abdominal collateralsAscitesAscitesSplenomegalySplenomegalyColloid shift to spleen and/or bone marrowColloid shift to spleen and/or bone marrowYesYesNoNoYesYesNoNoLiver biopsyLiver biopsyDIAGNOSTIC ALGORITHMMechanisms of Portal HypertensionMechanisms of Portal Hypertension Pressure(P)results from the interaction Pressure(P)results from the interaction of resistance(R)and flow(F):of resistance(R)and flow(F):P=R x FP=R x F Portal hypertension can result from:Portal hypertension can result from:increase in resistanceincrease in resistance to portal flow to portal flow and/or and/or increase in portal venous inflowincrease in portal venous inflowMECHANISMS OF PORTAL HYPERTENSIONNormal Liver Hepatic Hepatic veinveinSinusoidSinusoidPortal Portal veinveinLiverLiverSplenic Splenic veinveinCoronary Coronary veinveinTHE NORMAL LIVER OFFERS ALMOST NO RESISTANCE TO FLOWPortal Portal systemic systemic collateralscollateralsDistorted Distorted sinusoidal sinusoidal architecturearchitectureleads to leads to increased increased resistanceresistancePortal Portal veinveinCirrhotic Liver SplenomegalySplenomegalyARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCEAN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSIONMesenteric Mesenteric veinsveins FlowFlowSplanchnicSplanchnicvasodilatationvasodilatationDistorted Distorted sinusoidal sinusoidal architechurearchitechurePortal Portal veinveinAn Increase in Portal Venous Inflow Sustains An Increase in Portal Venous Inflow Sustains Portal HypertensionPortal Hypertension20Small varicesSmall varicesLarge varicesLarge varicesNo varicesNo varices7-8%/year7-8%/year7-8%/year7-8%/yearVarices Increase in Diameter Varices Increase in Diameter ProgressivelyProgressivelyMerli et al.J Hepatol 2003;38266Merli et al.J Hepatol 2003;38:266VARICES INCREASE IN DIAMETER PROGRESSIVELYA Threshold Portal Pressure of 12 mmHg is A Threshold Portal Pressure of 12 mmHg is Necessary for Varices to Form Necessary for Varices to Form P0.01P 50 mEq/dayUrine Na excretion 50 mEq/dayDiureticsDiuretics Should be spironolactone-basedShould be spironolactone-based A progressive schedule(spironolactone A progressive schedule(spironolactone furosemide)requires fewer dose adjustments than furosemide)requires fewer dose adjustments than a combined a combined therapy(spironolactone+furosemide)therapy(spironolactone+furosemide)MANAGEMENT OF UNCOMPLICATED ASCITESSodium 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 there is Fluid restriction is not necessary unless there is hyponatremia(125 mmol/L)hyponatremia(125 mmol/L)Goal:negative sodium balanceGoal:negative sodium balance Side effect:unpalatability may compromise Side effect:unpalatability may compromise nutritional statusnutritional statusManagement of Uncomplicated AscitesMANAGEMENT OF UNCOMPLICATED ASCITES:SODIUM RESTRICTION40Diuretic Diuretic TherapyTherapyDosageDosage Spironolactone 100-400 mg/day Spironolactone 100-400 mg/day Furosemide(40-160 mg/d)for inadequate weight loss or Furosemide(40-160 mg/d)for inadequate weight loss or if hyperkalemia developsif hyperkalemia develops Increase diuretics if weight loss Increase diuretics if weight loss 1 kg in the first week and 1 kg in the first week and 2 kg/week thereafter0.5 kg/day in patients Decrease diuretics if weight loss 0.5 kg/day in patients without edema and 1 kg/day in those with edemawithout edema and 1 kg/day in those with edema Side effectsSide effects Renal dysfunction,hyponatremiahyperkalemia,Renal dysfunction,hyponatremia,hyperkalemia,encephalopathy,gynecomastiaencephalopathy,gynecomastiaManagement of Uncomplicated AscitesMANAGEMENT OF UNCOMPLICATED ASCITES:DIURETIC THERAPYDefinition and Types of Refractory AscitesDefinition and Types of Refractory AscitesOccurs in 10%of cirrhotic patientsOccurs in 10%of cirrhotic patients Diuretic-intractable ascitesDiuretic-intractable ascitesTherapeutic doses of diuretics cannot be achieved Therapeutic doses of diuretics cannot be achieved because of diuretic-induced complicationsbecause of diuretic-induced complications Diuretic-resistant ascitesDiuretic-resistant ascitesNo 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%Arroyo et al.Hepatology 1996;23:164Arroyo et al.Hepatology 1996;23:164DEFINITION AND TYPES OF REFRACTORY ASCITESPeritoneo-Venous Shunt(PVS)is Useful in the Treatment of Refractory AscitesUse of jugular Use of jugular vein will hinder vein will hinder TIPS placement TIPS placement Intraabdominal Intraabdominal adhesions may adhesions may complicate liver complicate liver transplant surgerytransplant surgeryOne-way One-way valvevalvePERITONEO-VENOUS SHUNT(PVS)IS USEFUL IN THE TREATMENT OF REFRACTORY ASCITESTreatment of AscitesTreatment of AscitesHepatorenalHepatorenalSyndromeSyndromeRefractoryRefractoryAscitesAscitesUncomplicatedUncomplicatedAscitesAscitesPortal HypertensionPortal HypertensionNo AscitesNo Ascites1)LVP+albumin1)LVP+albumin2)TIPS2)TIPS3)PVS(in non-TIPS,non-transplant 3)PVS(in non-TIPS,non-transplant candidates)candidates)LVP=large volume paracentesisLVP=large volume paracentesisTIPS=transjugular intrahepatic portosystemic shuntTIPS=transjugular intrahepatic portosystemic shuntTREATMENT OF REFRACTORY ASCITES44Spontaneous Bacterial Peritonitis(SBP)Spontaneous Bacterial Peritonitis(SBP)Complicates Ascites and Can Lead to Renal Complicates Ascites and Can Lead to Renal Dysfunction Dysfunction SBPSBPHVPG 10 mmHgHVPG 10 mmHgExtreme VasodilationExtreme VasodilationHVPG 10 mmHgHVPG 10 mmHgSevere VasodilationSevere VasodilationHVPG 10 mmHgHVPG 10 mmHgModerate VasodilationModerate VasodilationHVPG 10 mmHgHVPG 250/mmPMN count 250/mm33Rimola et al.,J Hepatol 2000;32:142Rimola et al.,J Hepatol 2000;32:142EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS(SBP)EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS(SBP)TREATMENTINDICATEDDiagnosis and Management of Spontaneous Bacterial PeritonitisDiagnostic ParacentesisDiagnostic ParacentesisPMN250?PMN250?Culture Positive?Culture Positive?TREATMENT NOT INDICATEDNORepeat ParacentesisRepeat ParacentesisYESPMN250?PMN250?Culture Positive?Culture Positive?NONOYESYESYESNOMANAGEMENT ALGORITHM IN SPONTANEOUS BACTERIAL PERITONITIS(SBP)Treatment of Treatment of Spontaneous Bacterial Spontaneous Bacterial PeritonitisPeritonitis Recommended antibiotics for initial empiric Recommended antibiotics for initial empiric therapytherapy i.vi.v.cefotaxime,amoxicillin-clavulanic acid.cefotaxime,amoxicillin-clavulanic acid oral nofloxacin(uncomplicated SBP)oral nofloxacin(uncomplicated SBP)avoid aminoglycosidesavoid aminoglycosides Minimum duration:5 daysMinimum duration:5 days Re-evaluation if ascitic fluid PMN count has not Re-evaluation if ascitic fluid PMN count has not decreased by at least 25%after 2 days of decreased by at least 25%after 2 days of treatmenttreatmentRimola et al.,J Hepatol 2000;32:142Rimola et al.,J Hepatol 2000;32:142TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS(SBP)All SBPsAll SBPsSBP caused by gram-SBP caused by gram-negative bacterianegative bacteriaProbability Probability of SBP of SBP recurrencerecurrenceMonthsMonthsp=0.0063p=0.0063PlaceboPlaceboNorfloxacinNorfloxacinPlaceboPlacebop=0.0013p=0.0013NorfloxacinNorfloxacin001.01.0.8.8.4.4.2.2.6.6448812122020001616004488121220201616MonthsMonthsNorfloxacin Reduces Recurrence of Norfloxacin Reduces Recurrence of Spontaneous Bacterial PeritonitisSpontaneous Bacterial PeritonitisGines et al.,Hepatology 1990;12:716Gines et al.,Hepatology 1990;12:716NORFLOXACIN REDUCES RECURRENCE OF SPONTANEOUS BACTERIAL PERITONITIS(SBP)Indications for Prophylactic Antibiotics to Indications for Prophylactic Antibiotics to Prevent Spontaneous Bacterial Peritonitis Prevent Spontaneous Bacterial Peritonitis Cirrhotic patients hospitalized with GI hemorrhage Cirrhotic patients hospitalized with GI hemorrhage(short-term)(short-term)Norfloxacin 400 mg p.o.BID x 7 daysNorfloxacin 400 mg p.o.BID x 7 days Patients who have recovered from SBP(long-term)Patients who have recovered from SBP(long-term)Norfloxacin 400 mg p.o.daily,indefinitelyNorfloxacin 400 mg p.o.daily,indefinitely Weekly quinolones Weekly quinolones notnot recommended(lower efficacy,recommended(lower efficacy,development of quinolone-resistance)development of quinolone-resistance)INDICATIONS FOR PROPHYLACTIC ANTIBIOTICS TO PREVENT SPONTANEOUS BACTERIAL PERITONITIS(SBP)50Characteristics of Hepatorenal SyndromeCharacteristics of Hepatorenal Syndrome Renal failure in patients with cirrhosis,advanced liver Renal failure in patients with cirrhosis,advanced liver failure and severe sinusoidal portal hypertensionfailure and severe sinusoidal portal hypertension Absence of significant histological changes in the Absence of significant histological changes in the kid