Chronic Liver Diseases Review - CloudCME
Chronic Liver Diseases ReviewHesham Elgouhari, MD, FACPAssociate Professor of MedicineHepatologist and Medical DirectorAvera Center for Liver Disease
The Skeleton Acute Liver Diseases Chronic Liver diseases Cirrhosis and Portal Hypertension Liver Neoplasms Liver Transplantation
Nomenclature of Liver Disease Acute Liver Diseases: Acute Hepatitis: Hepatitic, Cholestatic, or Mixed Acute Liver Failure:– Jaundice-Encephalopathy-Coagulopathy Chronic Liver Diseases: Chronic inflammation with/without fibrosis Cirrhosis (stage 4 fibrosis) Liver Neoplasms Acute on top of Chronic Liver Diseases
Acute Liver Diseases Acute Hepatitis: New onset rise in LCTswith or without symptoms with no signsof ALF Acute Liver Failure (ALF): Acute Liverinjury with Jaundice, Encephalopathy,and Coagulopathy.
Question A 38 YOF with no known histroy of CLD presentswith progressive fatigue over the last 3 weeks. NoEvidence of AMS. Her LCT revealed ALT of 670,AST 500, AP 175, and TB of 2.4 with direct of 2. INRis normal at 1.0. Old record revealed normal LCT 2months ago. What is the cause of this abnormal LCTs? 1-Hepatocellular inflammatory process 2-Intrahepatic bile duct disease 3-Extrahepatic bile duct obstruction 4-Any of the above
Question A 45 YOF presents with Fever, RUQ pain over thelast 2 days with progressive course. She vomited 3times over the last 12 hours. She is known to haveMetabolic syndrome with DM and obesity. Her LCTshowed ALT of 67, AST 69, AP 430, and TB of 3.1with direct of 2.5. The likely cause of her abnormalLCT is: 1-Acute HBV infection2-AIH flare3-NASH4-Acute cholangitis
Acute Hepatitis Acute rise in transaminases (AST& ALT) and/or AP The clinical course ranges from asymptomatic diseaseto ALF Look at the pattern: Three Patterns for abnormal LCTs Hepatitic: AST and ALT elevation APelevation Cholestatic: AP elevation AST and ALTelevation Infiltrative: Mixed Bilirbubin: Does not help much!
Causes of Acute hepatitic hepatitis Alcoholic hepatitis Acute ischemic hepatitis Viral Hepatitis: Hepatotropic and nonhepatotropic Drug-induced: Acetaminophen, ABx Autoimmune hepatitis flare Wilson disease Others (acute BCS, VOD, HELLP, )
Acute Cholestatic Hepatitis Extrahepatic BD obstruction (U/S is a goodstart) Acute cholangitis/cholecystitis Drug and toxins associated with cholestasis Liver allograft rejection Infectious hepatobiliary diseases seen inpatients with AIDS Note that PBC does not present acutely
Question A 42 YOM with history of IVDU and ETOHdependence presents with Jaundice and abdominaldistension. No AMS. His LCTs showed ALT of 85,AST 305, AP 148 , TB 5.6 and PT of 18 with INR of1.4. His acute hepatitis panel is unremarkable. Thelikely cause of his abnormal LCT is: 1-Acute hepatitis B2-Acute alcoholic hepatitis3-Wilson disease flare4-Tylenol toxicity
Acute Alcoholic Hepatitis Usual symptoms /- AMS Not necessarily still an active drinker! HSM, Spider angiomatosis, Palmer erythema, /Asterixis AST ALT but less than 400 if more thinkof concomitant process as Tylenol, acute viralhepatitis, Rhabdo, or others
Acute Alcoholic Hepatitis MDF 4.6(patient’s PT-control PT) Totalbilirubin If 32 Increased short term mortality with1-month mortality of 30%-50% Steroid if MDF 32 or with AMS if no CIs Rule out infection, GI bleeding, HRS Nutrition (1.2 gm/kg/day protein & 35-40Kcal/Kg/day) Thiamine and Folate
Question A 78 YOM with ischemic cardiomyopathypresents with hypotension and AKI. His LCTrevealed AST 2300, ALT 3200, AP 230, and TBof 0.8. He was put on pressors. Next day hisLCT showed AST 1200, ALT 1500. The likelycause of his abnormal LCT is Tylenol overdose Acute ischemic hepatitis AIH flare Acute cholecystitis
Acute Ischemic Hepatitis Acute rise in AST and ALT followed by rapiddecline with Resuscitation Hemodynamic instability (Shock) Cocaine or Amphetamine Long acting Niacin Always rule out other relevant causes Supportive management
Question A 26 YOM came back from a summer campin Mexico 2 weeks ago. He started havingfatigue and RUQ discomfort over the last fewdays. His urine became dark yellow. OnExam, he has jaundice. No asterixis. Acutehepatitis A is suspected. What test should youorder? HAV-IgG HAV- IgM HAV PCR
Acute Viral Hepatitis (HAV& HEV) Outbreak or a recent travelIP is 2-6 weeks for HAV and 2-9 weeks for HEVFecal-oral routeJaundice, tender hepatomegalyPositive Anti HAV IgM (stays for 3-6 months)Positive Anti HEV IgM (Need to do PCR)Supportive measuresMight lead to ALF ( 1%)Case Fatality of HAV is about 0.3%Case fatality of HEV in pregnant women is 10%-20%Chronic HEV infection leading to cirrhosis couldhappen in immunosuppressed patients
Acute HBV infection DNA virusTransmitted by blood, IVDU, sexual route, and verticalAbout 2 million Americans are infected (Asians)IP is 4-24 weeksNon-specific symptomsArthritis or urticaria in few patientsHBsAg is the landmark except in the window phase withpositive HBc-IgM Supportive therapy except in certain cases (ALF) Chronicity risk is based on route of infection: 5-10% with horizontal route 90% with vertical route
Natural History of HBVInfectionEarlyChildhood 95%ImmuneToleranceAdulthood 5%HBeAgChronicHepatitis BHCCHBeAg ChronicHepatitis BInactiveCarrierCourtesy of W. Ray Kim, MD. Chen DS, et al. J Gastroenterol Hepatol. 1993;8:470-475.Seeff L, et al. N Engl J Med. 1987;316:965-970.
NAInterpretation --- Acute HBV,early phase-- -- Acute HBV,window phase - -- HBeAg chronichepatitis -- - HBeAgChronichepatitis -- - Inactivecarrier state--- -/ -Resolvedhepatitis B
Question A 31 YOM with history of IVDU was referredto you for elevated LCT (ALT 200, AST 159).His HBV markers showed HBsAg , HBc-IgM-, anti-HBc total , HBV DNA 2,000,000 IU/ml.HBe Ag -. His HCV antibody is negative. Thelikely stage of his HBV infection is: 1-Inactive carrier 2-Acute HBV infection 3-Chronic Hepatitis B 4-Resolved HBV infection
Herpes viruses EBV: 80-90% of cases of IM have mildly elevated liver enzymes Frank Jaundice in 5% IgM VCA CMV: Usually in Immunocompromized patients Scattered microscopic granulomas HSV: Immunocompromized patients Very ill with fever and markedly elevated transaminases Mortality is high VZV: Lymhoproliferative disorders Disseminated disease Rarely fatal
Drug induced liver injury (DILI) The most common mechanism is idiosyncratic reaction That reaction usually occurs during the first 6 months ofintake and very unlikely to occur after one year ofintake but it does occur (as with Nevarapine) ABx, NSAIDs, Anti-convulsants, and herbal meds If you suspect DILI, D/C all meds except the essentialones that have no alternatives. Use steroid with hypersensitivity reaction (Associatedrash, Eosinophils in the blood with or without increasedAEC, or with Eosinophils in the liver biopsy) Urso is sometimes used with cholestatic hepatitis May lead to ALF
Acetaminophen induced Hepatitis Dose dependant injury The most common form is acute injury 2/2mega dose ( 10 gram/day) but smaller dosescould do it especially in ETOH and patientswith CLD. The time of ingestion is important for thenomogram, but it is often unknown exactly. If the time is well known: give Charcol ifwithin 4 hours of it and give NAC even if theingestion was 2-3 days ago!!
NAC Indication In acute toxicity: In approved, suspected oreven unknown cases Negative or low blood level incases of unclear time frame does not rule out Tylenoloverdose and NAC is needed; so think thrice beforesaying “NAC is not needed”!! 2-Indication in chronic use: Having hepatitis picture as with RUQ tenderness and/or ALT regardless the level Level 20 mcg/mL Level 10 mcg/mL in susceptible patients as above How to give it: IV is recommended in a lot of situationsnot just AMS with no NGT, these situations include alsoileus, persistent hypotension, persistent N/V, and GIbleeding.
Question A 56 YOF presents with progressive fatigue andjaundice. LCT showed AST of 700, ALT 850,TB of 6 and INR of 1.4. ANA and SMA werehighly positive. Which one of the following isincorrect? IgG is usually high The typical liver biopsy finding is lymphoidaggregates Prednisone is the first line of therapy Prognosis of this patient is poor withouttherapy
AIH Relatively common Treatable, otherwise dangerous (40% mortalitywithin 6 months if severe) Types:AgeAIH-IBimodal:16-30& 50AIH-II2-14AIH-III20-40AbsANA, ASMALKM-1SLA/LPPrevalence in USA 80%4% 20%Extrahepatic dzProgression tocirrhosis35%82%58%75%40%45%
AIH, Auto-Antibodies Elevated IgG ANA: non-specific and of no specific pattern forAIH ASM: more sensitive and specific Anti-actin Ab: A subtype of ASM Highly specific to AIH Liver Biopsy: Lymphoplasmacytic infiltrate,Eosinophils, Interface hepatitis, necrosis Treat with Prednisone /- AZA
Acute Wilsonian Hepatitis Rare (1:30,000)Young patient with non-specific symptomsElevated AST and ALTIf AP (IU/L):T. Bili (mg/dL) is 2 Highly suspect itCoombs-negative hemolysisLow or low normal CeruloplasminKFR in 50% of patients but in 95% of those withNeuro manifestations lunulae ceruleae: Bluish discoloration at the base offingernails Liver Transplantation
Acute Liver Failure (ALF) Rapid onset of encephalopathy (HE) alongwith a marked decline in hepatic syntheticfunction within 28 days. Hepatic function measured by INR,bilirubin, Factor V levels Clinical triad:CoagulopathyJaundiceHE
Lines of Management of ALF Look for the cause and treat as feasible Assess the need& candidacy for OLT at LTCenter General therapeutic measures ICULook for, prevent, and treat infection aggressivelyMonitor blood glucose closelyGI prophylaxis, Avoid increasing ICP, Nutrition . Specific therapeutic Measures: Management of Coagulopathy Management of Brain edema
Chronic Liver Diseases
Natural history of chronic liver diseaseIncreasingliver fibrosis Jaundice Encephalopathy Variceal bleeding Ascites5%-7%/YChronicLiver eath2%- 7%/Y-Steatohepatitis-HBV& HCV Hepatitis-Autoimmune Hepatitis-Biliary liver disease-Metabolic/HereditaryLiver Disease-OthersHCCDeathLiverTransplantation
HCV RNA virus About 4 million Americans are infected The Natural History:
Question A 27 YOM who actively uses IV heroin. Hepresents with fatigue and abnormal LCTs.What is the best test to rule out HCV infectionin this person? 1-HCV RIBA2-HCV Antibody3-HCV PCR4-HCV Genotype
Whom should you screen, regardless LCT IVDU: In the recent or remote past even once Hemophiliacs who received clotting factor concentratesbefore 1987 Blood transfusion/ organ transplant before July 1992 Patients on HD HIV patients Children born to HCV-infected mothers Sexual partners of HCV-infected patients Elevated liver enzymes Others: Occupational exposure, ?Tattoo, Snortingcocaine Persons born in 1945-1965
HCV serology Not for acute HCV infection May give false negative results in patients withAIDS or in hemodialysis False positive results in those with AIH Always confirm positive ones with qualitativePCR testing
Recombinant Immunoblot Assay(RIBA) RIBA-2 has the same antigens as EIA-2 notmore sensitive 2/3 or 3/3 positive test RIBA is more technically demanding than EIA
HCV RNA by PCR Two weeks after infection The lower limit for Qualitative one is 50 IU/mL For Quantitative one: 10-43 IU/mL detected but below the limit ofQuantitation 43 IU/mL Will give the number
HCV Genotypes Genotype 1: The most common in the US (75%) Was the least responsive to therapy ( 48weeks) (about 45-50%) Now it is better with Direct Antiviral Agents Genotype 2& 3: About 20% More responsive to therapy (12-24 weeks) Genotype 4: Genotype 5: Genotype 6:
Interpretation of HCV Laboratory Tests If anti-HCV positive and HCV RNA positive– Acute or chronic HCV infection depending on clinicalcontext If anti-HCV positive and HCV RNA negative– Resolution of HCV; acute HCV infection during periodof low-level viremia; False positive anti-HCV If anti-HCV negative and HCV RNA positive– Early acute HCV infection; chronic HCV infection insetting of immunosuppression; false-positive HCVRNA test If anti-HCV negative and HCV RNA negative– Absence of HCV infection
Oral regimens for GT1aRegimenDurationCaveatsVelpatasvir/Sofosbuvir12 weeksTreatment-naïve or treatment-exp with/ withoutcompensated cirrhosisLedipasvir/Sofosbuvir12 weeksTreatment naïve with or without comp cirrhosis,treatment exp (PEG/RBV /- PI) without comp cirrhosisLedipasvir/Sofosbuvir24 weeksTreatment exp (PEG/RBV /- PI) without comp cirrhosisElbasvir/Grozoprevir12 weeksTreatment naïve or PEG/RBV-exp without baseline NS5Apolymorphisms; with/without comp cirrhosisElbasvir/Grazoprevir RBV16 weeksTreatment naïve or PEG/RBV-exp with baseline NS5ApolymorphismsOmbitasvir/Paritaprevir/Ritonavir Dasabuvir RBV12 weeksWithout comp cirrhosisOmbitasvir/Paritaprevir/Ritonavir Dasabuvir RBV24 weeksWith comp cirrhosisDaclatasvir SofosbuvirDaclatasvir Sofosbuvir RBV12 weeks12 weeksNo comp cirrhosisComp cirrhosisSimeprevir SofosbuvirSimeprevir Sofosbuvir1224 weeksweeksNo comp cirrhosisComp cirrhosis
Oral Regimens for GT1bRegimenDuratio CaveatsnVelpatasvir/ Sofosbuvir12 weeksTreatment naïve or treatment experienced with/without comp cirrhosisLedipasvir/ Sofosbuvir12 weeksTreatment naïve with or without comp cirrhosis;treatment exp (PEG/RBV /-) without compcirrhosisLedipasvir/ Sofosbuvir24 weeksTreatment- exp (PEG/RBV /- PI) withoutcomp cirrhosisElbasvir/ Grazoprevir12 weeksTreatment naïve or PEG/RBV; with/withoutcomp cirrhosisElbasvir/ Grazoprevir RBV12 weeksPEG/RBV/PI experienced; with or withoutcomp cirrhosisOmbitasvir/ Pariteprevir/Ritonavir Dasabuvir12 weeksWith or without comp cirrhosisDaclatasvir SofosbuvirDaclatasvir Sofosbuvir RBV12 weeks12 weeksNo cirrhosisComp cirrhosisSimeprevir SofosbuvirSimeprevir Sofosbuvir12 weeks24 weeksNo cirrhosisComp cirrhosis
Oral Regimens for Non- GT1 patientsGTRegimenDurationPopulationGT2Velpatasvir/ SofosbuvirSofosbuvir RBV12 weeksNo cirrhosis or compcirrhosisGT3Velpatasvir/ Sofosbuvir12 weeksNo cirrhosis or compcirrhosisGT3Daclatasvir SofosbuvirDaclatasvir Sofosbuvir RBV12 weeks12 weeksNo cirrhosis or compcirrhosisGT4Ledipasvir/ SofobuvirVelpatasvir/ Sofosbuvir24 weeksNo cirrhosis or compcirrhosisGT4Ombitasvir/ Paritaprevir/ Ritonavir RBV12 weeksNo cirrhosisGT4Elbasvir/ GrazoprevirElbasvir/ Grazoprevir RBV12 weeksTreatment naïve with/withoutcirrhosisTreatment exp with/ withoutcirrhosisGT5Ledipasvir/ SofobuvirVelpatasvir/ Sofosbuvir12 weeks16 weeksNo cirrhosis or compcirrhosisGT6Ledipasvir/ SofobuvirVelpatasvir/ Sofosbuvir12 weeksNo cirrhosis or compcirrhosis
Oral Regimens forDecompensated CirrhoticGTGT 1-6GT 1 or 3GT 1RegimenVelpatasvir/Sofosbuvir RBVDaclatasvir Sofosbuvir RBVLedipasvir/Sofosbuvir RBVDuration12 weeks12 weeks12 weeks
Chronic HCV therapy Genotype 1 and 4: Sofosbuvir /Ledipasvir for 12 weeks or Three DAA(ombitasvir, paritaprevir/ritonavir withdasabuvir) No more Telaprevir or Boceprevir Genotype 2:Ribavirin Sofosbuvir for 12 weeks Genotype 3: Ribavirin Sofosbuvir for 24 weeks
HBV, Whom should you screen Immigrants and adopted childrenHouseholds of HBs Ag positive patientsSexual contacts of HBs Ag positive patientsPersons who have ever injected drugPersons with multiple sexual partners or Hx of STDMen who have sex with menInmates of correctional facilitiesIndividuals with chronically elevated ALT or ASTIndividuals infected with HCV or HIVPatients undergoing renal dialysisAll pregnant women
What should we order with positiverisk factor screening of HBV infection Hepatitis B surface antigen: The cardinal sign of current HBV infection False negative is very rare Hepatitis B surface antibody: Positive in remote infection or with immunization Hepatitis B core Antibody (IgM) Positive in acute infection Hepatitis B core Antibody (Total) Positive in current or remote infection but NOT withimmunization Hepatitis B DNA Hepatitis B e antigen and antibody
Chronic HBV r biopsyfindingsImmuneTolerancePositiveNegative NormalNormal ornonspecificImmuneClearancePositiveNegative InactiveCarrierNegativePositive-/ Reactivation Negative Positive orPositiveorNegativeElevated Chronic hepatitis( )NormalNon-significanthepatitis(usually)Elevated Chronic hepatitis( )
The Natural History of CHBAcute HBV infectionPerinatal( 10%)Early Childhood( 90%)Resolved infection(50-80%)Chronic infectionReactivation phase(HBeAg- chronic hepatitis)(8-9( 95%)Resolved infectionImmune tolerance phasePrmu e-cotat re/ion coreDecompensation(20-50%)Adult( 15%)(( 85%)/20%01Inactive carrier phasear)5%/yearSpontaneous HBsAg lossCirrhosisChronic infectionImmune Clearance phase(HBeAg chronic Hepatitis)r)yea 1it h o nwi20% ers(4- o-revser0.5-2%/year%/ye( 5%)-6(22.5-3%/year%ea/yr)HCCElgouhari et al. Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis.Cleve Clin J Med. 2008 Dec;75(12):881-9
HBV TherapyElgouhari et al. Hepatitis B: A strategy for evaluation and management. Cleve Clin J Med. 2009Jan;76(1):19-35
Chronic HBV therapy
Question A 57 YOF with DM, HPL, and hypothyrodismpresents for chronically abnormal LCT with ALT 24 times ULN, AST of 2-3 times ULN, and normal AP.Her Abdominal U/S showed increased echogenicityof the liver. W/U for viral and autoimmune CLD wasnegative. Liver biopsy revealed Steatosis along withballooning degeneration, and moderate fibrosis.What is the likely diagnosis? AIH NASH Simple steatosis PBC
NAFLD Very common (About 23%)No alcoholMetabolic SyndromeClusters (Low thyroid/Low Pituitary/OSA/PCO)AST:ALT ratio not very helpfulU/S: Good to do, but not very sensitiveRule out concomitant diseaseLiver biopsy: Steatosis versus NASH (steatosis significant inflammation hepatocytes Ballooning /- fibrosis) Counsel your patient and treat MS aggressively
The Suggested Natural History ofNAFLDMajoritySimple SteatosisStableLiver cancer?NASH10%/7 yrs25% -35%65% -75%Stable or withRegressionFibrosis 9% -20%CirrhosisProgression50%/7 yrsLiver failure22% -33%Death or OLT
Hereditary Hemochromatosis (HH) In white people with Nordic or Celtic ancestry, theprevalence of HFE-related HH is 0.5%. But over all in whites, it is 1:300 HH is classified broadly into 2 groups: 1-HFE-related HH (about 90%):-C282Y/C282Y 85-90 %-C282Y/H63D (compound heterozygote) 5 %-Others including mis-sense mutations as S65C 2-Non -HFE-related HH (about 10%):-Hemojuvelin mutations (AR)-Hepcidin mutations (AR)-Ferroportin mutations (AD)-Others
Stages of HHNameAgeParenchymalironOrgandamageInsignificant ironaccumulation0-200-5 gramNoIron overload withno organ damage20-4010-20NoIron overload withorgan damage 40 20Yes
Diagnosis of HH//1-Iron studies Get the three; iron, TIBC, and ferritin (Not necessarilyfasting)TS %50% for Female60 % for Male45%Sensitivityfor HH92%Specificity for HH99%44%, the other 56%are with NASH,ETOH, CHC, orC282Y/normal93%
Diagnosis of HH//2-HFE genetesting All patients with abnormal iron studies (TS 45%) First degree relatives (at age of 20 years or more)of patients with C282Y/H63D mutations The result could be:1-wt/wt 6-C282Y/C282Y
Question A 48 YOF presents with fatigue and pruritusover the last 8 months. Her LCT revealedAST of 56, ALT 66, AP 480, and TB of 0.8.Which of the following will confirm thediagnosis of this patient disease.? ANASMAAMAIron studies
Primary Biliary Cholangitis (PBC) Autoimmune disease affecting the small IHBD Usually female Genetic predisposition and environmentaltriggers A progressive disease of variable rate Fatigue, pruritus, Sicca syndrome Diagnosis: At least two of the followings: Biochemical evidence of cholestasis Positive AMA (90%-95%) In negative cases Positive ANA/ASMA Biopsy showing Interlobular duct injury
Primary Biliary Cholangitis (PBC) Portal HTN even in pre-cirrhotic phaseOsteoporosis with RR of 4.4Elevated cholesterol with HDL elevationFat-soluble vitamin deficiency (ADEK)UrsoLiver Transplantation in advanced stage
Question A 48 YOM with PMH of UC presents withfatigue and pruritus over the last 8 months.His LCT revealed AST of 56, ALT 66, AP 480,and TB of 0.8. AMA is negative. Which of thefollowing will confirm the diagnosis of thispatient disease.? ANASMAIron studiesERCP
Primary Sclerosing Cholangitis (PSC) A male diseaseAbout 65% of patients with PSC have IBD4% of patients with IBD (UC CD) have PSCThe mean time of diagnosis to death or LT is 1012 years Cholangiocarcinoma (CC) occurs in about 10%with annual incidence of 1%-1.5% Accuracy of ERCP is 91% Vs 88% for MRCP
Cirrhosis and Portal hypertension
Natural history of chronic liver diseaseIncreasingliver fibrosis Jaundice Encephalopathy Variceal bleeding Ascites5%-7%/YChronicLiver eath2%- 7%/Y-Steatohepatitis-HBV& HCV Hepatitis-Autoimmune Hepatitis-Biliary liver disease-Metabolic/HereditaryLiver Disease-OthersHCCDeathLiverTransplantation
Liver Cirrhosis Stage 4 fibrosis (bridging fibrosis andregeneration nodules) Liver Biopsy is Not always needed
Skin signs of Chronic Liver Disease
Grading of Cirrhosis Child-Pugh score Cirrhosis Stages MELD score
Child-Pugh ScorePoints123EncephalopathyNoneGrade 1-2Grade 3-4AscitesAbsentSlightModerateBilirubin (mg/dL):In all except PBCIn PBC 21-42-34-10 3 10Albumin (g/dL) 3.52.8-3.5 2.8PT/INR:Seconds over controlINR 4 1.74-61.7-2.3 6 2.3
Child-Pugh Score Child A: 5-6 with 90% survival at 5 year Child B: 7-9 with 80% survival at 5 year Child C: 10-15 with 60% survival at 1year
Cirrhosis StagesCharactersStage IStage IINo varices ge IIIAscites20%Stage IVVaricealbleeding /Ascites57%
MELD (Model for End StageLiver Disease) Approved for organ allocation in February2002 Was initially studied to predict mortality afterTIPS MELD 3.8[Ln serum bilirubin (mg/dL)] 11.2[Ln INR] 9.6[Ln serum creatinine(mg/dL)] 6.4 The lowest is 6 and the highest is 40 It predicts the 3 month mortality
Complications of Cirrhosis Portal Hypertension AscitesEsophageal and Gastric VaricesHepatorenal SyndromePulmonary Complications (HH, HPS, PPHTN)HypersplenismCoagulopathyEncephalopathy? CardiomyopathyHepatocellular CarcinomaMalnutrition
Question A 58 YOM with HCV cirrhosis presents withprogressive abdominal distension. U/S revealsascites. The key underlying pathophysiologicalprocess(es) of ascites is/are: 1-Splanchnic vasodilation2-Splanchnic vasoconstriction3-Renal vasodilation4-Renal vasoconstriction1 and 42 and 3
Approach to Ascites.Easy! Do ParacentesisGet Cell count with diff always to rule out SBPGet ascitic albumin and proteinGet Serum Ascitic Albumin Gradient (SAAG)If 1.1 Portal Hypertension: If Protein 2.5 Think more of cardiac ascites If protein 2.5gm/dl Think more of cirrhotic ascites If 1.1 Others (Cancer, TB, Renal, Thyroid )
Ascites Management Salt not fluid restriction NO NSAIDs Diuretics especially Spironolactone andmaximize with monitoring Paracentesis: Always for any inpatient if feasible Get Cell count in a purple-top tube No limit but give Albumin if 5 Liters or even lesswith renal insufficiency Transjugular Intrahepatic PortosystemicShunt (TIPS)
Spontaneous Bacterial Peritonitis No specific or sensitive symptom or signAscitic fluid analysis is the only wayPMNLs 250 cells/cc and/or Positive CultureAscitic fluid culture in BC tubes (80% Vs 50%)The usual MOs are E. coli (43%), Klebsiella(11%), Pneumococci (9%), and others Treat with 3rd GCS and add Albumin if TB 4,Creatinine 1, or BUN 30 HRS & shortterm Mortality Indefinite secondary prophylaxis if ascites exists
Variceal Bleeding Despite every thing we have, the current mortality of EVbleeding is at least 20% at 6 weeks and the immediatemortality from uncontrolled bleeding is 50% Variceal bleeding ceases spontaneously in 40-50% ofcases& in 80% by active therapy if done in the 1st 24h With acute variceal bleeding: ICU Air way protection good IV lineSSS with IVF Octreotide IV (50 ug loading dose then 50 ug/hour for 3-5 d) Keep Hb around 8 gm/dL and do not replace all lost blood(increase rebleeding risk and the mortality if you give more) Ceftriaxone 1 gm IV daily for 7 days EGD within 12 hours Platelet and/or FFP transfusion if needed Alert IR for possible TIPS
Hepatic Encephalopathy (HE) HE-A for ALF-related; B for Bypass (shunt)without intrinsic liver disease; and C forcirrhosis-related HE Regarding B and C: Minimal HE: with 2 or more abnormalpsychomotor tests (Digit symbol test, Block designtest, Number connection test A and B) Episodic HE: Spontaneous, precipitated, orrecurrent (2 or more within 1 year) Persistent HE ( 28 days): Mild (grade I and II),Severe (grade III and IV), and treatment-dependent
HE, Lines of Management Make sure of Diagnosis (No alternatives orConcomitant problems) Look for and treat the Predisposing Factors Specific Therapy
Make sure of Diagnosis Cirrhotic patients are not immune to other causes ofAMS Gradual Onset Presence of precipitating factors Asterixis Non focal Neuro exam Ammonia level is not helpful Get CT head in the following scenarios: Severe HE (grade III or IV)Focal Neurological examinationHead trauma is suspected or confirmedAbsence of recovery/improvement with standard treatment
Specific Therapy Lactulose//Krystalose: Still first line and cheap Has side effects as Diarrhea that may Serum Na and Ileus Get 3-4 semisolid BM daily Rifaximin: Good Medicine with less side effects Expensive but may be cost-effective Neomycin: Rarely used now 4% get absorbed may lead to renal or Oto toxicity Flagyl: Do not give it for long dutration as it may lead to neuropathy Others: Do not restrict protein intake completely Compliance
Management of HRS Avoid Nephrotoxic drugs and diuretics Liver Transplantation Evaluation HRS-I: AlbuminVasoconstrictors (Octreotide& Midodrine)Terlipressin/NoradrenalineRRT if OLT candidate HRS-II LVP with Albumin ? TIPS ? Vasoconstrictors (Octreotide& Midodrine)
Liver Neoplasms
Question A 29 YOF presents with RUQ discomfort. HerU/S revealed a liver lesion of 6 cm. She hasbeen taking OCP over the last 5 years.Triphasic CT showed heterogenosenhancement with no central scarring orvenous washout. AFP is normal. The likely diagnosis in this patient is: 1-HCC 2-Adenoma 3-FNH 4-Hemangioma
Adenoma& Focal nodular hyperplasia (FNH)FNHAdenomaSexUsually femaleThe sameMultiple lesionsAbout 30%Relation to OCP/PregnancyNot clearVery clear except with liveradenomatosis which hasless strong formation/BleedingFindings on 3 phases CT/MRI:-Arterial enhancement-Central arterial scarResectionAbout 20%, called liveradenomatosis if 4 lesionsHomogenousHeterogeneousPresent (not always) AbsentIf symptomatic or ofuncertaindiagnosisLarge ( 4.5cm),Symptomatic, ORWith complications
Question A 58 YOM with HCV/ETOH cirrhosispresents with new onset ascites. AbdominalU/S showed a 4.5 cm mass in the liver.Triphasic CT showed the lesion with arterialenhancement and venous washout. AFP isnormal. The most likely diagnosis is: 1-Regeneration nodule2-Adenoma3-HCC4-Hemangioma
Hepatocellular Carcinoma (HCC) Increasing incidence and mortality The 3rd most lethal cancer in the world Usually on top of cirrhotic liver from any causewith an annual incidence of 2-8% Chronic hepatitis B is an important exception Do U/S and AFP every 6 months to screen AFP sensitivity is 60% at a level of 20 ng/mL If the screening is positive Triphasic CT/MRI Liver mass biopsy is RARELY needed
Hepatocellular Carcinoma (HCC) Liver Resection: Small focal mass with nometastasis or portal HTN Liver Transplantation: Milan Criteria: One lesion 5 cm OR 2-3 Lesions 3 cm No metastasis or Portal vein thrombosis 5-year survival is 70% Percutaneous ablation (RFA, PEI) Trans Arterial Chemoembolization (TACE) Sorafenib in advanced stage
A Question A 45 YOF presents with RUQ discomfort. HerU/S revealed a liver lesion of 6 cm. No OCP. U/Srevealed a well-demarcated homogeneoushyperechoic mass. MRI then showed Enhancedlesion more prominent in the delayed phase withcentripetal pattern. The likely diagnosis in this patient is: 1-HCC 2-Adenoma 3-FNH 4-Hemangioma
Question A 57 YOM with Hx of UC presented withhjaundice, weight loss for the last 6 weeks. Hisbilirubin was 6.2 with direct of 5. Triphasic CTshowed Perihilar liver mass and IHBD dilatationwith beaded appearance. His CA19-9 is 490U/mL. The most likely diagnosis is: PSC complicated with cholangiocarcinomaPSCPSC complicated with cholangitisCholangiocarcinoma
Orthotopic Liver Transplantation The same anatomic place The 1-year survival is now about 90% from 30% Forty years ago Refer patients with Child score B7, MELD 10, or with significant complication of Cirrhosis Extensive evaluation MELD score is used for allocation Demand is the available livers Livingdonor Liver Transplantation
Questions?
A 58 y.o. man with cirrhosis presents for ongoing management.Clinical exam reveals a soft protuberant abdomen with flankdullness. His laboratory tests are as follows: Na : 134 mmol/L,K : 3.8 mmol/L, Cl- 98
Nomenclature of Liver Disease Acute Liver Diseases: Acute Hepatitis: Hepatitic, Cholestatic, or Mixed Acute Liver Failure: - Jaundice -Encephalopathy - Coagulopathy Chronic Liver Diseases: Chronic inflammation with/without fibrosis Cirrhosis (stage 4 fibrosis) Liver Neoplasms Acute on top of Chronic Liver Diseases
Epidemiology of chronic liver disease/cirrhosis 95% of deaths from liver disease are due to chronic hep B and hep C, non-alcoholic fatty liver disease, liver cancer and alcoholic liver . Oxazepam - No change in Child A/B but caution in severe liver failure . END! References 1. Statistics Canada .
Chronic liver disease is a relevant cause of morbidity and mortality worldwide. Every year, more than one mil-lion patients die worldwide as a result of liver cirrhosis [1]. In particular the acute-on-chronic liver failure is as-sociated with a bad outcome. Due to the high short-term mortality, acute-on-chronic liver failure is not only
Diagnosis of Cirrhosis and Chronic Liver Failure History: Patient presents with signs and symptoms of chronic liver disease or has risk factors for chronic liver disease (e.g., alcohol abuse, risk of viral hepatitis, obesity). Physical examination: Patient has hallmark findings consistent with chronic liver disease (see Table 2).
Liver failure, or end-stage liver disease, occurs if the liver is losing or has lost all function. The first symptoms of liver failure are usually: Nausea Loss of appetite Fatigue Diarrhea As liver failure progresses, symptoms may include: Confusion Extreme tiredness Coma Kidney failure Chronic liver failure indicates the liver has been
Chronic Hep C can cause liver inflammation and scarring that can lead to moderate liver damage (fibrosis) and severe liver damage (cirrhosis). People with cirrhosis are at high risk for liver failure, liver cancer and even death. Liver damage often happens slowly, over 20 to 30 years. Hep C and Liver Health Tests
In recent years, a new clinical form of liver failure has been recognised. Traditionally there were two types of liver failure: Acute liver failure (ALF), a rapid deterioration of the liver function in the absence of pre-existing liver disease, in the setting of an acute hepatic insult and chronic liver failure (CLF), a progressive
The burden of liver disease and cirrhosis is increasing world-wide. Progression of liver disease andfibrosis fromfibrosis to cirrhosis and decompensation and critical illness is a major cause of mortality in this population. In patients with chronic liver disease, acute-on-chronic liver failure (ACLF), a relatively
there will be several sections to the written test in addition to reading comprehension; thus, it is to your benefit to carefully read the job bulletin to determine the knowledge, skill, and ability areas the written test will cover. In addition, it is important that you read the entire written test notice for the location and time of the written test as well as for parking instructions and .
