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Transcript of LIVER DISEASES
LEARNING OBJECTIVESLiver function testsViral HepatitisAutoimmune hepatitisPrimary Biliary CirrhosisPrimary Sclerosing CholangitisHemochromatosisWilsonsGallstones and cholecystitis
Complications of end stage liver diseaseAscitesSBPHepatorenal SyndromeEncephalopathy
LIVER FUNCTION TESTSALT AST (SGOT)ALKALINE PHOSPHATASEBILIRUBIN
ALT and ASTEnzymes, found in HepatocytesReleased when liver cells damagedALT is specific for liver injuryAST (SGOT) is also found in skeletal and cardiac muscle
Transaminitis: < 5 x normalALT predominantChronic Hep B / CAcute A-E, EBV, CMVSteatosis / SteatohepHemochromatosisMedications / ToxinsAutoimmune HepatitisAlpha-1-antitrypsinWilsons DiseaseCeliac DiseaseAST predominantAlcohol-related liver dzSteatosis/ SteatohepCirrhosis
Non-hepatic sourceHemolysisMyopathyThyroid diseaseStrenuous exercise
Severe AST & ALT Elev: >15xAcute Viral Hepatitisdoes not predict outcomeBili > 20 poor prognosisIschemic HepatitishypotensionsepsishemorrhageMI
Autoimmune HepatitisWilsons DiseaseAcute bile duct obstrHepatic Artery ligationBudd-Chiari SyndromeMedications / ToxinsacetaminophenCCl4
ALKALINE PHOSPHATASEFound in hepatocytes that line the bile canaliculiLevel is raised in Biliary obstruction (causes stretch of the bile canaliculi)BUT also found in BONE and PLACENTAGGT is also found in bile canaliculi and therefore can be used in conjunction with Alk Phos for predicting liver originBUT GGT can be raised by many drugs including Alcohol and therefore non specific
BILIRUBINWater insoluble product of heme metabolismTaken up by liver and conjugated to become water soluble so it can be excreted in bile and into bowel. Patient looks Jaundiced if bilirubin >2.5If patient is vomiting GREEN, then they have bowel obstruction below the level of the Ampulla of Vater.
WHAT IS THE DEAL WITH DIRECT AND INDIRECT BILIRUBIN?Prehepatic disease (eg hemolysis) causes high bilirubin which is non conjugated ie. Indirect fraction higherHepatic disease causes increased conjugated and unconjugated bilirubinPost hepatic disease eg. Gallstones have increased conjugated (direct) bilirubin and lead to dark urine and pale stool.
So these are markers of liver disease but are they tests of liver function?NO!
TESTS OF LIVER FUNCTIONPROTHROMBIN TIME/ INRALBUMIN
PROTHROMBIN TIME/INRMeasure of the Vitamin K dependent clotting factors ie. II, VII, IX and X. The liver is involved in activating Vitamin K. Therefore in liver damage, these clotting factors cannot be produced. Before you believe that prolonged INR is due to liver disease just make sure the patient has adequate Vitamin K by giving 10mg sc. Giving Vitamin K has no effect on INR if patient has impaired synthetic function.
ALBUMINAlbumin has a half life of 21 days, so the drop that occurs with hepatic dysfunction does not occur acutelyThat said, acute illness can cause albumin to drop rapidly a process thought to be due to cytokines increasing the rate of albumin metabolismHOWEVER, dont forget that low albumin also occurs in NEPHROTIC syndrome, so always check the urine for protein.
TYPICAL PATTERNSHEPATOCELLULARIncreased transaminases
Viral HepatitisDrugs/alcoholAutoimmuneNASHHemochromatosisCHOLESTATICIncreased Alk Phos and BilirubinAlso may cause increased transaminases
GallstonesPrimary Biliary CirrhosisSclerosing CholangitisPancreatic C/a
Alcoholic Liver DiseaseAST > ALT2:1 - 3:1 ratioAST < 300Why the discrepancy?ETOH AST synthesisVit B6 def inhibits ALTETOHSteatosis 90- 100%hepatitis 10- 35%cirrhosis 8- 20%GGT
VIRAL HEPATITISAll exam questions rely on you understanding that acute infection has IgM antibodies and chronic has IgG
Viral HepatitisNoneInterferon +InterferonRibavirinIFNLamivudine NONETherapyNONEHBV vaccine NONEImmune globulinRecombinan vaccImmune globulinInactivated vaccProphylaxis+++HCCancer
5 20 %Common
0.1 %Infect 80-90%Hepatitis 70%
0.1 1 %Neonates 90%Adults 1-10%
0.1 %NoneClinical Fulminant Progression to chronicityFecal - oral+++++++++variable+Parenteral +++Perinatal +++Sexual ++Fecal oralTransmissionAcuteAcute / insidiousInsidiousAcute / insidiousAcuteOnset 6 weeks4 12 weeks7 weeks 4 12 weeks 4 weeksIncubationHEVHDVHCVHBVHAV
HEPATITIS ARNA VirusFecal-oralIncubation 15-50 daysAnti -Hepatitis A IgM present during acute illness. TX/Prevention: Vaccine, Immune serum globulin for contactsPx: Good doesnt become chronic rarely fulminant liver failure.
HEPATITIS BDNA VirusConsists of surface and coreCore consists of Core antigen and e-antigenMost infections are subclinical, but can present with arthralgias, glomerulonephritis, urticariaParenteral or sexual transmission.
Hepatitis B continuedHepatocellular necrosis occurs due to the bodys reaction to the virus rather than due to the virus itselfTherefore patients who have a severe illness from hep B are more likely to clear the virus. SEROLOGY: Remember Acute infection has IgM chronic has IgGAnti Core IgM is present during acute phaseAnti Core IgG indicates chronic infection. Patients with Hep B e Ag have continued active replicationImmunized or previously exposed people have Negative HBsAg and HBeAg, they have IgG Anti HB Core, and Positive anti Hep Bs and e.
Hepatitis B Antigen and Serology
Core antigen (HepBcAg) - Nucleocapsid encloses viral DNA - Induces cellular immune response *E antigen (HepB e Ag) - Circulating peptide exported - Marker for active viral replicat / INFECTIVITY - Only persists in persons c/ circul. DNASurface Ag (HepB S Ag) - Protein found on envelope - First evidence of infection (before biochem ) - Signifies INFECTION & implies INFECTIVITY HBV DNA - Best indicator of viral replication - Usually parallels HB e Ag
CoreAntibody (Anti HepBc) - detected in anyone w/ previous exposure - does NOT confer protectivity - IgM - acute infection / lasts 3-6 mos. - IgG - implies chronic hep B - present in window period E Antibody (Anti HepB e ) - indicates antigen is cleared / virus not repli - decrease infectivitySurface Ab (Anti HepB S) - confers PROTECTIVITY - signifies recovery from HBV infection non-infectivity, vaccination
Serological Patterns of Acute & Chronic Hepatitis B
Serologic Patterns of Hep B Inf.
QuestionA 48 yo woman plans to travel to Mexico with her husband and 11 year old child. The family have no known history of liver disease or hepatitis and no members of the family have had immunizations for hepatitis. What immunizations would you recommend: Hepatitis A vaccination for both parents and childHepatitis A Vaccination for parents and child and Hepatitis B vaccination for the childHepatitis A and Hepatitis B vaccination for both parents and the childScreen parents for previous Hep A infection, and recommend Hep A vaccination for the childScreen all members of the family for Hep A and B exposure.
ANSWER BAll children should now get Hep B. vaccination as babies, if they miss this they should have catch up vaccination as 11-12 year oldsPrevious Hep A infection is unlikely in children and adults not in high risk populations therefore it is safe to vaccinate without antibody testing.
QUESTIONA 40 yo married man with two children was recently evaluated for fatigue and elevations of liver function tests and was found to have chronic Hep B. Physical examination reveals a few spider angiomata on his chest and upper extremities. Labs: HBsAgPosHBeAgPosHBV DNA90 (low)ALT156 U/LAlbumin3.8INR1.5A liver biopsy is performed and shows cirrhosis with moderate inflammatory activityThe most appropriate recommendation for this patient is He should receive the Hepatitis A VaccineHis Wife and Childern should receive the Hepatitis B VaccineHe should be treated with Interferon AlphaAll of the above
- ANSWER: DAll patients with Liver disease should have the Hepatitis A vaccine as they have decreased hepatic reserve and the mortality of Hepatitis A in a patient with Hepatitis B is considerably increased Household contacts of patients with Hepatitis B should be vaccinatedPatients with HBeAg are candidates for Interferon therapy, this is most likely to benefit patients with HBV DNA
Hepatitis CRNA virusBlood bourne ie. Transmission from IV drug use and transfusion of blood products prior to 1990. Can also be transmitted by snorting cocaine. Sexual transmission is low.Testing involves Anti HCV Antibody, and then viral load if positive.85% of patients develop chronic infection.
Complications of Hep CCirrhosisHepatocellular carcinomaCryoglobulinaemiaProphyria cutanea tarda
Management of Hep CInterferon alpha with ribavirin for 6 to 12 months clears virus in approx 40% of patients. There is an algorithm which is used to decide who is treated, but basically anyone with Hep C, high ALT and less than 40 yo. If older than 40 should have biopsy first which should at least show periportal inflammation or fibrosis.
Other issues re. Hep COnce pt with Hep C is cirrhotic their risk of developing hepatocellular Ca is 1-4% per yearAlcohol increases risk
Other viral hepatitisHep E: Acute hepatitis just like hep A unless you are PREGNANT in which case can progress to fulminant hepatitisEBV, CMV, Herpes viruses can all cause acute hepatitis especially in immunocompromised.