Languages
Pages
Legal
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
1 2%None
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
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.
QuestionA 38 yo woman was found to be Hep C positive 6 months ago after evaluation for raised AST. The infection was attributed to blood transfusions received during a car accident 15 years ago. She was pleased to learn last month that she is pregnant with her first child. The physical examination is within normal limitsShe would like further information concerning her prognosis and the risk of transmission of HCV to her husband and her child.All of the following statements about HCV infection are true except:The chance of transmission of HCV to the newborn is low in the 5% range.Barrier precautions including safe sex are recommended for all couples in a monogamous relationship because of high risk of transmission to the partnerLow level transmission of Hep C is recognized within households (5-10%), and the risk for such transmission should be minimized by practices that avoid blood-blood exposure such as sharing dental implements and razorsIn patients with Hep C the chance of developing cirrhosis over several decades is 20-35%
Answer BMaternal-fetal HCV transmission is approx 5%, however if mother is co-infected with HIV then risk increases to 30%Risk of sexual transmission between monogamous spouses is also low approx 5%Transmission can occur between non-sexual household contacts therefore should be told to avoid sharing razors etc. 20-35% of patients with Hep C develop cirrhosis
Three autoimmune liver diseasesThey are easily confused:Autoimmune hepatitisPrimary Biliary CirrhosisPrimary Sclerosing Cholangitis
AUTOIMMUNE HEPATITISANA positiveAnti smooth muscle positiveHigh bilirubin and ALT but normal Alk Phos (cf. Primary biliary cirrhosis)Presentation: tiredness, anorexia, RUQ pain, cushingoid facies despite no exogenous steroids. Stigmata of liver disease Pathology: Piecemeal necrosis with lymphocyte infiltrationTx: immunosupression, liver transplantComplications: All the complications of chronic liver disease
Primary Biliary CirrhosisIncreased Alk phos and Antimitochondrial positiveDamage to intralobular bile ducts by chronic granulomatous inflammationAssociated with other autoimmune diseases (Thyroid, RA, Sjogrens, Systemic Sclerosis)NB. See granulomas on Bx not piecemeal necrosisUnable to excrete bile, therefore present with malabsorption of fat soluble vitamins. And with evidence of portal hypertension.Present with lethargy, itching and increased Alk Phos in a middleaged woman.May have hyperlipidaemiaConsider in any patient with autoimmune disease presenting with liver disease.
Primary Sclerosing CholangitisSeen in patients with UC and HIVInflammation, fibrosis and strictures of biliary tree causing Beaded biliary tree on ERCPChronic biliary obstruction leads to cirrhosisPresentation: Asymptomatic high Alk Phos, Jaundice, pruritis abdo pain and fatigueDx: High bilirubin and Alk phos but NEGATIVE antimitochondrial Ab (Cf. primary biliary cirrhosis)Mgt: Steroids, Cholestyramine or ursodeoxycholic acid to treat the pruritis and cholestasis but does not affect disease processLiver transplant for endstage disease but 20% recur. NB. PSC is independent of activity of UC.
What does this ERCP show?
NASHNon-Alcoholic SteatohepatitisCommon cause of elevated liver function testsOften patients have metabolic syndrome with obesity, hyperlipidemia and diabetes20-30% progress to cirrhosisWeight loss, control of lipids and diabetes should reduce progression.
Genetic Liver diseaseWilsonsHemochromatosisAlpha-1-Antitrypsin deficiency
HemochromatosisAutosomal recessiveGene on Chromosome 6Increased Fe absorption from gut, depositied in tissues causing fibrosis and functional failure.Presentation: BRONZE DIABETES, but also arthralgias, Hepatosplenomegally and stigmata of liver disease, testicular atrophy, CCF due to restrictive cardiomyopathyDx: High Fe and Ferritin, low TIBC, Low testosterone, Diabetic. Joint XRays show chondrocalcinosisDual energy CT scan shows iron overloadLiver Bx shows Fe stainingNB. Hemochromatosis can be secondary to B Thalassemia and repeated blood transfusions.
Skin color of Hemochromatosis
QUESTIONDuring evaluation of an elevated ALT a 45 year old alcoholic man is found to have a serum iron concentration of 245mg/dL, a total iron binding capacity of 290 mg/dL 84% transferrin saturation and a serum ferritin of 2120ng/mL. The physical examination shows no evidence of chronic liver or cardiac diseaseWhich one of the following is the most appropriate course of management for this patient?Biopsy to make a definitive diagnosisMRI evaluation for iron overloadWeekly phlebotomyHLA typing
Answer ADefinitive diagnosis of Hemochromatosis requires liver biopsy to determine hepatic iron index. If positive the patients siblings should be screened
What is this sign called and what is it associated with ?
Wilsons DiseaseAutosomal RecessiveDeletion on Chromosome 13Defective intrahepatic formation of caeruloplasmin therefore failure of biliary excretion and high total body and tissue levels of copper. Dx High serum caeruloplasmin, increased urinary copper.PRESENTATION: Cirrhosis, Kaiser-Fleischer rings, hypoparathyroidism, arthropathy, Fanconi syndrome (renal tubular acidosis) CNS: Psychosis, extrapyramidal syndrome, mental retardation and seizures. Think of this in a young patient with strange neurology and liver diseaseTx: Copper chelation with penicillamine, can cure with liver transplant BUT the CNS sequalae will not resolve.
-1 Antitrypsin DeficiencyTHE AUTOSOMAL DOMINANT ONE!Severity of disease is dependent on which alleles are affected (ie which phenotype)Gene on Chromosome 14Intrahepatic accumulation of -1 Antitrypsin causes liver disease and can lead to cirrhosisMay have Lung disease (emphysema)
Budd Chiari SyndromeJust know that it is thrombosis of hepatic veinsMay be acute or chronicMay be associated with hypercoagulable state therefore must do thrombophilia screen. Also look for underlying maliganacyCan occur with hydatid cystsPresentation: Nausea, Vomiting, Abdo pain, Tender hepatomegally and loss of hepatojugular reflexTx: call a hepatologist: may need TIPPS or may need portocaval or splenorenal anastomosis. May be thrombolysable. Always call for help.
Hepatocellular CarcinomaRisk factors: Hep B and C, Cirrhosis of any cause, Exposure to Aspergillus Flavus toxinScreening Alphafetoprotein should be checked annually in patients with cirrhosis. Need USS if highLess than 15% are resectable at diagnosis.
To understand gallstonesYou first need to know the anatomy of the biliary tree
Complications of gallstones
In the gall bladder:biliary colicAcute and chronic cholecystitisEmpyema, mucoceleCarcinomaIn the bile ductsObstructive JaundicePancreatitisCholangitisIn the GutGallstone ileus
Acute CholecystitisStone impacting in neck of gallbladderContinuous RUQ pain, vomiting, fever, MURPHYS SIGN PositiveUSS: Thickened gall bladder wallHIDA scan: Blocked cystic ductTx NPO, IV Abx, analgesiaNeeds cholecystectomy either within 48 hours or wait 3 months
Chronic CholecystitisVague abdominal pain, flatulence, fat intoleranceFair fat fertile females of fortyUSS and ERCP reveal stones. May need sphincterotomy
Biliary colicRUQ pain radiating to backTx analgesia and cholecystectomy
CholangitisRUQ pain, rigors and Jaundice.Needs IV Abx
Gallstone ileusSo rare there is hardly any point mentioning itStone perforates Gallbladder into duodenum passes through bowel and obstructs terminal ileum. Abdo XR diagnositic: Air in CBD with small bowel obstruction
ERCPIndicationsJaundice with dilated ducts on USSRecurrent pancreatitisPost cholecystectomy pain (check for retained stone)ComplicationsAcute pancreatitisBleedingInfection cholangitisPerforationProcedureSideviewing endoscope used to insert catheter into CBD and inject contrast. XRay screening will then show up lesions in biliary treeYour job ie. what prep does my patient needNPO for 12 hoursCheck clotting and plt countProphylactic antibiotics as per endoscopy department protocol
What is the signand who was it named for?
Medusa
Stigmata of liver diseaseHANDS: Palmar ErythemaClubbingDupytrensLeuconychiaFLAPPING TREMORHEENT/UPPER BODYJaundiceSpider AngiomataGynaecomastia and scant body hairScratch marksABDOMENAscites HepatosplenomegallyCaput MedusaHemorrhoids on PRSmall testes
Cirrhosis4 StagesLiver cell necrosisInflammatory cell infiltateFibrosisNodular regeneration which may be macronodular (alcohol), micronodular (viral) or mixed
CAUSES OF CIRRHOSISAlcoholViral B/CCryptogenicPrimary Biliary CirrhosisHemochromatosisWilsonsAlpha 1 antitrypsin deficiencyAutoimmuneSclerosing Cholangitis
COMPLICATIONSPortal Hypertension causing variceal bleedSplenomegally causing low plateletsAscitesEncephalopathySBPHepatorenal syndrome
Demonstrate the examination necessary to identify the cause of abdominal distension
AscitesAccumulation of free fluid in peritoneumAssessment involves taking sample of fluid and checking albumin contentSAAG: Serum Ascites Albumin GradientSAAG = Serum Albumin Ascites Albumin
Management of AscitesSalt RestrictFluid RestrictDiuretics Spironolactone 100-200mg /day to increase urinary sodium excretion. Aim to reduce weight by 1Kg per dayMay also need LasixLarge volume paracentesisShould give 6g Salt poor Albumin per liter of Ascitic fluid removed in patients with HIGH SAAG otherwise can cause precipitous fall in BP and Hepatorenal syndrome.
Varices and portal gastropathy
Variceal HemorrhageVarices develop at Esophagogastric junction due to portal hypertensionFirst bleed has 10-30% mortalityEarly endoscopy band ligationOctreotide decreases the portal pressure and may stop the bleeding80% rebleed within 2 yearsBblockers esp Propranolol reduce portal pressure and may prevent rebleedingSerial endoscopy and banding to obliterate the varices is also indicated to prevent rebleeding
Spontaneous Bacterial PeritonitisOccurs in 10-20% of cirrhotic patients with ascitesCell count and culture of ascitic fluid should be performed in all patients PMN cells >250 is criteria for diagnosis
Hepatorenal syndromeRenal failure with normal tubular function in patient with portal hypertension. May be ppted by aggressive diuresis.Low urine sodium (but so does pre-renal)No casts in urineRenal function returns to normal after transplant.
EncephalopathyDecreased consciousness in patient with severe liver diseaseAlways look for cause InfectionBleedingElectrolyte disturbanceConstipationIncreased protein intakeUsually has increased serum ammonia which you should check, although, it doesnt need to be that high for pt to be encephalopathicTx: Lactulose
Childs-Pugh classificationDont learn this, just know the name and the principle. It is a scoring system used to assess how risky surgery will be in pts with liver diseaseMeld scores and Mayo scores used to assess pts for liver transplant and transplant allocation
LEARNING OBJECTIVESLiver function testsViral HepatitisAutoimmune hepatitisPrimary Biliary CirrhosisPrimary Sclerosing CholangitisHemochromatosisWilsonsGallstones and cholecystitis
Complications of end stage liver diseaseAscitesSBPHepatorenal SyndromeEncephalopathy
Top Related