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Hepatobiliary Board review. Darrell Laudate 6-16-10 AM Report. Approach to Abnormal LFTs. First important to attempt to sort out hepatitis vs cholestatic liver disease. Hepatitis. Hepatitis typically has elevations of AST/ALT - PowerPoint PPT Presentation

Text of Hepatobiliary Board review

Hepatobiliary review

Hepatobiliary Board reviewDarrell Laudate6-16-10 AM ReportFirst important to attempt to sort out hepatitis vs cholestatic liver diseaseApproach to Abnormal LFTsHepatitisHepatitis typically has elevations of AST/ALTPresent typically with fatigue, nausea, mild upper abdominal pain, and juandiceRecall the typical culprits of AST/ALT elevations of the thousandsViral, toxins, shock/ischemia, occasionally AIHHowever, an acute increase in biliary pressue (e.g. from choledocolithiasis can also cause transient AST elevations as high as 1000 but returns to normal after 48hrsSerum Alk Phos may not be elevated

Cholestatic DiseasesTypically heralded by elevations of Alk PhosRefers to injury of the microscopic ducts (e.g PBC), large bile ducts, (e.g pancreatic cancer with CBD obstruction) or both (PSC)Infiltrative diseases can also cause elevated Alk Phos yet near normal serum bilirubin

Any systemic inflammatory process such as an infection or immune disorder may result in a mixed pattern Serum BilirubinWhat is the fraction?Overproduction of bilirubin (e.g. hemolysis or hematoma resorption) is associated with 20% conjugated bilirubin fractionHepatocyte dysfunction or impaired bile flow typically causes a hyperbilirubinemia with 50% conjugated bilirubin fractionDirect hyperbilirubinemia more common than indirect in those with jaundiceAbdominal pain, fever, and/or palpable GB with direct hyperbilirubinemia suggests a large bile duct obstructionBilirubin (continued)Viral hepatitis risk factors, a total bilirubin > 15mg/dL and persistent AST/ALT elevations suggest hepatocellular injuryIn patients with acute hepatocellular dysfunction, improvement in serum bilirubin levels often lags behind improvement in ALT/ASTSynthetic Liver Function (PT and Alb)Abnormal PT and Alb levels imply severe hepatocellular injuryNote that PT may also be elevated from Vit K deficiency (via Abx administration, prolonged fasting, samll-bowel mucosal disorders (celiac), or severe cholestasis leading to fat-soluble deficiencies)Vitamin K will improve the INR within 2 days with Vitamin K but will have no effect if due to liver disease with poor synthetic dysfunctionMKSAP QuestionsQuestion 2430-year-old woman is evaluated because of an abnormal serum total bilirubin level detected when she had a life insurance examination. Medical history is unremarkable. Her only medication is an oral contraceptive agent. Physical examination is normal.

Labs: Hgb 13; MCV 90; Total bilirubin 2.4; Direct bilirubin 0.2; AST 23; ALT 25; Alk phos 90

Question 24 (continued)Which of the following is the most appropriate management at this time? Discontinue the oral contraceptive agentCholestasis due to an oral contraceptive agent will typically cause conjugated (direct) hyperbilirubinemia and an elevated serum alkaline phosphatase level Repeat the liver chemistry tests in 3 months

Evaluate for the presence of hemolysisPatients with hemolysis significant enough to cause unconjugated hyperbilirubinemia typically low Hgb and abnormal MCV Schedule abdominal ultrasonographyUltrasound may be a helpful study for direct hyperbilirubinemia as it is usually associated with liver disease No additional diagnostic studies are indicatedAn isolated indirect (unconjugated) hyperbilirubinemia in an asymptomatic patient with a normal Hgb level suggestive of Gilbert's syndrome, no further work-up indicated.

Gilberts SyndromeCommon, benign inherited disorder associated with indirect hyperbilirubinemia (with serum total bili > 3.0mg/dL but direct is 0.3mg/dL)Recall that the Bilirubin will typically rise during illness or fasting periodsPresumptive diagnosis can be made in an otherwise healthy individual with an isolated indirect hyperbilirubinemia and a normal Hgb.Question 3237yo F with history of hypothyroidism (on Levothyroxine) presents with 1-week history of fatigue, jaundice, and slight fever. She traveled to Mexico 5 months ago and received one dose of hepatitis A vaccine before her trip. Physical examination significant for mild jaundice and hepatomegaly.

Labs: CBC normal; TSH normal; AST 310; ALT 450; Alk phos 180; total bili 2.3

Question 32 (continued)Which will confirm the diagnosis?Anti-mitochondrial antibodySerologic marker for PBC, a cholestatic disease, thus will have a typically higher Alk Phos and T bili, lower AST/ALTAntinuclear antibody and antismooth muscle antibodyMost likely AIH given concomitant autoimmune thyroid disease and abnormal liver test results. Antinuclear antibody and antismooth muscle antibody titers should therefore be obtained (titers >1:80 for both assays support the diagnosis)IgM antibody to hepatitis A virus (IgM anti-HAV)Does have travel risk factor but this was 5 months ago, incubation period for Hep A is typically 2-6 weeks of exposure. Furthermor she also received 1 dose of the Hep A vaccine before travel, which typically protects people for at least 4 weeksSerum acetaminophenMeasurement of Acetaminophen level is appropriate for acute hepatitis of uncertain cause but is typically associated with more significantly elevated AST/ALT values and is typically not associated with the week-long prodrome noted prior to presentationEndoscopic retrograde cholangiopancreatographyERCP is indicated for evaluation of suspected biliary obstruction and could be considered given the fever, jaundice and acutely elevated ALT/AST values but the absence of pain makes obstruction very unlikely

Autoimmune HepatitisTypically develops in patients 20-40 years oldFemales> Males (3.6:1)1/3rd to 1/2 have concomittant autoimmune diseaseMost pts have features of chronic disease but up to 40% will have an acute or fulminant presentationFatigue present in 85%; jaundice (46%), anorexia (30%), myalgias (30%), diarrhea (28%)Acne, hirsutism, menstrual irregularities, and fever are less commonPruritis and weight loss are uncommon thus alternative etiologies should be consideredAIH (continued)Some patients have features of both autoimmune hepatitis and a cholestatic liver diseaseReferred to as an overlap syndromeExam often shows enlarged liver (78%) but otherwise typically normal despite presence of advanced diseaseAST/ALT typically elevated (typically 150->1000 but often < 500)Serum gamma globulin 1.5 of upper limit of normalMild hyperbilirubinemia (often < 3mg/dL) present in 83%Elevated AlkP often present but values > 2x normal suggest another disorderANA, Anti-smooth muscle Ab, or antibody to liver/kidney microsome type 1 (anti-LKM1) is present in 87%typically titers 1:80 support diagnosisBiopsy shows Interface hepatitis with portal plasma cell infiltrate.Treatment of AIHPrednisone alone or Pred + Azathioprine associated with remission in 80% at 3 yearsRelapse occurs in 50-86%, typically within 6 months of withdrawal of therapy & associated with an increase in AST/ALTRelapse treatment is same as initial treatmentLiver transplant reserved for patients who do not respond to treatment aloneAIH can develop in the transplanted liver but is typically mildPrognosis excellent for patients with treated AIH and is same for that of healthy persons matched for age, sex, and geographic locationQuestion 13321yo F brought to ER by her roommate for slurred speech, tremor, and clumsy gait. Roommate last saw patient 2 days ago and does not know how long these changes have been present. Roommate believes the patient is health and does not take any prescription medications. However, a decline in her school performance over the last several months has been noted. PE shows she is jaundiced, tremulous, and delirious.

Labs: Hgb 8.2, WBC 6000/L, plts 250,000/LAST 250, ALT 275, AlkP 40, t bili 8.5 (direct 1.5)Question 133 (continued)Which of the following studies is most likely to suggest the diagnosis?Measurement of serum acetaminophenShould always be obtained for evaluation of her AST/ALT but does not explain all of her features, e.g. prolonged cognitive decline, hemolytic anemiaMeasurement of serum ceruplasminHer chronic progressive decline along with her liver test abnormalities and evidence of hemolytic anemia (via a disproportionate elevation of the T bili) are highly suggestive of Wilsons. A ceruplasmin level 250ug/24h is also characteristicBiopsy will confirm the diagnosis via hepatic copper concentrationTreatment of WilsonsPencillamine is in the initial therapy of choice, is lifelongSide effects include neurologic deficits, hypersensitivity reactions, bone marrow suppression, and autoimmune disordersTrientine and zinc acetate are alternative agentsTransplant indicated for those with fulminant disease or ESLD who do not respond to medical therapySignificant improvement in neurologic function may occur s/p transplantation thus severe neurologic dysfunction should not be a contraindication to transplantationQuestion 942yo F w/ history of dysmenorrhea (on estrogen/ progesterone) and hypothyroidism (on levothyroxine) has progressive fatigue without dyspnea, chest pain, or systemic symptoms. She sleeps well at night with no features of sleep apnea. Exam significant for slight but nontender thyromegaly and xanthomas on extensor surfaces.

Labs: nml CBC & TSH; AST 25, ALT 32, t bili 1.1, AlkP 278Question 9 (continued)In addition to fasting serum lipid profile, which of the following studies would most likely be helpful in establishing the diagnosis?Antimitochondrial antibody assay80% of PBC pts report fatigue but presence of xanthomas and elevated AlkP are characteristeic of PBC; Antimitochondrial Antibody titer 1:40 present in > 90% of PBC ptsSerum 25-OH Vitamin DAlthough metabolic bone disease is associated with PBC, it vitamin D deficiency would not explain exam/lab findingsERCPIndicated for assessing cholestatic disease that affects large ducts (such as PSC) but would not be helpful in the diagnosis of PBCAbdominal U/SHelpful in detecti

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