An Approach to Abnormal LFTs

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An Approach to Abnormal LFTs. Robert C. Lowe, M.D. Boston Medical Center July 17, 2013. INR. ALP. AST. T. BIL. GGT. ALT. ALB. Chessboard. AST. ALT. ALB. ALP. GGT. T. BIL. Case 1. 30 year old woman 4 days of malaise, fevers to 101, nausea 1 day of RUQ pain and jaundice - PowerPoint PPT Presentation

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  • An Approach to Abnormal LFTsRobert C. Lowe, M.D.Boston Medical CenterJuly 17, 2013

  • ASTALTALPT. BILALBINRGGT

  • Chessboard

  • ALTASTT. BILALPALBGGT

  • Case 130 year old woman4 days of malaise, fevers to 101, nausea1 day of RUQ pain and jaundice

    Exam - T 100.5Icteric sclerae and jaundiceTender hepatomegaly, no spleen tip

  • Case 1AST 1535WBC 8.1ALT 1602HCT 41ALP 128PLT 353T. Bil 7.3Albumin 3.9

  • TransaminasesAST - aspartate aminotransferase

    ALT - alanine aminotransferase

    Released when hepatocytes are injured - a sign of necrosis.

  • AST - less specific for liver disease Muscle (skeletal and cardiac) Kidney Erythrocytes

    ALT - very little outside of liver. A better marker of liver disease.

  • Differential DiagnosisSky high transaminases > 15x normal

  • Differential DiagnosisSky high transaminases > 15x normal

    Virus

    DrugIschemia

    }>80% of cases

  • AST/ALT>1000

    Virus

    Toxin

    IschemiaHistory and Exam Points

  • AST/ALT>1000

    Virus

    Toxin

    IschemiaHistory and Exam Points

    IVDUArthralgiasSexual partnersUrticariaTravelHerpetic lesionsFood exposuresStigmata of liver dz

  • AST/ALT>1000

    Virus

    Toxin

    IschemiaHistory and Exam Points

    IVDUArthralgiasSexual partnersUrticariaTravelHerpetic lesionsFood exposuresStigmata of liver dz

  • AST/ALT>1000

    Virus

    Toxin

    IschemiaHistory and Exam Points

    IVDUArthralgiasSexual partnersUrticariaTravelHerpetic lesionsFood exposuresStigmata of liver dz

    MedsOTC medsHerbs and supplements

  • AST/ALT>1000

    Virus

    Toxin

    IschemiaHistory and Exam Points

    IVDUArthralgiasSexual partnersUrticariaTravelHerpetic lesionsFood exposuresStigmata of liver dz

    MedsOTC medsHerbs and supplements

    Recent surgeryHypotensionCardiac arrestCMP

  • AST/ALT>1000

  • AST/ALT>1000

    Autoimmune

    Wilson Disease

    Bile DuctObstruction

    Budd-Chiari

  • AST/ALT>1000

    Autoimmune

    Wilson Disease

    Bile DuctObstruction

    Budd-ChiariClinical Clues

    Female gender

    Personal or Family Hx of autoimmune dz

  • AST/ALT>1000

    Autoimmune

    Wilsons Disease

    Bile DuctObstruction

    Budd-ChiariClinical Clues

    Female gender

    Personal or Family Hx of autoimmune dz

    ANAASMAIg levels

  • AST/ALT>1000

    Autoimmune

    Wilsons Disease

    Bile DuctObstruction

    Budd-Chiari

  • AST/ALT>1000

    Autoimmune

    Wilsons Disease

    Bile DuctObstruction

    Budd-ChiariClinical Clues

    Male gender

    < age 40

    Neuropsychiatric syndromePsychosisMovement disorder

  • AST/ALT>1000

    Autoimmune

    Wilsons Disease

    Bile DuctObstruction

    Budd-ChiariClinical Clues

    Male gender

    < age 40

    Neuropsychiatric syndromePsychosisMovement disorder

    Low ALPHemolysisCeruloplasmin less useful in acute disease

  • KF Rings

  • Head CT

  • AST/ALT>1000

    Autoimmune

    Wilson Disease

    Bile DuctObstruction

    Budd-Chiari

  • AST/ALT>1000

    Autoimmune

    Wilson Disease

    Bile DuctObstruction

    Budd-ChiariClinical Clues

    H/O biliary colic or GS diseaseFH of gallstones

    RUQ painN/V

    Transaminases fall rapidly - over 1-3 days

    U/S often diagnostic, but may need further imaging with MRCP/ERCP

  • AST/ALT>1000

    Autoimmune

    Wilson Disease

    Bile DuctObstruction

    Budd-Chiari

  • AST/ALT>1000

    Autoimmune

    Wilson Disease

    Bile DuctObstruction

    Budd-ChiariClinical Clues

    OCP usePrior venous thrombosisMyeloproliferative disorderMalignancy

    Abdominal PainAscites

  • Laboratory TestingHepatitis A - IgM and IgGHepatitis B - sAg, cAb, eAg, HBV DNAHepatitis C - RNA levelANA, ASMA, Ig levelsRUQ U/S with Doppler Study

    Consider other viral serologies, ceruloplasmin, MRCP

  • Prognostic Features

  • Prognostic FeaturesCoagulopathyINR elevation

    EncephalopathyMental StatusAsterixisApraxia

  • Case 2Asymptomatic 45 year-old womanCholesterol 245, Trig 266No significant FHNo medsWorks as an accountant

  • Case 2

    AST 84WBC 6.6ALT 46HCT 37ALP 121PLT 165T. Bil 0.8ALB 3.7

  • Alcoholic LFT PatternAST/ALT > 2:1

    Absolute AST and ALT < 300

    GGT elevation is helpful, but nonspecific.

  • Alcoholic LFT PatternWHY?

    ALT synthesis is decreased in EtOH hepatitis.

    Partially due to pyridoxine deficiency - may correct with B6 therapy.

  • Case 2

    AST 84WBC 6.6ALT 46HCT 37ALP 121PLT 165T. Bil 0.8ALB 3.7

  • Case 2

    AST 84WBC 6.6ALT 89HCT 37ALP 121PLT 165T. Bil 0.8ALB 3.7

  • Mildly Elevated TransaminasesABCD E

    FGH

  • Mildly Elevated TransaminasesAlcohol / AutoimmuneB HepatitisC HepatitisDrugExoticWilson DiseaseAlpha-1-antitrypsin deficiencyFatty liverGluten sensitive enteropathyHemochromatosis

  • Mildly Elevated TransaminasesAlcohol / AutoimmuneB Hepatitis C HepatitisDrugExoticWilson DiseaseAlpha-1-antitrypsin deficiencyFatty liverGluten sensitive enteropathyHemochromatosis

    Thyroid disease, myopathies

  • Mildly Elevated TransaminasesAlcohol / AutoimmuneAlcohol HxB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrugDrug HxExoticWilson DiseaseAlpha-1-antitrypsin deficiencyFatty liverRUQ U/S, TGGluten sensitive enteropathyHemochromatosis

    Thyroid disease, myopathies

  • Mildly Elevated TransaminasesAlcohol / AutoimmuneANA, ASMA, Ig levelsB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrugDrug HxExoticWilson DiseaseAlpha-1-antitrypsin deficiencyFatty liverRUQ U/S, TGGluten sensitive enteropathyHemochromatosisFe, TIBC, Ferritin

    Thyroid disease, myopathies

  • Mildly Elevated TransaminasesAlcohol / AutoimmuneANA, ASMA, Ig levelsB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrugDrug HxExoticWilson DiseaseCeruloplasminAlpha-1-antitrypsin deficiencyA-1-AT levelFatty liverRUQ U/S, TGGluten sensitive enteropathyHemochromatosisFe, TIBC, Ferritin

    Thyroid disease, myopathies

  • Mildly Elevated TransaminasesAlcohol / AutoimmuneANA, ASMA, Ig levelsB Hepatitis HBsAg, HBcAb, HBsAbC Hepatitis HCV AbDrugDrug HxExoticWilson DiseaseCeruloplasminAlpha-1-antitrypsin deficiencyA-1-AT levelFatty liverRUQ U/S, TGGluten sensitive enteropathyAnti-TTGHemochromatosisFe, TIBC, Ferritin

    Thyroid disease, myopathiesTSH, CK, Aldolase

  • Liver Biopsy 1124 pts referred for elevated ALT ---81 cases with negative serologic workup

  • Liver Biopsy 1124 pts referred for elevated ALT ---81 cases with negative serologic workup

    Biopsies -- 41 pts with steatosis 26 pts with NASH

    8% normal biopsiesDaniel, et al. Am J Gastro, 1999

  • Liver Biopsy 354 patients with elevated ALT and negative workup

    Biopsies -- 32% with steatosis 34% with NASH 9% cryptogenic 7.6% Drug-induced 5.9% normal histology 2.8% ETOH

    Granulomatous dz, PBC, PSC, hemochromatosis,amyloidosis, glycogen storage disease = 6.3%

    In 18%, management was changed based on the pathology.Skelly, et al. J Hepatol, 200166% with NAFLD

  • PAS with Diastase digestion

  • An Approach to Abnormal LFTsRobert C. Lowe, M.D.Boston Medical CenterJuly 17, 2013

  • An Approach to Abnormal LFTsPart 2Robert C. Lowe, M.D.Boston Medical CenterJuly 25, 2013

  • AST/ALT>1000

    Virus

    Toxin

    Ischemia

  • AST/ALT>1000

    Virus

    Toxin

    Ischemia

    Autoimmune

    Wilsons Disease

    Bile DuctObstruction

    Budd-Chiari

  • Alcohol / AutoimmuneB Hepatitis C HepatitisDrugExoticWilsons DiseaseAlpha-1-antitrypsin deficiencyFatty liverGluten sensitive enteropathyHemochromatosis

    Thyroid disease, myopathies

  • Case 335 year old womanMild fatigueNo significant PMHNo meds

    Exam - cervical LAN 0.5 cm, nontender Liver 3 cm below RCM

  • Case 3AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0

  • Case 3AST 42ALT 34ALP 442T. BIL 0.7Albumin 3.9INR 1.0GGT = 650

  • Alkaline PhosphataseProduced in liver, bone, placenta, intestine.

    Blood group O and B may release intestinal ALP after a fatty meal.

    Elevations up to 2x normal are very nonspecific. Up to 1/3 have no disease.

  • Elevated ALPBone disease -- Pagets Metastases Myeloma

    Use GGT or 5NT to distinguish bone from liver.

  • GGT and 5 NTGGT - not found in bone, present in biliary epithelium.

    Problems - induced by EtOH, anticonvulsants, warfarin, so specificity is a problem.

    GGT/ALP > 2.5 suggests EtOH, but only 33% sensitive!

  • 5 Nucleotidase

    More specific than GGT

    Rises over several days after bile duct obstruction, slower than GGT.

  • Elevated ALP

  • Elevated ALPBiliary obstruction Tumor masses - primary or metastaticDrug Effect

  • Elevated ALPSpecial circumstances -

    Malignancy without liver involvement -- tumors produce Regan isoenzyme of ALP (gonadal and urologic)

    Hodgkins Disease and RCC - can cause nonspecific hepatitis with elevated ALP

  • Workup of ALP Elevation1) Confirm liver origin with 5-NT or GGT

  • Workup of ALP Elevation1) Confirm liver origin with 5-NT or GGT

    2) U/S or CT to R/O mass and dilated ductsMass -- biopsyDilated ducts -- MRCP/ERCP

  • AS