An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013

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Transcript of An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013

  • Slide 1
  • An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013
  • Slide 2
  • AST ALT ALP T. BIL ALB INR GGT
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  • Chessboard
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  • ALTAST T. BIL ALPALB GGT
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  • Case 1 30 year old woman 4 days of malaise, fevers to 101, nausea 1 day of RUQ pain and jaundice Exam - T 100.5 Icteric sclerae and jaundice Tender hepatomegaly, no spleen tip
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  • Case 1 AST 1535WBC 8.1 ALT 1602HCT 41 ALP 128PLT 353 T. Bil 7.3 Albumin 3.9
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  • Transaminases AST - aspartate aminotransferase ALT - alanine aminotransferase Released when hepatocytes are injured - a sign of necrosis.
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  • AST - less specific for liver disease Muscle (skeletal and cardiac) Kidney Erythrocytes ALT - very little outside of liver. A better marker of liver disease.
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  • Differential Diagnosis Sky high transaminases > 15x normal
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  • Differential Diagnosis Sky high transaminases > 15x normal Virus Drug Ischemia } >80% of cases
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  • AST/ALT>1000 Virus Toxin Ischemia History and Exam Points
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  • AST/ALT>1000 Virus Toxin Ischemia History and Exam Points IVDUArthralgias Sexual partnersUrticaria TravelHerpetic lesions Food exposuresStigmata of liver dz
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  • AST/ALT>1000 Virus Toxin Ischemia History and Exam Points IVDUArthralgias Sexual partnersUrticaria TravelHerpetic lesions Food exposuresStigmata of liver dz
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  • AST/ALT>1000 Virus Toxin Ischemia History and Exam Points IVDUArthralgias Sexual partnersUrticaria TravelHerpetic lesions Food exposuresStigmata of liver dz Meds OTC meds Herbs and supplements
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  • AST/ALT>1000 Virus Toxin Ischemia History and Exam Points IVDUArthralgias Sexual partnersUrticaria TravelHerpetic lesions Food exposuresStigmata of liver dz Meds OTC meds Herbs and supplements Recent surgery Hypotension Cardiac arrest CMP
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  • AST/ALT>1000
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  • Autoimmune Wilson Disease Bile Duct Obstruction Budd-Chiari
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  • AST/ALT>1000 Autoimmune Wilson Disease Bile Duct Obstruction Budd-Chiari Clinical Clues Female gender Personal or Family Hx of autoimmune dz
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  • AST/ALT>1000 Autoimmune Wilsons Disease Bile Duct Obstruction Budd-Chiari Clinical Clues Female gender Personal or Family Hx of autoimmune dz ANA ASMA Ig levels
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  • AST/ALT>1000 Autoimmune Wilsons Disease Bile Duct Obstruction Budd-Chiari
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  • AST/ALT>1000 Autoimmune Wilsons Disease Bile Duct Obstruction Budd-Chiari Clinical Clues Male gender < age 40 Neuropsychiatric syndrome Psychosis Movement disorder
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  • AST/ALT>1000 Autoimmune Wilsons Disease Bile Duct Obstruction Budd-Chiari Clinical Clues Male gender < age 40 Neuropsychiatric syndrome Psychosis Movement disorder Low ALP Hemolysis Ceruloplasmin less useful in acute disease
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  • KF Rings
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  • Head CT
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  • AST/ALT>1000 Autoimmune Wilson Disease Bile Duct Obstruction Budd-Chiari
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  • AST/ALT>1000 Autoimmune Wilson Disease Bile Duct Obstruction Budd-Chiari Clinical Clues H/O biliary colic or GS disease FH of gallstones RUQ pain N/V Transaminases fall rapidly - over 1-3 days U/S often diagnostic, but may need further imaging with MRCP/ERCP
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  • AST/ALT>1000 Autoimmune Wilson Disease Bile Duct Obstruction Budd-Chiari
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  • AST/ALT>1000 Autoimmune Wilson Disease Bile Duct Obstruction Budd-Chiari Clinical Clues OCP use Prior venous thrombosis Myeloproliferative disorder Malignancy Abdominal Pain Ascites
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  • Laboratory Testing Hepatitis A - IgM and IgG Hepatitis B - sAg, cAb, eAg, HBV DNA Hepatitis C - RNA level ANA, ASMA, Ig levels RUQ U/S with Doppler Study Consider other viral serologies, ceruloplasmin, MRCP
  • Slide 32
  • Prognostic Features
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  • Coagulopathy INR elevation Encephalopathy Mental Status Asterixis Apraxia
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  • Case 2 Asymptomatic 45 year-old woman Cholesterol 245, Trig 266 No significant FH No meds Works as an accountant
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  • Case 2 AST 84WBC 6.6 ALT 46HCT 37 ALP 121PLT 165 T. Bil 0.8 ALB 3.7
  • Slide 40
  • Alcoholic LFT Pattern AST/ALT > 2:1 Absolute AST and ALT < 300 GGT elevation is helpful, but nonspecific.
  • Slide 41
  • Alcoholic LFT Pattern WHY? ALT synthesis is decreased in EtOH hepatitis. Partially due to pyridoxine deficiency - may correct with B6 therapy.
  • Slide 42
  • Case 2 AST 84WBC 6.6 ALT 46HCT 37 ALP 121PLT 165 T. Bil 0.8 ALB 3.7
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  • Case 2 AST 84WBC 6.6 ALT 89HCT 37 ALP 121PLT 165 T. Bil 0.8 ALB 3.7
  • Slide 44
  • Mildly Elevated Transaminases ABCDEFGHABCDEFGH
  • Slide 45
  • Alcohol / Autoimmune B Hepatitis C Hepatitis Drug Exotic Wilson Disease Alpha-1-antitrypsin deficiency Fatty liver Gluten sensitive enteropathy Hemochromatosis
  • Slide 46
  • Mildly Elevated Transaminases Alcohol / Autoimmune B Hepatitis C Hepatitis Drug Exotic Wilson Disease Alpha-1-antitrypsin deficiency Fatty liver Gluten sensitive enteropathy Hemochromatosis Thyroid disease, myopathies
  • Slide 47
  • Mildly Elevated Transaminases Alcohol / AutoimmuneAlcohol Hx B Hepatitis HBsAg, HBcAb, HBsAb C Hepatitis HCV Ab DrugDrug Hx Exotic Wilson Disease Alpha-1-antitrypsin deficiency Fatty liverRUQ U/S, TG Gluten sensitive enteropathy Hemochromatosis Thyroid disease, myopathies
  • Slide 48
  • Mildly Elevated Transaminases Alcohol / AutoimmuneANA, ASMA, Ig levels B Hepatitis HBsAg, HBcAb, HBsAb C Hepatitis HCV Ab DrugDrug Hx Exotic Wilson Disease Alpha-1-antitrypsin deficiency Fatty liverRUQ U/S, TG Gluten sensitive enteropathy HemochromatosisFe, TIBC, Ferritin Thyroid disease, myopathies
  • Slide 49
  • Mildly Elevated Transaminases Alcohol / AutoimmuneANA, ASMA, Ig levels B Hepatitis HBsAg, HBcAb, HBsAb C Hepatitis HCV Ab DrugDrug Hx Exotic Wilson DiseaseCeruloplasmin Alpha-1-antitrypsin deficiencyA-1-AT level Fatty liverRUQ U/S, TG Gluten sensitive enteropathy HemochromatosisFe, TIBC, Ferritin Thyroid disease, myopathies
  • Slide 50
  • Mildly Elevated Transaminases Alcohol / AutoimmuneANA, ASMA, Ig levels B Hepatitis HBsAg, HBcAb, HBsAb C Hepatitis HCV Ab DrugDrug Hx Exotic Wilson DiseaseCeruloplasmin Alpha-1-antitrypsin deficiencyA-1-AT level Fatty liverRUQ U/S, TG Gluten sensitive enteropathyAnti-TTG HemochromatosisFe, TIBC, Ferritin Thyroid disease, myopathiesTSH, CK, Aldolase
  • Slide 51
  • Liver Biopsy 1124 pts referred for elevated ALT --- 81 cases with negative serologic workup
  • Slide 52
  • 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 biopsies Daniel, et al. Am J Gastro, 1999
  • Slide 53
  • 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, 2001 66% with NAFLD
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  • PAS with Diastase digestion
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  • An Approach to Abnormal LFTs Robert C. Lowe, M.D. Boston Medical Center July 17, 2013
  • Slide 58
  • Slide 59
  • An Approach to Abnormal LFTs Part 2 Robert C. Lowe, M.D. Boston Medical Center July 25, 2013
  • Slide 60
  • AST/ALT>1000 Virus Toxin Ischemia
  • Slide 61
  • AST/ALT>1000 Virus Toxin Ischemia Autoimmune Wilsons Disease Bile Duct Obstruction Budd-Chiari
  • Slide 62
  • Alcohol / Autoimmune B Hepatitis C Hepatitis Drug Exotic Wilsons Disease Alpha-1-antitrypsin deficiency Fatty liver Gluten sensitive enteropathy Hemochromatosis Thyroid disease, myopathies
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  • Slide 64
  • Case 3 35 year old woman Mild fatigue No significant PMH No meds Exam - cervical LAN 0.5 cm, nontender Liver 3 cm below RCM
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  • Case 3 AST 42 ALT 34 ALP 442 T. BIL 0.7 Albumin 3.9 INR 1.0
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  • Case 3 AST 42 ALT 34 ALP 442 T. BIL 0.7 Albumin 3.9 INR 1.0 GGT = 650
  • Slide 67
  • Alkaline Phosphatase Produc