A General Approach

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    Source: MKSAP 16

    Introduction to Liver Chemistry

    • Abnormal liver chemistry is found in 13% of patients undergoing medical evaluation.
      • Markers of hepatocyte injury (Hepatocellular pattern)
        • Aspartate Aminotransferase (AST)
          • Also produced in heart, skeletal muscle, kidneys
          • ALT is more specific, but still done for help with ddx based on pattern of AST/ALT.
        • Alanine Aminotransferase (ALT)
          • Mostly in liver, much more SPECIFIC for hepatocyte injury.
      • Markers of biliary stasis (Cholestatic pattern)
        • Alkaline Phosphatase (ALP)
          • Also seen in bone, pregnancy (placental production).
          • Lab can fractionate ALP to help clarify tissue of origin.
        • Gamma-glutamyl transpeptidase (GGT)
          • If elevated with ALP, more likely that ALP is hepatic (vs. extra-hepatic).
        • Bilirubin
          • Direct vs. Indirect
          • Conjugated (Direct) - Indicates diseases of liver.
          • Unconjugated (Indirect) - Non-liver disease
            • (i.e. Hemolysis or Gilbert Syndrome [Bilirubin conjugation dysfunction])
      • Markers of liver synthetic function
        • Serum Albumin
          • Affected by nutritional state, renal, or GI protein loss.
        • Prothrombin Time
          • Affected by nutrition, Vitamin K deficiency, drugs.
      • Acute hepatitis: abnormalities < 6mo
      • Chronic hepatitis: abnormalities >6mo

    Patterns of Liver Injury

    • Pattern of injury will have refine the diagnosis.
    • ALT > AST   (ALT > AST reliably only in Viral Hepatitis, NAFLD and chronic autoimmune, but classically other causes listed)
    • AST > ALT    (AST > ALT reliably only in Alcoholic Hepatitis (i.e. > 2:1 ))
      • Alcoholic Hepatitis
      • Cirrhosis from other causes of hepatitis.
      • Non-Hepatic Causes:
        • Hemolysis
        • Myopathy
        • Thyroid Disease
        • Strenuous Exercise
        • Macro-AST
    • Cholestatic  (ALP) - found in hepatic cannicular membrane, but also bone, placenta, intestines, kidney    
      • Confirm liver origin by doing GGT
      • Autoimmune
        • Primary Biliary Cirrhosis (small bile ducts).  AMA (high Sn+Sp) - ursodexycholic acid, cholestyramine (pruritis)
        • Primary Sclerosing Cholangitis (large bile ducts).  MRCP +/- ERCP - multifocal beading, onion skin fibrosis

        Biliary Obstruction:

        • Cholelithiasis
        • Choledocholithiasis
        • Ascending Cholangitis
        • Cancer:
          • Cholangiocarcinoma
          • Pancreatic cancer etc...
    • Other:
      • Vascular (Ischemic, congestive, Budd-chiari, VOD)
        • I.e. Shock liver with high LDH and delayed Tbili elevation.

    Workup

    • Acute Workup:
      • Toxins (EtOH, acetaminophen)
      • Vascular (U/S w/ doppler)
      • Viral Tests:
        • IgM anti-HAV, HBsAg, IgM anti-HBc, HBV DNA, HCV RNA, anti-HEV, +/- EBV, CMV, HSV, VZV
      • Autoimmune: ANA, Anti-SMA, Anti-LKM)
      • Ceruloplasmin
    • Chronic Workup:
      • Viral: HBsAg, anti-HCV
      • Inherited: Ferritin, TIBC, ceruloplasmin, alpha-1-antitrypsin
      • Metabolic: glucose, HbA1C, TG, TSH
      • Autoimmune: ANA, Anti-SMA, Anti-LKM, Anti-tissue transglutaminase
      • Vascular (U/S with doppler)

    Fulminant Hepatic Failure (FHF)

    See Fulminant Hepatic Failure

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