A General Approach

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)
  • Viral hepatitis (HAV, HBV, HCV, HDV, HEV, CMV, EBV, HSV, VZV)
  • Non-Alcoholic Fatty Liver Disease (Obesity, DM, hyperlipidemia)
  • Autoimmune Hepatitis:
    • Type I - ANA or anti-SMA (microsomal) in adults.
    • Type II - anti-LKM (liver disease) in children.
  • Drug/Toxin Induced
  • Metabolic Diseases
    • Hemachromatosis
    • alpha-1-antitrypsin deficiency
    • Wilson's Disease
• 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