Table of contents
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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.
- Aspartate Aminotransferase (AST)
- 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])
- Alkaline Phosphatase (ALP)
- 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.
- Serum Albumin
- Markers of hepatocyte injury (Hepatocellular pattern)
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- 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
- 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.
- Vascular (Ischemic, congestive, Budd-chiari, VOD)
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)
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