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2 0 1 3
M I N I - L E C T U R E
Liver “Function” Test
Objectives
 Understand the significance of Liver Function Tests
 Identify the patterns that indicate specific disease
categories
 Identify the appropriate further work up of
abnormalities
Case
 49 year old Female presents with chest pain and
negative troponins admitted for monitoring, LFT in
ED show AST: 57, ALT: 62, Alk Phos: wnl, T. Bili:
wnl. What is the next step in management?
 A: RUQ Ultrasound
 B: Hepatitis Panel
 C: Screen for Alcohol Use
 D: CT Scan Abdomen
Etiology
 Synthetic Function: Total protein, serum albumin,
total bilirubin, prothrombin time
 ALT: found primarily in Hepatocytes
 AST: found in many sources- Liver, heart, intestine,
pancrease
 Alkaline phosphatase: found in liver, bones,
intestines, and placenta
 Bilirubin: Two sources- indirect (old red cells),
Direct (conjugated in liver)
Patterns
 Elevation in ALT & AST: primarily cellular injury
 Etiology: Acute Viral Hepatitis, Acetaminophen toxicity, shock
liver
 Elevation in Alk Phos and Bilirubin: cholestasis or
obstruction
 Etiology: choledocholithiasis, biliary stricture, malignancy
 Mixed: Serum Bilirubin can be elevated in both
conditions
Pearls for further evaluation
 Albumin
 Low Albumin- suggests chronic process (cirrhosis/cancer)
 Normal- suggests acute process
 Prothrombin
 Prolonged
 suggests vitamin K deficiency 2/2 prolonged jaundice or
malabsorption
 Significant hepatocellular dysfunction (failure to correct w/ vit K
administration indicates severe injury)
 Bilirubin in Urine
 Indicates hepatobiliary disease (indirect not excreted by kidney)
Mild Aminotransferase Elevation Workup
 Primary Causes
 Screen for alcohol abuse (AST/ALT > 2:1)
 Review medications
 If Negative: then serology for hepatitis B/C, screen for
hemochromatosis, then evaluate for fatty liver w/ RUQ US
 Secondary
 Exclude muscle disorders
 Thyroid function tests
 Celiac disease
 Adrenal insufficiency
 IF All negative: Autoimmune, Wilson’s dx, alpha 1 antitrypsin, consider
biopsy or observe (pt w/ ALT/AST less that 2x ULN)
Hyperbilirubinemia
 Unconjugated
 Over production: hemolysis, extravasation of blood into tissue,
ineffective erythropoiesis
 Impaired Uptake: Heart failure, portosystemic shunts,
Gilberts, Drugs (Rifampicin and probenecid)
 Impaired conjugation: Gilberts, hyperthyroidism, Liver Dx,
Crigler-Najjar
 Conjugated
 Extrahepatic: choledocholithiasis, tumors, PSC, AIDS,
pancreatitis, strictures, parasitic infxn
 Intrahepatic: hepatitis, PBC, Drugs, Sepsis/hypoperfusion,
infiltrative disease, TPN, Sickle cell, pregnancy, Dubin
Johnson and Rotor Syndrome
Alkaline Phosphatase
 Source includes: bone, liver, placenta, varies w/ age
 Serum GGT: elevated in Liver Disease not Bone disease
 Most common cause: chronic cholestasis or infiltrative disease
 Primary biliary cirrhosis, primary sclerosis cholangitis
 Sarcoidosis, amyloidosis, liver metastasis
 Initial Workup:
 RUQ Ultrasound
 Anti-mitochondrial Antibody
 Consider- MRCP or ERCP
 Observe: if Alk phos <50% above normal
Elevation of Several LFT’s
 Hepatocellular pattern
 ALT/AST > 25 ULN only seen in hepatocullular dx
 With Jaundice
 Alcholic
 AST:ALT.2
 AST rarely > 300 units/L
 Viral
 Aminotransferase> 500 u/L w/ ALT >AST
 Toxic: i.e. Acetaminophen
 Shock liver
 Autoimmune and Wilson’s Dx
Elevation of Several LFT’s
 Predominantly Cholestatic Pattern
 Determine Intra vs Extra hepatic
 RUQ U/S: assess for Biliary dilation
 Extrahepatic: consider CT or MRCP or ERCP
 Common Causes: choledocholithiasis, malignancy, PSC,
Pancreatitis
 Intrahepatic: broad differential
 Work-up determined by clinic situation
Summary
 Described significance of each Liver function test
 Identified common LFT abnormalities
 Familiarized with basic initial work up of elevated
Liver function Tests

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Liver function test abnormalities: When to order an ultrasound or further testing

  • 1. 2 0 1 3 M I N I - L E C T U R E Liver “Function” Test
  • 2. Objectives  Understand the significance of Liver Function Tests  Identify the patterns that indicate specific disease categories  Identify the appropriate further work up of abnormalities
  • 3. Case  49 year old Female presents with chest pain and negative troponins admitted for monitoring, LFT in ED show AST: 57, ALT: 62, Alk Phos: wnl, T. Bili: wnl. What is the next step in management?  A: RUQ Ultrasound  B: Hepatitis Panel  C: Screen for Alcohol Use  D: CT Scan Abdomen
  • 4. Etiology  Synthetic Function: Total protein, serum albumin, total bilirubin, prothrombin time  ALT: found primarily in Hepatocytes  AST: found in many sources- Liver, heart, intestine, pancrease  Alkaline phosphatase: found in liver, bones, intestines, and placenta  Bilirubin: Two sources- indirect (old red cells), Direct (conjugated in liver)
  • 5. Patterns  Elevation in ALT & AST: primarily cellular injury  Etiology: Acute Viral Hepatitis, Acetaminophen toxicity, shock liver  Elevation in Alk Phos and Bilirubin: cholestasis or obstruction  Etiology: choledocholithiasis, biliary stricture, malignancy  Mixed: Serum Bilirubin can be elevated in both conditions
  • 6. Pearls for further evaluation  Albumin  Low Albumin- suggests chronic process (cirrhosis/cancer)  Normal- suggests acute process  Prothrombin  Prolonged  suggests vitamin K deficiency 2/2 prolonged jaundice or malabsorption  Significant hepatocellular dysfunction (failure to correct w/ vit K administration indicates severe injury)  Bilirubin in Urine  Indicates hepatobiliary disease (indirect not excreted by kidney)
  • 7. Mild Aminotransferase Elevation Workup  Primary Causes  Screen for alcohol abuse (AST/ALT > 2:1)  Review medications  If Negative: then serology for hepatitis B/C, screen for hemochromatosis, then evaluate for fatty liver w/ RUQ US  Secondary  Exclude muscle disorders  Thyroid function tests  Celiac disease  Adrenal insufficiency  IF All negative: Autoimmune, Wilson’s dx, alpha 1 antitrypsin, consider biopsy or observe (pt w/ ALT/AST less that 2x ULN)
  • 8. Hyperbilirubinemia  Unconjugated  Over production: hemolysis, extravasation of blood into tissue, ineffective erythropoiesis  Impaired Uptake: Heart failure, portosystemic shunts, Gilberts, Drugs (Rifampicin and probenecid)  Impaired conjugation: Gilberts, hyperthyroidism, Liver Dx, Crigler-Najjar  Conjugated  Extrahepatic: choledocholithiasis, tumors, PSC, AIDS, pancreatitis, strictures, parasitic infxn  Intrahepatic: hepatitis, PBC, Drugs, Sepsis/hypoperfusion, infiltrative disease, TPN, Sickle cell, pregnancy, Dubin Johnson and Rotor Syndrome
  • 9. Alkaline Phosphatase  Source includes: bone, liver, placenta, varies w/ age  Serum GGT: elevated in Liver Disease not Bone disease  Most common cause: chronic cholestasis or infiltrative disease  Primary biliary cirrhosis, primary sclerosis cholangitis  Sarcoidosis, amyloidosis, liver metastasis  Initial Workup:  RUQ Ultrasound  Anti-mitochondrial Antibody  Consider- MRCP or ERCP  Observe: if Alk phos <50% above normal
  • 10. Elevation of Several LFT’s  Hepatocellular pattern  ALT/AST > 25 ULN only seen in hepatocullular dx  With Jaundice  Alcholic  AST:ALT.2  AST rarely > 300 units/L  Viral  Aminotransferase> 500 u/L w/ ALT >AST  Toxic: i.e. Acetaminophen  Shock liver  Autoimmune and Wilson’s Dx
  • 11. Elevation of Several LFT’s  Predominantly Cholestatic Pattern  Determine Intra vs Extra hepatic  RUQ U/S: assess for Biliary dilation  Extrahepatic: consider CT or MRCP or ERCP  Common Causes: choledocholithiasis, malignancy, PSC, Pancreatitis  Intrahepatic: broad differential  Work-up determined by clinic situation
  • 12. Summary  Described significance of each Liver function test  Identified common LFT abnormalities  Familiarized with basic initial work up of elevated Liver function Tests

Editor's Notes

  1. Not all values are markers of function
  2. The answer is C. Most transaminitis <2 ULN 2/2 alcohol or fatty liver
  3. Highlight Albumin as negative acute phase reactant
  4. -Any medication can cause elevation liver enzymes: common include NSAIDS, ABX, statins, antieplicptics, antituberculous, and acetaminiophen. Consider illicit drugs and herbals as well. -Instudy of 100’s patients w/ liver biopsy confirmed liver disease 90% w/ AST/ALT >2 had alcoholic liver disease. -Initial Hepatitis Screen: HBsAg, anti-HBs, anti-HBc, anti-HC -Hemachromatosis screen: Serum Iron and TIBC Muscle disorders: can order CK or aldolase, Thyroid: unclear mechanism of liver injury Celiac dx: serum IgA antiendomysial or IgA transglutaminase AB
  5. Highlight the importance of determining conjugated vs unconjugated Within Conjugated; the importance of differentiating extra vs intrahepatic causes
  6. Algorhythm on the following page