1. Liver “Function” Test 2013 Mini-Lecture
Not all values are markers of function

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
The answer is C. Most transaminitis <2 ULN 2/2 alcohol or fatty liver

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)
Highlight Albumin as negative acute phase reactant

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)
-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

8. Hyperbilirubinemia Unconjugated Conjugated
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
Highlight the importance of determining conjugated vs unconjugated
Within Conjugated; the importance of differentiating extra vs intrahepatic causes

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
Algorhythm on the following page

12. Summary Described significance of each Liver function test
Identified common LFT abnormalities
Familiarized with basic initial work up of elevated Liver function Tests