Liver Tests

Question 1

List the LFTs. Why is LFT a misnomer?

Answer 1

1. Routinely used term but a misnomer

a. These really don’t measure the function of the liver
b. No good quantitative measures of liver function have been developed

2. The following blood tests are commonly referred to as LFT’s:
   a. ALT (alanine aminotransferase) (old name: SGPT)
   b. AST (aspartate aminotransferase) (old name: SGOT)
   c. Alkaline phosphatase
   d. Albumin
   e. Bilirubin

Question 2

What are some hepatocellular enzymes that can be found in the blood? What do these levels reflect? Normal Ranges? What are 5 major causes of ALT in the thousands?

Answer 2

Liver enzymes in the blood—a measure of liver cell injury:

1. Hepatocellular enzymes
   a. Alanine aminotransferase ALT (SGPT) normal: 10-40 U/L
   b. Aspartate aminotransferase AST (SGOT) normal: 10-40 U/L
   c. Lactate dehydrogenase (LDH)
   d. Levels in the blood roughly reflect the degree of hepatocellular necrosis
   e. Only 5 major causes of ALT in the thousands:
   i. Acute viral hepatitis (hepatitis A and B)
   ii. Autoimmune hepatitis
   iii. Drugs/toxins (e.g., acetaminophen, cocaine)
   iv. Shock
   v. Acute biliary obstruction (the non-intuitive cause)

Question 3

What is the main cholestatic enzyme found in the blood? What do elevations indicate? What are major sources? When is it naturally higher? What are two other cholestatic enzymes found in the blood?

Answer 3

2. Cholestatic enzymes
   a. Elevations indicate cholestasis (blockage of bile flow)
   b. Alkaline phosphatase (Alk Phos)
   c. Major sources = BLIP = bone, liver, intestine, placenta
   d. Higher in children (bone growth) and third trimester of pregnancy
   e. Two other enzymes sometimes used to as indicators of cholestasis (placental source)

i. Gamma-glutamyl transpeptidase (GGT)
– Gamma glutamyl transferase (GGT) confers liver specificity
ii. 5’-nucleotidase
iii.Bilirubin

Question 4

What is normal value for serum bilirubin? When does jaundice become apparent? What are the two major types? List various common causes of each type.

Answer 4

1. Normal: about 1.0 mg/dL
2. Jaundice apparent at 3-4 mg/dL
   – Jaundice obvious at > 10 mg/dL
3. Can be measured as total bilirubin or “fractionated” into 2 major types: conjugated and unconjugated
4. Conjugated bilirubin (diglucuronide) = “direct bilirubin” (old term)
5. Common causes of elevated conjugated bilirubin:
   a. Acute hepatitis
   b. Intrahepatic cholestasis (sepsis, drugs, PSC, PBC)
   c. Extrahepatic biliary obstruction (cancer, stones, PSC)
   d. Note that it doesn’t take many functioning hepatocytes to conjugate bilirubin whereas it takes a fairly healthy liver to get conjugated bilirubin from the hepatocyte cytoplasm into the biliary tract.
6. Unconjugated bilirubin = “indirect” (old term)
7. Common causes of an elevated unconjugated bilirubin (defined as >70% of total as unconjugated)

a. Neonatal jaundice
b. Developmental delay in expressing the enzyme that conjugates bilirubin
c. Hemolysis
d. Massive hematoma
e. Gilbert’s syndrome (decreased glucuronosyl transferase)
i. Very common—about 7% of people
ii. Gilbert’s is not a disease—does not cause disability or death
iii. Usually pronounced like the French might: zhil-bear’s syndrome
f. Crigler-Najjar (defective glucuronosyl transferase)

Question 5

What does the PT, INR tell you concerning liver function? What do factor V and factor VIII tell you concerning liver funciton?

Answer 5

1. Prothrombin time, INR (internationalized ratio)
   a. Elevation of the INR is an indication of significant loss of liver synthetic function
   b. Note that an elevated INR caused by liver disease is less of a risk of bleeding than an elevated INR caused by warfarin use.
2. Factor V
   a. Useful in the setting of severe acute injury (eg acetaminophen overdose) because of its short half life
   b. Factor VIII can be measured at the same time since it is not made by the liver. If the factor VIII level is low too, then the problem may be consumption of coagulation factors rather than lack of liver synthesis.

Question 6

What is good and bad about US, CT, and MRI?

Answer 6

• Ultrasound

– Good: Less expensive, non-invasive

– Bad: Operator-dependent

• CT

– Good: Excellent for tumors, examines remainder of abdomen

– Bad: More expensive, radiation exposure

• MRI

– Good: Excellent for tumors, blood flow, fat, bile ducts

– Bad: Most expensive

• Note: imaging cannot identify inflammation or early fibrosis

Question 7

What are the advantages and disadvantages of a liver biopsy?

Answer 7

1. Shows features not seen by imaging: degree (grade) of inflammation, nature of inflammation, stage of fibrosis, zonality of abnormalities, signs of passive congestion, signs of viral infection by immunohistochemistry
2. Subject to sampling artifact (only 1/50,000th of the liver is examined)
3. Invasive
4. Can cause pain
5. About a 1:1000 risk of serious bleeding requiring blood transfusion or surgery