Approach to the Patient with Liver Diseases (and Pre-work) - Franco

Question 1

What is an alternative name for AST (aspartate aminotransferase) used in the laboratory setting?

ALT (alanine aminotransferase)?

Answer 1

SGOT (serum glutamic oxaloacetic transaminase)

SGPT (serum glutamic pyruvic transaminase)

Question 2

What cellular compartments typically contain AST?

ALT?

Why might this observation be important to the diagnosis of alcoholic liver disease?

Answer 2

AST: cytoplasm and mitochondria

ALT: cytoplasm only

Alcohol is particularly toxic to mitochondria, resulting in increased release of AST relative to ALT.

Question 3

Which is more specific for liver disease: AST or ALT?

Answer 3

ALT

Question 4

Where is Alkaline Phosphatase (ALK PHOS) found in the liver? What type of liver injury is it associated with?

Where else is it found?

If we are not sure that the source of elevated ALK PHOS is the liver, what else can we check?

Answer 4

ALK PHOS is found on the surface of liver cells adjacent to the bile canaliculi. Therefore, it is more closely associated with cholestatic/obstructive liver disease.

Also found in: bone, intestine, placenta

If unsure of hepatic source, check:

• isoenzymes
• 5’-nucleotidase
• GGT (most commonly used)

Question 5

Increased direct (conjugated) bilirubin might indicate what?

Increased indirect (unconjugated) bilirubin might indicate what disease processes?

Answer 5

Direct

• Liver injury
• Bile duct problems
• Rare metabolic problems

Indirect

• Hemolysis
• Gilbert’s

Question 6

What lab values are useful indicators of liver synthetic function?

Answer 6

INR

Serum albumin may be used if the patient is on chronic warfarin therapy (would have diagnostically-useless elevated INR)

Question 7

Give the normal ranges for:

1. AST
2. ALT
3. ALK PHOS
4. Total bilirubin
5. Direct bilirubin
6. INR
7. Serum albumin
8. GGT

Answer 7

1. 10-45 U/L
2. 8-40 U/L
3. 40-129 U/L
4. 0.2-1.0 mg/dL
5. 0-0.2 mg/dL
6. 0.9-1.3
7. 3.5-5 g/dL
8. 0-50 U/L

Question 8

Give the type of liver disease typically caused by each of the following (hepatocellular or cholestatic/obstructive)

1. Stones
2. Alcohol
3. Autoimmune hepatitis
4. Wilson’s disease
5. Fatty liver
6. Primary biliary sclerosis (PBC)
7. Medications
8. Primary sclerosing cholangitis (PSC)
9. Viral hepatitis
10. Alpha-1-antitrypsin deficiency
11. Hemochromatosis

Answer 8

1. CO
2. HC
3. HC
4. HC
5. HC
6. CO
7. CO and HC
8. CO
9. HC
10. HC
11. HC

Question 9

What is elevated in infiltrative liver disease?

Give some examples

Answer 9

ALK PHOS and (occasionally) bilirubin

Examples: tumors, amyloid, sarcoid

Question 10

What is GGT useful for determining?

Answer 10

The source of ALK PHOS elevation (Is this the liver? If GGT elevated, then yes)

Question 11

Name some diseases associated with ALT > 500?

What about the transaminase levels expected in alcoholic liver disease?

Answer 11

ALT > 500

• Hepatitis A, B
• Autoimmune hepatitis
• Medications
• Ischemia (shock liver)
• Stone passage (rare)

Alcoholic liver disease rarely presents with transaminase levels > 300. The expected AST:ALT ratio is >2:1.

Question 12

In the case of chronic liver disease, why do ALT and AST ultimately fall, but INR continues to increase?

Answer 12

As the liver scars and degrades, it ‘burns out’ - ALT and AST fall because there just isn’t enough injured/dying tissue left to maintain these at elevated levels. However, INR continues to rise because the synthetic capacity of the liver continues to degrade.

Question 13

High total bilirubin in the abscence of elevated AST, ALT, ALK PHOS, or INR is indicative of what?

Answer 13

A hemolytic process

Question 14

What other diagnoses/states are important to consider in the setting of isolated ALK PHOS elevation (ALT, AST, and INR normal)?

What might be helpful in determining if these are relevant?

Answer 14

Consider: bone disease, biliary disease, or pregnancy

GGT, 5’-nucleotidase, or fractionation of ALK PHOS are all useful in determining liver origin (but GGT is way cheaper)

Question 15

What is the differential diagnosis for a man with elevated ALT & AST (~500) with normal INR?

Answer 15

Hepatitis and ischemia are most likely. The normal INR suggests an acute process and autoimmune hepatitis is more likely in a female patient.

Question 16

What is the differential diagnosis for an isolated elevated alkaline phosphatase?

Answer 16

Primary biliary cirrhosis (not discussed: stones, parasites or other ductal obstructions).

Question 17

A patient presents with an ALT 35, AST 87, elevated bilirubin and INR. What treatment is indicated?

Answer 17

This patient has alcoholic fatty liver; treat with steroids & pentoxifylline.

Question 18

A patient presents mildly elevated aminotransfersases and joint pain. What workup should this patient receive?

Answer 18

The suspicion is of hereditary hemochromatosis; check the patient’s transferrin and for HFE mutations. If the patient is >40yo or has sufficiently elevated labs, biopsy for cirrhosis.

Treatment is phlebotomy.

Question 19

A caucasian woman presents with a history of hypothyroidism and markedly increased aminotransferases.

What lab is appropriate to check?

Answer 19

Suspicion is of autoimmune hepatitis; check ANA/ASMA.

Question 20

A patient with a history of 90g/day alcoholism presents with severe jaundice, elevated AST/bilirubin/INR.

Is a vitamin K infusion indicated?

Answer 20

Probably not. The elevated INR indiates that this is a chronic process potentially with hepatocyte “blowout”; the synthetic capacity may have been lost.