Liver Function Tests

Question 1

What are the markers of liver injury?

Answer 1

alanine aminotransferase (ALT) - enzyme found mainly in the liver, but also in smaller amounts in the kidneys, heart, muscles, and pancreas => more specific to liver than AST
aspartate aminotransferase (AST) - enzyme normally found in red blood cells, liver, heart, muscle tissue, pancreas, and kidneys
alkaline phosphatase - enzyme made mostly in the liver and in bone with some made in the intestines and kidneys

Question 2

What are the markers of liver function?

Answer 2

albumin
prothombin time (PT)/International normalized ratio (INR)
bilirubin

Question 3

What is suggested if ALT/AST are elevated more than alkaline phosphatase?

Answer 3

injury to hepatocytes (cells of the main parenchymal tissue of the liver)

Question 4

What is suggested if alkaline phosphatase levels are elevated more than ALT/AST levels?

Answer 4

injury to cholangiocytes (epithelial cells of the bile duct) - suggests obstruction of bile flow

Question 5

What are common causes of injury to hepatocytes?

Answer 5

viral hepatitis
drugs affecting hepatocytes (Tylenol and Augmentin)
alcohol liver disease
non-alcohol liver disease
autoimmune hepatitis
hereditary diseases (hereditary hemochromatosis, Wilson disease)

Question 6

What are common causes of injury to cholangiocytes?

Answer 6

gallstones in common bile duct
pancreatic/hepatic mass
drugs affecting bile flow

Question 7

What are normal values for ALT and AST?

Answer 7

< 40 u/L

Question 8

Which enzyme is normally more elevated in the presence of liver injury?

Answer 8

ALT > AST

Question 9

What is the cause of liver injury if AST is elevated more than ALT (AST 2:ALT 1 or AST = 100-200 u/L)?

Answer 9

alcoholic liver disease

Question 10

What are the likely causes of liver injury if ALT > 1,000 u/L?

Answer 10

acute viral hepatitis (A/B), acute drug induced injury (acetaminophen >7.5 g/day) => order Hep A/B serology and check acetaminophen levels

Question 11

What are the likely causes of liver injury if ALT > 100 u/L?

Answer 11

Chronic viral hepatitis (B/C), drug-related injury (TB medications, antiepileptic, methotrexate, statins, amiodarone, acetaminophen, amoxicillin-clavulanate), non-alcoholic fatty liver disease, congestive liver disease, autoimmune hepatitis => order hepatitis B/C serology, autoantibodies (ANA), review medication history (obesity, T2DM, hyperlipidemia)

Question 12

What is the normal level of alkaline phosphatase?

Answer 12

< 120 u/L

Question 13

What are the causes of elevations in alkaline phosphatase?

Answer 13

cholestatic injury - requires evaluation of biliary tree (initial test = ultrasound, followed by MRCP to detect a stone or CT to detect a tumor)

Question 14

What is the implication if alkaline phosphatase is elevated and ultrasound shows ductal dilation?

Answer 14

extrahepatic cholestasis (common bile duct obstructed/compressed)

Question 15

What are potential causes of extrahepatic cholestasis?

Answer 15

=> choledocholithiasis - stone blocking the common bile duct (sharp pain)
=> pancreatic cancer compressing the bile duct (painless or dull pain)

Question 16

What is the implication if alkaline phosphatase is elevated and ultrasound shows NO ductal dilation?

Answer 16

intrahepatic cholestasis

Question 17

What are potential causes of intrahepatic cholestasis?

Answer 17

=> metastatic disease (colon, prostate)

=> hepatocellular carcinoma

Question 18

What is the most sensitive marker of liver function?

Answer 18

PT/INR (increase in either indicates decrease in synthetic liver function)

Question 19

What are normal levels of PT/INR?

Answer 19

11-15 sec/< 1.0

Question 20

Which is the best marker of acute liver injury?

Answer 20

PT - includes all clotting factors (including Factor VII, which has a half-life of 6 hours) => PTT will also be elevated but has a half-life of 20 days (does not include Factor VII), so does not increase as rapidly

Question 21

What is a normal level of albumin?

Answer 21

3.5-5.3 g/dL - decrease indicates decrease in liver function => not as specific an indicator of liver function because it can also be decreased with nephrotic syndrome or malnutrition

Question 22

What is a normal level for total bilirubin?

Answer 22

0.5-1.0 mg/dL - increases indicate decrease in liver function

Question 23

At what level of bilirubinemia does jaundice become evident?

Answer 23

> 2 mg/dl

Question 24

What is direct/conjugated bilirubin?

Answer 24

bilirubin that has been metabolized in the liver and is able to be excreted via the bile or the urine

Question 25

What is indirect/unconjugated bilirubin?

Answer 25

bilirubin that has not yet been metabolized and that cannot be excreted => cannot be measured via blood tests

Question 26

What is the implication of an increase in indirect/unconjugated bilirubin (e.g., total bilirubin increased but direct bilirubin normal)?

Answer 26

hemolysis - increased destruction of red blood cells => overwhelmed liver is unable to conjugate all unconjugated bilirubin

Question 27

What is the implication of an increase in direct/conjugated bilirubin (e.g., total and direct/conjugated bilirubin increased)?

Answer 27

obstruction of the bile ducts or damage to the hepatocytes so that the usual amount of conjugated bilirubin cannot be excreted into GI tract (e.g., results in clay colored stools)

Question 28

What are the types of extrahepatic jaundice?

Answer 28

intraluminal obstruction (stones or strictures) and extraluminal compression (tumors or strictures of common bile duct)

Question 29

What are the types of intrahepatic jaundice?

Answer 29

compression of small bile ducts inside the liver (due to hepatitis, alcoholic liver disease, drug-induced liver injury, liver tumor)

Question 30

What are some of the S and S of bilary tract obstruction (intra or extrahepatic)?

Answer 30

due to inability to excrete conjugated bilirubin, serum levels increase - since conjugated bilirubin is water soluble, it can be reabsorbed back into the blood and excreted in the urine (giving it a dark color = bilirubinuria) but cannot be excreted through the gut (resulting in clay-colored stools)

Question 31

What are the S and S of jaundice due to excessive hemolysis?

Answer 31

elevation of unconjugated bilirubin - not water-soluble and cannot be excreted => urine and stool unaffected so no change in color (pale stool and dark urine virtually exclude pre-hepatic [hemolytic] jaundice)

Question 32

What should be the first imaging test done for PTs with jaundice?

Answer 32

ultrasound (visualizes common bile duct, texture of liver, and gallbladder) => magnetic resonance cholangiography and endoscopic ultrasound can be obtained to further evaluate the intra and extrahepatic biliary tree

Question 33

What should be the expected Dx if the common bile duct is dilated (> 4 mm) and jaundice is painless?

Answer 33

pancreatic tumor => should obtain CT scan of abdomen/pelvis to visualize the pancreas

Question 34

What should be the expected Dx if the common bile duct is dilated (> 4 mm) and jaundice is painful?

Answer 34

stone obstructing the common bile duct

Question 35

What should be the expected Dx if the common bile duct is not dilated on ultrasound?

Answer 35

intrahepatic compression

Question 36

When should liver biopsy be conducted?

Answer 36

cases of jaundice in which Dx is unclear after initial evaluation => should only be performed if results will determine treatment or prognosis