A PowerPoint presentation covering the basics of liver function tests. Specifically, which tests are ordered, what they represent and how they can reflect a certain diagnosis. Albumin, INR, Bilirubin, AST, ALT, Alkaline phosphatase, GGT

1. Liver Function Tests
Dr. Joseph A. Di Como

2. What are “Liver Function Tests”
Few are truly associated with function
Albumin: protein synthetic function
INR: clotting factor synthesis
Most are related to cell injury
Patterns point to specific cell injury

3. Tests of Liver Injury
AST/ALT
Cytoplasmic enzymes found in hepatocytes
The half-life in the circulation is about 47 hours for ALT,
about 17 hours for total AST
Very sensitive marker for hepatocyte injury
Specificity is poor (other sources, e.g. muscle)
Mitochondrial isoenzyme
AST increased by ethanol (explains 2:1 ratio)
Alkaline Phosphatase/GGT
Canicular enzymes
Gradual increase in plasma levels with obstruction of canicular
flow

4. Alkaline Phosphatase
 Of cytosolic origin in the liver
Present in placenta, ileal mucosa, kidney, bone
Half life = 3 days
Elevated in 3d trimester of pregnancy
Blood types O and B: can have elevated ALP after fatty
meal due to influx of intestinal ALP
Liver origin: elevated GGT
Bone origin: normal GGT

5. Increased Bilirubin
Sources
Increased production
 Hemolysis, hematoma reabsorption
Impaired uptake/conjugation
 Dubin-Johnson, Gilbert’s
Impaired excretion
 Renal failure, biliary obstruction
Conjugated=direct=processed by liver
Unconjugated=indirect=not processed by liver
Fractionation – helpful to assess for unconjugated
hyperbilirubinemia
< 20% direct AND indirect >1.2

6. Bilirubin
Although the terms direct and indirect bilirubin are used
equivalently with conjugated and unconjugated bilirubin,
this is not quantitatively correct, because the direct
fraction includes both conjugated bilirubin and δ
bilirubin.
Delta bilirubin is a conjugated bilirubin that is covalently
bound to albumin. Therefore, the clearance of delta
bilirubin from the serum is similar to the clearance of
albumin which has a half-life of approximately 21
days

7. Bilirubin
 bilirubin (bilirubin covalently bound to albumin, whichδ
appears in serum when hepatic excretion of conjugated
bilirubin is impaired in patients with hepatobiliary disease).
Covalent attachment of bilirubin to human albumin could
result in persistence of hyperbilirubinemia long after the
resolution of disease
 Direct bilirubin tends to overestimate conjugated bilirubin
levels due to unconjugated bilirubin that has reacted with
diazosulfanilic acid, leading to increased azobilirubin levels
(and increased direct bilirubin).

8. Causes of Biliary Obstruction
 Extrahepatic
 Choledocholithiasis
 Malignancy
Cholangiocarcinoma
Pancreatic cancer
Gallbladder cancer
Ampullary cancer
 Primary sclerosing cholangitis
 AIDS Cholangiopathy
 Intrahepatic
 TPN
 Sepsis
 Primary sclerosing cholangitis
 Primary biliary cirrhosis
 Intrahepatic mass

9. Biliary Obstruction
Canicular cell injury
Alkaline phosphatase
Liver and bone major sources
Increased synthesis and release in liver disease
 Up to 3x normal in variety of liver disease
GGT
Sensitive indicator of canicular cell injury
Parallels alkaline phosphatase increase when of liver origin

10. Patterns of Enzyme Elevation
Hepatocellular injury
AST/ALT
Cholestatic
Bilirubin/alkaline phosphatase
Mixed
Isolated/predominant alkaline phosphatase elevation

11. Caveats to Patterns
Hepatocellular injury
Also results in release of bilirubin
Alkaline phosphatase also found in hepatocyte
Cholestatic
Biliary obstruction can lead to hepatocellular injury

12. What targets the hepatocyte?
 Toxins
 Alcohol
 Medications
Tylenol
 Mushrooms
 Viral
 Hepatitis A/B/C
 EBV/HSV/CMV
 Ischemia
 Severe hypotension
 Vasoconstriction
 Sepsis
 Autoimmune
 Wilson’s
 Alpha-1 antitrypsin deficiency

13. Degree of elevation points to
etiology
>1000 to 2000
Ischemia
Toxin
Virus
>500 to 1000
Acute biliary obstruction
<300
Alcoholic liver disease, cirrhosis, chronic obstruction
AST/ALT>2 and each <300 suggests EtOH or cirrhosis
If >500, unlikely EtOH

14. Mixed Patterns of Elevated Liver
Function
Chronic Liver disease
Hepatitis B, Hepatitis C
NASH
Alcoholic liver disease
Hemochromatosis
Autoimmune hepatitis

15. Isolated or Predominant Alk Phos
Chronic Biliary Disease
Primary biliary cirrhosis
Primary sclerosing cholangitis
Infiltrative disorder
Amyloid
Granulomatous diseases
Metastatic carcinoma
abscesses

16. Elevation after surgery
An elevation of the liver enzymes is not always
suggestive of retained stones.
Studies have shown change in liver function tests of up
to 70% has been reported with no adverse clinical
outcome.
Elevation has been attributed to increased
pneumoperitoneum pressure during the procedure,
which causes hepatic dysfunction.

17. Elevation after surgery
Negative effects of pneumoperitoneum pressure on
cardiac function.
Decrease in cardiac output and stroke volume =
decreases in gastrointestinal and hepatic perfusion