1. Evaluation of Liver Function
Dr. Baghbanian M.
Gastroenterologist
Shaheed Sadoughi hospital / 2012

2. liver tests (1) detect the presence of liver disease
(2) distinguish different types of liver disorders
(3) extent of liver damage
(4) follow the response to treatment

3. Liver tests Can be normal in serious liver disease
Can be abnormal in non hepatic diseases
Rarely suggest a specific diagnosis
They suggest a general category of liver disease, such as hepatocellular or cholestatic

4. liver carries out thousands of biochemical functions
most cannot be easily measured by blood tests.
Laboratory tests measure only a limited number of these functions.

5. Aminotransferases /Alkaline phosphatase
do not measure liver function at all.
Rather, they detect:
liver cell damage
interference with bile flow.
Thus, no one test FOR assess the liver's total functional capacity.

6. Liver test Bilirubin aminotransferases alkaline phosphatase albumin
prothrombin time tests.

7. USE MULTIPLE TEST for detection of liver disease
probability of liver disease is high When :
more than one of these tests are abnormal
tests persistently abnormal on serial determinations
probability of liver disease is lowWhen:
all test results are normal

8. Tests Based on Detoxification and Excretory Functions
Serum Bilirubin
Blood Ammonia
Serum Enzymes

9. Serum Bilirubin
breakdown product of the porphyrin of heme-containing proteins
two fractions:
Conjugated = direct
water soluble
excreted by the kidney.
Unconjugated = indirect
insoluble in water
bound to albumin in the blood.

10. Normal Serum Bilirubin
Total = mg/dL.
Direct <15% of the total → considered indirect
upper limit of normal for conjugated = 0.3 mg/dL.

11. Isolated unconjugated hyperbilirubinemia
is rarely due to liver disease
Causes:
hemolytic disorders
genetic conditions such as :
Crigler-Najjar
Gilbert's syndromes

12. bilirubin elevated but <15% direct
should prompt a workup for hemolysis
In the absence of hemolysis, an isolated, unconjugated hyperbilirubinemia in an otherwise healthy patient can be attributed to Gilbert's syndrome, and no further evaluation is required.

13. conjugated hyperbilirubinemia
always implies liver or biliary tract disease.
In most liver diseases, both conjugated and unconjugated fractions of the bilirubin tend to be elevated

14. rate-limiting step in bilirubin metabolism
transport of conjugated bilirubin into the bile canaliculi
not conjugation

15. Fractionation of the bilirubin
rarely helpful in determining the cause of jaundice
Except : purely unconjugated hyperbilirubinemia,.

16. Degree of elevation of bilirubin
not as a prognostic marker
But is important in :
viral hepatitis: higher bilirubin→ greater hepatocellular damage.
alcoholic hepatitis: Total serum bilirubin correlates with poor outcomes
component of the Model for End stage Liver Disease (MELD)
drug-induced liver disease: elevated total serum bilirubin indicates more severe injury.

17. Urine Bilirubin
Unconjugated bilirubin binds to albumin in the serum and is not filtered by the kidney.
any bilirubin in urine is conjugated bilirubin;
the presence of bilirubinuria implies the presence of liver disease.
In patients recovering from jaundice, the urine bilirubin clears prior to the serum bilirubin.

18. Blood Ammonia is produced
during normal protein metabolism
intestinal bacteriain the colon.
liver plays : detoxification of ammonia by converting it to urea→ excreted by the kidneys
Striated muscle →detoxification of ammonia(combination with glutamic acid )

19. Elevated ammonia levels
Has very poor correlation with:
presence or severity of acute encephalopathy
hepatic function.

20. Elevated ammonia levels
occasionally useful for occult liver disease in mental changes.
correlate with outcome in fulminant hepatic failure.
in severe portal hypertension and shunting around the liver even in normal or near-normal hepatic function.

21. Serum Enzymes The liver contains thousands of enzymes
These enzymes have no known function
probably cleared by reticuloendothelial cells
liver cells damage → entrance of Enzymes into serum

22. 3 type of LIVER enzyme tests
enzymes whose elevation reflects damage to hepatocytes
2) enzymes whose elevation reflects cholestasis
3) enzyme tests that do not fit either pattern.

23. Enzymes that Reflect Damage to Hepatocytes
include:
aspartate aminotransferase (AST) =
serum glutamic oxaloacetic transaminase (SGPT)
alanine aminotransferase (ALT) =
serum glutamic pyruvic transaminase(SGPT)
sensitive indicators of liver cell injury
most helpful in recognizing acute hepatocellular diseases (hepatitis)

24. AST is found in Liver cardiac muscle skeletal muscle kidneys brain
pancreas
lungs
leukocytes, and erythrocytes

25. ALT is found primarily in the liver and is more specific for liver injury.
The aminotransferases are normally present in the serum in low concentrations.

26. Aminotransferases
damage to the liver cell → enzymes release into blood
Liver cell necrosis is not required
poor correlation with degree of liver cell damage
not prognostic in acute hepatocellular disorders.

27. Levels of aminotransferases
normal : U/L.
<300 U/L are nonspecific and may be found in any type of liver disorder.
Minimal ALT elevations in asymptomatic blood donors rarely indicate severe liver disease; fatty liver is the most cause.

28. Aminotransferases >1000 U/L
Extensive hepatocellular injury such:
viral hepatitis
ischemic liver injury (prolonged hypotension or acute heart failure)
toxin- or drug-induced liver injury.

29. The pattern of the aminotransferase
acute hepatocellular disorders: ALT ≥ AST.
chronic viral hepatitis : ALT ≥ AST
cirrhosis : AST ≥ ALT

30. Alcoholic liver disease
AST/ALT >2:1 is suggestive
AST/ALT >3:1 is highly suggestive
The AST is rarely >300 U/L
ALT is often normal.
A low level of ALT in the serum is due to an alcohol-induced deficiency of pyridoxal phosphate.

31. Aproach to asymptomatic elevation of serum aminotransferase

32. Obstructive jaundice Aminotransferases not greatly elevated
Exception: passage of a gallstone into the common bile duct → acute biliary obstruction → aminotransferases 1000–2000 → decrease quickly → liver-function tests rapidly evolve typical of cholestasis.

33. Aproach to isolated elevation of bilirubin

34. Enzymes that Reflect Cholestasis
Are usually elevated in cholestasis
Alkaline phosphatase
5'-nucleotidase
Gama glutamyl transpeptidase (GGT)

35. Gama glutamyl transpeptidase (GGT)
GGT is more diffuse in liver→ is less specific for cholestasis than alkaline phosphatase or 5'-nucleotidase.
GGT in occult alcohol use?
lack of specificity / questionable.

36. Serum alkaline phosphatase
found in :
Liver
Bone
Placenta
Small intestine

37. ALKP non pathologically elevated
Age > 60
Blood types O and B after fatty meal (influx of intestinal ALKP into the blood.)
Children and adolescents undergoing rapid bone growth, (bone)
Late in normal pregnancies (influx of placental )

38. Elevation of liver-derived alkaline phosphatase
Not specific for cholestasis
< 3 fold occur in :
any type of liver disease.
>4 fold occur in:
cholestatic liver disorders
infiltrative liver diseases such as cancer and amyloidosis

39. If an elevated ALKP is only finding
First aproach : ALKP electrophoresis.
Second approach : inactivation by heat
heat-stable : placenta or a tumor is the source.
heat –unstable: intestinal, liver, and bone
measurement of serum 5'-nucleotidase or GGT

40. In the absence of jaundice or elevated aminotransferases, an elevated ALKP of liver origin
Often: early cholestasis
less often: hepatic infiltration by tumor or granulomata.

41. isolated elevations of the alkaline phosphatase
Hodgkin's disease
diabetes
hyperthyroidism
congestive heart failure
amyloidosis
inflammatory bowel disease.

42. Level of ALKP IS NOT helpful in distinguishing
between intrahepatic and extrahepatic cholestasis
obstructive jaundice due to cancer, common duct stone, sclerosing cholangitis, or bile duct stricture.

43. Alkaline phosphatase increased in :
intrahepatic cholestasis due to drug-induced hepatitis
primary biliary cirrhosis
rejection of transplanted livers
rarely, alcohol-induced steatohepatitis.

44. Serum alkaline phosphatase
Greatly elevated in hepatobiliary disorders in AIDS
AIDS cholangiopathy due to cytomegalovirus or cryptosporidial infection
tuberculosis with hepatic involvement

45. Aproach to isolated elevation of ALKP

46. Serum Albumin Synthesized exclusively by hepatocytes.
Long half-life: 18–20 days
Not a good indicator of acute or mild hepatic dysfunction (slow turnover)

47. Hypoalbuminemia
Common in chronic liver disorders such as cirrhosis than in acute liver disease
Reflects severe liver damage and decreased albumin synthesis.
is not specific for liver disease and occur in:
protein malnutrition
protein-losing enteropathies
nephrotic syndrome
chronic infections that inhibit albumin synthesis.

48. Serum Globulins Immunoglobulins produced by B lymphocytes
Globulins are increased in chronic hepatitis and cirrhosis.

49. increased Serum Globulins
In cirrhosis: due to the increased synthesis of antibodies against intestinal bacteria.
Cause : cirrhotic liver fails to clear bacterial antigens that normally reach through the hepatic circulation.

50. Specific globulins are helpful in recognition of certain liver diseases
Diffuse polyclonal IgG ↑ in autoimmune hepatitis
IgM ↑in primary biliary cirrhosis
IgA ↑ in alcoholic liver disease.

51. Coagulation Factors Are made exclusively in hepatocytes.
Exception: factor VIII,
(which is produced by vascular endothelial cells)

52. Coagulation Factors Half-lives are shorter than albumin
6 h for factor VII to 5 days for fibrinogen.
Single best acute measure of hepatic synthetic function FOR diagnosis and assessing the prognosis of acute parenchymal liver disease.

53. Coagulation Factors
Prothrombin time : measures factors II, V, VII, and X.
(25710)
Depends on vitamin K: synthesis of factors II, VII, IX, and X
(29710)

54. Prothrombin time May be elevated in : hepatitis cirrhosis
vitamin K deficiency
obstructive jaundice
fat malabsorption

55. prothrombin time >5 s above control
If not corrected by parenteral vitamin K
is a poor prognostic sign in acute viral hepatitis and other acute and chronic liver diseases.

56. MELD (model of end stage liver disease)
Allocate for liver transplantation.
Has 3 component:
INR,
Total serum bilirubin
Creatinine

57. Percutaneous Liver Biopsy
Is a safe procedure
Easily performed at the bedside
With local anesthesia and ultrasound guidance.

58. Percutaneous Liver Biopsy Indication
Hepatocellular disease of uncertain cause
Prolonged hepatitis (chronic active hepatitis)
(3) Unexplained hepatomegaly
(4) Unexplained splenomegaly
(5) Hepatic filling defects IN imaging
(6) Fever of unknown origin
(7) Staging of malignant lymphoma

59. Liver biopsy
is most accurate in disorders causing diffuse changes IN liver
Sampling error in focal infiltrative disorders such as hepatic metastases.
Should not be the initial procedure in cholestasis.

60. Liver biopsy Contraindications
Significant ascites
Prolonged INR
Under these circumstances, the biopsy can be performed via the transjugular approach

61. Ultrasonography First diagnostic test in cholestasis:
dilated intrahepatic
extrahepatic biliary tree
gallstones.
space-occupying lesions IN liver, →distinguish between cystic and solid masses, and helps direct percutaneous biopsies.

62. Ultrasound with Doppler
Detect the patency of the :
portal vein
hepatic artery
hepatic veins
First test in patients suspected Budd-Chiari syndrome.

63. Abnormal in...
Liver Test
Cirrhosis, severe hepatocellular injury
Albumin
Cholestasis, hepatocellular enzyme induction, canalicular injury, children during bone growth, bone disease, pregnancy (placenta origin)
Alkaline phosphatase
Hepatocellular injury (ethanol, drug-induced hepatitis, hepatitis B and C, ischemic injury, chronic liver disease, NAFLD, chronic viral hepatitis, alcoholism, nonspecific viral injury, and cholestatic or replacement disease); acute biliary obstruction; rarely in hyperthyroidism, celiac disease, skeletal muscle disease
Aminotransferases (AST, ALT)
Any acute or chronic liver disease; congenital disorders of bilirubin metabolism.
Bilirubin
Cholestasis
5′ nucleotidase
Cholestasis; medications, ethanol; rarely anorexia nervosa, hyperthyroidism, myotonic dystrophy
GGT
Impaired synthesis of vitamin K-dependent coagulation factors
INR
Ischemic injury, Epstein-Barr virus infection, hemolysis, solid tumor
Lactate dehydrogenase
Alcohol consumption, gout
Uric acid

64. Aproach to cholestatic liver enzyme elevations