liver function tests evaluation

1. EVALUATION OF
LIVER FUNCTION
TESTS
Guide - Dr. Manohar Lal Prasad
Presenter - Dr. Dhiraj Kumar
Source - Harrison’s principles of internal medicine
19th edition.
Sleisenger and Fortrans textbook of
gastrointestinal and liver disease.

2. LIVER FUNCTION TEST USED TO:
Detect presence of liver disesase
To know the extent of known liver diseases
Distinguish among different types of liver diseases
Follow the response to treatment

3. Liver function tests
Can be normal
in pt. with
serious liver
diseases
Rarely suggests
specific diagnosis
rather suggest
general
categories of liver
disease
Hepatocellular
Cholestatic , or
infiltrative
They detect –
liver cell
damge,
interference
with bile flow

4. Functions of liver
Metabolic
functions
Excretory
functions
Synthetic
functions
Storage
functions
Detoxification
functions

5. Tests based on detoxification function:
Blood
ammonia
level

6. Tests based on excretory functions:
Sr. bilirubin
Urine
bilirubin
Urine and
fecal
urobilinogen
Urine bile
salts

7. Tests based on synthetic functions:
Plasma
protein
Prothrombin
time

8. Tests based on metabolic functions
Carbohydrate metabolism
• Galactose tolerance test
Lipid metabolism
• Sr Cholesterol
Protein metabolism
• Sr Protein
• Aminoaciduria

9. Enzymes in diagnosis of liver diseses
ENZYMES
•AST(SGOT)
•ALT(SGPT)
ENZYMES
•ALP
•GGT
•5’NT

10. Tests used in clinical practice
Sr . Bilirubin ALT(SGPT) AST(SGOT)
Alkaline
phosphatase
Serum
Albumin
Prothrombin
time

11. Sr. Bilirubin
• Breakdown product of porphyrin ring of heme
containing protein( myoglobin, cytochrome,
peroxidase)
• Two fractions:
• Conjugated(Direct)(water soluble)(excreted by kidney)
• Unconjugated (indirect)(water insoluble) (bound to
albumin)
• Normal value- 1- 1.5mg/dl
• In case of hyperbilirubinemia, if direct fraction <15% -
Unconjugated hyperbilirubinemia
• Direct fraction- Upper limit of normal range is 0.3mg/dl

14. CAUSES OF HYPERBILIRUBINEMIA
Isolated increase in unconjugated bilirubin is due to –
1. Hemolytic disease
2. Genetic disorders – crigler najjar and gilbert’s syndrome
3. Neonatal jaundice/physiological jaundice
Isolated increase in conjugated bilirubin is due to –
1. Cholestasis
2. Genetic disorders – Dubin johnson syndrome and rotor’s
syndrome
Increase in both conjugated and unconjugated bilirubin is due
to –
1. Intrahepatic /liver disorders

17. Degree of elevation of Sr bilirubin
significant in:
Viral hepatitis
Alcoholic hepatitis
Drug induced liver disease

18. Model for End Stage Liver
Disease(MELD) Score
• Criteria for listing a pt. for liver transplantation
• Range of MELD score is 6 to 40
• Liver tansplantation done in those pt who
have >15 MELD score
• MELD score – bilirubin, creatinine, PT as INR
• MELD score >= 21 high mortality in alcoholic
hepatitis

19. Urine Bilirubin:
Any bilirubin in urine- Conjugated bilirubin
Unconjugated fraction is water insoluble and albumin
bound, hence not filtered
Phenothiazine give false positive
Recovering from jaundice urine bilirubin clears prior to
Sr bilirubin

20. Bile salts:
• Are products of cholesterol metabolism
• Facilitate absorption of fat from intestine
• Primary bile salts- cholate & chenodeoxycholate,
produced in liver
• Metabolised by bacteria in intestine
• Produces secondary bile salts-lithocholate &
deoxycholate

21. Bile salts
In cirrhosis- decreased ratio of primary to secondary bile salts
In cholestasis - secondary bile salts not formed – increased ratio of
primary to secondary bile salts
Normally renal excretion of bile salt is negligible
Cholestasis increase renal excretion of bile salt
Measured by- Hay’s test, HPLC

22. BLOOD AMMONIA:
Produced in body during normal protein metabolism
& by intestinal bacteria( specially in colon)
Detoxification of ammonia
In liver – get converted to urea-excreted in kidney
In striated muscles- combines with glutamine –
glutamic acid

23. Advanced liver
disease
• Significant muscle wasting
• Contributes to hyperammonemia
Increased blood
ammonia
• Detect occult liver disease with mental status
change
Increased blood
ammonia
• In severe portal hypertension
• Portal blood shunts around liver
Increased arterial
ammonia
• Correlates with fulminant hepatic failure
outcome

24. ENZYMES IN LIVER DISEASES
• Sr transaminases
• Aspartate
aminotransferases
(AST)(SGOT)
• Alanine aminotransferases
(ALT)(SGPT)
• Alkaline phosphatase(ALP)
• Gamma glutamyl
transpeptidase(GGT)
• 5’ Nucleotidase(5’NT)

26. Sr enzyme test grouped in two
categories:
Enzymes whose elevation reflect
damage to hepatocytes
Enzyme whose elevation reflect
cholestasis
Enzyme showing infiltrative pattern

27. Enzymes that reflect damage to
hepatocytes:
Aspartate aminotransfersase(AST)(SGOT)
Alanine aminotransferases(ALT)(SGPT)
AST(SGPT) is found in liver > cardiac muscles > skeletal muscles> kidney>
brain >pancreas> lungs> WBC >RBC
ALT(SGPT) is found primarily in liver.( more liver specific)
Normal range is 10-40 IU/L

28. • Sr aminotransferases upto 300 IU/L are non
specific
• Minimal ALT elevation Fatty liver disease
• If levels >1000 IU/L reflects extensive
hepatocellular injury seen in:
1. Viral hepatitis
2. Ischemic liver injury( prolonged hypotension
or acute heart failure
3. Toxin/drug induced liver injury
In most acute hepatocellular disorder ALT >=AST

29. AST/ALT Ratio:
• Normal ratio 0.7 to 1.4
• Useful in 1. Wilson disease
2. Chronic liver disease
3. Alcoholic liver disease
• AST/ALT <1 seen in 1.Chronic viral hepatitis
2.NAFLD
• AST/ALT >2:1 suggestive & 3:1 is highly suggestive of
alcoholic liver disease
• In alcoholic liver disease : ALT rarely >300 & ALT often
normal( alcohol induced deficiency of PYRIDOXAL
PHOSPHATE)

30. Aminotransf
-erases not
increased in
obstructive
jaundice
except
During
the
acute
phase of
biliary
obstructi
on
Due to
passage of
gall stone
into CBD
In this
aminotran-
sferases
1000-2000
IU/L

31. AST(SGOT)
• 2 forms
1. Cytosolic
2. Mitochondrial (mAST) – synthesized in
precursor form( pre-mAST)
converted to mature form
• Account for 80% of total AST activity in liver cells
• mAST/ total AST ratio- marker of chronic alcohol
consumption

32. • Isolated rise of ALT is seen in
1. Chronic HepC infection
2. Fatty liver
• Isolated AST elevation
1. Alcohol related
2. Drug induced liver injury
3. Hemolysis
4. Myopathic processes
These enzymes distinguish hepatocellular from
cholestatic jaundice
• Increase in ALT and AST (>500 IU/L) in hepatocellular
jaundice than in cholestatic jaundice(>200 IU/L)
• Persistence of elevated AST & ALT beyond 6 month in
case of hepatitis – chronic hepatitis

34. Enzymes showing cholestasis:
• 3 enzymes are elevation in cholestasis
1. Alkaline phosphatase(ALP)
2. 5’Nucleotidase(5’NT)
3. Gamma glutamyl transpeptidases(GGT)
ALP & 5’NT – in or near bile canalicular membrane
of hepatocytes
GGT located in ER & bile duct epithelial cells(less
specific for cholestasis)
GGT (sometimes) used to identify occult alcohol use

35. • ALP isoenzyme is found in 1. Liver
2. Bone
3.Placenta
4. Small intestine
• Physiological rise in ALP
1. Age >60 years ( 1-1.5 times)
2. Blood type O & B (after eating a fatty meal due
to influx of intestinal ALP in blood)
3. Children and adolescents ( rapid bone growth)
4. Late in normal pregnancies( placental ALP)

36. • ALP < 3 times – any liver disease
• ALP> 4 times 1. Cholestatic liver disease
2. Infiltrative liver disease(cancer
& amyloidosis)
3. Pagets disease of bone( rapid
bone turnover)
If ALP is raised – source of isoenzyme by:
1. Fractionation of ALP by electrophoresis
2. Measure GGT &5’NT –elevated only in liver disease
3. Different isoenzymes have different heat
susceptibility
i. Increased heat stable fraction – MC from placenta
ii. Sensitive to heat inactivation- Bone ALP

38. Normal levels
Sr GGT 10 to 47 IU/L
Sr 5’ NT 2 to 17 IU/L
Sr ALP 39 to 117IU/L

39. Tests based on Biosynthetic function
Plasma proteins
Coagulation
factors(Prothrombin
time P.T.)

40. Plasma proteins
• Liver is the sole source of plasma proteins except for
immunoglobulins( by plasma cells)
• Sr albumin comprises 60% of all plasma proteins
• Tests of plasma protein include:
1. Total Sr protein
2. Sr albumin
3. Sr globulin
4. Sr A/G ratio
5. Pre albumin
6. Pro collagen III peptide
7. Ceruloplasmin

41. Albumin
• Synthesized exclusively by hepatocytes
• Long half life 18 – 20 days; 4% is degraded per day
• Slow turn over – not a good indicator of acute or mild hepatic
dysfunction
• In hepatitis , albumin < 3 mg/dl – Chronic liver disease like
cirrhosis, reflects liver damage and decreased albumin synthesis
• Non hepatic cause of low albumin:
1. Protein malnutrition
2. Protein losing enteropathy
3. Nephrotic syndrome
4. Chronic infection(increased levels of IL-1, TNF, Cytokines- inhibit
albumin synthesis

42. Sr Globulin
• Made of alpha, beta , gamma globulin
• Alpha & beta globulin produced primarily in
hepatocytes
• Gamma globulin produced by B lymphocytes
• In Cirrhosis and Chronic hepatitis – gamma globulin is
increased ( Cirrhotic liver fails to clear bacterial antigen
from intestine which come through hepatic circulation)
• Diffuse polyclonal IgG – Auto immune hepatitis
• Increased IgM – Primary biliary cirrhosis
• Increased IgA- Alcoholic liver disease

43. • Pre Albumin
1. Level falls in liver diseases
2. Half life 2 days
3. Sensitive indicator of change in synthetic & catabolic
function
4. Useful in drug induced hepato toxicity
• Ceruloplasmin
1. Acute phase protein
2. Normal plasma level 0.2 – 0.4g/l
• Decreased in Increased in
1. Wilson disease 1.Copper toxicity
2. Menke’s disease 2. Pregnancy
3. Aceruloplasminemia 3. OCPs
4. Copper deficiency

44. Pro collagen III peptide
• Cleavage product of type III procollagen molecule
• Radioimmuno assay
• Increased when there is transformation of viable
hepatic tissue into connective tissue / fibrosis
• Used in evolution of liver disease like:
1. Chronic active hepatitis
2. Liver fibrosis
3. Liver cirrhosis

45. Coagulation factors
• Except factor VIII, clotting factors synthesized in
liver
• Half life ranges 6 hrs( factor VII) to 5 days
(fibrinogen)
• Measurement is single best measure of hepatic
synthetic function
• Diagnosis and prognosis of acute parenchymal
liver diseases
• Test – Prothrombin time(PT)
• PT measures II, VII, IX, X activity - Vit K dependent

46. PT & INR
• INR- Degree of anti coagulation on warfarin therpy
• International Sensitivity index(ISI): INR standardise PT
measured according to thromboplastin reagent used in any
lab expressed as ISI.
• ISI is used to calculate INR
• PT is increased in
1. Hepatitis
2. Cirrhosis
3. Vit k deficiency- obstructive jaundice, fat malabsorption
4. If PT > 5 times , not corrected by parenteral Vit k - poor
prognostic sign in acute viral hepatitis & other liver
disease
INR is part of MELD Score

47. LFT in Anti TB treatment
• LFT should be preferred before starting anti TB
treatment
• With use of rifampicin & isoniazid , onset of liver
damage may be as soon as 10 days or may be upto 1yr
after commencing therapy
• So LFT should be repeated routinely
• High risk groups are –
1. Malnourished
2. Children and elderly
3. Known liver disease
- Alcoholic liver disease
- Hepatitis B &C

48. Percutaneous liver biopsy
Can be performed bedside with LA
Done in
• Hepatocellular disease of uncertain cause
• Prolonged hepatitis with possibility of auto immune
hepatitis
• Unexplained hepatitis
• Fever of known origin
• Staging of malignant lymphoma
Contradiction of percutaneous liver biopsy
• Significant ascites
• Prolonged INR
In these conditions transjugular approach is done.

49. Transient Elastography (FibroScan)
• Ultra sound waves to measure hepatic stiffness
non invasively
• Useful for early fibrosis in
1. Chronic Hep C
2. Primary Biliary Cirrhosis
3. Hemochromatosis
4. NAFLD
5. Recurent chronic hepatitis after liver
transplantation

51. Evaluation of chronically abnormal
liver tests