Liver Function Tests from Surgeon's point of view. Hope you find it useful.

1. Liver Function
Test
Dr.Badhrinath J.

2. What ??
• No test can accurately assess Liver’s total
functional capacity
• LFT, preferably called as Liver Biochemical
tests
• Distinguish Liver Disorders
• Severity and progression of Liver disease
• Monitoring the therapy.
• Battery of tests used for evaluation and
Management of patients with Liver Disorders

4. Hepatic Lobule

5. Lobule of Liver

6. Lobule

7. Cell Types
• Parenchymal Cells
• Hepatocytes
• Cytoplasmic = LDH, AST, ALT
• Mitochondrial = ASTm
• Canalicular = ALP, GGT
• Bile Duct Epithelial Cells- active role in the
secretion and absorption of biliary components and
regulation of the extracellular matrix composition

8. Cell Types
• Sinusoidal Cells
• Hepatic Sinusoidal Endothelial Cells- (secrete
PGs,IL-1,IL-6,TNF-α,Endothelin)
• Kupffer Cells (Specialised
Macrophages,removal toxic ,foreign substances
in portal blood)
• Peri-Sinusoidal Cells
• Hepatic Stellate Cells (Vit A storage, Hepatic
Fibrosis)
• Pit Cells(NK cells of liver,Tumour Cell killing
activity,removal of virus infected
cells,growth&diff, Liver Graft Rejection)

9. Functions of Liver
• Metabolic Functions
• Excretory Functions
• Protective functions & detoxification
• Hematological and synthetic functions
• Storage functions
• Serum enzymes

10. The Function of Liver
1. Metabolic Functions
Liver actively participates in carbohydrate metabolism,
lipid, protein, mineral and vitamin metabolisms.
2. Excretory Functions
Bile pigments, bile salts and cholesterol are excreted in bile
into intestine.

11. 3. Protective functions & detoxification
Kupffer cells of liver perform phagocytosis to eliminate foreign
compounds. For example ammonia is detoxified to urea and
metabolism of xenobiotics (detoxification).
Clearance of hormones such as insulin, parathyroid hormone,
oestrogen, cortisol
4. Hematological and synthetic functions
Liver participates in formation of blood (particularly in embryo)
• Synthesis of plasma proteins (albumin and prothrombin),
hormones e.g angiotensinogen, insulin-like growth factor and
triiodothyronine.
• Destruction of erythrocytes by excreting its end products
(Bilirubin)

12. 5. Storage functions
Glycogen, vitamins A, D and B12
6. Serum enzymes
Acting as markers of liver damage

13. Test to assess liver
function
•Liver function tests(LFT) are helpful to detect the
abnormalities and extent of liver damage.
•Typically the LFT comprises of:
•Synthetic Functions
• Albumin
• Prothrombin Time
• Liver Injury
• Transaminases – AST & ALT
• Alkaline PO4ase
• Bilirubin, usually fractionated
• Gamma Glutamyl Transpeptidase (GGT)

14. Bilirubin
• Bilirubin is a breakdown product of heme
(ferroprotoporphyrin IX)
• Bilirubin formed in the reticuloendothelium is lipid
soluble and virtually insoluble in water.
• Transported to liver by binding to albumin.
• After conjugation in hepatocytes, excreted via bile.

15. Bilirubin
• Elevated Total serum bilirubin correlates with
poor outcomes in alcoholic hepatitis -- a critical
component of the model for end-stage liver
disease (MELD) score
• The presence of conjunctival icterus suggests a
total serum bilirubin level of at least 3.0 mg/dL
• Tea- or cola-colored urine may indicate the
presence of bilirubinuria and thus conjugated
hyperbilirubinemia.

16. Bilirubin
• Total bilirubin: 1.0-1.5 mg/dl
• Conjugated bilirubin (Direct ; glucuronide): 0.2-
0.9 mg/dl
• Unconjugated bilirubin ( Indirect; bilirubin -
albumin complex): 0.8-1.2 mg/dl

17. Isolated Bilirubin 

19. Transaminases
• Tests of liver injury
• Hepatocytes contain high levels of enzymes
that can leak into the plasma when there is
liver injury
• Enzymes found in hepatocytes are:
• Cytoplasmic = LDH, AST, ALT
• Mitochondrial = ASTm
• Canalicular = ALP, GGT
• Below normal-chronic kidney disease on
hemodialysis caused in part by vitamin B6
deficiency.

20. Alanine Aminotransferase (ALT)
• The test is primarily used to diagnose liver disease, to monitor
the course of treatment for hepatitis, active postnecrotic
cirrhosis, and the effect of drug therapy.
• The level of ALT abnormality is increased in conditions where
cells of the liver have been inflamed or undergone cell death
• As the cells are damaged, the ALT leaks into the bloodstream
leading to a rise in the serum levels
• Any form of hepatic cell damage can result in an elevation in the
ALT
• ALT level may or may not correlate with the degree of cell death
or inflammation
• ALT is the most sensitive marker for liver cell damage. ALT
differentiates between hemolytic jaundice and jaundice due to
liver disease.

21. Alanine Aminotransferase (ALT)
• serum glutamic-pyruvic transaminase (SGPT)
• Increased ALT levels are found in the following conditions:
- Hepatocellular disease
- Active cirrhosis (mild increase)
- Metastatic liver tumor
- Obstructive jaundice or billiary obstruction (mild to moderate
increase)
- viral, infectious or toxic hepatitis (30-50x normal)

22. Aspartate Aminotransferase (AST)
• serum glutamic oxaloacetic transaminase (SGOT).
• Also reflects damage to the hepatic cell
• It is less specific for liver disease
• It may be elevated and other conditions such as a myocardial
infarct and muscle disease
• Although AST is not a specific for liver as the ALT, ratios between
ALT and AST are useful to physicians in assessing the aetiology of
liver enzyme abnormalities
• Viral heptitis, mononucleosis, and acute hepatotoxicity typically
show elevations in ALT that are equal to or greater than AST
elevations (AST/ALT less than or equal to 1.0)
• ALT is elevated to a lesser degree than AST in alcoholic liver
disease and cirrhosis, passive congestion, bile duct obstruction,
or metastatic tumor to the liver (AST/ALT greater than 1.0)

24. Asymptomatic Transaminases 

25. Alkaline Phosphatase
• The primary value of an elevated serum level
of alkaline phosphatase of liver -recognition of
cholestatic disorders.
• 4 fold elevation of serum ALP -approximately
75% of patients with chronic cholestasis, both
intrahepatic or extrahepatic

26. Alkaline Phosphatase
• Source: liver, bone, placenta and intestine.
• ↑ ALP activity in liver disease are the result of increased
synthesis of the enzymes by cells lining the bile canaliculli,
usually in response to cholestasis (intra or extra-hepatic).
• Also ↑ in infiltrative diseases of liver, when space occupying
lesions (e.g tumours) are present.
• Growing bones need ALP.
• ↑ serum ALP by osteoblast-rapid growth of bone (growth,
healing of fracture, bone cancer, Paget’s disease,rickets).
• For pregnant women, ALP is produce by the placenta.
• ALP from the intestine is increased in a person with
inflammatory bowel disease such as ulcerative colitis.

27. Approach on ALP
Isolated ALP  Cholstatic enzymes

28. Gamma Glutamyl Transferase (GGT)
Enzyme • GGT is used by the body to synthesize glutathione tri peptide
• GGT is present in liver, kidney, pancreas, intestinal cells and
prostrate glands
• Elevated levels (> 10 - 30 IU/l) are observed in :
chronic alcoholism, pancreatic disease, myocardial infarction,
renal failure, chronic obstructive pulmonary disease and in
diabetes mellitus
• In liver diseases, GGT elevation parallels that of ALP
• In alcoholic liver disease GGT levels may be parallel to alcohol
intake

29. Albumin
•Albumin
• Most abundant protein in serum [ 300-500g]
• ↓albumin
• Impaired synthesis (malnutrition, malabsorption,
hepatic dysfunction, cirrhosis)
• Loss (ascites, protein losing-nephropathy,
enteropathy)
• May result in peripheral oedema/unreliable in ascites
• ­albumin
• Unusual – can occur in dehydration or as artifact fm
tourniquet use

30. Albumin
• Unreliable as a marker of hepatic synthetic function in acute
liver injury due to long serum half life 14-21 days
• Serum albumin levels less than 3 g/dL in a patient with
newly diagnosed hepatitis should raise suspicion of a
chronic process
• Serum albumin is an excellent marker of hepatic synthetic
function in patients with chronic liver disease and cirrhosis

31. Prothrombin Time
• Measure of the rate at which prothrombin is
converted to thrombin, reflecting the extrinsic
pathway of coagulation.
• Synthesis of prothrombin Factor- II,V, VII, X.
• Factor VII-shortest serum half-life 6hrs
• Most useful in diagnosis of acute liver disease
• PT INR is useful for monitoring oral anti-coag
therapy Warfarin, not very useful for liver
disease

32. • Causes of prolonged P.T
• hepatic dysfunction,
• congenital deficiency of clotting factors,
• vitamin K deficiency (vitamin K is required for normal
functioning of factors II, VII, IX, and X)
• disseminated intravascular coagulation (DIC).
• DIC identified by measuring a factor VIII level in
serum.
• Vitamin K deficiency -subcutaneous administration
of vit K (e.g., 10 mg) leads to improvement in P.T
by 30%.

33. Ceruloplasmin
• Cu containing enzyme (ferroxidase) in serum
• ↓ in Wilson’s d/s
• Associated with chronic hepatitis (occ acute) and
may have neurologic/ psychiatric sequelae

34. a-Fetoprotein
• One of the major plasma proteins in foetal life
• Function not known, similar structure to albumin
• Falls thru-out gestation (~10,000 ng/mL at birth) and by
age one yr (<10 ng/mL – adult levels)
• In acute hepatic injury AFP ­ 10 – 20X upper ref limits
• Abt 10% pt with viral hepatitis have ­ AFP
• Fibrosis post chronic liver d/s, AFP ­
• Used to screen and diagnose HCC & hepatoblastoma

35. TESTS TO DETECT HEPATIC
FIBROSIS
• liver biopsy is the standard for the assessment of
hepatic fibrosis.
• noninvasive measures of hepatic fibrosis have
been developed.
• measures include single serum biochemical
markers and multiparameter tests aimed at
detecting and staging the degree of hepatic
fibrosis.
• hyaluronan is the best to date

36. Hyaluronan
• Hyaluronan is a glucosaminoglycan produced in
mesenchymal cells .
• Typically degraded by hepatic sinusoidal cells,
• serum levels of hyaluronan are elevated in patients with
cirrhosis as a result of sinusoidal capillarization .
• A fasting hyaluronan level greater than 100 mg/L had a
sensitivity of 83% and specificity of 78% for the detection of
cirrhosis.
• useful for identifying advanced fibrosis in patients with
chronic hepatitis C, chronic hepatitis B, ALD, and
NASH

37. QUANTITATIVE LIVER
FUNCTION TESTS
• Evaluate the excretory or detoxification capacity of the
liver more specifically than the serum bilirubin level.
• lack of specificity and often cumbersome methodology
have limited their widespread acceptance
• Indocyanine green (ICG)
• galactose elimination capacity
• Caffeine clearance tests
• Lidocaine metabolite formation
• 14C and 13C aminopyrine breath tests

38. Take home message
• initial evaluation : assess in clinical context
• classified in 3 groups
1. synthetic function : albumin, clotting
time
2. cholestasis : bilirubin, ALP, GGT
3. hepatocyte injury : AST, ALT

39. LIVER BIOCHEMICAL
TESTING
• Liver biochemical tests have been used to
• monitor for and assess the severity of drug-induced
liver injury,
• assess operative risk,
• identify candidates for liver transplantation,
• direct donor organ allocation.
• Post-op Graft Rejection

40. Thank you