1. Liver function tests evaluate the liver's excretory, synthetic, and biochemical functions through markers like bilirubin, aminotransferases, alkaline phosphatase, albumin, and prothrombin time. 2. Elevated aminotransferases indicate hepatocellular injury from factors like viral hepatitis, drugs, or ischemia. Alkaline phosphatase is elevated in cholestatic conditions from intrahepatic or extrahepatic bile duct obstruction. Albumin and prothrombin time reflect synthetic function. 3. Interpreting liver function tests involves considering the pattern of marker elevations, clinical history of exposures, and additional tests to determine the specific cause and severity of liver disease.

1. APPROACH TO ABNORMAL
LIVER FUNCTION TEST
DR SOURAV PATRA
GUIDED BY: PROFESSOR
DR SOUMYA SARATHI MONDAL
DEPARTMENT OF GENERAL MEDICINE
MEDICAL COLLEGE, KOLKATA

2. OVERVIEW
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Liver- Perform various kinds of biochemical ,synthetic ,excretory
functions
No single test can detect global liver dysfunction
Clinical history, physical examination most important in
interpretation of liver function test

3. History
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Exposure to any chemical or medication (prescription/OTC/
herbal)
Accompanying symptoms: fever, jaundice, arthralgias, myalgias,
rash, anorexia, weight loss, abdominal pain, pruritus, blood in
stool.
Parenteral exposures: Blood transfusions, IV drug use, tattoos
High risk sexual behaviour
Alcohol consumption
Occupational exposure to hepatotoxins

4. LIVER FUNCTION TEST
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A. Excretory Function
1. Bilirubin
Total bilirubin
Direct bilirubin
B. Measurement of Enzymes
2. Serum aminotransferases
Aspartate Aminotransferase(AST)
Alanine Aminotransferase(ALT)
3. Gamma Glutamyl Transferase
4. Alkaline phosphatase
C. Synthetic Function
5.Albumin
6. Prothrombin Time

5. Uses
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1. Detect the presence of liver disease
2. Distinguish among different types of liver disorders
Hepatocellular
Cholestatic
Mixed
3. Gauge the extent of known liver disease
4. Follow the response to treatment

6. Patterns of abnormal Liver Function TEST
Pattern Cause
AST , ALT > ALP
Bilirubin
Hepatocellular Injury
ALP > AST , ALT
Bilirubin
Cholestasis
Albumin Chronic process
Albumin Acute process
PT/INR Vitamin K deficiency, Obstructive Jaundice

7. R value
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To differentiate hepatocellular-mixed-cholestatic pattern
R = (ALT value / ALT ULN) ÷ (ALP value / ALP ULN)
R value:
>5 hepatocellular pattern
Between 2-5 mixed pattern
<2 cholestatic pattern

8. Hepatocellular Damage

9. Markers of Hepatocellular Damage
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ALT & AST most frequently used
Released when hepatocytes damaged
Normal values:
ALT: <35 IU/L (Clinical biochemistry laboratory, MCK)
AST: <45 IU/L (Clinical biochemistry laboratory, MCK)
Patterns to note:
AST:ALT ratio
Level of elevation
Rate of decline

10. ALT AST
Cytosol
• Cytosol 20%, mitochondria 80%
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More specific for liver
• Other tissues: Cardiac muscle, smooth muscle, kidney,
brain, pancreas, lung, leucocytes, erythrocytes
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SGPT (Serum Glutamic Pyruvate Transaminase) SGOT (Serum Glutamic Oxaloacetic Transaminase)

11. Ratio of AST to ALT
A.
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The ratio of AST to ALT in serum is helpful in few specific circumstances--
Alcoholic liver disease: AST level is less than 300 U/L , a ratio –
>2 suggests alcohol associated liver disease
>3 highly suggestive of alcohol- associated liver disease
B. <1: Chronic viral hepatitis and NAFLD. As cirrhosis develops the ratio rises and may
become greater than 1

12. Level of Elevation
Serum aminotransferase levels are typically elevated in all forms of liver injury

13. Chronic Mild Elevations, ALT>AST(
<150U/L 0r 5 x Normal)
Hepatic Nonhepatic
Wilson Disease Celiac disease
Autoimmune hepatitis Hyperthyroidism
Chronic viral hepatitis(hepatitis B, hepatitis C)
Hemochromatosis
Steatosis
Alpha1-Antitrypsin deficiency

14. Severe, Acute Elevations,
ALT>AST(>1000U/L or >20-25 x Normal)
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Acute Viral Hepatitis
Drugs and Toxins
Ischemic Hepatitis

15. Severe Acute Elevations, AST>ALT
(>1000U/L or >20-25 x Normal)
Hepatic Nonhepatic
Medications or toxin in a patient with underlying
alcohol-associated liver injury
Acute rhabdomyolysis

16. Chronic mild Elevations, AST>ALT(<300
U/L)
Hepatic Non hepatic
AST/ALT > 2 is suggestive and >3 is highly
suggestive of alcohol associated liver disease
Strenuous exercise
Cirrhosis

17. Rate of Decline
Fast Slow
Drugs Acute Viral Hepatitis
Ischemic Hepatitis Autoimmune Hepatitis
Acute biliary tract obstruction Metabolic Disorders

18. Elevation of serum Aminotransferase
levels
Drug history, including
Ayurvedic and
homeopathy,
Alcohol history
Stop potential toxins
Follow response of
Aminotransferase
levels
Measure CK to
exclude muscle
injury
Scrub typhus Ig M
antibody test
HBsAg, Anti-HCV, anti HAV
Anti HEV antibody
History of fever
jaundice
HCV RNA
Anti-
HCV+
HBV DNA ,HBeAg
HBsAg+
+drug
history

19. Continued--
Iron profile,
ANA,SMA,LKM-1
Ceruloplasmin
Ultrasonography
Alpha-AT phenotype
TTG antibody
HFE gene
testing
Liver Biopsy
Liver Biopsy
ANA+,SMA+,
Globulin
Increased iron,
increased ferritin
Ophthalmoscopic
examination
24-hr urine copper
Liver biopsy
Recommend
Weight loss
Liver biopsy if
aminotransferase
levels elevated >2
times ULN
Fatty liver
on USG
Ceruloplasmi
n
Evaluation
unrevealing
Evaluation
unrevealing

20. Cholestasis

21. Alkaline Phosphatase (ALP)
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Marker of cholestasis
Half life: 7days
Sources:
Canalicular membrane of hepatocytes
Osteoblasts
Gut
Kidney
Placenta

22. Raised ALP Causes
Physiologic Causes Pathologic Causes
Age > 60 years Intrahepatic cholestasis
Children, adolescents Extrahepatic cholestasis
Pregnancy
Blood group O and B
Post fatty meal

23. Raised ALP: Pathologic Causes
Intra hepatic obstruction Extra hepatic obstruction
Drugs Intraluminal: Choledocholithiasis
Sepsis Bile duct wall: Cholangiocarcinoma
Infiltrative liver disease Extraluminal: Pancreatic cancer, metastases,
Mirizzi syndrome
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Infections (Brucellosis, Tb, histoplasmosis)

24. Gamma Glutamyl Transpeptidase(GGTP)
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Sources:Liver, Kidney, pancreas, spleen ,Heart, Brain and seminal vesicles
The primary use of serum GGTP level is to identify the source of an isolated elevation in the serum
ALP level
Not found in bone and not raised in pregnancy
Serum level are not different between men and women
Drugs like antiepileptics, barbiturates and some antiretroviral drugs elevates GGTP
Serum GGTP levels are elevated in alcoholics

25. Evaluation of Alkaline phosphatase
elevation with biochemical and radiological
investigations Fractionate ALP or
measure GGTP Bone Evaluation
Bone origin
Ultrasonography
Liver
origin
CT, ERCP
Dilated
intrahepatic
Bile ducts
Drug history, viral
serologies
AMA, ACE level
Intrahepatic
Bile ducts
Not dilated
Liver
Biopsy
MRCP
Liver Biopsy
AMA+ Evaluation
negative

26. Biosynthetic Function

27. Albumin
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Albumin is the most important plasma protein, accounts for 75% of the plasma colloid
oncotic pressure
Synthesis: 15g/day
Half life: 14 -21 days
The long half life of albumin in serum accounts for its unreliability as a marker of hepatic
synthetic function in acute liver injury.
Not specific:
Depends on nutrition, volume status, vascular integrity, catabolism, stool/urine losses

28. Prothrombin time
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Measurement of the rate at which prothrombin is converted to thrombin
The extrinsic pathway depends on the activity of clotting factors II, V, VI
& X– all of which are synthesized in liver.
Therefore prothrombin Time is the reflection of synthetic function of
liver
In acute liver diseases, it is a reliable indicator of synthetic function due
to shorter half lives of the clotting factors.
Prothrombin Time more than 5 second of control is poor prognostic
sign in acute viral hepatitis and other acute and chronic liver disease
PT(II,V,VII,X) is dependent on vit K, can be increased in vit K
deficiency(obstructive jaundice or fat malabsorption)

29. Bilirubin
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Normal value of total bilirubin is (.1- 1.5) mg/dl and half life 4 hrs
If direct bilirubin is less than 15% of total, the bilirubin can be considered
to be entirely indirect
Increase in total bilirubin level correlates with poor outcomes in
alcoholic hepatitis and greater hepatocellular damage in viral hepatitis
It is a critical component of MELD score, which is used to estimate
survival of patients with end-stage liver disease

30. Direct Bilirubin
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Conjugated
Water soluble
Polar
Seen in urine
Elevated with biliary
obstruction and
hepatocellular disease
Indirect Bilirubin
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Unconjugated
Lipid soluble
Non-polar
Not in urine
Elevated with haemolysis,
ineffective erythropoiesis ,
drugs

31. Causes of isolated hyper bilirubinaemia
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A Unconjugated
Increased bilirubin production
Haemolysis
Ineffective erythropoiesis
Hypersplenism
Decreased hepatic uptake
Drugs-rifampicin
Decreased conjugation
Gilbert’s syndrome
Criggler-Najjar syndrome
B Conjugated
1. Dubin-Johnson syndrome
2. Rotor’s syndrome

33. Limitations
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Lack sensitivity ( may be normal in cirrhosis )
Lack specificity ( aminotransferase levels may be elevated in
musculoskeletal or cardiac disease)
Aminotransferases and ALP do not measure liver function at all,
rather they detect liver cell damage or interference with the bile flow
Result suggest general category of liver disease, not a specific
diagnosis

34. •
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Interpretation of laboratory values in patients with
abnormalities in liver function testing is critical to developing
a differential diagnosis and initiation an adequate work-up.
The initial step is determination of an acute, chronic or acute-
on-chronic process
Upon establishment of disorder, the role of us is to establish
the severity of hepatic dysfunction, potential for reversibility
and the need for treatment
Conclusio
n

35. Sources

36. THANK YOU