1. Liver Funtion tests
Dr Abdul Qayyum Khan

2. Liver Function profile (LFT)

3. LIVER FUNCTION TESTS
• USED TO ;
• Detect presence of liver disease.
• Distinguish among different types of liver dieases.
• Estimate the extent of known liver damage.
• Follow the response of treatment

4. LIVER FUNCTION TESTS
• Disadvantages ;
• Rarely suggest a specific diagnosis.
• Can be normal in pts with serious liver disease and
abnormal in pts with diseases that do not affect the liver
• Only categorises into hepatocellular or cholestatic or
pre-hepatic.

5. Clinical Lab tests
Liver Function Test (LFT) profile
Synthetic function
Execratory function
Integrity of liver cells
Bilirubin
Proteins
TP, Alb, A/G ratio
Liver enzymes
AST, ALT, GGT, ALP

6. Tests based on detoxification & excretory
functions
• Serum bilirubin
• Urine bilirubin
• Blood ammonia

7. RE cell plasma hepatocyte
HEME UCB UCB
+
albumin
UCB+ligandin
BMG
BDG
bile
urobilinogen stercobilinogen
Bilirubin
UDP-glucoronyltransferase

8. Bilirubin Metabolism

9.  Total bilirubin = D+ ID
 Direct bilirubin: is conjugated (water soluble bilirubin).
 Indirect bilirubin: is unconjugated (water insoluble bilirubin).
 Normal levels are:
 Direct (also called conjugated) bilirubin: 0 to 0.3 mg/dL
 Total bilirubin: 0.3 to 1.0 mg/dL
 Unconjugated is calculated by subtracting direct from
total and so called indirect.

10. Gilbert’s syndrome
Benign, unconjugated hyperbilirubinemia with
otherwise normal liver chemistries
up to 5% of normal population
Polymorphisms of gene encoding bilirubin UDP-GT
 impaired ability to conjugate bilirubin
Prominent in fasting state, systemic illnesses,
hemolysis, some medications

11. Blood Ammonia
• Produced by normal protein metabolism, by
intestinal bacteria in colon.
• Liver – detoxification – converting into urea which is
excreted by kidneys.
• Patients with advance liver disease- significant
muscle wasting contributes to hyperammonemia
• Used for detecting hepatic encephalopathy or
hepatic synthetic functions.

12. Tests for bio-synthetic function of the liver
 Estimation of plasma proteins Total Protein ;
Serum Albumin ; Serum Globulins
Tests for reversal of A:G ratio
Tests for coagulability of blood ; PT ,INR
Plasma protein Normal levels
Total 6.4 – 8.3 g%
S. Albumin 3 – 5 g%
Serum globulin 2 – 3 g%
Serum fibrinogen 0.3 g%
Serum prothrombin 40 mg%
A:G ratio 1.7 : 1

13. Serum albumin
• Produced by hepatocytes Normal : 3.5 – 5 g/dl
• S. albumin <3 g/dl  suspect chronic liver disease.
• About six months stores are present in liver therefore
S. Albumin is not a good indicator of acute/mild hepatic
dysfunction
• Hypoalbuminemia – not specific for liver disease
– Protein malnutrition of any cause
– Protein losing enteropathies
– Nephrotic syndrome
– Chronic infections
– Burns
• Reversal of A : G ratio  chronic liver dysfunction.

14. Prothrombin Time ,INR
Normal : 11.5 – 12.5 sec
Prolongation of PT by 2 sec / more – Abnormal.
PT – factors II,V, VII, X
Rapid turnover –
Best measure of hepatic synthetic functions & helpful
for diagnosis of acute parenchymal liver disease.
• Most present in excess, clotting abnormality occurs
only when substantial impairment in ability of liver
to synthesise the Clotting factors.
PT prolonged – hepatitis, cirrhosis,
vit K deficency ( obs.jaundice, fat malabsorption)

15. Serum Enzymes
• Aminotransferases (AST,ALT) .
Sensitive indicators of liver cell injury
Helpful in recognizing hepatocellular
disease such as hepatitis.

16. Evaluation of abnormalities of ALT (SGPT) and
AST (SGOT) levels
 AST and ALT are markers of hepatocellular injury
 AST present in cytosol and mitochondria in liver, cardiac
muscle, skeletal muscle, kidney, brain, pancreas, lungs,
WBC and RBC.
 ALT a cytosolic enzyme, highest concentration in the liver.
 ALT considered a “liver specific” enzyme.

17. Alanine Aminotransferase(SGPT)
Normal : 7 – 41 U/L
ALT found primarily in liver.
Upto 300U/L – Nonspecific , any type of liver
disorder(CLD…cirrhosis /malignancy)
>1000U/L – Extensive hepatocellular damage
( viral hepatitis, ischemic liver injury ,
toxin /drug induced liver injury )

18. Aspartate Aminotransferase (SGOT)
 Normal – 12 – 38U/L
 Two Iso enzymes- cytoplasmic, mitochondrial
 Mild degree of tissue injury – cytoplasmic form in serum
 Severe injury – mitochondrial type in serum
 Significant elevation – Myocardial Infarction.
 Moderate elevation – liver disease
 AST – liver , cardiac muscles, skeletal muscle, kidneys,
brain, pancreas, lungs, leucocytes,
RBC in decreasing order.

19. Serum Enzymes – that reflect cholestasis
Three enzymes
Alkaline Phosphatase
5’Nucleotidase
Gamma glutamyl transpeptidase

20. Alkaline Phosphatase
• Normal :40 – 125 U/L
• Iso enzymes
• Alpha -1 ALP – Epithelial cells of biliary canaliculi ,
increased in obs.jaundice.
• Alpha-2 heat labile ALP – Hepatic cells , increased in
hepatitis
• Alpha -2 heat stable ALP – Placental origin, normal
pregnancy
• Pre Beta ALP – Bone origin , increased in bone disease.
• Gamma ALP – Intestinal cells, increased in
Ulcerative colitis
• Leucocyte ALP – Increase – lymphoma,
Decrease – CML .

22. Gamma glutamyl transpeptidase
• Used in body for synthesis of glutathione
• 11 iso enzymes.
• Present in liver, kidney, pancreas, intestinal cells,
prostate.
• Normal : 9 – 58 U/L.
• Unlike ALP , the level is unrelated with osteoblastic
activity ie.. Unaffected by bone disease.
• Slightly high normally in males due to prostate.
• To detect alcohol abuse.

23. GGT
• Raised even when other LFT are normal in
alcohalics.
• GGT falls rapidly within few days after abstinence.
• Mod rise – infectious hepatitis, prostate Ca
• High rise – Alcoholism,
Obstructive jaundice,
Neoplasms of liver

24. Take home message
Classified in 3 groups
1. Synthetic function : albumin, clotting time.
2. Cholestasis : bilirubin, ALP, GGT
3. Hepatocyte injury : AST, ALT

25. Patterns of Abnormal
• Elevations in ALT & AST only:
Suggests cellular injury
• Elevations in Alk Phos & Bilirubin:
Suggests cholestasis or obstruction
• Mixed pattern: ALT, AST, AP & Bili:
Probably the most common scenario

26. Summary
• Liver tests are numerous and somewhat
confusing.
• Not all liver disease is associated with
abnormal test results.
• Some of the worst liver disease has relatively
normal appearing LFT’s and can only be
noticed with a look at synthetic functions.

27. Misnomer
– Does not effectively assess actual function
– Not always specific for the liver
– limited information regarding presence or
severity of complication
Liver Function Tests

28. Liver Synthetic Function
• Total Protein and serum albumin
• Total Bilirubin
• Prothrombin Time (PT / INR)
• These are “true” tests of liver function

29. LFTs
• 1) Markers of acute hepatocyte injury & death:
AST (SGPT), ALT (SGOT), Alk Phos.
• 2) Measures of hepatocyte synthetic functions :
PT, Albumin
• 3) Indicators of hepatocyte catabolic activity:
Direct & indirect bilirubin , ammonia
• 4) Others:
Lactate dehydrogenase, viral hepatitis serology

30. Neonatal Jaundice
 Neonatal jaundice is common
50% healthy term infants
Chances of kernicterus
 In utero bilirubin is handled by placenta and mother’s liver
 After birth, neonate to has cope with increase in bilirubin
production and the immature liver can not handle for a few days

31. Basis of photo therapy
• UCB is not water soluble in its form
• Blue light confrontational change in UCB
• Its Photo Isomers are water soluble
• Blue light converts the UCB into its photo isomers
• The soluble photo isomers pass through the Glomerular
filter and get excreted
• Thus conjugation in liver is by passed.

32. Jaundice in Newborn

33. Liver Cirrhosis

35. Serum-to-ascites albumin gradient
• The serum-to-ascites albumin gradient (SAAG) accurately
identifies the presence of portal hypertension and is more
useful than the protein-based exudate/transudate concept.
• The SAAG is easily calculated by subtracting the ascitic
fluid albumin value from the serum albumin value,
which is obtained on the same day.
• The presence of a gradient 1.1 g/dL (11 g/L) indicates
that the patient has portal hypertension with 97 percent
accuracy.
• A gradient <1.1 g/dL (<11 g/L) indicates that the patient
does not have portal hypertension . The SAAG need not be
repeated after the initial measurement.

36. Indirect markers of liver fibrosis
• Liver fibrosis may be predicted by using
• A single routine laboratory test that reflects
alteration in hepatic function, or
• A combination of such tests.

37. Individual serum indirect markers of fibrosis
• Serum ALT levels
• AST / ALT ratio
• Platelet count (PLT);Trombocytopenia is a valuable
marker of advanced liver disease, but it may be related
to many mechanisms: hypersplenism, myelosuppression
by HCV, decreased trombopoetin production,
autoimmune process.
• Combined assessment of the AST/ALT ratio and PLT had a
high diagnostic value for cirrhosis.

38. Multicomponent indirect serologic markers for liver fibrosis
• AST /platelet count.
• Protrombin index, GGT, apolipoprotein A1.
• Protrombin index, GGT, apolipoprotein A1,
α2- macroglobulin
• Age, platelet count, GGT.
• Age, sex, ALT, GGT, bilirubin.
• apolipoprotein A1, α2-macroglobulin,
haptoglobin

39. Prognostic Tools for chronic liver disease
• MELD is a prospectively developed and validated
chronic liver disease severity scoring system
that uses a patient's laboratory values for serum
bilirubin, serum creatinine, and the international
normalized ratio for prothrombin time (INR) to
predict survival.
• MELD (model for end-stage liver disease)
– Identify patients whose predicted survival post-procedure
would be three months or less
• MELD = 3.8[serum bilirubin (mg/dL)] + 11.2[INR] + 9.6[serum
creatinine (mg/dL)] + 6.4

40. Acute liver failure (ALF)
• Prognostic criteria are based primarily either
on clinical and laboratory (coagulation tests,
serum bilirubin) parameters, or on other
parameters like liver volume.
• The criteria from one institute found
prothrombin time >25 s, serum bilirubin >15
mg/dL, age >40 years, and cerebral edema to
be bad prognostic markers.