1.Detect presence of liver disease. 2.Distinguish among different types of liver diseases. 3.Estimate the extent of known liver damage. 4.Follow the response of treatment

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.