27-11-2024

Liver
Function
Tests (LFTs)

Objectives
Understand the major metabolic functions of the

liver and causes of liver dysfunction.

Discuss markers of liver function tests such as liver

enzymes, bilirubin, albumin and prothrombin time

that can diagnose hepatic injury and assess hepatic

function.

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What is Purpose of LFTs?

• LFTs alone do not give the physician full information,
but used in combination with a careful history, physical
examination, can contribute to making an accurate
diagnosis of the specific liver disorder.
• Different tests will show abnormalities in
response to
liver inflammation
liver injury due to drugs, alcohol, toxins, viruses
Liver malfunction due to blockage of the flow of bile
Liver cancers

Functions of liver
① Excretory function: bile pigments, bile salts and
cholesterol are excreted in bile into intestine.

② Metabolic function: liver actively participates in

carbohydrate, lipid, protein, mineral and vitamin
metabolisms.

③ Hematological function: liver is also produces clotting

factors like factor V, VII. Fibrinogen involved in blood
coagulation is also synthesized in liver. It synthesize
plasma proteins and destruction of erythrocytes.

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④ Storage functions: glycogen, vitamins A, D

and B12, and trace element iron are stored in
liver.
⑤ Protective functions and detoxification:
Ammonia is detoxified to urea. kupffer cells of
liver perform phagocytosis to eliminate
foreign compounds.

• LFTs are divided into

 True tests of liver function:

such as serum albumin, bilirubin, and
prothrombin time
 Tests that are indicators of liver injury or
biliary tract disease.

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Classification of liver functions test

Classified based on the major functions of liver:
① Excretion: Measurement of bile pigments,
bile salts.
② Serum enzymes: Transaminase (ALT, AST),
alkaline phosphate(ALP), 5’-nucleotidase,
LDH isoenzyme.
③ Synthetic function: Prothrombin time,
serum albumin.

Classification of LFTs

Group I: Markers of liver dysfunction

▫ Serum bilirubin: total and conjugated

▫ Urine: bile salts and urobilinogen

▫ Total protein, serum albumin and albumin/globulin ratio

▫ Prothrombin Time

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Classification of LFTs
Group II: Markers of hepatocellular injury

▫ Alanine aminotransferase (ALT)

▫ Aspartate aminotransferase (AST)

Classification of LFTs

Group III: Markers of cholestasis

▫ Alkaline phosphatase (ALP)

▫ -glutamyltransferase (GGT)

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Limitations of LFTs

• Normal LFT values do not always indicate absence of

liver disease
 Liver a has very large reserve capacity

• Asymptomatic people may have abnormal LFT results

 Diagnosis should be based on clinical examination

Common serum liver chemistry tests

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Bilirubin
• A byproduct of red blood cell breakdown

• It is the yellowish pigment observed in jaundice

• High bilirubin levels are observed in:

 Gallstones, acute and chronic hepatitis

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BLOOD
CELLS Stercobilin
excreted in feces Urobilin
Hemoglobin excreted in urine

Globin
Heme Urobilinogen
O2 formed by bacteria KIDNEY
reabsorbed
Heme oxygenase
INTESTINE into blood
CO

Biliverdin IX via bile duct to intestines

NADPH
Biliverdin Bilirubin diglucuronide
reductase (water-soluble)
NADP+
2 UDP-glucuronic acid
Bilirubin Bilirubin
(water-insoluble)
(water-insoluble) via blood LIVER
to the liver

Metabolism of bilirubin

1. serum bilirubin:
Normally, a small amount of bilirubin circulates in the blood.
Serum bilirubin is considered a true test of liver function, as it
reflects the liver's ability to take up, process, and secrete bilirubin
into the bile.

A. indirect bilirubin

(normal value = 0.3 - 1.2 mg/dl)

B. direct bilirubin

(normal value ≤ 0.4 mg/dl)

C. total bilirubin

Normal value for = 0.3- 1.2 mg/dl.

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VD Bergh reaction

Direct Bilirubin + Diazotized Sulfanilic Acid → Azobilirubin

(Redish purple)
total bilirubin + dimethylsulfoxide (DMSO)+methanol
+diazotized sulfanilic acid to form azobilirubin.
Indirect bilirubin react with diazotized sulfanilic acid after
addition of methanol.

The absorbance of the reaction mixture at 555 nm is directly

proportional to the concentration of direct bilirubin.

Difference of two bilirubins

indirect direct
bilirubin bilirubin
Binding with Glucuronic
no yes
acid
Reacting with the diazo Slow and Rapid and
reagent indirect direct
solubility in water small large
Discharged via kidney no yes
Pass through the
yes no
membrane of cell

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 Bilirubinurine:

Bilirubin is not normally present in urine and feces since

bacteria in intestine reduce it to urobilinogen. The kidneys do not
filter unconjugated bilirubin because of its avid binding to
albumin.

Conjugated bilirubin can pass through glomerular filter.

Bilirubin is found in the urine in obstructive jaundice due to

various causes and in cholestasis.

Who is a candidate for the test?

Bilirubin is used to diagnosis of jaundice. Abnormal
bilirubin levels can be found in many disorders, including:
blocked bile ducts, cirrhosis, hepatitis and other liver
diseases or immature liver development in newborns.

Hemolytic Jaundice
Hepatic Jaundice
Obstructive jaundice ( Cholestasis)
Congenital Jaundice

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Sample Indices Normal Hemolytic Hepatic Obstructive

Jaundice Jaundice Jaundice

Serum Total Bil ＜1mg/dl ＞1mg/dl ＞1mg/dl ＞1mg/dl

Direct Bil 0～0.8mg/dl ↑ ↑↑

Indirect Bil ＜1mg/dl ↑↑

Urine Color normal deeper deep deep

Bilirubin — — ＋＋ ＋＋

Urobilinogen A little ↑ uncertain ↓

Urobilin A little ↑ uncertain ↓

Stool Color normal deeper lighter or Argilous

normal (complete
obstruction)

Synthetic functions:

1. Total plasma proteins/Albumin/Globulin/

A:G ratio

2. Formation of prothrombin by liver

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Serum Albumin
• The most abundant protein synthesized by the liver

• Normal serum levels: 3.5 – 5 g/dL

• Synthesis depends on the extent of functioning liver cell mass

• Longer half-life: 20 days

• Its levels decrease in all chronic liver diseases

Serum Globulin
• Normal serum levels: 2.5 – 3.5g/dL

•  and -globulins mainly synthesized by the liver

• They constitute immunoglobulins (antibodies)

• High serum -globulins are observed in chronic hepatitis and cirrhosis:

 IgG in autoimmune hepatitis
 IgA in alcoholic liver disease

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Albumin to globulin (A/G) ratio

• Normal A/G ratio: 1.2/1 – 1.5/1

• Globulin levels increase in hypoalbuminemia as a compensation

Prothrombin Time (PT)

• Prothrombin: synthesized by the liver, a marker of liver function

• Half-life: 6 hrs. (indicates the present function of the liver)

• PT is prolonged only when liver loses more than 80% of its reserve
capacity

• Vitamin K deficiency also causes prolonged PT

• Intake of vitamin K does not affect PT in liver disease

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2. Serum enzymes
A large number of enzyme estimations are available
which are used to ascertain liver function. They are be
divided into two groups:

I: most commonly and routinely done in the

laboratory.
serum transaminase(ALT/AST)
serum alkaline phosphate(ALP)
II: not routinely done in the laboratory.

Aspartate aminotransferase (AST)

• Normal range: 8 – 20 U/L

• A marker of hepatocellular damage

• High serum levels are observed in:

 Chronic hepatitis, cirrhosis and liver cancer

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 AST reflects damage to the hepatic cells

and is less specific for liver disease. It can also
be released with heart, muscle and brain
disorders.

 Therefore, this test may be ordered to help

diagnose various heart, muscle or brain disorders,
such as a myocardial infarction (heart attack).

Elevated levels of AST may indicate :

 acute hemolytic anemia,
 acute pancreatitis or inflammation of the pancreas.
 acute renal failure or loss of kidney function.
 cirrhosis of the liver.
 Hepatitis

heart attack

primary muscle disease

 recent surgery

 severe burns

 muscle injury

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Alanine aminotransferase (ALT)

• More liver-specific than AST

• Normal range (U/L):

▫ Male: 13-35
▫ Female: 10-30
• High serum levels in acute hepatitis (300-1000U/L)

• Moderate elevation in alcoholic hepatitis (100-300U/L)

• Minor elevation in cirrhosis, hepatitis C and non-alcoholic steatohepatitis

(NASH) (50-100U/L)

Alanine aminotransferase (ALT)

• Appears in plasma many days before clinical signs appear

• A normal value does not always indicate absence of liver damage

• Obese but otherwise normal individuals may have elevated ALT levels

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‼ Therefore, when the liver is injured, ALT is

released into the bloodstream.
Elevated levels of ALT may indicate :
 alcoholic liver disease
 cancer of the liver
 cholestasis or congestion of the bile ducts
 cirrhosis or scarring of the liver with loss of function
 death of liver tissue
 Hepatitis or inflammation of the liver
 noncancerous tumor of the liver
 use of medicines or drugs toxic to the liver

 Although AST is not a specific for liver as the ALT,

ratios between ALT and AST are useful to physicians in
assessing the etiology of liver enzyme abnormalities.

◆ normally: ALT is normal, AST is normal, ALT/AST

is about 1.15.
◆ Virus hepatitis: ALT↑, AST is normal ,ALT/AST＞
1,even more than 2.5；
◆ chronic hepatitis : ALT↑ ,AST ↑ALT/AST is about 1.
◆ Liver cancer, cirrhosis, Alcohol-induced hepatitis:
ALT↑ ,AST ↑ < 1, about 0.6~0.7.
◆ Accute myocardial infarct :< 1

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Alkaline phosphatase (ALP)

• A non-specific marker of liver disease

• Produced by bone osteoblasts (for bone calcification)

• Present on hepatocyte membrane

• Normal range: 40 – 125 U/L

• Modearte elevation observed in:

 Infective hepatitis, alcoholic hepatitis and hepatocellular carcinoma

Alkaline phosphatase (ALP)

• High levels are observed in:

 Extrahepatic obstruction (obstructive jaundice) and intrahepatic cholestasis

• Very high levels are observed in:

 Bone diseases

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-glutamyltransferase (GGT)
• Used for glutathione synthesis

• Normal range: 10 – 30U/L

• Moderate elevation observed in:

 Infective hepatitis and prostate cancers

• GGT is increased in alcoholics despite normal liver function tests

 Highly sensitive to detecting alcohol abuse

Take Home Messages

• LFTs help detect liver injury and function.

• LFTs do have some limitations.

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