Liver function tests and functional

tests of liver, ultrasound, biopsy

Liver Function Tests (LFTs)

These tests can be used to
(1) detect the presence of liver disease
(2) distinguish among different types of liver disorders
(3) gauge the extent of known liver damage
(4) follow the response to treatment.
Liver tests have shortcomings
They can be normal in patients with serious liver
disease and abnormal in patients with diseases that do
not affect the liver
Liver tests rarely suggest a specific diagnosis; rather,
they suggest a general category of liver disease, such
as hepatocellular or cholestatic, and will help to decide
whether the disease is acute or chronic

The Battery of Blood Tests

To increase both the sensitivity and the specificity of laboratory tests in the
detection of liver disease, it is best to use them as a battery.
Those tests usually employed in clinical practice include:
bilirubin
Aminotransferases (ALT and AST)
alkaline phosphatase
Albumin
+/- prothrombin time
When more than one of these tests provide abnormal findings, or the
findings are persistently abnormal on serial determinations, the probability of
liver disease is high.
When all test results are normal, the probability of missing occult liver
disease is low.

Our Patients Results

Albumin = 36 g/l (Ref range 35-45 g/l)
Bilirubin(Total) = 38 umol/l (Ref range 0-17 umol/l)
AlkP = 142 Units/l (Ref range 35-100 Units/l)
GGT = 240 Units/l (Ref range 0-50 Units/l)
ALT = 85 Units/l (Ref range 0-35 Units/l)
AST = 160 Units/l (Ref range 0-42 Units/l)
Coagulation profile:
Prothrombin time = 14 sec (Ref range 8-13s)
APTT = 40 sec (Ref range 25-38s)
Plasma Fibrinogen = 3.3 g/l (Ref range 1.5-4.0 g/L)

Whats What???
Enzymes that reflect damage to Hepatocytes:
Serum Aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Serum lactate dehydrogenase (LDH)

All cytosolic heptocellular enzymes. ie increase in blood indicates

damage or death of hepatocytes
ALT is the more specific to the liver
The pattern of the aminotransferase elevation can be helpful
diagnostically. In most acute hepatocellular disorders, the ALT is
higher than or equal to the AST. An AST:ALT ratio > 2:1 is suggestive
while a ratio > 3:1 is highly suggestive of alcoholic liver disease. The
AST in alcoholic liver disease is rarely >300 U/L and the ALT is often
normal. A low level of ALT in the serum is due to an alcohol-induced
deficiency of pyridoxal phosphate.

Enzymes that Reflect damage to Bile Canaliculi:

alkaline phosphatase
5'-nucleotidase
-glutamyl transpeptidase (GGT)
Alkaline phosphatase can be elevated in many other conditions.
GGT is not specific for cholestasis, also can reflect hepatocyte damage.
In combination raised GGT can help determine if raised alkaline
phosphatase elevations are due to liver disease
Alkaline phosphatase and 5'-nucleotidase are found in or near the bile
canalicular membrane of hepatocytes, while GGT is located in the
endoplasmic reticulum and in bile duct epithelial cells. Reflecting its
more diffuse localization in the liver, GGT elevation in serum is less
specific for cholestasis than are elevations of alkaline phosphatase or
5'-nucleotidase.

 Indicators of biliary excretory function:

Serum Bilirubin
Total (conjugated and unconjugated)
Direct: conjugated
Urine Bilirubin

Indicators of Hepatocyte Function:

Proteins secreted into blood
Serum albumin
Clotting factors ( prothrombin time)
Serum albumin is synthesized exclusively by hepatocytes. Because of this slow turnover,
the serum albumin is not a good indicator of acute or mild hepatic dysfunction; only
minimal changes in the serum albumin are seen in acute liver conditions such as viral
hepatitis, drug-related hepatoxicity, and obstructive jaundice. Hypoalbuminemia is more
common in chronic liver disorders such as cirrhosis and usually reflects severe liver
damage and decreased albumin synthesis. albumin levels < 3 g/dL should raise the
possibility of chronic liver disease
With the exception of factor VIII, the blood clotting factors are made exclusively in
hepatocytes. Their serum half-lives are much shorter than albumin, ranging from 6 h for
factor VII to 5 days for fibrinogen. Because of their rapid turnover, measurement of the
clotting factors is the single best acute measure of hepatic synthetic function and helpful
in both the diagnosis and assessing the prognosis of acute parenchymal liver disease.
Useful for this purpose is the serum prothrombin time, which collectively measures
factors II, V, VII, and X. Biosynthesis of factors II, VII, IX, and X depends on vitamin K. The
prothrombin time may be elevated in hepatitis and cirrhosis as well as in disorders that lead
to vitamin K deficiency such as obstructive jaundice or fat malabsorption of any kind.

 Indicators of Hepatocyte Metabolism

Blood Ammonia
Ammonia is produced in the body during normal
protein metabolism and by intestinal bacteria,
primarily those in the colon. The liver plays a role in
the detoxification of ammonia by converting it to urea,
which is excreted by the kidneys. Striated muscle also
plays a role in detoxification of ammonia, which is
combined with glutamic acid to form glutamine.
Patients with advanced liver disease typically have
significant muscle wasting, which likely contributes to
hyperammonemia in these patients.

Other laboratory tests

hepatitis serology to define the type of viral hepatitis

Reduced a1 antitrypsin levels, phenotypes PiZZ or PiSZ
Decreased serum ceruloplasmin and increased urinary copper; increased
hepaticcopper level
Elevated iron saturation and serum ferritin; genetic testing for HFE gene
mutations
autoimmune markers
to diagnose primary biliary cirrhosis (antimitochondrial antibody; AMA),
sclerosing cholangitis (peripheral antineutrophil cytoplasmic antibody; PANCA), and autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody)
Serum Vitamin levels
not only in bile responsible for the absortption of fat-souble vitamins, the
liver is respobsible for storage of all vitamins including water-soluble

Type of Disorder

Bilirubin

Aminotransfera
ses

Alkaline Phosphatase

Albu
min

Prothrombin Time

Hemolysis/Gilbert's syndrome

Normal to
86 mol/L (5
mg/dL)
85% due to
indirect
fractions
No
bilirubinuria

Normal

Normal

Normal

Acute hepatocellular necrosis

(viral and drug hepatitis,
hepatotoxins, acute heart
failure)

Both
fractions
may be
elevated
Peak usually
follows
aminotransf
erases
Bilirubinuria

Elevated, often
>500 IU
ALT >AST

Normal to <3 times normal

elevation

Usually normal. If >5X above

control and not corrected by
parenteralvitamin K, suggests po
prognosis

Chronic hepatocellular
disorders

Both
fractions
may be
elevated
Bilirubinuria

Elevated, but
usually <300 IU

Normal to <3 times normal

elevation

low

Often prolonged
Fails to correct with
parenteralvitamin K

Alcoholic hepatitis
Cirrhosis

Both
fractions
may be
elevated
Bilirubinuria

AST:ALT > 2
suggests
alcoholic
hepatitis or
cirrhosis

Normal to <3 times normal

elevation

low

Often prolonged
Fails to correct with
parenteralvitamin K

Intra- and extra-hepatic

cholestasis
(Obstructive jaundice)

Both
fractions
may be
elevated
Bilirubinuria

Normal to
moderate
elevation
Rarely >500 IU

Elevated, often >4 times

normal elevation

Normal
If prolonged, will correct with
parenteralvitamin K

Infiltrative diseases (tumor,

granulomata); partial bile
duct obstruction

Usually
normal

Normal to slight
elevation

Elevated, often >4 times

normal elevation
Fractionate, or confirm liver
origin with 5' nucleotidase or
glutamyl transpeptidase

Normal

Imaging

Ultrasound is the first diagnostic test to use. It shows

dilation of intrahepatic or extrahepatic biliary tree

Gallstones
Steatosis
space-occupying lesions within the liver (enables the clinician to distinguish between cystic
and solid masses)
Doppler imaging can detect the patency of the portal vein, hepatic artery, and hepatic veins
and determine the direction of blood flow

CT and MRI are indicated for:

identification and evaluation of hepatic masses

staging of liver tumours
preoperative assessment.
With regard to mass lesions, sensitivity and specificity remains a problem, and often two
and sometimes three studies are needed before a diagnosis can be reached.

Radiographic studies that strongly suggest cirrhosis include a small, nodular liver, ascites,
splenomegaly, intra-abdominal varices, or portal and hepatic vein thrombosis; however, no
test is considered a diagnostic gold standard. The current best test for diagnosing cirrhosis
is liver biopsy.

Magnetic resonance cholangiopancreatography (MRCP) and endoscopic

retrograde cholangiopancreatography (ERCP) are the procedures of choice
for visualization of the biliary tree. (Through the endoscope, the physician
can see the inside of the stomach and duodenum, and inject dyes into the
ducts in the biliary tree and pancreas so they can be seen on xray)
Recently, methods using elastrography have been developed to measure
hepatic stiffness as a means of assessing hepatic fibrosis. US elastrography
is now undergoing evaluation for its ability to detect different degrees of
hepatic fibrosis and to obviate the need for liver biopsy in assessing disease
stage.
Nuclear Medicine Scans: show gallbladder filling and emptying. Inject
radioactive dye, excreted by bile ie. accumulated in gallbladder, infusion of
CCK, then can watch empty.
Interventional radiologic techniques allow the biopsy of solitary lesions,
insertion of drains into hepatic abscesses, measurement of portal pressure,
and creation of vascular shunts in patients with portal hypertension.

Percutaneous biopsy

There have been great advances made in hepatic imaging, although no method is suitably
accurate in demonstrating underlying cirrhosis. Cirrhosis is identified by histopathologic
examination of the liver
In selected instances, liver biopsy is necessary for diagnosis but is more often useful in
assessing the severity (grade) and stage of liver damage, in predicting prognosis, and in
monitoring response to treatment

Biopsy of the liver is a safe procedure that can be easily performed at the bedside with local
anesthesia. Liver biopsy is of proven value in the following situations:
(1) hepatocellular disease of uncertain cause
(2) prolonged hepatitis with the possibility of chronic active hepatitis
(3) unexplained hepatomegaly
(4) unexplained splenomegaly
(5) hepatic filling defects by radiologic imaging
(6) fever of unknown origin
(7) staging of malignant lymphoma.
Liver biopsy is most accurate in disorders causing diffuse changes throughout the liver and is subject
to sampling error in focal infiltrative disorders such as hepatic metastases. Liver biopsy should
not be the initial procedure in the diagnosis of cholestasis.