Sild 2021

Diagnostic strategy in liver
diseases
Tikrit medical college
Department of Biochemistry
Prof. Dr.Nihad N. Hilal
M B Ch B , FIBMS
(chem.pathology)
Objectives:
we need to know
1. General metabolic functions of liver

2. Tests of Hepatic Function
3. Normal values
General metabolic functions
 Synthetic functions:
Plasma protein, most coagulation factors,
primary bile acid, lipoprotein.
 Excretion and detoxification:
Cholesterol, amino acids, steroid hormones,

many drugs and toxins.
 Formation and excretion of bilirubin :
Normal functional liver cells, normal blood

flow through the liver, patent biliary ducts
Biochemical tests of liver disease
to assess:
 Hepatocyte damage
 Hepatic synthetic function
 Hepatic excretory function

Liver function tests are useful in:
- detecting
- diagnosing
- evaluating severity
- monitoring therapy
- and dysfunction.
They are also useful in directing
further diagnostic workup.
 Theyarray of tests useful for these
purposes include measurement :
serum level of total bilirubin , protein ,
and albumin levels
 and the activity of enzymes such as the

aminotransferase (AST and ALT ) ,
ALP , lactate dehydrogenase ( LD ) ,
and y- glutamyltransferase ( GGT ).
Tests of Hepatic Function
Test Utility
Bilirubin Diagnosing Jaundice, modest
correlation with severity.
Alkaline Diagnosing disorders of metabolism
phosphatase and disorders of the newborn.
Bilirubin Diagnosing cholestasis and space
fractionation occupying lesions.
Aspartate Sensitive test of hepatocellalar disease;
aminotransferase AST > ALT in alcoholic disease.
Alanine Sensitive and more specific test of
aminotransferase hepatocellular disease.
Albumin Indicator of chronicity and severity.
Prothrombin time Indicator of severity of cholestasis .
Serum Enzymes
The serum aminotransferases and ALP

are the most useful tests as they allow
differentiation of hepatocellular disease
from cholestatic disease.
Failure to recognize cholestatic disease

caused by extrahepatic biliary
obstruction will result in liver failure if
the obstruction is not quickly corrected.
 In practice, an isolated increase in ALP
activity is difficult to interpret.
 In children, benign transient

hyperphosphatasemia should always be
considered.
 In adults , it is necessary to first confirm that
the ALP is of hepatobiliary origin.
This can be done by isoenzyme fractionation or

by measuring another phosphodiesterase
enzyme such as nucleotidase. or by measuring
y- glutamyltransferase.
 ALP is divided into 4 iso-enzymes
depend on site of tissues expression
 Intestinal ALP , placental ALP, Germ
cell ALP, and tissue non-specific ALP
(L/B/K)
 NR: 44 to 147 IU/L
 It helps break down proteins in body

and exists in different forms,
depending on where it originates
Elevation of serum levels of AST and ALT is
common in many disorders.
To determine if this elevation is liver related,
administration of all drugs and alcohol intake
(especially if AST is higher than ALT) should
be discontinued.
If the elevation persists, ultrasound (looking
for nonalcoholic fatty liver) and hepatitis B and
C serology should be performed.
Abnormal Liver Function Tests
AST > 3x URL

ALP < 2x URL AST < 3x URL
ALP > 2x URL
Hepatocellular Disease Cholestatic Disease
Normal Decreased Normal Decreased

Albumin Albumin Albumin Albumin
Acute Chronic Acute Chronic

Hepatitis Hepatitis Cholestasis Cholestasis
Ultrasound or
percutaneous cholangiography
Intrahepatic Extrahepatic
Cholestasis Cholestasis
Increased Alkaline Phosphatase
Confirm with 5' nuceotidase or GGT
Not increased Increased
Consider bone disease Obstructive liver disease
Ultrasound or Computed tomography or both
Dilated ducts Non - dilated ducts
Consider stones, strictures, Consider biliary cirrhosis, Measure

or space – occupying lesion antimitochondrial antibodies
If diagnosis is an Negative Positive

certain
Perform percutaneous chlagiography to diagnosis Primary

selerosing cholangitis , Stricture, or stones biliary
cirrhosis
Serum Albumin
 Serum albumin measurements are

useful in assessing the chronicity and
severity of liver disease.
 The serum albumin concentration is
decreased in chronic liver disease.
 Serial measurements of serum albumin
can be used to assess the severity of liver
disease.
Prothrombin Time
 Serial PT measurements can also be

used to differentiate between
cholestasis and severe hepatocellular
disease.
 In practice, PT should be measured
after vitamin K injection, because
cholestasis will cause a decrease in PT
due to malabsorption of vitamin K.
Serum Bilirubin
Serial measurement of bilirubin is
helpful in measuring the severity of
liver disease.
Bilirubin fractionation is helpful :

- in jaundice of the newborn
- or in isolated elevations of bilirubin in
the absence of other liver test
abnormalities.
 Patients are occasionally seen with isolated
elevations in bilirubin concentration.
In most cases this is due to inherited
disorders of bilirubin metabolism.
 Familial hyperbilirubinemia or hemolysis.

It is not difficult to distinguish,
hemolysis severe enough to cause
hyperbilirubinemia, because the patient with
hemolysis will have many other disease
manifestations.
 A22 years old female intravenous drug addict
was referred to the hepatololgy clinic because of
the following abnormal liver test results:
 Plasma Bilirubin 93umol/L(<20)

 ALT 76 IU/L (<42)
 ALP 306U/L(<250)
 Albumin 44g/L(35-45)
 GGT 324 U/L(<55)
 Urinary bilirubin +ve
 Hepatitis +ve
 A 50 year old known alcoholic male attended the
general medical clinic because of ascites and the
following abnormal- liver test results
 Plasma bilirubin 52umol/L(<20)

 ALT 76 U/L(42)
 Alkaline phosphatase 271U/L(<250)
 Albumine 18g/L(35-45)
 GGT 324 U/L(<55)
 Urinary bilirubin and protein normal
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Diagnostic strategy in liver

1. General metabolic functions of liver

Cholesterol, amino acids, steroid hormones,

Normal functional liver cells, normal blood

 Hepatic excretory function

 and the activity of enzymes such as the

The serum aminotransferases and ALP

Failure to recognize cholestatic disease

 In children, benign transient

This can be done by isoenzyme fractionation or

 It helps break down proteins in body

AST > 3x URL

Hepatocellular Disease Cholestatic Disease

Normal Decreased Normal Decreased

Acute Chronic Acute Chronic

Confirm with 5' nuceotidase or GGT

Not increased Increased

Consider bone disease Obstructive liver disease

Ultrasound or Computed tomography or both

Dilated ducts Non - dilated ducts

Consider stones, strictures, Consider biliary cirrhosis, Measure

If diagnosis is an Negative Positive

Perform percutaneous chlagiography to diagnosis Primary

 Serum albumin measurements are

 Serial PT measurements can also be

Bilirubin fractionation is helpful :

 Familial hyperbilirubinemia or hemolysis.

 Plasma Bilirubin 93umol/L(<20)

 Plasma bilirubin 52umol/L(<20)

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