The liver biochemical tests is preferreble
term than liver function tests ?
It should be appropriately ordered with
knowledge of history and physical
examination of the patient.
They have potential to identify liver
disease and distinguish among types of
disorders, guage the severity, progression
of dysfunction and also response to
4. No test can accurately assess the liver’s
total functional capacity
They measure only few functions among
several functions performed by liver.
Singly they don’t have sensitivity and
specifity so always battery of tests has to
be performed to evaluate the liver
5. 1. TOTAL BILURUBIN AND DIRECT AND
2. ALANINE AMINOTRANSFERASE(ALT)
3. ASPARTATE AMINOTRANSFERASE(AST)
4. ALKALINE PHOSPHATASE(ALP)
5. GAMMA GLUTAMYL
7. SERUM ALBUMIN
8. PROTHROMBIN TIME
7. Bilirubin is a breakdown product of heme
About 4 mg/kg body weight of bilirubin is
produced each day
Heme is converted to biliverdin by the
microsomal enzyme heme oxygenase.
Biliverdin is then converted to bilirubin by
the cytosolic enzyme biliverdin reductase.
Bilirubin formed in the reticuloendothelium is
lipid soluble and virtually insoluble in water .
This process of making insoluble to soluble
by liver is called conjugation.
9. The terms direct and indirect bilirubin, which
correspond roughly to conjugated and unconjugated
Test is called as vandenbergh test or diazo reaction.
In this assay, bilirubin is exposed to diazotized sulfanilic
The conjugated fraction of bilirubin reacts promptly,
or “directly,” with the reagent without the need for an
accelerant ,and thereby allows measurement of the
conjugated bilirubin fraction by photometric analysis
within 30 to 60 seconds.
The total bilirubin is measured 30 to 60 minutes after
the addition of an accelerant such as alcohol or
The unconjugated, or indirect, fraction is then
determined by subtracting the direct component
from the total bilirubin.
10. DELTA BILURUBIN
Delta bilirubin, a conjugated bilirubin tightly linked
to albumin through covalent binding.
Delta bilirubin is found in cases of prolonged and
severe elevation of serum conjugated bilirubin
Delta bilirubin has the half-life of albumin,
approximately 14 to 21 days, which far exceeds
the usual half-life of bilirubin in serum of 4 hours
because of the strength of the covalent binding.
The identification of delta bilirubin explains why
the decline in serum bilirubin in some patients
with prolonged jaundice seems to lag behind
Why some patients with conjugated
hyperbilirubinemia do not have bilirubinuria.
11. Total serum bilirubin 1.0 -1.5 mg/dL, with
95% of a normal population falling
between 0.2 and 0.9 mg/dL.
If the direct acting fraction is less than 15%
of the total, the bilirubin can be
considered to be entirely indirect.
The most frequently reported upper limit of
normal for conjugated bilirubin is 0.3
Indirect component 0.8-1.2 mg/dL.
12. HYPER BILURUBINEMIA: It is due to
1. overproduction of bilirubin through
excessive breakdown of hemoglobin
2. Impaired hepatocellular uptake
3. Conjugation defect
4. Excretion of bilirubin
5. Regurgitation of unconjugated and
conjugated bilirubin from damaged
hepatocytes or bile ducts
13. Presence of conjunctival icterus suggests
a total serum bilirubin level of at least 3.0
mg/dL but does not allow differentiation
between conjugated and unconjugated
Tea- or cola-colored urine may indicate
the presence of bilirubinuria and thus
14. Isolated elevation of the serum bilirubin
Patient with an elevated bilirubin
associated with elevated liver enzyme
16. Hemolytic Disorders
Drugs like Rifampin, Probenecid impairs
Inherited Conditions : Crigler-Najjar
syndrome types I and II and Gilbert’s
syndrome causes Impaired conjugation
Hematoma most common in neonates.
19. The serum aminotransferases are most sensitive markers of
acute hepatocellular injury.
ALT and AST catalyze the transfer of the α-amino groups of
alanine and L-aspartic acid, respectively, to the α-keto group
of ketoglutaric acid.
AST, found in cytosol and mitochondria, is widely distributed
throughout the body
AST is present in liver>cardiac muscle>skeletal
ALT, a cytosolic enzyme also found in many organs, is present
in greatest concentration by far in the liver.
More specific indicator of liver injury is ALT
20. Increases in serum values of the
aminotransferases reflect either damage
to tissues rich in these enzymes or changes
in cell membrane permeability that allow
ALT and AST to leak into serum.
Hepatocyte necrosis is not required for the
release of aminotransferases
The degree of elevation of the
aminotransferases does not correlate with
the extent of liver injury.
21. Aminotransferases have no function in
serum and act like other serum proteins.
They are distributed in plasma and
interstitial fluid and have half-lives
measured in days.
Cleared by cells in the reticuloendothelial
system, with AST cleared more rapidly than
Normal values for aminotransferases in
serum vary widely among laboratories, but
values gaining general acceptance
are <30 U/L for men and <19 U/L for women
Upper values are determined by reference
22. levels up to 300 U/L are nonspecific.
Degree of elevation?
Pattern of elevation (AST/ALT)
Then have to be interpreted with history
and physical examination
23. Viral hepatitis (A to E)
Toxin or drug-induced liver injury
•Acute Budd-Chiari syndrome
•Fulminant Wilson disease
•Acute obstruction of the biliary tract
25. The ratio of AST to ALT in serum is helpful in
the recognition of alcoholic liver disease.
If the AST level is less than 300 U/L, a ratio of
AST to ALT of more than 2 suggests ,and a
ratio of more than 3 is highly suggestive of
alcoholic liver disease.
When a patient with chronic alcoholic liver
disease sustains a superimposed liver injury,
particularly acetaminophen toxicity, the
aminotransferase level can be strikingly
elevated, yet the AST/ALT ratio is
28. AST to ALT ratio is typically less than 1 in
patients with chronic viral hepatitis and
nonalcoholic fatty liver disease (NAFLD), a
number of investigators have observed that,
as cirrhosis develops, the ratio rises and may
become greater than 1.
The increase in AST/ALT ratio with the
development of cirrhosis is believed to result
from impaired functional hepatic blood flow,
with a consequent decrease in hepatic
sinusoidal uptake of AST.
Studies have shown that an AST/ALT ratio of
greater than 1 as an indicator of cirrhosis in
patients with chronic hepatitis C has a high
specificity (94% to 100%)
31. The term alkaline phosphatase applies
generally to a group of isoenzymes
distributed widely throughout the body.
Isoenzymes of greatest clinical importance
in adults are in the liver and bone because
these organs are the major sources of
serum alkaline phosphatase.
Other isoenzymes originate from the
placenta, small intestine, and kidneys.
32. In the liver, alkaline phosphatase is found on
the canalicular membrane of hepatocytes; its
precise function is undefined.
Alkaline phosphatase has a serum half-life of
approximately seven days, and although the
sites of degradation are unknown.
Clearance of alkaline phosphatase from
serum is independent of either patency of the
biliary tract or functional capacity of the liver.
Hepatobiliary disease leads to increased
serum alkaline phosphatase levels through
induced synthesis of the enzyme and leakage
into the serum, a process mediated by bile
33. serum alkaline phosphatase level be checked
in the fasting state because of intestinal
Serum alkaline phosphatase values vary with
age. Male and female adolescents have
serum alkaline phosphatase levels twice the
level seen in adults.
Level of serum alkaline phosphatase increases
after age 30 years in both men and women,
the increase is more pronounced in women
than in men; a healthy 65-year-old woman
has a serum alkaline phosphatase level 50%
higher than that of a healthy 30-year-old
Pregnancy values are high.
34. Isolated elevation of the serum alkaline
phosphatase level, the serum GGTP or 5′NT
are used to distinguish a liver origin from
bone origin of the alkaline phosphatase
A low serum alkaline phosphatase level
may occur in patients with Wilson disease,
especially those presenting with fulminant
hepatitis and hemolysis, possibly because
of reduced activity of the enzyme owing to
displacement of the co-factor zinc by
35. GGTP is found in the cell membranes of a
wide distribution of tissues including liver
(both hepatocytes and cholangiocytes),
kidney, pancreas, spleen, heart, brain, and
GGTP is not elevated in bone disease
Use of serum GGTP levels is to identify the
source of an elevation in the serum ALP.
Phenytoin, barbiturates,NNRTI and the
protease inhibitor abacavir causes
36. Serum GGTP levels are also elevated in
patients who drink alcohol so some experts
have advocated use of the GGTP level for
identifying unreported alcohol
use(sensitivity 52-94%) low specificity.
For bile duct stones GGTP has high
negative predictive value (97.9%).
37. 5′NT is associated with the canalicular
and sinusoidal plasma membranes.
Primary role of the serum 5′NT level is to
identify the organ source of an isolated
serum alkaline phosphatase elevation.
The 5′NT level is not increased in bone
disease and is primarily increased in
38. Serum alkaline phosphatase elevation
out of proportion to the level of the
aminotransferases suggests a cholestatic
A four-fold elevation of the serum
alkaline phosphatase is seen in both
intrahepatic and extrahepatic
41. DRUGS – vanishing bile duct syndrome
Primary biliary cirrhosis(PBC)-AMA and
Primary sclerosing cholangitis (PSC)
association with inflamatory bowel
Granulomatous liver disease-sarcoidosis.
Viral hepatitis-Epsteinbarr,CMV,Hep B&C
42. Genetic –
1. Progressive familial intrahepatic cholestasis-
Type 1 (Byler’s disease),Type 2,Type 3
2. Benign recurrent intrahepatic cholestasis-
Type 1&Type 2
Intrahepatic Cholestasis of Pregnancy
Total Parenteral Nutrition
43. INTRINSIC & EXTRINSIC causes
Requires CT and ERCP for evaluation
Most common is choledocholitiasis,
malignacy, rarely parasitic infections
Extrinsic causes like pseudocyst of
46. Quantitatively accounts for 75% of the
plasma colloid oncotic pressure and is
synthesized exclusively by hepatocytes.
Daily production nearly-15 g/day and has
300 to 500 g of albumin distributed in body
Half-life of albumin is 14 to 21 days makes it
unreliable in acute liver failure.
Albumin synthesis is regulated by changes in
nutritional status, osmotic pressure, systemic
inflammation, and hormone levels.
47. Serum albumin levels less than 3 g/dL in a
patient with newly diagnosed hepatitis
should raise suspicion of a chronic
Check for other causes of
48. All clotting factors are produced in the
liver except factor VIII, which is produced
by vascular endothelial cells.
Prothrombin time is a measure of the rate
at which prothrombin is converted to
thrombin, reflecting the extrinsic pathway
Factors involved in the synthesis of
prothrombin include II, V, VII, and X.
49. Hepatic parenchymal disease.
Congenital deficiency of clotting factors
Vitamin K deficiency.
Disseminated intravascular coagulation
HOW TO DIFFERENTIATE ?
50. prothrombin time allows an assessment of
current hepatic synthetic function,as
factor VII has the shortest serum half-life
(six hours) of all the clotting factors.
It is also used for prognosis scores like
The prothrombin time is not an accurate
measure of bleeding risk in patients with
cirrhosis because it assesses only the
activity of procoagulant clotting factors,
not anticoagulants such as protein C and
antithrombin, the production of which is
also reduced in cirrhosis.
51. liver biopsy is the standard for the
assessment of hepatic fibrosis.
Need has arrived to go for non invasive
Single serum biochemical markers that
potentially reflect the activity level of
hepatic fibrogenesis - Hyaluronan.
52. Hyaluronan is a glucosaminoglycan
produced in mesenchymal cells and widely
distributed in the extracellular space.
Typically degraded by hepatic sinusoidal
A fasting hyaluronan level greater than 100
mg/L (sensitivity83% & specificity78%)for the
detection of cirrhosis in patients with a
variety of chronic liver diseases like chronic
hepatitis C, chronic hepatitis B, alcoholic
liver disease, and nonalcoholic
53. It is the best evaluated among
multiparameter blood tests.
The test incorporates
4. Apolipoprotein A-I
54. FIBROSpect II assay incorporates
2. Tissue inhibitor of metalloproteinase 1
3. Alpha 2-macroglobulin.
55. Transient elastography (TE) well known as
Uses ultrasound waves to measure
hepatic stiffness noninvasively.
Principle behind the technique’s
1. “fibrosis leads to increased stiffness of
the hepatic tissue”
2. “A shear wave would propagate faster
through stiff material than through
56. The ultrasound transducer emits a low-frequency
(50 Hz) shear wave, and the
amount of time required for the wave to
go through a set “window” of tissue is
The window of tissue is 1 cm by 4 cm, 100
times the area of an average liver biopsy
60. MRE is another noninvasive technique
The shear elasticity of the liver is
measured after low-frequency (65 Hz)
waves are transmitted into the right lobe
of the liver.
In one study MRE was found to be
superior to TE for staging liver fibrosis in
patients with a variety of chronic liver
61. Developed in the hope of evaluating
the excretory or detoxification capacity
of the liver more specifically.
Lack of specificity and often
cumbersome methodology have limited
their widespread acceptance.
1. Indocyanine Green Clearance
2. Galactose Elimination Capacity
3. Caffeine Clearance
4. Lidocaine Metabolite Formation
5. Aminopyrine Breath Test
65. NORMAL RANGES
1. TOTAL BILURUBIN - 0.3-1.3 mg/dl
2. DIRECT - 0.1-0.4 mg/dl
3. INDIRECT - 0.2-0.9 mg/dl
4. AST - 12- 38 IU/ml
5. ALT - 7- 41 IU/ml
6. TOTAL PROTEINS- 5.5 -9.0 gm/dl
7. ALBUMIN – 3.5- 5.5 gm/dl
8. Globulin – 2.0- 3.3 gm/dl
66. A 30-year-old man is referred for
evaluation of elevated serum
weighed 103.5kg during his high school,
112.5kg after graduation. 135kg 5 years
later. Results of all liver tests are normal
except for a serum AST level of 65U/L
and a serum ALT level of 80U/L.
1) APPROACH TO THIS CASE
68. A 30-year-old man has severe flu
symptoms for 5 days. Cough, myalgia,
headache, and anorexia have resulted
in markedly diminished intake of food
and liquid. He has been ingesting crocin
tablets 3.5g/day. He was found to have
a serum AST level of 5,000U/L and an ALT
level of 5,500U/L.
69. A 28-year-old man who has had
ulcerative colitis for 10 years is found
through routine screening to have a
serum alkaline phosphatase level of
500U/L. Results of all other liver tests are
1. What is the possible diagnosis?
2. Investigation of choice?
70. A 17-year-old boy is referred for evaluation
of hepatomegaly and jaundice. On
examination he is found to have a
72. What are these tremors ?
Investigations of choice in this patient?
73. A62-year-oldwoman has pruritus and is found to have
jaundice. Except for scleral icterus, the findings of the
physical examination are normal.
The liver span measures 12cm at percussion.
Liver tests reveal the serum bilirubin level to be
6.0mg/dL, AST, 280U/L , ALT 300U/L, serum alkaline
phosphatase, 500U/L .
prothrombin time and normal serum albumin and
1. Pattern of liver enzymes elevation?
2. Next investigation of choice?
75. A 40-year-old woman is admitted to hospital
for therapy for alcohol withdrawal and
impending delirium tremens.Laboratory studies
1. serum bilirubin 2.0mg/dL,
2. serum AST-225U/L
3. serum ALT-45U/L
5. Serum iron level -170ug/dL(50-150ug/dl)
6. Total iron-binding capacity- 200ug/dL(250-370)
7. Iron saturation-85%(22-46%)
8. Serum ferritin- 700ug/L. (50-150).
77. Sleisenger and Fordtran’s gastrointestinal
and liver diseases 9th edition.
Schiff’s diseases of the liver 11th edition
Goldman’s cecil medicine 24th edition
Harrisons principles of internal medicine
Robbins and cotran pathology 8th