LIVER FUNCTION TESTS

BY ALAA ABAAS
PROFESSIONAL MASTER OF BIOCHEMISTRY.
YEAR 2023-2024
 What is the liver?
• The liver is reddish-brown and shaped
approximately like a cone or a wedge, with
the small end above the spleen and
stomach and the large end above the small
intestine. The entire organ is located below
the lungs in the right upper abdomen. It
weighs between 3 and 3.5 pounds.
 Functions of liver:

1-Synthetic functions : Synthesis of plasma proteins, Cholesterol, Triacylglycerol and

Lipoprotein .
2-Metabolic function: Protein metabolism, Ketogenesis, TCA cycle, Production of ATP.
3-Detoxification & Excretion: Ammonia to urea, Bilirubin, Cholesterol, Drug metabolites.
4- Homeostasis : Blood glucose regulation.
5-Storage function: Vitamin A,D,K,B12.
6-Production of bile salts.
 Why liver function tests are done?

I. Screening: they are non invasive yet sensitive modality for liver dysfunction.
II. Pattern of disease: they are helpful to recognize pattern of various diseases. Like being
helpful in differentiating between acute viral hepatitis and various cholesteric disorders
and chronic liver disease.(Cld)
III. Assess severity : they are helpful to assess the severity and predict the outcome of certain
diseases like primary biliary cirrhosis.
IV. Follow up: they are helpful in the follow up of certain liver diseases and also helpful in
evaluating response to therapy like autoimmune hepatitis.
Classification of liver functions tests:
Tests based on excretory function:
Tests based on detoxification function:
Tests based on synthetic function:
Tests based on metabolic function:
Enzymes in diagnosis of liver disease :
 Serum Bilirubin:

• Bilirubin: is the end product of heme degradation derived from breakdown senescent
(aging) erythrocytes by mononuclear phagocytes system specially in the spleen, liver and
bone marrow.
• The major pigment present in bile is the orange compound bilirubin.
• It is highly soluble in all cell membranes (hydrophobic) and is also very toxic. Therefore, its
excretion in the bile is one of the very important functions of the liver.
• Classification of bilirubin into direct & indirect bilirubin is based on original van den
Bergh method of measuring bilirubin.
 Bilirubin Metabolism:

• Bilirubin is the excretory product formed by the catabolism of heme part of hemoglobin.
• Porphyrin part of heme are converted to bilirubin in reticuloendothelial cells of liver,
spleen, bone marrow.
• Unconjugated bilirubin is bound to serum albumin &transferred to liver where it is
conjugated to glucoronate by UBD glucuronyl transferase.
• Conjugated bilirubin is excreted into bile. A fraction of bilirubin from stool is reabsorbed
into blood via portal circulation (enterohepatic circulation).
Differences Between The Conjugated And
Unconjugated Bilirubin:
 Diagnostic Importance Of Bilirubin:

• Disruption of bilirubin metabolism and excretion can cause Hyperbilirubinemia and

Subsequent Jaundice.

• Hyperbilirubinemia maybe unconjugated (indirect) or conjugated (direct) depending on

the type of bilirubin present in plasma.
Classification Of Jaundice According To Etiology:
 Urine Bilirubin:

• Normally bilirubin is absent in urine.

• Unconjugated bilirubin is insoluble in water and always absent in urine conjugated
bilirubin being water soluble is excreted in urine in obstructive jaundice.
• This can be detected by fouchet’s test.
 Urine Urobilinogen:

• Normally trace amounts is present in urine.

• In obstructive jaundice no urobilinogen is present in urine because bilirubin cannot enter intestine.
• Note: presence of bilirubin in urine and absence of urobilinogen in urine is seen in OBSTRUCTIVE
JAUNDICE.
• In hemolytic jaundice increased production of bilirubin causes increased formation of urobilinogen
which appears in urine.
• Note: increased urobilinogen in urine and absence of bilirubin in urine is seen in HEMOLYTIC
JAUNDICE.
 Fecal Urobilinogen

• Normally urobilinogen in faeces is excreted is 50-250mg/day.

• In HEMOLYTIC JAUNDICE faecal urobilinogen is increased which is dark colored.
• In OBSTRUCTIVE JAUNDICE faecal urobilinogen is decreased or absent; as there is
obstruction in flow of bile and the color of the feces is pale or clay-colored.
• A complete absent of faecal urobilinogen shows MALIGNANT OBSTRUCTION.
• A decrease may also occur in extreme cases of diseases affecting HEPATIC
PARENCHYMA.
 Galactose Tolerance Test:

• Galactose is monosaccharide exclusively metabolized by the liver.

• The liver function can be assessed by measuring the utilization of galactose.
• The normal liver is able to convert galactose into glucose ;but this function is impaired in
INTRAHEPATIC DISEASE and the amount of blood galactose and galactose in urine is
excessive.
 Cholesterol-cholesteryl Ester Ratio:

• The liver plays an important and active role in the metabolism of cholesterol including its synthesis ,
esterification, oxidation and excretion.
• Normal total blood cholesterol ranges 150 to 250mg/dl and about 60- 70% in esterified form.
• In OBSTRUCTIVE JAUNDICE, total blood cholesterol level is increased and the esterified form is
also increased.
• In LIVER DAMAGE, no change in total blood cholesterol level but its esterified form is decreased.
• In SEVERE ACUTE HEPATIC NECROSIS, total blood cholesterol level is decreased up to
100mg/dl and there is marked reduction in % present as esters.
 Determination Of Total Plasma Protein Albumin,
globulin & A:G Ratio:
• Liver is the site of albumin synthesis and also possibly of some α and β globulin.
• Albumin has a half-life of 20-25 days.
• It is a good marker to assess chronic liver damage.
• Albumin is also decreased in malnutrition.
• In ADVANCED PARENCHYMAL LIVER DISEASE AND IN CIRRHOSIS LIVER albumin is grossly
decreased and globulin are often increases .So that A:G ratio is reversed.
 Total plasma protein conc.--- 6.0 to 8.0g/dl.
 Albumin level --- 3.5 to 5.3 g/dl.
 Globulin level --- 2.5 to 3.5 g/d.
 Hippuric Acid Synthesis

• The liver is the major site for the metabolism of xenobiotic (detoxification).
• Measurement of Hippuric acid synthesis is an ideal test for assessing the detoxification
function of liver.
• Hippuric acid is produced in the liver when benzoic acid combines with glycine.
• A reduction in Hippuric acid excretion (< 3g) hepatic damage.
 Determination Of Blood Ammonia

• The major source of ammonia in blood is bacteria of gastrointestinal tract(GIT).

• Ammonia is later converted to urea by the liver then it is excreted by kidneys.
• This test used for detecting hepatic encephalopathy.
• Normally, blood ammonia varies from 40-75μg/ 100ml of blood.
• Increased in ammonia in blood is found in cases of CIRRHOSIS OF LIVER .
• In liver damage, blood ammonia levels may be >200μg/100ml.
 Prothrombin Time:

• The liver synthesizes all the factors concerned with blood clotting.
• A decrease in the concentration of plasma clotting factors is found in the impairment of
liver function.
• Prothrombin time is prolonged in patients with liver damage, compared to normal.
• Prothrombin time prolonged – hepatitis, cirrhosis, vitamin K deficiency ( obstructive
jaundice, fat malabs ).
 AST (Aspartate Transaminase)/SGOT (Serum
Glutamate Oxaloacetate Transaminase):
• AST is found in both cytoplasm & mitochondria.
• AST/GOT also reflects damage to the hepatic cells & is less specific for liver disease.
• It is a cardiac marker.
• AST help diagnose various heart, muscle or brain disorders, such as a myocardial infarct
(heart attack).
 Elevated Levels Of AST May Indicate:

1. Acute hemolytic anemia.

2. Cirrhosis of the liver.
3. Hepatitis.
4. Acute pancreatitis or inflammation of pancreas.
5. Acute renal failure or loss of kidney function.
6. Heart attack.
7. Primary muscle disease.
8. Recent surgery.
 Alanine Transaminase (ALT/SGPT):

• ALT is a cytoplasmic enzyme.

• The activity of these enzymes is low in normal serum.
• ALT is specific for liver disease.
• Its elevations favor liver cell necrosis as a cholestasis.
 Elevated Levels Of ALT/SGPT May Indicate:

1. Alcoholic liver disease.

2. Cancer of liver.
3. Hepatitis or inflammation of the liver.
4. Noncancerous tumor of the liver.
5. Use of medicines or drugs toxic to the liver.
6. Cirrhosis or scarring of the liver.
7. Death of liver tissue.
 ALP(Alkaline Phosphatase):

• ALP occurs in in all tissues, especially liver, bone, bile duct, kidney & the placenta.
• The ALP used to help diagnose certain liver diseases and bone disorders.
• ALP is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules,
including nucleotides & proteins.
• Most effective in an alkaline environment.
• Levels are significantly higher in growing children.
• A rise in serum ALP (normal 3-13 KA units/dl), usually associated with elevated serum bilirubin is an
indicator of BILIARY OBSTRUCTION (OBSTRUCTIVE/POST HEPATIC JAUNDICE).
• ALP is also elevated in cirrhosis of liver & hepatic tumors.
 Gama Glutamyl Transpeptidase (GGT):

• This is a microsomal enzyme widely distributed in body tissues, including liver.

• Measurement of GGT activity provides a sensitive index to asses liver abnormality.
• Serum GGT is highly elevated in biliary obstruction & alcoholism.
• GGT elevation parallels than of ALP.
• Increased level of GGT are observed in chronic alcoholism ,pancreatic disease,renal
failure ,diabetes mellitus.
• Several drugs (e.g. Phenytoin) induce (liver synthesis) & increase this enzyme in circulation.
 5'-Nucleotidase:

• The serum activity of 5'-Nucleotidase is elevated in hepatobiliary disease & this parallels
ALP.
• It is highest in post-hepatic obstructive jaundice.
• The 5'-nucleotidase is normal in patients with bone disease where as serum ALP increased .
Hepatitis
 Introduction:

• Hepatitis is a broad term that means inflammation of liver.

• It is most commonly caused by viruses but also be caused by drugs(alcohol), chemicals,
autoimmune diseases and metabolic abnormalities.
• Etiology Of Hepatitis:
 Viral Hepatitis:

• Five types of hepatitis have been identified: hepatitis A, B, C, D , E.

• Hepatitis A is always an acute, short-term disease, while hepatitis B, C, and D are most
likely to become ongoing and chronic.
• Hepatitis E is usually acute but can be particularly dangerous in pregnant women.
• The hepatitis A and E viruses typically cause only acute, or short-term, infections.
 Hepatitis A:

• A highly contagious liver infection caused by the hepatitis A virus(HAV).

• Hepatitis A virus is a ribonucleic acid(RNA) virus of the enterovirus family.
• It can cause ACUTE HEPATITIS WITH JAUNDICE. Also cause ACUTE LIVER FAILURE.
• It does not cause long term infection.
• Incubation period is 3-5 weeks with an average of 28 days.
• Transmission: Ingestion of fecal matter, even in microscopic amounts, from close person-to-
person contact or ingestion of contaminated food or drinks.
• HAV replicates in the liver and is shed in high concentrations in feces from 2 weeks before
to 1 week after the onset of clinical illness.
• HAV infection produces a self-limited disease that does not result in chronic infection or
chronic liver disease.
• Antibody produced in response to HAV infection persists for life and confers protection
against reinfection.
 Signs & Symptoms:

1) Fatigue.
2) Fever.
3) Abdominal pain.
4) Nausea.
5) Jaundice.
6) Weight loss.
7) Itching.
8) Sharp pain in right upper quadrant of abdomen.
9) Anorexia.
Diagnosis & Examination:
 Hepatitis B:

• Hepatitis B virus can cause acute and chronic infection.

• Acute hepatitis B infection may last up to 6 months (with or without symptom) and infected
persons are able to pass these virus during these time( acute) to a serious long-term
(chronic) illness that can lead to liver disease or liver cancer.
• Chronic hepatitis b is defined as persistence of HBsAg for 6 months or more after acute
infection with HBV.
• Incubation period is 2-5 months.
• Hepatitis B virus is a complex structure with 3 distinct antigens:
1. HBcAg: hepatitis B core antigen.
2. HBsAg: hepatitis b surface antigen.
3. HBeAg: an independent protein circulating in the blood.
• Transmission: Contact with infectious blood, semen, and other body fluids from having sex
with an infected person, sharing contaminated needles to inject drugs, or from an infected
mother to her newborn.
 Signs & Symptoms:

1. Abdominal pain.
2. Dark urine.
3. Fever.
4. Joint pain.
5. Loss of appetite.
6. Nausea/ vomiting.
7. Fatigue  jaundice
 Diagnosis & Examination:

• Blood Tests: AST, ALT, ALP,GGT, Serum Proteins, PT, Urinary Bilirubin, Urinary
Urobilinogen, Total Serum Bilirubin.
• Serological Tests: HBsAg, Anti-HBsAg, HBeAg, Anti-HBe, Anti-HBe IgM, Anti- HBe IgG,
HBV genotyping.
• Liver ultrasound
• Liver biopsy.
• Fibro tests.
 Hepatitis C:

• Hepatitis C virus is an RNA virus.

• Incubation period is 14-180 days(average 56).
• It is found in I.V. Drug users and renal dialysis patients.
• It can result in both acute and chronic illness.
• Chronic HCV infection results in liver cirrhosis.
• There is no vaccine for HCV.
• Transmission: Contact with the blood of an infected person, primarily through sharing
contaminated needles to inject drugs.
 Signs & Symptoms:

• Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal

pain, jaundice, itching, and flu-like symptoms.
• Associated With Chronic Hepatitis C :
Fatigue, Marked Weight Loss, Flu-like Symptoms, Muscle Pain, Joint Pain Intermittent Low-
grade Fevers, Depression, Headaches, Mood Swings, Itching, Sleep Disturbances, Abdominal
Pain (Especially In The Right Upper Quadrant), Appetite Changes, Nausea, Diarrhea,
Dyspepsia, Cognitive Changes.
 Diagnosis & Examination:

HCV genotyping.
Hepatitis C antibody.
Thank You