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Table of Contents

  • Hepatitis B Virus (HBV)
      • Sample for Hepatitis B Virus (HBV)
      • Purpose of tests (Indications) for Hepatitis B Virus (HBV)
      • Definition of the Hepatitis B Virus (HBV)
      • Biology of the Hepatitis B Virus (HBV)
      • The outcome of the Hepatitis B Virus (HBV) disease is:
      • Hepatitis B virus (HBV) is transmitted by:
      • Hepatitis B Virus (HBV) is common in (high-risk groups):
      • The incubation period of the Hepatitis B Virus (HBV)
      • Structure of Hepatitis B Virus (HBV)
      • Hepatitis B Virus (HBV) antigens and antibodies:
        • There are three antigens:
        • There are three Antibodies:
      • Hepatitis B surface antigen (HBsAg)
      • Hepatitis B surface antibody (HBsAb)
      • Hepatitis Core antigen (HBcAg):
      • Hepatitis B Core Antibody (HBcAb):
        • HBcAb interpretations:
      • Hepatitis Be antigen (HBeAg):
      • Hepatitis Be antibody (HBeAb):
        • HBeAb interpretations:
      • Clinical presentations of Hepatitis B Virus:
        • Table showing the difference between HAV and HBV:
      • The significance of various hepatitis markers:
        • Summary of the serological profile of HBV infection:
      • Treatment of Hepatitis B Virus (HBV)
      • Prevention of Hepatitis B Virus (HBV)
      • Questions and answers:

Hepatitis B Virus (HBV)

Sample for Hepatitis B Virus (HBV)

  1. The best sample for the viral hepatitis B markers or profile is serum.
  2. A random sample can be taken. No need for a fasting sample.

Purpose of tests (Indications) for Hepatitis B Virus (HBV)

  1. Viral hepatitis B marker is done for:
    1. The diagnosis of HBV infection.
    2. The diagnosis of the carrier.
    3. The diagnosis of chronic hepatitis.
    4. Screening of blood for transfusion.

Definition of the Hepatitis B Virus (HBV)

  1. HBV is also called serum hepatitis or long incubation hepatitis. This DNA virus causes viral hepatitis B. This is a double-stranded DNA virus, and one strand is incomplete.

Biology of the Hepatitis B Virus (HBV)

  1. This virus belongs to the Hepadnaviridae family.
  2. HBV is found in the blood and body secretions.
  3. In the HBs antigen-positive serum, there are three types of particles:
    1.  The most common are spherical, 20 nm in diameter.
    2. The second particle is 200 nm long and 20 nm in width.
    3. Dane particles, also called virions, 42 nm spherical, are few in the blood.
Hepatitis B Virus (HBV): Hepatitis B virus (HBV) composition

Hepatitis B Virus (HBV): Hepatitis B virus (HBV) composition

  1. HBsAg particles (sphericle and tubular) are not infectious. While Dane particle is infectious.

Summary of the features of Hepatitis B virus (HBV)

Parameters HBV features
Family Hepadnaviridae
Genus Orthohepadnavirus
Genome dsDNA
Genome size 3.2 kb
Virus particle (Viron) 42 nm, spherical
Mode of transmission Parenteral
Prevalence High
Fulminant disease Rare
Chronicity usually seen
Oncogenicity It is an oncogenic virus
Stability
  1. It is acid-sensitive
  2. It is stable at 37 °C for 60 minutes
  3. HBsAg is stable at pH 2.4 for 6 hours
  4. Sodium hypochlorite destroys within 3 minutes
  5. Ultraviolet rays do not destroy HBsAg

The outcome of the Hepatitis B Virus (HBV) disease is:

  1. Acute hepatitis.
  2. Chronic hepatitis.
  3. Cirrhosis.
  4. Liver cell carcinoma.
  5. This is usually seen in young adults.

Hepatitis B virus (HBV) is transmitted by:

  1. Blood and blood products.
  2. Contaminated needles can spread it.
    1. In I/V, drug abusers are seen in about 25% to 30% every year in the USA.
    2. It is also seen in renal dialysis patients.
  3. It can spread through sexual contact through the rectum or by sexual intercourse.
    1. It is quite common in male homosexuals.
    2. It is less common in heterosexuals.
  4. It can spread through bodily fluids like infected blood, saliva, and semen through a small break in the skin or mucous membrane.
    1. There is an increased risk in renal transplantation patients and patients with leukemia and lymphoma.
  5. There is transplacental spread.
  6. Hospital workers are also at risk, roughly 5% of yearly cases in the USA.
    1. This usually happens by accidental needle prick.
    2. It is also common among dentists and dental workers.

Hepatitis B Virus (HBV) is common in (high-risk groups):

  1. Multiple Blood transfusion recipients.
  2. Male homosexuals.
  3. Dialysis patients.
  4. Transplant patient.
  5. I/V drug user.
  6. Hospital worker because of needle pricks.
  7. Patient with leukemia and lymphoma.
  8. During delivery can infect the newborn if the mother is a carrier.
  9. A family member with close contact.

The incubation period of the Hepatitis B Virus (HBV)

  1. This incubation lasts from 5 weeks to 6 months (60 to 90 days).
  2. This virus can cause acute infection and may develop into a chronic disease.

Structure of Hepatitis B Virus (HBV)

  1. This is a DNA virus called a Dane particle (Virion).
  2. It has an inner core surrounded by an outer capsule.
  3. The outer capsule contains the antigen called the hepatitis B surface antigen (HBs-Antigen). This is also called the Australian antigen (HBsAg).
  4. The inner core contains HBV core antigen one is called HBcAg, and another antigen incorporated into the Core antigen is HBeAg.
  5. The HBcAg is in a very small amount, so not detectable, but its Antibody is found in circulation.
Hepatitis B Virus (HBV): HBV structure

Hepatitis B Virus (HBV): HBV structure

Hepatitis B Virus (HBV) antigens and antibodies:

  1. Dane particle (Virion) has a double-shell structure containing several antigens (antigenic material).
    1. The outer envelope is called a surface antigen (HBsAg), the Australian antigen.
    2. The inner core contains HBV core antigen (HBcAg), and HBV e antigen (HBeAg).
    3. Within the core is double-stranded DNA (double-stranded viral deoxyribonucleic acid).
    4. There is an enzyme called DNA polymerase.
  2. There are three antigens:

    1. HBsAg
    2. HBcAg
    3. HBeAg
  3. There are three Antibodies:

    1. Anti-HBsAb
    2. Anti-HBcAb
    3. Anti-HBeAb
Hepatitis B Virus (HBV): Hepatitis B virus (HBV) serological profile

Hepatitis B Virus (HBV): Hepatitis B virus (HBV) serological profile

Hepatitis B surface antigen (HBsAg)

  1. HBV surface antigen (HBsAg) is detected by immunoassay or nucleic acid probe.
  2. HBsAg appears first in the blood, so its detection in the blood is a very common test.
  3. HBsAg rises before clinical signs and symptoms appear and is detectable.
  4. The peak is during the first week of symptoms.
  5. It returns to a normal level by the time jaundice subsides.
  6. If it persists, the patient will be a carrier or develop chronic hepatitis.
  7. HBsAg interpretations:
    Parameters Clinical presentation
    Appearance of HBsAg
    1. It appears after 2 to 6 weeks after exposure
    2. 5% to 15% of patients are negative at the onset of jaundice
    Peak level
    • 1 to 2 weeks before or 1 to 2 weeks after the onset of symptoms
    When it is not detected in the blood
    1. It disappears 1 to 3 months after the peak
    2. This range may be 1 week to 5 months

Hepatitis B surface antibody (HBsAb)

  1. This antibody appears after roughly 4 weeks after the disappearance of HBsAg.
  2. It indicates the end of the acute phase and the patient’s complete recovery from the infection.
  3. The patient will develop immunity to HBV infection.
  4. After vaccination, there is the appearance of HBsAb.

HBsAb interpretations:

Parameters Clinical interpretations
Appearance of HBsAb
  1. 2 to 6 weeks after the disappearance of HBsAg
  2. Few cases may not produce HBsAb
Peak level
  • 2 to 8 weeks after the appearance
When it is not detected
  1. Around 85% of the cases have the presence of HBsAb-total
  2. It may persist for many years of life
  3. There is a slow decline in the titer
  4. HBsAb disappear in 6 months in around 15% of the cases
Hepatitis B virus (HBV) showing HBs antigen and antibody

Hepatitis B virus (HBV) showing HBs antigen and antibody

Hepatitis Core antigen (HBcAg):

  1. This is not detectable because of the very small quantity, and it is incorporated with HBeAg.
  2. There are no commercial kits available to detect HBcAg.

Hepatitis B Core Antibody (HBcAb):

  1. There are kits available for HBc-IgM and total HBcAb (HBc-IgM and IgG)
  2. This antibody appears after one month of infection.
  3. This will be HBcAb-IgM type in acute infection and later replaced by HBcAb-IgG type.
  4. HBc-IgM is detected in active acute or recent acute HBV infection.
    1. HBc-IgM rises during active acute infection of HBV and will remain in the convalescent stage.
    2. It will be seen during the period when HBsAg disappears and HBsAb appears (window period).
    3. It is also called a “core window” marker.
  5. This antibody persists in circulation for several years.
  6. This antibody will be present in chronic hepatitis cases.
  7. In the window period when HBsAg is negative, and still there are no HBsAb, then this is the antibody present in the patient.
  8. It is not detected in the early weeks or months of the recovery phase.
  9. HBcAb total has been elevated for many years and gives positive results in the:
    1. Late-stage active acute infection.
    2. Convalescent stage.
    3. Chronic stage (chronic infections).
    4. Recovery early stage.
  10. HBcAb total may be found with HBsAg.

HBcAb interpretations:

Parameters  HBcIgM HBcAb total
Appearance of HBcAb
  • Around 2 weeks after the appearance of HBsAg
  • About 3 to 4 weeks after the appearance of HBsAg
Peak level
  • Around one week after the onset of symptoms
  • 3 to 4 weeks after the detection of HBcIgM
When it is not detected
  • 3 to 6 months after the appearance
  1. It is raised throughout the life
  2. It may decline over many years
Hepatitis B Virus (HBV): Hepatitis B virus (HBV) HBc antibody

Hepatitis B Virus (HBV): Hepatitis B virus (HBV) HBc antibody

Hepatitis Be antigen (HBeAg):

  1. HBeAg is not usually advised for the diagnosis of HBV infection.
  2. HBeAg is a marker of infectivity and continued replication of the HBV infection.
    1. HBeAg without the appearance of the HBeAb will indicate greater potential for spreading the infection to other people.
    2. HBeAg disappeared shortly before the disappearance of the HBsAg.
  3. HBeAg appears immediately after the appearance of HBsAg.
  4. HBeAg indicates early and acute disease.
  5. HBeAg positive in chronic hepatitis patients is a sign of a bad prognosis.
  6. The persistence of HBeAg indicates the development of chronic hepatitis.

HBeAg interpretations:

Parameters HBeAg
The appearance of the HBeAg
  • Around 3 to 5 days after the appearance of HBsAg
Peak level
  • It is at the same time as the HBsAg
When it is not detected
  1. Around 2 to 4 weeks before the HBsAg disappears in 70% of the cases
  2. Approximately 1 to 7 days after the HBsAg disappears in about 20% of the cases

Hepatitis Be antibody (HBeAb):

  1. The appearance of HBeAb is a sign of recovery.
  2. HBeAb appears after the disappearance of the HBeAg or in 1 to 2 weeks later.
    1. HBeAb appearance indicates that HBV infection is over and infectivity for other people is less common.
  3. This antibody shows the end of the acute phase.
  4. The presence of HBeAb indicates less infectivity.

HBeAb interpretations:

Parameters HBeAb
When it appears
  1. It appears at the same time or within 1 to 2 weeks after HBeAg disappears
  2. 2 to 4 weeks before HBsAg disappear
Peak level
  • During window period
When not detected
  • It persists for several years

 

Hepatitis B virus (HBV), HBeAg and HBeAb

Hepatitis B virus (HBV), HBeAg and HBeAb

Clinical presentations of Hepatitis B Virus:

  1. There is variation in the symptoms from mild to severe.
    1. It is fatal in about 1% to 3% of patients.
    2. 30% to 40% of patients develop acute hepatitis.
  2. Most of the children and 50% of the adults are asymptomatic.
    1. Infants are almost always asymptomatic, and most children do not develop jaundice.
  3. The symptoms are insidious.
  4. The prodromal period often shows :
    1. Fever.
    2. Malaise.
    3. Myalgia.
  5. The patient may have nausea and vomiting.
  6. There is weight loss.
  7. The acute period with jaundice lasts about one month.
  8. The patient will have jaundice and dark-colored urine.
  9. <1.5% may develop fulminant hepatitis.
  10. Chronicity decreases with age.
    1. 85% are seen in neonates.
    2. 25 to 50% of children.
    3. 6 to 10% of adults.
  11. These patients are at high risk for liver cell carcinoma.
  12. Pregnant ladies may get an infection during 3rd trimester or early postpartum or HBV carrier, frequently transmitting HBV infection to their babies after birth.
    1. When a mother is HBsAg and HBeAg positive, it will transmit the infection to babies from 12.5% to 40%, and this may be high as 70% to 90%.
    2. In one of the studies, when PCR is negative but routine HBsAg and HBeAg are positive, fewer infants get infected.
    3. Without treatment, 80% to 90% of babies become chronic carriers of HBsAg. These babies are prone to develop a risk of fatal cirrhosis or liver cell carcinoma.
    4. If newborns are given vaccines and immunoglobulin, it will reduce the risk of the chronic carrier state.

Table showing the difference between HAV and HBV:

Presentation HBV HAV
Mode of transmission Parenteral Feco-oral
Incubation period 60 to 160 days 15 to 40 days
Time of spread All the year Fall and winter
Onset Slow Sudden
Chronicity Roughly 5 to 10% Complete recovery
Mortality <0.01% <1%
Prophylaxis γ-globulin protects Some pools of γ-globulin

The significance of various hepatitis markers:

Acute infection

  1. HBsAg positive.
  2. HbcAb- IgM positive.

Chronic infection (Chronic carrier):

  1. Chronic hepatitis is defined when >6 months surface antigen (HBsAg) is present with normal liver function tests and normal microscopic findings on the liver biopsy.
  2. 2 to 10 % develop chronic disease.
  3. Chronic hepatitis is divided into:
    1. Chronic persistent hepatitis where abnormal liver function tests, relatively normal microscopic findings on liver biopsy. This condition is seen in 6% of the patients.
    2. Chronic active hepatitis where abnormal liver function tests and abnormal microscopic findings on liver biopsy. This condition may be seen in 3% of the patients.
  4. These patients may develop cirrhosis.
  5. Cirrhotic patients have more chances of cancer, which almost increased 500 times.
  6. Lab findings are:
    1. HBsAg positive.
    2. HbcAb-IgG (Total) is positive.
  7. HBeAg positive indicates a highly infective stage and poor prognosis.
HBV chronic hepatitis profile

HBV chronic hepatitis profile

Recovery stage parameter:

  1. HBsAg is negative.
  2. HBsAb is positive.

Window period marker:

  1. HBsAg is negative.
  2. HBsAb is negative.
  3. HBcAb-IgM will be positive.

For the HB viral load advice PCR:

  1. PCR qualitative for the HBV genome.
  2. PCR quantitative by HBV DNA by RNA probe.

Table showing various HBV antigens and antibodies:

HBV Ag/AB Appears Disappears Significance
HBsAg 4 to 12 weeks 1 to 3 months Acute or chronic infection
HBeAg 1 to 3 weeks 6 to 8 weeks Acute infection
HbcAg not detected
HBsAb 3 to 10 months 6 to 10 years Indicate immunity
HbeAb 4 to 6 weeks 4 to 6 years End of acute infection
HbcAb IgM 2 to 12 weeks 3 to 6 months Acute HBV infection
HbcAb total 3 to 12 weeks Life long Past HBV infection/recovery stage

Table showing various stages of HBV infection:

Test Acute Chronic Recovery Carrier Window period Vaccination
HBsAg positive  positive negative/positive positive negative negative
Anti-IgM HBc positive neg/pos negative negative positive negative
Anti-IgG HBc negative positive positive positive neg/pos positive
HBeAg positive neg/pos negative negative negative negative
Anti-HBeAb negative positive positive positive pos/neg negative
Anti-HBs Ab negative negative positive negative negative positive
PCR positive positive negative negative positive negative
Hepatitis B Virus (HBV): Hepatitis B Virus (HBV) serological profile

Hepatitis B Virus (HBV): Hepatitis B Virus (HBV) serological profile

Hepatitis B Virus (HBV) infection possible outcome

Hepatitis B Virus (HBV) infection is a possible outcome

Summary of the serological profile of HBV infection:

Serological profile Clinical presentation
  1. HbS-Ag positive
  2. Hbc-Ab negative
  1. Early acute HBV infection (Around 5%)
  2. Hbc-Ab rises later on.
  1. HbS-Ag positive
  2. Hbc-Ab positive
  3. HbS-Ab negative
  1. Patients develop clinical symptoms
  2. Chronic HBV carrier without evidence of liver disease
  3. Chronic HBV hepatitis:
    1. Chronic persistent hepatitis
    2. chronic active hepatitis
  1. HbS-Ag negative
  2. Hbc-Ab positive
  3. HbS-Ab negative
  1. Late clinical symptomatic stage
  2. Early convalescent stage (window period)
  3. Chronic HBV infection
  4. Old previous HBV infection
  1. HbS-Ag negative
  2. Hbc-Ab positive
  3. HbS-Ab positive
  1. Old infection
  2. Complete recovery stage
  3. Late convalescent stage

Treatment of Hepatitis B Virus (HBV)

  1. In the case of fulminant hepatitis, liver transplantation is needed.
  2. Treatment of chronic HBV infection is indicated when HBV-DNA  >2000 IU/L and serum SGPT is raised.
  3. Antiviral medications are Lamivudine (Epivir), Adefovir (Hepsera), Telbivudine (Tyzeka), and Entecavir (Baraclude).
  4. Interferon alpha-2 is used mainly for young patients.

Prevention of Hepatitis B Virus (HBV)

  1. Vaccination is the method of choice.
  2. This should be given at birth to infants born to carrier mothers.

Questions and answers:

Question 1: What is the best marker for the window period?
Show answer
The best marker for the window period is Hbc-IgM.
Question 2: What is the best marker for the acute hepatitis B infection?
Show answer
The best marker for the diagnosis of acute hepatitis B infections are HbsAg and Hbc-IgM antibody.

Possible References Used
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Comments

Mulazim Hussain Bukhari Reply
February 18, 2020

Excellent

Dr. Riaz Reply
February 20, 2020

Thanks for the comments.

Dr.Sharifullah Sadaat Reply
August 11, 2022

Good detailing about the HBV. Appreciable .

Dr. Riaz Reply
August 11, 2022

Thanks.

Add Comment Cancel


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