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

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

Summary of the features of Hepatitis B virus (HBV)

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) 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 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	It appears after 2 to 6 weeks after exposure 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	It disappears 1 to 3 months after the peak 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:

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:

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:

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:

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:

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

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:

Table showing various stages of HBV infection:

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

Hepatitis B Virus (HBV) infection is a possible outcome

Summary of the serological profile of HBV infection:

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: