Hepatitis B Virus – Part 1 – Hepatitis B Virus, HBV

Sample

1. The best sample for the viral hepatitis B markers or profile is serum.
2. A random sample can be taken.

Purpose of tests (Indications)

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.

Pathophysiology

1. HBV is also called serum hepatitis.
2. Viral hepatitis B is caused by the DNA virus. This is a double-stranded DNA virus and one strand is incomplete.
3. This virus belongs to the Hepadnaviridae family.
4. 42 to 47 nm particles are infectious.
   1. 20 nm spherical and 20 nm by 1-micrometer particles are not infectious.
5. The outcome of the disease is :
   1. Acute hepatitis.
   2. Chronic hepatitis.
   3. Cirrhosis.
   4. Liver cell carcinoma.
6. This is usually seen in young adults.
7. Transmitted by:
   1. Blood and blood products.
   2. It can spread by contaminated needles.
   3. It can spread through sexual contact.
   4. It can spread through other body fluids.
   5. There is transplacental spread.
8. It is Common in (high-risk group):
   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.
9. Incubation period
   1. This has long incubation varying from 5 weeks to 6 months.
   2. This viral can give acute infection and may develop chronic disease.
10. Structure of HBV
    1. This is a DNA virus and called a Dane particle.
    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 as Australia antigen (HBsAg).
    4. The inner core contains HBV core antigen one is called HBc Ag and another antigen is incorporated into the Core antigen is called HBeAg.
    5. The HBcAg is a very small amount so not detectable but its Antibody is found in circulation.

12. There are three antigens:

    1. HBsAg
    2. HBcAg
    3. HBeAg

13. There are three Antibodies:

    1. Anti-HBsAb
    2. Anti-HBcAb
    3. Anti-HBeAb

14. Hepatitis B surface antigen (HBsAg)

    1. 1. HBsAg appears first in the blood, so this is a more common test.
       2. HBsAg rises before the appearance of clinical signs and symptoms appear and is detectable.
       3. The peak is during the first week of symptoms.
       4. It returns to a normal level by the time jaundice subsides.
       5. If it persists then the patient will be a carrier or may develop chronic hepatitis.

15. Hepatitis B surface antibody (HBsAb)

    1. 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 complete recovery from the infection.
       3. The patient will develop immunity to HBV infection.
       4. After vaccination, there is the appearance of HBsAb.

16. Hepatitis Core antigen (HBcAg)

    1. 1. This is not detectable because of the very small quantity and it is incorporated with HBeAg.

17. Hepatitis B Core Antibody (HBcAb )

    1. 1. This antibody appears after one month of infection.
       2. In acute infection, this will be HBcAb-IgM type and later replaced by HBcAb-IgG type.
       3. This antibody persists in circulation for several years.
       4. This antibody will be present in chronic hepatitis cases.
       5. In the window period when HBsAg is negative and still there are no HBsAb, then this is the antibody present in the patient.
       6. HbcAb-IgM is the marker in the window period in acute infections.
       7. This is also called as the window period marker.

18. Hepatitis Be antigen (HBeAg)

    1. 1. HBeAg is a marker of the infectivity.
       2. HBeAg appears immediately after the appearance of HBsAg.
       3. HBeAg indicates early and acute disease.
       4. HBeAg positive in chronic hepatitis patients is a sign of a bad prognosis.
       5. The persistence of HBeAg indicates the development of chronic hepatitis.

19. Hepatitis B e antibody (HBeAb)

    1. The appearance of HBeAb is a sign of recovery.
    2. This antibody shows the end of the acute phase.

Clinical presentation

1. There is variation in the symptoms from mild to severe.
2. Most of the children and 50% of the adults are asymptomatic.
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 color urine.
9. <1.5% may develop fulminant hepatitis.
10. Chronicity decreases with age.
    1. 85% seen in the neonates.
    2. 25 to 50% of children.
    3. 6 to 10% of the adult.
11. These patients are at high risk for liver cell carcinoma.

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:

1. Acute infection
   1. HBsAg positive.
   2. HbcAb- IgM positive.
2. Chronic infection
   1. 2 to 10 % develop chronic disease.
   2. HBsAg positive.
   3. HbcAb-IgG (Total) is positive.
   4. HBeAg positive indicate highly infective and poor prognosis.

1. Recovery stage
   1. HBsAg is negative.
   2. HBsAb is positive.
2. Window period marker
   1. HBsAg is negative.
   2. HBsAb is negative.
   3. HBcAb-IgM will be positive.
3. 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

Treatment

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

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

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