In this essay we will discuss about Hepatitis B Virus (HBV). After reading this essay you will learn about: 1. Discovery of Hepatitis B Virus (HBV) 2. Antigenic Structure of HBV 3. Hepatitis B Carriers 4. Transmission of HBV 5. Immune Response of HBV 6. Laboratory Diagnosis of HBV.
- Essay on the Discovery of Hepatitis B Virus (HBV)
- Essay on the Antigenic Structure of HBV
- Essay on Hepatitis B Carriers
- Essay on the Transmission of HBV
- Essay on the Immune Response of HBV
- Essay on the Laboratory Diagnosis of HBV
Essay # Discovery of Hepatitis B Virus (HBV):
Blumberg et al (1965) described an antigenic substance (protein) in serum of an Australian aborigine that gave a positive precipitation reaction with sera of two multiple transfused haemophiliacs. This antigen was designated as Australia antigen. Later it was confirmed that this antigen was the surface component of Hepatitis B virus and named Hepatitis B surface Antigen (HBs Ag).
Hepatitis B virus is 42 nm in diameter with one molecule of double-stranded DNA and DNA dependent DNA polymerase core of 27 nm diameter, with 2 nm thick shell and an envelope of 7 nm thickness. The core has an icosahedral symmetry. Replication of HBV occurs in primary duck hepatocyte culture system. Only 10% of the duck hepatocytes become infected in tissue culture.
Essay # Antigenic Structure of HBV:
1. HBs Ag:
surface antigen (envelope protein).
2. HBC Ag:
27 nm core (nucleocapsid) of the virus with group specific protein which is not detected in patient’s blood.
3. HBe Ag :
Hidden antigenic component of core which may be a conversion product of HBe Ag. It is soluble and appears in serum with HBs Ag. Later it disappears within a few weeks. The particles of HBs Ag are complex and are of four antigenic types: adw, adr, agw, and ayr.
These types are useful in the study of epidemiology spread through Iran, Pakistan to India. Additional surface antigens of HBV (q, x, f, t, j, n, g) are yet to be characterised.
Essay # Hepatitis B Carriers:
There are two types of Hepatitis B carriers:
(a) Simple carriers;
(b) Super carriers.
(a) Simple carriers are persons who do not have HBe Ag but low titre of HBs Ag in blood. They contain anti-HBe in blood and the infection is transmitted only with large volume of blood.
(b) Super carriers are persons with HBe Ag in blood.
They are highly infectious as very little (0.0001 ml) quantity of infected plasma can transmit the disease. Their blood contains high titre of HBs Ag and DNA polymerase. HBV can be demonstrated in blood.
Persistence of HBV infection is indicated by:
(1) The presence of HBs Ag for more than 6 months.
(2) The infection in 5-10% adults, 30% children, and 90% newborn.
(3) The susceptibility of immuno-compromised hosts to persistent infection.
Essay # Transmission of HBV:
It is mainly due to artificial inoculation of infected blood and blood products. Therapeutic, prophylactic and diagnostic procedures by percutaneous route may also transmit the infection.
Essay # Immune Response of HBV:
(I) Antibody to HBV:
Following the HBV infection, anti-core antibody rises rapidly. It is not protective; during viral replication in liver and in carrier state, it is persistent in serum in high titre.
Its presence in serum is an indication of past infection and recent immunity. It rises between 3 and 26 weeks. Later it persists in blood for indefinite period. Both B and T cells response is induced by core and surface antigens. By both antibody- dependent and cytotoxic action of T-cell, the hepatocyte can be damaged.
(II) Cell Mediated Immunity (CMI):
With development of chronic liver damage, T-cell function becomes defective. However, in self-limited courses of hepatitis B, T-cell function is within normal limits.
Essay # Laboratory Diagnosis of HBV:
Since there is limitation in the isolation of HBV in tissue culture, enzyme linked immunosorbent assay, radioimmunoassay, latex agglutination and haemagglutination tests, which are sensitive and specific laboratory tests, can be used for the diagnosis.
(I) HBV Antigens:
(a) HBs Ag:
It can be detected in blood a month after exposure to infection. It reaches its peak during prehistoric phase, it disappears mostly with recovery from clinical disease and persists only in small number of cases. After disappearance of HBs Ag in serum, anti-HBs Ag antibody appears and persists for decades.
(b) HBc Ag:
It can be detected in liver cells, by immunofluorescence not in patient’s serum, by immunofluorescence Anti-HBc antibody is detected in the early stage of illness and persists in blood for longer period.
(c) HBe Ag:
HBe Ag and HBs Ag appear in patient’s blood at the same time. HBe Ag disappears in a few weeks and its persistence in blood is indicative of adverse prognosis, sera of such patient is highly infectious.
(d) Viral Polymerase:
During pre-icteric phase, it appears transiently in serum.
Prevention of HBV can be carried out by Active Immunization:
(i) HBs Ag vaccine is prepared by purifying small 22 nm particles of HBs Ag from plasma of healthy carriers and by inactivating with formalin, urea or heat. These particles are separated by ultra-centrifugation, protection is offered by antibody to the “a” antigen (group specific). The product is safe and immunogenic. It is successfully used.
(ii) Hepatitis B vaccine is produced by a recombinant DNA technique in yeast cells or in continuous mammalian cell lines in which a plasmid containing the gene of HBs Ag has been incorporated. The product is particulate and 15-30 nm in diameter with morphological characteristics of free HBs Ag (surface antigens) in plasma.
This vaccine is claimed to be as immunogenic as that derived from plasma of carriers. Both vaccines are safe and local swelling and reddening may occur in some 20% cases accompanied by slight fever. Three doses at 0,1 and 6 months are administrated (with alum as adjuvant) intramuscularly into deltoid muscle.
Chronic infection with HBV is an important aetiological factor in hepatocellular carcinoma (HCC). In areas where HBV infection is highly endemic, HCC is more frequently observed. It occurs at a very early stage. An interval of 30-40 years is needed between infection and development of tumour.
Precise mechanism of oncogenesis is not yet clear. DNA of hepatitis B virus most probably gets integrated with the nucleus of liver cells. Tumour cells collected from Hepatitis B carriers show integrated viral DNA with the tumour cell.
HBV, (Table 53.3) the cause of serum hepatitis is a hepadna virus. Hepatitis B surface Antigen (HBs Ag) is associated with hepatitis B infection.
Electron microscopy of HBs Ag reactive serum revealed 3 morphological forms:
(1) the most numerous are small spherical particles of 22 mm in diameter made up of HBsAg;
(2) Tubular or filamentous forms;
(3) Large, 42 nm spherical particles (HBV) called Dane particles—are less frequently observed.
These particles are more complex. Their envelope contains HBcAg. A form of HBcAg designated as HBeAg may be present in the serum during HBV infection. HBcAg and HBeAg are serologically distinct.
HBV (but not HBsAg) is sensitive to high temperature. HBV infectivity is lost at pH2, but HBsAg is stable. HBsAg is not destroyed by ultraviolet irradiation of plasma and blood product. Transmission can be during dental surgery.
Immunofluorescence studies indicate that during HBV infection HBcAg is found primarily in the nucleus, whereas HBsAg is localised in the cytoplasm. HBsAg and HBcAg are rarely found in the same cell.
In man, HBV is not cytopathogenic because there is existence of HBV carrier state for many years without evidence of parenchymal liver damage.