Hepatitis B

Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease.

Hepatitis B virus- DNA virus belonging to the Hepadnaviridae family 

1965, Blumberg-discovered Hepatitis B surface antigen from the serum of an Australian aborigine, hence named Australian antigen

Family: Hepadnaviridae

Genus: Orthohepadnavirus

Species: Hepatitis B virus

Structure  

Contains icosahedral nucleocapsid, the core (27 nm) and outer envelope (42 nm)

There is an outer shell (or envelope) composed of lipid and protein that is termed “surface antigen” or “HBsAg”.

Inner protein shell that is referred to as the core particle or “HBcAg”, contains the viral DNA and enzymes used in viral replication ( “DNA polymerase”).

HBeAg (hepatitis B e antigen) is also associated with the nucleocapsid of HBV.  It is soluble, secreted and seen in circulation

 

Three types of viral particles are visualized in infectious serum by electron microscopy.

• 42 nm in diameter (Dane particle- Complete Virion)
• 20 nm in diameter (Spherical Structures)
• 22 nm in diameter (Filamentous Particles)

 The 42-nm spherical Dane particle (Associated with it is, HbsAg) can be disrupted by nonionic detergents to release the 27-nm core that contains the partially double-stranded viral DNA genome. Associated with the core is, HBcAg, hepatitis B core antigen. A soluble antigen, termed hepatitis B e antigen (HBeAg), may be released from core particles by treatment with strong detergent. .

Genome 

• Is partially double-stranded DNA held in circular configuration 
• One strand incomplete (positive), associated with it is a viral DNA polymerase with DNA dependent DNA polymerase and RNA dependent reverse transcriptase activity

• The genome is 3020–3320 nucleotides long (for the full length strand) and 1700–2800 nucleotides long (for the short length strand).

• Compact organization, with four overlapping genes (S, C, P, X genes) and no non-coding regions.
• S gene, codes for Surface antigen HbsAg 
• C gene, codes for nucleocapsid Core antigen- HbcAg and a soluble antigen-HbeAg 
• HbcAg is associated with the nucleocapsid core and is not secreted or circulated in blood -can be detected in hepatocytes
• HbeAg is secreted and present in circulation during infection-presence indicates HBV replication and infectivity
• Detection of HbeAg -marker for HBV 
• P gene, for DNA polymerase
• X gene, for nonparticulate antigen, HbxAg-has activating effects on viral and some cellular genes.
• HbxAg- present in patients with severe chronic hepatitis and hepatocellular carcinoma

General symptoms include

· Fever

· Nausea and vomiting

· Loss of appetite

· Flu-like symptoms

· Fatigue and weakness

· Lack of nutrition

· Aching in the abdomen

· Pale or clay-colored stool

· Dark urine

· Yellowing of skin or eyes

Ø  Symptoms similar to HAV; but severe and prolonged; Onset is insidious, fever not prominent

Ø  Extrahepatic complications – arthralgia, urticaria,  polyarteritis, glomerulonephritis (due to circulating immune complexes carrying the viral antigens)

Ø  90-95% adults with acute Hep B infection recover in 1-2 months- remain immune thereafter

Ø  0.5-2% cases- mortality, more in post transfusion cases

Ø  1% adults, with simultaneous delta virus infection develop fatal fulminant hepatitis

Ø  1-10% cases, remain chronically infected- asymptomatic carriers or develop recurrent/chronic liver disease or cirrhosis- some develop hepatocellular carcinoma

Ø  Vaccine against HBV present- hepatocellular carcinoma is the only human cancer which is vaccine preventable

 Pathogenesis is immune mediated

Ø  Hepatocytes carry viral antigens- Attacked by antibody dependent NK cells and cytotoxic T cells

Ø  In the absence of adequate immune response, HBV infection may not cause hepatitis but lead to carrier state

Ø  Infants and immunodeficient persons become asymptomatic carriers following infection

Epidemiology

•        Hepatitis B occurs throughout the world- no seasonal distribution

•        Natural Infection only in humans

•        Virus maintained in carriers- their blood contains circulating viruses for a long time, even lifelong

•        Infection is usually sporadic- Occasional outbreaks occurs mostly in hospitals, orphanages and institutions for mentally handicapped.

•        The prevalence of hepatitis carriers varies- Overpopulated, underdeveloped regions have high endemicity , developed countries have low endemicity

•        India has intermediate endemicity (2-7% carriers), with higher rates in the southern part of the country

 

Carriers

          Super carriers

•        Highly infectious

•        High titre of HBsAg along with HBeAg, DNA polymerase and HBV in circulation

•        Elevated transaminases

•        Enormous antigenemia and viremia (10¹³ HBsAg particles and 10⁸ HBV per ml blood)

          Simple Carriers

• Low infectivity
• Low titre HBsAg in blood, with negative HBeAg, DNA polymerase and HBV in circulation

Elevated transaminases

Transmission

HBV is a bloodborne virus and the infection is transmitted by parenteral, sexual and perinatal modes.

Blood of carriers, and less often of patients, is the most important source of iniection. The virus may also be present in other body fluids and excretions, such as saliva, breast milk, semen, vaginal secretions, urine, bile and faeces. Of these, semen and saliva are known to transmit the infection; others may also do though much less efficiently than blood. Faeces are not known to be infectious.

Transfusion of carrier blood, once the most widely known mode of infection has largely been eliminated wherever donor screening is strictly enforced. Therapeutic and prophylactic preparations from pooled human blood and serum have led to hepatitis but this risk is now minimal, with sçreening of donors and production techniques ensuring virus inactivation. However, HBSAg screening is not a totally safe method as infection has occurred even with HBSAg- and anti-HBc positive blood, which may have had undetectable amounts of virus.

Many other therapeutic, diagnostic. prophylactic and even nonmedical procedures are now the main modes of infection.  HBV is very highly infectious, far more than HIV. Any object or procedure than can convey minute traces of infected blood or other material,  can be infectious.

Infection by direct contact with open skin lesions such as pyoderma, eczema, cuts and scratches is very common among young children in developing countries, as also through household transmission where opportunities exist for contact with blood or saliva among members.

HBV has been said to survive in mosquitoes and bed bugs for about 2 weeks after blood meal, but no virus multiplication occurs. They do not appear to transmit the infection.

Congenital or vertical transmission is quite common from carrier mothers. The risk to babies is high if the mother is HBeAg positive (60-90 per cent) and low if negative (5-15 percent). True congenital infection (in utero), transplacental is rare. Infection is usually acquired during birth by contact of maternal blood with the skin and mucosa of the fetus, or in the immediate postnatal period.

Infection by ingestion has been reported, but its efficiency is very low. It is better that carrier mothers do not breastfeed when proper nutrition of their babies can be otherwise ensured. HBV infected neonates generally do not suffer from any clinical illness but remain carriers tor life and some of them may develop hepatocellular carcinoma after many decades

Sexual transmission of HBV occurs everywhere, but is more important in the developed countries particularly in the promiscuous homosexual. The risk of transmission by heterosexual and homosexual contact increases with the number of partners and the duration of Such relationships. HBV infection has occurred after artificial insemination. Semen donor screening is therefore obligatory.

Certain groups and occupations carry a high risk of infection. These include medical and paramedical personnel, staff of blood banks, dialysis units, medical laboratories and mental health institutions, barbers and sex workers. Dentists and doctors have been responsible for small outbreaks. In countries like Britain, HBV carriers are barred from invasive medical practice. Carriers are also not permitted to be medical Students.