Hepatitis B is an inflammation of the liver and is caused by the Hepatitis B virus (HBV), a member of the Hepadnavirus family and one of hundreds of unrelated viral species which cause viral hepatitis. It was originally known as “serum hepatitis” and has caused current epidemics in parts of Asia and Africa.

Hepatitis B is recognized as endemic in China and various other parts of Asia. The proportion of the world’s population currently infected with the virus is 3 to 6%, but up to a third have been exposed.

Symptoms of the acute illness caused by the virus include liver inflammation, vomiting, jaundice, and rarely, death. Chronic hepatitis B may cause liver cirrhosis which may then lead to liver cancer, a fatal disease with very poor response to current chemotherapy. Hepatitis B usually gets better on its own after a few months. It may, however, cause a more serious chronic infection.

Structure

Virions consist of an outer lipid envelope and an icosahedral nucleocapsid core, the latter being composed of both protein and DNA. The outer envelope contains embedded proteins which are involved in viral binding of, and release into, susceptible cell. Virion shape is generally spherical with a diameter of 40-48 nanometers (nm) but pleomorohic forms exist, including filamentous and spherical bodies lacking a core. These “subviral” particles are not infectious.

The DNA genome is not segmented but rather partially double-stranded, containing a long and short segment which overlap approximately 240 nucleotides to form an open circle. The longer strand is 3020-3320 nucleotides long, and the shorter is 1700-2800 nucleotides long.

The virus can be divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes present on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome. Different genotypes have distinct geographic distributions. For example, genotypes B and C are prevalent in China and neighbouring countries.

Replication

Hepatitis B is one of a few known non-retroviral viruses which employ reverse transcription as a part of its replication process. (HIV, a completely unrelated virus, also uses reverse transcription, but it is a retrovirus.) HBV invades the cell by binding to surface receptor and become internalized.

The viral core particles then migrate to the hepatocyte nucleus and the partially double-stranded, Relaxed circular genomes (RCDNA) are repaired to form a covalently closed circular DNA (cccDNA), which is the template for viral genomic and sub-genomic RNAs by cellular RNA polymerase II.

Of these, the pregenomic RNA (pgRNA) is selectively packaged into progeny capsids and is then reverse-transcribed into new RC-DNA. The core can either bud into the endoplasmic reticulum to be enveloped or exported from the cell or recycled back into the genome for conversion to cccDNA.

Transmission

Possible forms of transmission include (but are not limited to) unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, and vertical transmission from mother to child during childbirth.

The primary method of transmission depends on the prevalence of the disease in a given area. In low prevalence areas, such as the continental United States, injection drug abuse and unprotected sex are the primary methods, although other factors may be important. In moderate prevalence areas, the disease is predominantly spread among children.

In high prevalence areas, such as South East Asia, vertical transmission is most common. Without intervention, a mother who is positive for the Hepatitis B surface antigen confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for the Hepatitis B e antigen.

Roughly 16-40% of unimmunized sexual partners of individuals with Hepatitis B will be infected through sexual contact. The risk of transmission is closely related to the rate of viral replication in the infected individual at the time of exposure.

Symptoms and complications

Hepatitis B virus infection may either be acute (self-limited) or chronic (long-standing). Persons with self-limited infection clear the infection spontaneously within weeks to months. The greater a person’s age at the time of infection, the greater the chance their body will clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus.

However, only 5% of new-borns that acquire the infection from their mother at birth will clear the infection. Of those infected between the age of one to six 70% will clear the infection. When the infection is not cleared, one becomes a chronic carrier of the virus.

Acute infection with Hepatitis B virus is associated with acute viral hepatitis - an illness that begins with general ill-health, loss of appetite, nausea, vomiting, bodyaches, mild fever, dark urine, and then progresses to development of jaundice. It has also been noted that itchy skin all over the body, has been an indication as a possible symptom of all hepatitis virus types.

The illness lasts for a few weeks and then gradually improves in most of the affected people. A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result of it. The infection may also be entirely asymptomatic and may go unrecognized.

Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of liver cancer.

Hepatitis D infection requires a concomitant infection with hepatitis B. Co-infection with Hepatitis D increases the risk of liver cirrhosis and subsequently, liver cancer. Polyarteritis nodosa is more common in people with hepatitis B infection.

Diagnosis

The original assays for detection of Hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host.

Treatment

There are currently several treatments for chronic Hepatitis B that can increase a person’s chance of clearing the infection. Treatments are available in the form of antivirals such as lamivudine and adefovir and immune system modulators such as interferon alpha (Uniferon). There are several other antivirals under investigation.

Roughly, all of the currently available treatments, when used alone, are about equally efficacious. However, some individuals are much more likely to respond than others. It does not appear that combination therapy offers any advantages. In general, each works by reducing the viral load by several orders of magnitude thus helping a body’s immune system clear the infection.

Treatment strategies should be individualized by a doctor and patient. Considerations include the risks associated with each treatment, a person’s likelihood of clearing the virus with treatment, a person’s risk for developing complication of persistent infection, and development of viral resistance with some of the treatments.

Chronic carriers should be strongly encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and hepatocellular carcinoma (liver cancer). Infants born to mothers known to carry Hepatitis B can be treated with antibodies to the Hepatitis B virus (Hepatitis B immune globulin or HBIg).

When given with the vaccine within twelve hours of birth, the risk of acquiring Hepatitis B is reduced 95%. This treatment also allows a mother to safely breast-fed her child. An individual exposed to the virus who has never been vaccinated may be treated with HBIg immediately following the exposure. For instance, a health care worker accidentally stuck by a needle used in a Hepatitis B carrier would qualify. Treatment must be soon after exposure, however.

How to Control & Prevent

While abstinence is the only guaranteed way of preventing sexual transmission of Hepatitis B, latex condoms, if used properly, greatly reduce the chances of transmission. Several vaccines have been developed for the prevention of Hepatitis B virus infection. These rely on the use of one of the viral envelope proteins (Hepatitis B surface antigen or HBsAg).

The vaccine was originally prepared from plasma obtained from patients who had long-standing Hepatitis B virus infection. However, currently, these are more often made using recombinant-DNA technology, though plasma-derived vaccines continue to be used; the two types of vaccines are equally effective and safe.

Many countries now routinely vaccinate infants against Hepatitis B. Babies born to HBeAg positive mothers are strongly recommended to be vaccinated and injected with immune globulin immediately after birth, so as to prevent transmission of infection.

In many areas, vaccination against Hepatitis B is also required for all health-care workers. Some college campus housing units now require proof of vaccination as a prerequisite. Booster doses are not needed for low-risk general population. Some recommend such doses every five to ten years for health-care workers, though the evidence supporting such doses is quite limited.

The vaccine is highly effective. In endemic countries with high rates of Hepatitis B infection, vaccination of new borns has not only reduced the risk of infection, but has also led to marked reduction in liver cancer. This was reported in Taiwan where the implementation of a nationwide Hepatitis B vaccination programme in 1984 was associated with a decline in the incidence of childhood hepatocellular carcinoma.

In the above mentioned sense, this vaccine can be thought of as an anti-cancer vaccine. Patients with HIV appear to have inferior antibody responses to Hepatitis B vaccination.

Types of Hepatitis

• Hepatitis A,
• Hepatitis B in China,
• Hepatitis C,
• Hepatitis D,
• Hepatitis E,
• Hepatitis F,
• Hepatitis G