Hepatitis B virus

Hepatitis B virus

Hepatitis B virus (HBV) is a double-stranded DNA virus in the Hepadnaviridae family. The transmission electron micrograph (TEM) at right shows numerous hepatitis B virus (HBV) virions, also known as Dane particles. In infected persons HBV is found in highest concentrations in the blood, and lower concentrations in saliva, semen, vaginal secretions, and wound exudates. Hepatitis B virus can remain viable for >7 days on environmental surfaces at room temperature (Chang, 2007; Lock & McMahon, 2001).

The average incubation period is 90 days from time of exposure to onset of symptoms, but may vary from 6 weeks to 6 months. Acutely infected individuals develop clinically apparent hepatitis with loss of appetite, nausea, vomiting, fever, abdominal pain and jaundice. Some may have dark urine and gray stool. About one half of acute Hepatitis B virus infections in adults are symptomatic. About 1% of cases result in acute liver failure and death. Sexual transmission accounts for most adult Hepatitis B virus infections in the United States (Brooks et al., 2004).

Approximately 25% of the regular sexual contacts of infected individuals will themselves become seropositive. 10-20% of women seropositive for HBsAg transmit the virus to their neonates in the absence of immunoprophylaxis. In women who are seropositive for both HBsAg and HBeAg vertical transmission is approximately 90%. In patients with acute hepatitis B vertical transmission occurs in up to 10% of neonates when infection occurs in the first trimester and in 80 -90% of neonates when acute infection occurs in the third trimester. (Hollinger and Lau, 2006).
The disease has caused outbreaks in parts of Asia and Africa, and it is now only common in China. About a third of the world population has been infected at one point in their lives, including 350 million who are chronic carriers.

MODE OF TRANSMISSION

Hepatitis B virus is transmitted horizontally (transmission which occurs between genetically unrelated groups) (Dienstag et al., 2007). Horizontal transmission occurs by the exchange of body fluids like serum, breast milk, and in certain circumstances saliva. Transmission of HBV occurs mainly through the following routes:

•  Through unprotected sex (without a condom), penetrative sex (when the penis enters the anus, vagina or mouth) with someone who is infectious.
• By sharing contaminated needles or other drug-injecting equipment.
• By using unsterilized equipment for tattooing, acupuncture or body piercing.
• From an infected mother to her baby, most commonly during delivery (immunization of the baby at birth prevents transmission of Hepatitis B).
• Transmission is also achieved through broken skin or through contact of the mucosa with blood and other contaminated fluids.

Electron microscopic studies reveal up to 10 virions per milliliter of infected blood. The abundance of circulating virions is so high and the minimal dose so low such that, simple practices like sharing a toothbrush or a razor, can transmit infections (Chang, 2007; Barker et al., 1996). However, HBV cannot be spread through sneezing, coughing, or coming in contact with the faeces of someone who is infected.

 EPIDEMIOLOGY

Hepatitis B virus is an ancient disease that has been found in all populations though the incidence and risk is higher among people living in crowded conditions, drug occupations involving blood and blood products such as serum (Lavenchy, 2006). Homosexual males constitute another risk group because, such practice traumatize membranes and permit transfer of the virus into injured tissues. Heterosexual intercourse can also spread infection but it is less likely to do so.

Infection of the newborn in chronic carrier state readily and predisposes to development of the carrier state and the risk of liver cancer in the child.
The tropism of HBV for the liver becomes a significant epidemiological complication in some people (5 – 10% of infected individuals). Persistent or chronic carriers harbor the virus for many years (Willey et al., 2008). The of mosquito which can harbor for several days after biting an infected person has been well documented in the tropics and in some parts of the United States. Hepatitis B infection is more prevalent in Africa, Asia and the western pacific, and least prevalent in North America and Europe.

PATHOGENESIS

The Hepatitis B virus enters the body through a break in the skin or mucous membrane or by injection into the bloodstream (Samuel et al., 2004). Eventually, it reaches the liver cells (hepatocytes), where it multiplies and releases viruses into the blood (viraemia). After an incubation period of 4 – 24 weeks (7 weeks average), some individuals experience malaise, fever, chills, anorexia, abdominal discomfort and diarrhea.

Surprisingly, the majority of those infected exhibit fever, overt symptoms and develop immunity to HBV. In those who experience the disease, the severity of the symptoms and the aftermath of hepatic damage vary widely. Fever, jaundice and rash are common reactions, and a small number of patients develop glomerulonephritis and arterial inflammation.

In 90% of patients, complete liver regeneration and restored functions occur, but for reasons that are not entirely clear, a small number of predisposed older persons develop chronic liver disease in the form of necrosis or cirrhosis (permanent liver scarring and loss of tissue) (Brooks et al., 2004).

The association of HBV with hepatocellular carcinoma is based on the following observations:

I. Certain HBV antigen are found in malignant cells and more often, detected as integrated components of the host genome.

II. Persistent carriers of the virus are more likely to develop this cancer.

Young men from different areas of the world with a high incidence of Hepatitis B (Africa and the Far East) are more frequently affected. The condition is probably as a result of infection early in life and the long-term carrier state. In general, people with chronic Hepatitis B are 200 times likely to develop liver cancer, though the exact role of the virus is still a subject of molecular analyses (Pungpagong et al., 2007).

CLINICAL FEATURES

In typical Hepatitis B infection, elevation of Alanine Aminotransferase (ALT) is the first clinical evidence (Lavency, 2004). It is possible to be infected with the HBV and experience no symptom till very late. Different people show different symptoms while others spread the virus even if they do not show symptoms of the infection, thus called the “Silent Disease” (Samuel et al., 2004).

In some instances, onset of jaundice is often preceded by gastrointestinal symptoms such as nausea, vomiting, anorexia and mild fever. Jaundice may appear within a few days of the prodromal period. Extrahepatic manifestations of HBV infections include a transient serum sickness-like prodromes consisting of fever, skin rash, and polyarteritis; necrotizing vasculitis (polyarteritis nodosa) and glomerulonephritis (Brook et al., 2004). Circulating immune complexes have been suggested as the cause of these syndromes.

Many people who become infected with Hepatitis B virus experiences mild symptoms or no symptoms at all but they may still carry the infectious virus and pass it onto others. In a nutshell, when symptoms appear, they may include:

• A short, mild, flu-like illness
• Nausea, vomiting and diarrhea
• Loss of appetite
• Anorexia (weight loss)
• Jaundice (yellow skin and scleral of the eyes, darker yellow urine and pale feaces
• Itchy skin

IMMUNOLOGY

Infection with HBV of a specific subtype, example HBsAgladw, appears to confer immunity to others HBsAg subtypes probably because of other groups “A” specificity. The immune pathogenic mechanism that results in viral persistence and hepatocellular injury in type B hepatitis remains to be eliminate (Brooks et al., 2004). As the virus is not cytopathic, it is believed that hepatitis presents a host immune attack against HBV infected hepatocytes. Host responses both immunologic and genetic have been proposed to account for the frequency of HBV chronicity in those infected as infants.
About 95% of newborns are infected at birth become chronic carriers of the virus, often for life. The risk decreases steadily with time so that the risk of infected adult becoming carries decreases to 10% (Willey et a, 2007).
Hepatocellular carcinoma is most likely to occur in adult who experienced HBV infection at a very early age and carriers. There for, vaccination to be maximally effective against the carrier states, cirrhosis and hepatoma, it must be carried out within the first week of life. (Brooks et al., 2004).

2.6 DIAGNOSIS
The diagnosis of HBV infection is generally made on the basis of serological findings, virtually all individuals infected with HBV either acutely or chronically will have detectable serum Hepatitis B surface antigen (HBsAg). In acute infection, HBsAg is detectable several weeks after infection and its appearance coincides with the onset of clinical symptoms (punpapong et al., 2007).
The serological pattern of HBV is complex and involves several antigens and antibodies. Routine screening for the virus requires at least two serological markers for completeness. HBsAg is also detectable in acute infection which is characterized by a high rate of viral replication during which immunoglobulin M (IgM) antibodies against core antigens are detectable in the serum and subsequently, IgG antibodies. As acute infection resolves, IgG antibodies against core antigen persists and IgM antibodies and HBsAg become undetectable (Hui and Lau, 2005).

The detection of Hepatitis B antibody (Anti-HBs) means that:

• The individual has antibodies against HBV and is immune to the disease.
• The individual was either vaccinated against HBV or exposed to it as some point in his or her lifetime.

The detection of Hepatitis B core antibody (Anti-HBc) means that:

• The individual has been exposed to HBV and has developed an antibody to only part of the virus.
• The test should be conducted again to find out if the individual has the disease.

The detection of Hepatitis B surface antigen (HBsAg) means that:

• The individual has HBV infection
• The individual can spread the virus to others.

 

The detection of Hepatitis B envelope antigen (HgeAg) means that:

• The individual has a high level of viral infection.
• The individual can be very contagious to others.

In chronically infected individuals, infection can switch from ‘non-replicative’ to replicative and vice versa. One of the goals of treatment is to convert patients with chronic Hepatitis B infection from replicative to HBeAg negative state (Samuel et al.,2004).

By definition, HBV chronic carriers are those in whom HBsAg persist for more than 6 months in the presence of HBeAg or Anti-HBe. In contrast to high titers of IgM-specific anti-HBc observed in the acute phase of the disease, low titers of IgM-specific anti-HBc are observed in the sera of most HBsAg carriers. Small amount of HBV DNA are usually detectable in the serum as long as HBsAg is present (Hollinger and Lau, 2006).

The most useful detection methods are Enzyme-Linked Immunosorbent Assay (ELISA) for HBV antigens and antibodies and Polymerase Chain Reaction (PCR) for the viral DNA.

TREATMENT

The treatment of acute HBV infection is supportive. Patients should be hospitalized if they have coagulopathy, encephalopathy, or severe debilitation. Persons with chronic hepatitis B should be referred to health-care professionals with experience in the treatment of hepatitis B for treatment with alpha-interferon or lamivudine (Barker et al., 1996) Interferon does not appear to adversely affect the embryo or fetus. However, the data is limited, and the potential benefits of interferon use during pregnancy should clearly outweigh possible hazards. Initial data do not suggest that Lamivudine is teratogenic. Lamivudine has been used in the latter half of pregnancy in attempt to prevent perinatal transmission of hepatitis B virus infection with mixed success.
Antepartum
Pregnant Hepatitis B carriers should be advised to
• Obtain vaccination against hepatitis viruses A as indicated.
• Abstain form alcohol use
• Avoid hepatotoxic drugs such as acetaminophen (Tylenol) that may
• Worsen liver damage.
• Not donate blood, body organs, or other tissue.
• Not share any personal items that may have blood on them (e.g., toothbrushes and razors).
• Inform the infant’s pediatrician, OB/GYN, and labor staff that they are a hepatitis B carrier.
• Make sure their baby receives hepatitis B vaccine at birth, one month, and six months of age as well as H-BIG at birth.
• Be seen at least annualy by their regular medical doctor.
• Discuss the risk for transmission with their partner and discuss the need for counseling and testing
• Liver function testing is recommended for women who test positive for HBsAg
The following recommendations from The Society of Obstetricians and Gynecologists of Canada may be helpful in counseling women considering amniocentesis.