Direct Questions and Comments to:
Emily Westheimer - Emily_Westheimer@brown.edu
Jean-David Barnea - Jean-David_Barnea@brown.edu
Laurence Freitas - Laurence_Freitas@brown.edu

Introduction

Hepatitis B is common viral infection that can cause severe liver damage. Symptoms of hepatitis B vary but may include flu-like illness, tiredness, fever, body aches, nausea, vomiting, loss of appetite, and occasional diarrhea. Some percentage of people may develop jaundice (a yellowing of skin and whites of eyes) accompanied by the darkening of urine and lightening of stool. However, many people experience no symptoms at all.

Hepatitis B is both easily transmitted and easily prevented. Prevention measures involve avoiding contact with contaminated body fluids. The virus is quite widespread, but still somewhat concentrated in particular high-risk groups, including intravenous drug users and commercial sex workers. If acquired, the condition is treatable with interferon-alpha; in addition, a prophylactic vaccine is available.

Epidemiology

Hepatitis B infection is a concern for everyone. Hepatitis B is the disease caused by the Hepatitis B virus (HBV) that may result in chronic liver disease, cirrhosis (scarring of liver), liver cancer, liver failure, and some cases, death. Currently, e ach year more than 240,000 persons get Hepatitis B in the United States, and more than 300,000,000 persons (close to U.S. population) become infected in the world yearly. There are approximately 1-1.25 million people in the U.S. who have chronic Hepatiti s B infection or are carriers. Because of large incidence and prevalence of infection, about 5% of all persons in the U.S. will become infected with Hepatitis B virus in their lifetime. In addition, chronic Hepatitis B infection accounts for about 5-10% of all cases of chronic liver disease and liver cirrhosis in the U.S.

The Hepatitis B virus is found in the blood and other body fluids of Hepatitis B infected individuals. Similarly to HIV transmission, Hepatitis B is transmitted by exchange of blood and bodily fluids as in with sharing needles, or having sex with a Hepa titis B infected individual. In addition, newborn infants become infected during childbirth from their infected mothers. Hepatitis B cannot be spread through air or food unlike other hepatitis viruses, but spreads through exchange of body fluids. Becau se there is no cure, it is crucial for all of us to take initiative in our lives to prevent the spread of Hepatitis B virus. Fortunately there is a safe and 90-95% effective vaccine that has been available since 1981. This vaccine can provide lifetime i mmunity to healthy individuals of all ages. The vaccine is usually administered by entramuscular injections with three timely spaced doses.

Hepatitis B infection is very serious for women who wish to become pregnant or who are currently pregnant because the virus frequently infects their babies, which may cause serious liver disorders and premature death. Thus all pregnant women are encoura ged to be tested for early detection of Hepatitis B infection and should consider giving their infants the vaccine upon birth.

Symptoms of Hepatitis B disease vary buy may include flu-like illness, fatigue, fever, body aches, nausea, vomiting, loss of appetite, and occasional diarrhea. Some percentage of people may develop jaundice (a yellowing of skin and eye white), accompani ed by the darkening of the urine and the lightening of the stool. However many people experience no symptoms at all, therefore if you are in doubt...ask a doctor.

Mode of Infection

Hepatitis B is contracted parenterally through contact with blood, blood products and other bodily fluids. The virus was first contracted through contaminated measles and yellow fever vaccines and was also prevalent among blood transfusion recipients. Re cently, through advancements in blood screening and vaccine technology, contamination and post-transfusion infection have been rapidly reduced. There are still large numbers of infections in homosexual males and intravenous drug users. Hepatitis B can als o be passed from mother to child. The virus has a long incubation period and infection is detected by antibodies in the blood. The early stage of infection is characterized by a long period of flu-like symptoms and fatigue until full manifestation of the disease which results in liver damage.


The liver damage results because of the virus infects liver cells (hepatocytes) and replicates in them. Upon replication, the cells begin to express viral antigens on their cell surfaces, which evokes an immune response against the infected cells. In the case of hepatitis B, cytotoxic T lymphocytes (CTLs) produce an immune response which results in lysis (killing) of the hepatocytes. The virus infects numerous cells which are subsequently lysed by the CTLs, and liver function becomes impaired. Because th e manifestation of the disease, liver damage, is caused by the host immune response, infected persons who are immunosuppressed due to cancer treatment, for example, show less pronounced liver damage.

The hepatitis B virus is found in the blood and other body fluids of infected persons. Similarly to HIV transmission, hepatitis B is transmitted easily by exchange of blood and bodily fluids as in with sharing needles, or having sex with hepatitis B-infe cted individuals. In addition, newborn infants can become infected during childbirth from their infected mothers. Unlike other hepatitis viruses, hepatitis B cannot be spread through air or food, it can only be spread through body fluids.

Hepatitis B infection is particularly serious for women who wish to become pregnant or are pregnant, because the virus is frequently transmitted to their babies, which may cause serious liver disorders and premature death. Thus, all pregnant women should be tested for early detection of hepatitis B infection and consider vaccination for their infants upon birth.

Vaccines

Numerous vaccines are currently available against hepatitis B. Vaccination is most strongly recommended for children under 20, health-care workers, persons with multiple sexual partners, intravenous drug users, and anyone having intimate contact with tho se people. The common version of the vaccine involves a surface molecule of the hepatitis B virus (HBsAg). In the United States, the recommended regimen consists of three vaccinations; the second one month after the first, and the third six months after t he first (0, 1, and 6 months). This vaccine has been shown to be highly effective at preventing infection. A fourth booster shot will greatly increase chances of successful seroconversion (achieving a state of immunity).

Since the early 1980s, vaccines have existed against hepatitis B. Until today, the most commonly used form of this vaccine makes use of the hepatitis B surface antigen (HBsAg). These particles are either collected from patient serum and inactivated, or m ade in recombinant yeast. A DNA vaccine under development would make use of the same protein. The actual effectiveness of producing an anti-HB response has only very recently been confirmed.

In recent years, researchers have made use of additional proteins to target immune responses, particularly in those patients who do not respond to the HBsAg vaccine. These vaccines make use of the pre-S, pre-S1, pre-S2, and S proteins of the HB genome. W ith one exception (pre-S2) these vaccines are just as effective as the HBsAg vaccine, at least according to preliminary data. Nonetheless, most research has been targeted to the HBsAg vaccine.

The HBsAg vaccine is normally administered three times (at 0, 1, and 6 months) with 10 µg antigen. A fourth booster shot has been shown to decrease nonresponsiveness by 25%. In certain cases, an accelerated schedule (0, 1, and 2 months) has been adopted, which improves program completion rates, but decreases seroconversion rates. In addition, preliminary studies show that intradermal vaccination with 1/10 of the intramuscular dose produces comparable results to the standard vaccine, which is very signifi cant considering the exorbitant cost of the vaccine.

The vaccine has very few side effects besides mild injection-site reactions. However, in rare cases, multiple evanescent white dot syndrome (MEWDS), a rare eye disorder, and lichen planus, normally associated with liver disease, have been reported. In ad dition, low response rates to the vaccine have been reported in patients with renal insufficiency, in children receiving chemotherapy, in substance abusers, persons with malnutrition, and in immune-suppressed patients. Response to the vaccine is also know n to be HLA-dependent, with genotypes HLA-B8 and HLA-DR3 being nonresponders.

The last few years have produced a consensus among the health care policy (WHO) community that implementation of the vaccine should be universal. However, a recent study shows that at least 1/3 of general practitioners and family doctors do not believe t hat this would be the best strategy. Notwithstanding, there are certain groups that are known to be at a higher risk for hepatitis B infection. Nurses and health care workers in general need to be immunized not only for their own protection, but also for the protection of their patients. In addition, while children are most often targeted for immunization programs, the disease occurs much more frequently in adults (100-times as commonly) , warranting increased awareness. In particular, pregnant women must be immunized because of the high risk of transmission to the fetus. Finally, homosexual men have long been known to be a high-risk group for hepatitis B, and the vaccine has been recomme nded for them since 1982.

The last few years have seen a proliferation in vaccine development research. In addition to the vaccines mentioned above, a combined hepatitis A/B vaccine has been developed and shown to be effective. In addition, the existing HBsAg vaccine has been sho wn to treat existing hepatitis B infections, when given in combination with herbal extracts.

Non-Vaccine Treatments

In the event that infection with hepatitis B occurs, the treatment consists of a 4 to 6 month course of interferon-alpha. This compound induces the immune system to clear the virus from the body. Long-term remission has been seen in 25-40% of patients, h owever, its efficacy in children has not been conclusively shown. Treatment is often accompanied by adverse side effects such as the flu-like symptoms of fever, chills, weakness, myalgia, and headaches. These side effects subside within 12 hours after inj ection. This treatment is not effective in immunosuppressed or immunocompromised persons.

Hepatitis A

Hepatitis A disease is caused by the hepatitis A virus (HAV) which causes liver infection. Hepatitis A infection is the seventh most commonly reported infectious disease in the United States. Hepatitis A virus is the cause of 65% of all hepatitis-related cases each year and results in 100 deaths per year. Hepatitis A virus is usually spread by an oral-fecal route where improper hygiene methods are used at eating establishments which contaminate food such as shellfish, or in contaminated drinking water in developing countries. Additionally, very close contact with those persons infected with hepatitis A can lead to transmission. The infection rate is 143,000 cases per year in the United States, but hepatitis A infection is endemic in developing countries. Fortunately, the hepatitis A disease is acute and mild and often asymptomatic, 50% of the time with only flu-like symptoms. However, rarely the illness can be more severe with patients experiencing prolonged anorexia and occasional jaundice and with extr eme infections resulting in liver failure which requires biochemical testing for detection. Until recently, only immunogloblin (IgG) treatments were available to protect at-risk groups from severe infection. This treatment was also offered to alleviate sy mptoms for those who suffered symptoms. Unfortunately, with this treatment symptoms return after a 4-6 month period.

Since 1992, Europe has been using a nearly 100% effective vaccine containing whole inactivated hepatitis A virus to attain immunity. Patients receive two doses (2-4 weeks apart) that provide immunity up to one year. After that, an additional booster can ensure long term protection against hepatitis A. Vaccination or IgG treatment is strongly recommended for asyone planning international travel or vacations.

Hepatitis C

Hepatitis C is the most common cause of chronic hepatitis in the Western world. Infection with this virus is often symptomless, and only 20-30% of patients develop cirrhosis of the liver. Interferon-alpha is the only proven beneficial therapy and is give n in a 6 month course with a sustained response rate of 15-25%. It has been shown that therapy during the acute phase of infection greatly reduces the development of chronic hepatitis. Recently it has been shown that treatment with interferon-alpha in com bination with ribavirin reduces the rate of relapse. A vaccine is currently under development.

Links

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