Hepatitis B and D

Hepatitis B and D were formerly called serum hepatitis. Hepatitis B is mainly transmitted through blood transfusions, contaminated needles, and sexual contact. Blood screening has reduced the risk from transfusions. It can also be passed from cuts, scrapes, and other breaks in the skin. Hepatitis D virus can replicate only by attaching to hepatitis B and therefore cannot exist without the B virus being present.

Risk Factors for Hepatitis B. About 1.2 million Americans are chronically infected with HBV and between 20 - 30% acquired the infection when they were children. Men are at higher risk than women. Among ethnic groups living in the United States, Asians are at highest risk, due to the high rate of HBV in Asian countries. Fortunately, in the US the number of new infections has declined dramatically--by 67% between 1990 and 2002. In 2003, 7526 cases were reported compared to over 20,000 in 1990. The greatest decrease has occurred in children. Among young adults and people living in the Northeast, however, the incidence has increased since 1999. This may indicate that sexual activity is an important route for viral transmission and that the protective effect of the vaccine has not yet reached older, high-risk groups. Also, as with hepatitis A, the increase in travelers to underdeveloped nations may be responsible for the steady rate.

HBV is far more common overseas and about 600,000 people die each year from conditions, such as liver cancer or cirrhosis, that are related to chronic hepatitis B. Nearly 70% of these infections were acquired during infancy or early childhood.

People at risk include:

• Drug users who share needles.
• Children of infected mothers. Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing HBV before age 5. Children are more likely than adults to become chronic carriers, although between 6 - 12% of children spontaneously recover each year.
• People with multiple sex partners or other high-risk sexual behavior.
• Hospital workers and others exposed to blood products. Contaminated medical instruments, including fingerstick devices used for more than one individual, have been known to transmit the virus.
• Staff members and clients of institutions for the developmentally disabled.
• Prisoners.
• Immigrants from areas where the disease rate is high. (International travelers who spend long periods in such areas may also be at risk.)

People at highest risk for becoming chronic carriers of the virus include:

• Children infected before age 5, including newborns, most of whom become carriers.
• Infected people with damaged immune systems, such as AIDS patients.

Risk Factors for Hepatitis D. Hepatitis D occurs only in people with hepatitis B. It is not common in the U.S. and the incidence of this hepatitis is declining rapidly overseas. Experts anticipate that it will be extremely rare in the near future. Those who recover from hepatitis B are immune to further infection from both hepatitis B and D viruses.

Symptoms of Hepatitis B

Symptoms appear long after the initial infection, usually 4 to 24 weeks. Many patients may not even experience them or they may be mild and flu-like. About 10 - 20% of patients have a fever and rash. Nausea is not common. Sometimes there is general aching in the joints. The pain can resemble arthritis, affecting specific joints and accompanied by redness and swelling.

Outlook for Patients with Hepatitis B

The virus does not kill cells directly, but seems to activate cells in the immune system that cause inflammation and damage in the liver.

Acute Form. Acute hepatitis B is generally mild, but it can be lethal in about 1% of patients. Patients who are coinfected with hepatitis D or C are at risk for serious complications. In patients whose immune systems are severely compromised, such as in HIV/AIDS, there is risk of a rapidly progressive form of HBV called fibrosing cholestatic hepatitis. Even patients with mild symptoms can remain chronically infected with the virus.

Chronic Form. About 70% hepatitis B cases eventually resolve on their own without any treatment. The rest will progress to chronic hepatitis. Hepatitis B can also become chronic without an acute stage. The risk for developing a chronic form of hepatitis D is the same as for hepatitis B.

Most people with hepatitis B have a good long-term outlook, especially children infected with the virus. Still, about 5 - 10% eventually develop cirrhosis. Worldwide, about 2 million people die each year from hepatitis B, making it the ninth leading global cause of death. Co-infection with hepatitis D or C increases the risk for cirrhosis. HBV also poses a risk for liver cancer.

Specific Tests for Identifying Hepatitis B

A diagnosis of hepatitis B relies on measuring the liver enzymes aspartate (AST) and alanine (ALT) -- released when the liver is damaged -- assays to identify the viral DNA, and a liver biopsy.

Doctors must then determine if the condition is chronic but inactive or whether it is more aggressive. This is done by identifying a specific antigen called HBsAg, which is a protein that is found in the blood in early stages of hepatitis B and suggests the presence of a viral replication. Most people develop antibodies to this antigen during convalescence. Their condition is referred to as HBeAG negative or anti-HBe and suggests that infection is on the wane. About 5 - 10% of people do not clear the infection but become carriers of the antigen (called HBsAG-positive). Evidence of its persistence for more than 6 months suggests that the condition is chronic.

Tests can identify specific genetic types of hepatitis B virus (designated A to G). It is not clear how significant they are in treating patients with HBV.

It is important to remember, however, that viral levels are not an accurate measure of actual liver damage. Only a biopsy can determine this.

To diagnose hepatitis D using an antibody test, hepatitis B must already have been identified.

Preventing Hepatitis B and its Transmission

General precautions for preventing hepatitis B when traveling are the same as those for hepatitis A. In infected people, precautions for preventing transmission are similar to those for hepatitis C.

Vaccinations for Prevention of Hepatitis B. Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B and are safe even for infants and children. A triple-antigen hepatitis B vaccine (Hepacare) is proving to be effective for people who do not respond to the standard vaccines. Vaccination programs are also helping to reduce the risk for liver cancer. A combination vaccine (Twinrix) that contains Engerix-B and Havrix, a hepatitis A vaccine, is now approved for people with risk factors for both hepatitis A and B.

Click the icon to see an image discussing hepatitis B vaccine.

Until recently, the vaccine contained a mercury-based preservative called thimerosal. In response to concerns, professional organizations recommended suspending vaccinations in infants with noninfected mothers. In 1999, a thimerosal-free vaccine became available and medical centers are now urged to continue vaccinations. Unfortunately, even after the thimerosal-free vaccine became available, a number of hospitals still have not restored vaccination of all infants. This is a safe vaccine. Parents should be sure their children are immunized.

Candidates for HBV Vaccinations. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade.

Typical schedules for hepatitis B vaccinations in childhood are as follows:

• All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be given by age 2 months if the mother has no evidence of infection. Infants of mothers infected with HBV should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. Vaccinating the newborn prevents infection from being transmitted from mother to child.)
• The second dose should be given at least 4 - 6 weeks after the first dose. The third dose is given at least 8 weeks after the second dose (typically when the baby is 6 – 23 months old.
• Children who are 11 - 12 years old and who have not been immunized should receive two or three doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection lasts at least 10 years. Booster shots after that may be recommended depending on continuing risk, such as sexual exposure.

The following adults are at very high risk and should be vaccinated:

• Healthcare and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B virus that ranges from 15 - 30%.
• People in the same household as HBV infected individuals. (Unvaccinated people who have had intimate exposure to people with HBV may be protected with immune globulin, which is sometimes administered with the vaccine.)
• Travelers to developing countries.
• Patients who require transfusions and have not been infected with HBV. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)
• Sexually active homosexual or heterosexual individuals with multiple partners or who engage in high-risk sexual behavior.
• People with any sexually transmitted diseases.

Other people at risk who may benefit from vaccinations include:

• Patients and workers in mental institutions and morticians.
• Patients on hemodialysis. (People on hemodialysis may need larger doses or boosters. They also may need to be re-vaccinated if blood tests indicate they are losing immunity.)
• People who use injected drugs.
• Pregnant women at risk for the virus should be vaccinated. There is no evidence that the vaccine is dangerous to the fetus.
• People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

The regimen in adults is typically three doses given over 6 months. People with alcoholism may need high doses.

Soreness at the injection site is the most common side effect. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and there has been some concern about three small studies associating the vaccine with an insignificant increase in multiple sclerosis. Recent studies, however, have found no evidence to support these concerns. Nonetheless, some groups oppose the vaccination in children who are not in high-risk groups. It should be strongly stressed that worldwide 65 million people with chronic hepatitis are expected to die from liver disease. Vaccinations save lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer.

Treatments for Chronic Hepatitis B

Five drugs are currently approved in the United States for treatment of chronic hepatitis B:

• Peginterferon alfa-2a (Pegasys)
• Interferon-alfa-2b (Intron)
• Adefovir (Hepsera)
• Lamivudine (Epivir)
• Entecavir (Baraclude)

These drugs block the replication of HBV in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine and Entecavir. These two drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the FDA approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating HBV. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of HBV. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with HBV. The HIV drug tenofovir (Viread) should not be used to treat patients who are co-infected with HBV as the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate HBV. Patients with lymphoma should be screened for HBV.

Investigational Drugs.

• Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic HBV.
• Telbivudine is another nucleoside analog drug. It is in Phase III trials for treatment of chronic hepatitis B. Studies suggest that it may work better than lamivudine or adefovir.
• Pegylated interferon alfa-2b (Peg-Intron) is currently approved for treatment of chronic hepatitis C. It is being investigated alone and in combination with lamivudine for treatment of HBV.
• Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Liver Transplantation. If the disease progresses to the point where it becomes life-threatening, liver transplantation may be an option. It is not foolproof, however. Viral recurrence is high in hepatitis B patients, although it can be significantly reduced using monthly infusions of hepatitis B immune globulin (HBIg), particularly when used with lamivudine. These injections may need to be administered life long. Eventually, about 40% of patients develop resistance to lamivudine. In such cases, alternative drugs such as adefovir are proving to be effective.