Hepatitis

Description

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% and 30% acquired the infection when they were children. Men are at higher risk than women. Fortunately, in the US the number of new infections has declined dramatically--by 67% between 1990 and 2002. In 2002, 8064 cases were reported compared to over 20,000 in 1990. And 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.

The following are some people at risk:

• 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 it before age five. Children are more likely than adults to become chronic carriers, although between 6% and 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 of institutions for mentally impaired people.
• Prisoners.
• Emigrants 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 are the following:

• Children infected before they are five, 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 US 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 four to 24 weeks. Many patients may not even experience them or they may be mild and flu-like. About 10% to 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, which 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 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% of patients infected with hepatitis B will eventually eliminate the virus 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 alone.

The great majority of people with hepatitis B have a good long-term outlook, especially children infected with the virus. Still, about 5% to 10% eventually develop cirrhosis, and worldwide, approximately two million people die each year from hepatitis B, globally making it the ninth leading cause of death. Co-infection with hepatitis D or C increases the risk for cirrhosis. HBV also poses a risk for liver cancer. In Asia about 15% of people who have chronic hepatitis B develop liver cancer, but this high rate is not seen in other parts of the world. Diet may play a role in a higher or lower 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), are released when the liver is damaged, assays to identify the viral DNA, and a liver biopsy.

Physicians then must determine if the condition is chronic but inactive or whether it is more aggressive. This is suggested 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 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% to 10% of people do not clear the infection but become carriers of the antigen (called HBsAG-positive). Evidence of its persistence for more than six months suggests that the condition is chronic.

Tests have been developed that 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 at those for hepatitis A. In infected people, 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 (HBV) 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 proving 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 September 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 haven't restored vaccination of all infants. This is a safe vaccine and it is reducing the need for hospitalization in children. 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 also be given by age 2 months if the mother has no evidence of infection.) The second dose should be given at one to four months (at least four to six weeks after first dose); and the third between six and 18 months (at least 16 weeks after first dose and eight weeks after second dose). (A fourth dose may also be given as part of a combination vaccine.) This is a safe vaccine, even in newborns, and parents should be sure their infants are immunized.
• Infants of mothers infected with HBV should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. The second dose should be given at one to two months and the third at six months. Infants should be tested for antibody status at nine to 15 months to see if they are chronic virus carriers or need to be re-vaccinated.
• When it is not known if a mother is infected or not, the infant should receive the vaccine within 12 hours of birth. The mother's blood should then be tested right away. If she is infected, the infant should receive immune globulin as soon as possible (no later than a week).
• Children who are between 11 and 12 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 eight to 10 years. Booster shots after that may be recommended depending on continuing risk, such as sexual exposure. In fact, a 2002 study suggested that there is risk for infection in teenagers who were vaccinated in infancy, although protection against chronic hepatitis B may be maintained.

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% to 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 would benefit from vaccinations are the following:

• 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 six months. One study reported that older adults would benefit from a fourth dose without incurring serious side effects. People with alcoholism may need high doses.

A small percentage of people do not develop immunity even after a vaccine has been given repeatedly. A more potent vaccine is proving to be effective in these people; it loses its effect after five years in about a third of those who receive it.

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. Studies in 2001, 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. And, vaccinations are saving 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

Interferon alpha and nucleoside analogues are the important treatments at this time for hepatitis B. At this time, interferon alpha-2b is the standard agent but experts expect the nucleoside analogue lamivudine to replace it as the primary agent. Lamivudine is not only effective, it is less expensive than the interferon. Most likely, the best approach in the future will be combinations of these and other agents to achieve the greatest possible viral reduction and to minimize the chances of drug resistance.

Interferon Alpha for Hepatitis B. Interferon alpha-2b (Intron) is the standard drug for hepatitis B. It has eliminated the virus and sustained significant remission in 25% to 40% of patients with chronic hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to be effective for 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. A 2001 study suggested that it may temporarily disrupt growth, but it should be noted that hepatitis itself, even without interferon treatment, can compromise growth.

Lamivudine and Other Nucleoside Analogues. Nucleoside analogues are drugs that can block viral replication, and they are important in hepatitis B. The primary agent used in hepatitis is lamivudine (Zeffix). It can be taken orally, has few severe side effects, and is less expensive than interferon. Experts expect it to become the first-line treatment for hepatitis B. Famciclovir is an alternative. Newer nucleoside analogues, adefovir (Hepsera) and entecavir, may prove to be even more effective than the older agents.

Lamivudine has reduced viral count in over half of hepatitis B patients who have taken it as sole therapy for about a year. It also appears to significantly reduce the risk for liver damage and cirrhosis, and appears to be effective and safe in patients with decompensated cirrhosis. The drug even suppresses hepatitis B viral replication in HIV-positive patients and liver transplant recipients. It appears to be effective for children as well as adults. It is not yet clear if it protects against liver cancer, particularly in patients who have harbored the virus since childhood.

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. The specific genetic hepatitis B strain may be an important marker for predicting resistance. Combinations with interferons may be able to help control viral breakthroughs from mutated viruses and help sustain its effectiveness. Other nucleosides, such as adefovir and entecavir, are proving to be effective in patients who become resistant to lamivudine.

Lamivudine causes muscle aches and chills but does not appear to have some of the distressing side effects of interferon, such as depression, hair loss, weight loss, or a drop in white blood cells (leukopenia). Of some concern, however, is eventual resistance to the drug in many patients.

Investigative Therapies. A number of drugs are being studied that boost the body's own immune system to fight the virus.

• Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors call T-cells). It is injected and has few side effects. It appears to be safe for hepatitis B patients when used alone or in combination. Combinations with interferon and nucleoside analogues are showing promise.
• Vaccines as Treatments. Some hepatitis B vaccines, including Hepagene, are being investigated for treating and preventing hepatitis B.

Some important research is targeting agents that inhibit RNA--the genetic molecules that serve as messengers for regulating cellular processes. In animal studies on hepatitis B, scientists were able to turn off viral replication by targeting HBV RNAs.

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 events, alternative agents, such as adefovir, are proving to be effective.