Why does hepatitis B virus become resistant to nucleoside/nucleotide analogues?
The major challenge associated with long-term therapy with NAs is the development of viral resistance to the NAs. This resistance results from a change (mutation) in the genetic material of the virus.
- For lamivudine (Epivir-HBV, Heptovir, Heptodin), the incidence of resistance is 25% after one year and as high as 50% after three years of treatment.
- With telbivudine (Tyzeka), resistance rates are 5% to 11% after one year.
Therefore, some guidelines do not recommended lamivudine or telbivudine alone as the first treatment for chronic hepatitis B.
For other NAs such as adefovir (Hepsera), resistance is less common after one year of therapy but rises to 30% after five years. Early results with entecavir (Baraclude) suggest that resistance may be uncommon with this agent. When resistance occurs, the viral load may rise or blood liver tests may become abnormal.
Is there a preferred treatment for chronic hepatitis B?
There are no clear guidelines to recommend which agent to use first in treating chronic hepatitis B. Interferon is given for a defined period of time and may have a more prolonged response after the medication is discontinued than NAs. However, interferon is given as an injection, and side effects often are troublesome. NAs are given as a pill and have few side effects, but the duration of treatment is unclear, and prolonged therapy may be required. NAs may be preferred in patients with unstable disease and cirrhosis because they are thought to be less likely to cause serious flares of hepatitis with more severe liver disease.
What are the effects of alcohol on hepatitis B virus?
Agents that damage the liver are particularly harmful in patients who already have hepatitis B. For this reason, it is recommended that persons with hepatitis B avoid drinking alcohol.
What are the effects of immunosuppressive medications on hepatitis B virus?
Even in people with chronic hepatitis B, the immune system is working to suppress the virus. Medications that suppress the immune system allow the virus to reproduce in large numbers and may cause the hepatitis to flare.
Examples of medications that suppress the immune system are:
- prednisone: used to treat many diseases, including asthma, inflammatory bowel disease, and certain types of skin disease and arthritis
- methotrexate (Rheumatrex, Trexall): used to treat certain types of skin disease, arthritis, and cancer;
- cyclophosphamide (Cytoxan): used to treat some cancers.
If an immunosuppressant drug is stopped, the body's immune system's activity may rebound and cause severe inflammation of the liver.
What is delta hepatitis?
Delta hepatitis is caused by a virus that only infects people who already have hepatitis B. The delta hepatitis virus (also known as hepatitis D or HDV) is an RNA virus, meaning that its genetic material is made up of ribonucleic acid. It is spread through exposure to contaminated blood, especially with illicit, intravenous drug use, and by sexual contact. Delta hepatitis can be acquired at the same time as acute hepatitis B. When this happens, infected people are quite sick but more than 95% are eventually able to eliminate the viruses from their bodies. People who already have chronic hepatitis B can acquire delta hepatitis as well. This often causes severe inflammation of the liver, and the viruses are less likely to be cleared.
Delta hepatitis makes chronic hepatitis B much worse. It increases the risk of complications, especially cirrhosis, which occurs in up to two-thirds of patients.
There is no vaccine against delta hepatitis. Interferon treatment may cause improvement in the hepatitis, but relapse is common after therapy is stopped. Prevention includes avoiding contaminated needles and practicing safer sex (abstaining or limiting the number of partners, using barrier methods of contraception). Universal vaccination of newborns with hepatitis B vaccine effectively prevents delta hepatitis because the delta hepatitis virus only causes disease in the presence of hepatitis B virus.
What about co-infection with hepatitis B virus and hepatitis C virus?
Hepatitis C is caused by a virus that is spread through contaminated needles or blood products and, less commonly, through sexual intercourse. About 10% of patients with chronic hepatitis B also are co-infected chronically with hepatitis C virus (HCV). The two viruses interfere with each other and one usually predominates. If hepatitis C is the predominant infection, treatment is directed against the hepatitis C. Patients infected with both viruses are at higher risk for complications of liver disease. There is no effective vaccine against hepatitis C. Persons with hepatitis C should be vaccinated against hepatitis B to prevent co-infection.
What happens in co-infection with hepatitis B virus and HIV?
The human immunodeficiency virus (HIV) and hepatitis B virus are transmitted in similar ways, and it is not uncommon for an individual to have both infections. Persons with HIV who acquire hepatitis B are more likely to become chronically infected with hepatitis B than persons who do not have HIV. The reason for this is thought to be that HIV suppresses the immune system and impairs the ability of the body to eliminate the hepatitis B virus. Some nucleoside/nucleotide analogues (a class of antiretroviral drugs) are used to treat both HIV and hepatitis B, although dosages may vary in the two different infections. Stopping one of these agents when the HIV regimen is adjusted may cause hepatitis to flare.
What is the role of liver transplantation in hepatitis B infection?
Liver transplantation has been successful in patients who have irreversible, life-threatening complications of hepatitis B. This includes patients with liver failure due to end-stage cirrhosis or unusually severe (fulminant) hepatitis. Liver transplantation does not cure hepatitis B, and hepatitis may occur in the new liver. The incidence of recurrent hepatitis has been reduced to less than 10% through use of lamivudine and HBIG in transplant recipients. Use of these agents has also improved long-term survival, with 75% to 85% of patients alive after five years.
What can be done to prevent hepatitis B?
Hepatitis B is a preventable disease. Vaccination and post-exposure prophylaxis have significantly reduced rates of infection. Risk can also be reduced by avoiding unprotected sex, contaminated needles, and other sources of infection.
How effective is vaccination for hepatitis B?
The hepatitis B vaccine contains a protein (antigen) that stimulates the body to make protective antibodies. Examples of hepatitis B vaccines available in the United States include hepatitis b vaccine-injection (Engerix-B, Recombivax-HB). Three doses (given at 0, 1, and 6 months) are necessary to assure protection. There are also combination vaccines on the market that provide protection against hepatitis B and other diseases.
Examples include:
- Hepatitis-b-hepatitis-a vaccine - injection (Twinrix), which provides protection against both hepatitis A and hepatitis B.
- Haemophilus B/hepatitis B vaccine - injection (Comvax) provides protection against hepatitis B and Haemophilus influenzae type b (a cause of meningitis).
- Pediarix provides protection against hepatitis B, tetanus, pertussis (whooping cough), and polio.
Hepatitis B vaccines are effective and safe. Up to 95% of vaccinated individuals form effective antibodies when they get the vaccine and are protected from hepatitis B. In healthcare workers, high-risk public safety workers, dialysis patients, and sexual partners of infected persons, a blood test for antibodies is recommended after vaccination to ensure that the person produced antibodies. For the few who do not form antibodies, revaccination may improve response, especially in infants. However, a small proportion of individuals will never respond to hepatitis B vaccination. Side effects from the vaccine are usually mild and include soreness at the site of injection. The risk of serious allergic reactions (anaphylaxis) is less than one per million doses. Vaccination has reduced the number of new cases of hepatitis B by more than 75% in the United States.
In the United States, hepatitis B vaccination is recommended for all infants at birth. Older children and adolescents should receive the vaccine if they did not do so at birth.
Adults in high risk situations also are advised to receive hepatitis B vaccine. This includes:
- health care workers
- dentists
- intimate and household contacts of patients with chronic hepatitis B infection
- public safety workers who may be exposed to blood
- men who have sex with men
- individuals with multiple sexual partners
- dialysis patients
- injection drug users
- persons with chronic liver disease
- residents and staff in institutions that care for persons with developmental disabilities
- persons infected with HIV
- persons who require repeated transfusions or blood products.
Centers that serve high-risk individuals are encouraged to provide the vaccine to their clients. Such centers include dialysis units, drug treatment facilities, sexually transmitted diseases clinics and correctional facilities. Some countries have a high prevalence of hepatitis B in their population. Travelers who visit these countries for a prolonged period of time (usually six months) and those who may be exposed to blood or semen should consider vaccination.
How effective is hepatitis B immune globulin (HBIG) in preventing hepatitis B?
HBIG is a product that contains antibodies against hepatitis B. When injected, it provides temporary protection against hepatitis B. HBIG is used when people have had significant exposure to the virus. An example would be an accidental needle stick in an unvaccinated health care worker from a needle contaminated with blood from a person with hepatitis B. HBIG should be given as soon as possible after exposure, preferably within seven days. Persons who need HBIG should also receive hepatitis B vaccine. HBIG also is given to patients with hepatitis B following liver transplantation to suppress the hepatitis B virus in the transplanted liver.
What is post-exposure immunoprophylaxis for hepatitis B virus?
Unvaccinated individuals who are exposed to a known case of hepatitis B or to a person at high risk for hepatitis B should be evaluated by a physician. Examples of such exposures include needle stick injuries in health care workers or sexual intercourse with an infected person. If the exposure is significant, the physician will recommend vaccination and also may recommend an injection of hepatitis B immune globulin (HBIG). HBIG is prepared from the plasma of blood donors and contains antibodies to hepatitis B. Vaccination and HBIG can substantially reduce the risk of disease in persons exposed to hepatitis B if given within one week of a needle stick or two weeks of sexual intercourse.
Vaccination provides long-term immunity in people who respond to the vaccine. There is no need for HBIG if an exposure occurs to a vaccinated person who is known to respond to the vaccine; however, a blood test might be drawn to verify that the person did respond to the vaccine.
How is transmission of hepatitis B virus from mother to newborn infant prevented?
Infected mothers can pass hepatitis B to their newborn infants. All pregnant women should have blood tested to determine if they are infected. Infants born to infected mothers should receive HBIG and hepatitis B vaccine at birth. This is 85% to 95% effective in eliminating the risk of hepatitis B in the infant.
What is new in the treatment of hepatitis B virus?
New agents are under development to treat hepatitis B. Many of these are nucleoside/nucleotide analogues that investigators hope will be more effective than older agents. Experts also are working on treatment guidelines and the use of multi-drug therapy. Vaccination remains the key to preventing hepatitis B and holds the most promise for reducing disease burden.
Hepatitis B At A Glance
- The hepatitis B virus is a DNA virus belonging to the Hepadnaviridae family of viruses. Hepatitis B virus is not related to the hepatitis A virus or the hepatitis C virus.
- Some people with hepatitis B never clear the virus and are chronically infected. Approximately 350 million individuals in the world and one million in the United States are chronically infected with hepatitis B. Many of these people appear healthy but can spread the virus to others.
- Hepatitis B infection is transmitted through sexual contact, contact with contaminated blood (for example, through shared needles used for illicit, intravenous drugs), and from mother to child. Hepatitis B is not spread through food, water, or casual contact.
- Serologic (blood) markers specifically for hepatitis B virus are used to diagnose hepatitis B viral infection. The blood tests can also identify people who are at highest risk for complications.
- Injury to the liver by hepatitis B virus is caused by the body's immune response as the body attempts to eliminate the virus.
- In the United States, 95% of adults who get hepatitis B are able to clear the virus and cure themselves of infection. The remaining 5% of adults with acute hepatitis B go on to develop chronic hepatitis B. Those who acquire the infection in childhood are much more likely to have chronic infection. Chronic hepatitis B may lead to cirrhosis or liver failure. Approximately 15% to 25% of persons with chronic infection will die prematurely as a result of the infection.
- Progression of chronic hepatitis B viral infection occurs insidiously (subtly and gradually), usually over several decades. The course is determined primarily by the age at which the hepatitis B viral infection is acquired and the interaction between the virus and the body's immune system.
- Treatment with interferons or nucleoside/nucleotide analogues suppresses viral reproduction in about 40% to 90% of patients with chronic hepatitis B. The medications are also effective in reducing inflammation and improving blood tests. This can delay or reduce complications such as cirrhosis. However, most people do not have a permanent response and relapse is common. The medications do not cure the infection.
- Liver transplantation should be considered for patients with impending liver failure due to acute (initial) infection or advanced cirrhosis.
- Hepatitis B is preventable through vaccination. All children should receive the vaccine. In addition, adults at high risk for hepatitis B should be vaccinated. Unvaccinated people who are exposed to hepatitis B should be evaluated by a physician to determine if they need specific immune globulin (HBIG).
Reference: Centers for Disease Control and Prevention, "Viral Hepatitis FAQs for the Public," January 15, 2009
Previous contributing medical author and editor: Tse-Ling Fong, MD and Leslie J. Schoenfield, M.D., Ph.D. |
