Update: In May 2011, the FDA approved GlaxoSmithKline’s Twinrix®, a vaccine against hepatitis A and B viruses, for people 18 years old and older.
Vaccinations are not just for kids. Two in particular—hepatitis A and hepatitis B—are strongly recommended for everyone in the bleeding disorders community. Despite being one of the National Hemophilia Foundation’s (NHF’s) “Do the 5!” prevention tips, and despite being strongly recommended by its Medical and Scientific Advisory Council (MASAC) for well over a decade, these vaccinations still are overlooked.
“There are a lot of people with hemophilia who have not been vaccinated for hepatitis B, nor for hepatitis A,” says Kenneth Sherman, MD, PhD, Gould Professor of Medicine and director of the Division of Digestive Diseases at the University of Cincinnati College of Medicine. He is a member of MASAC. “If they have underlying liver disease, they definitely should be vaccinated for both.”
National statistics underscore the widespread prevalence of both viruses. An estimated 1.25 million people have chronic hepatitis B infection, and nearly one-third of the US population has been exposed to the hepatitis A virus, according to the Centers for Disease Control and Prevention (CDC).
Vaccine adherence varies, even among the general population. “In 2006, for instance, only 50% of the children in the state of Colorado had up-to-date vaccinations,” says Amy Eiss, RN, CPNP, of the Mountain States Regional Hemophilia and Thrombosis Center in Aurora, Colorado. For the bleeding disorders community, ignorance is not bliss. “There’s very little risk to having the hepatitis A and B vaccinations; there’s fairly significant risk to contracting the diseases,” Eiss says.
Acute and Chronic Infection
Hepatitis viruses cause inflammation of the liver. Of the six main viruses, the most common are hepatitis A, B and C. Hepatitis A is predominantly spread from person to person via the fecal-oral route. When cells shed in a person’s stool come into contact with his or her hands, anything the person touches can become infectious, including food or beverages. Common vehicles for transmission include improperly treated drinking water and shellfish originating from water contaminated by sewage. Previous outbreaks of hepatitis A have occurred in several cities in the US. Globally, the virus is endemic in the Pacific Islands and among several countries in Africa and Asia.
Two to six weeks after exposure, symptoms of hepatitis A may appear. Children tend to be asymptomatic or show mild symptoms. Adults, however, can have flulike symptoms, stomach pain, diarrhea and jaundice. The virus can cause illness for up to six months, but is then usually cleared from the body.
In contrast, hepatitis B can cause both acute and chronic infection. Its incubation period is one to five months. Symptoms of acute infection are similar to hepatitis A, but with diminished appetite and energy. Chronic infection is often indicated by weight loss and fatigue. The hepatitis B virus can be passed from a mother to her baby during childbirth. If not treated within the first week of life, 95% of those babies become chronic carriers. However, few adults—less than 5% of those infected—become chronic carriers. It should be noted that in some adults, particularly those who have HIV/AIDS or are immunocompromised from another health condition, the risk of developing chronic hepatitis is much higher.
Hepatitis B is transmitted in several ways, including: unprotected sex with someone who is infected; contact with contaminated objects, such as razors or toothbrushes; sharing needles when injecting drugs; needle sticks when drawing blood; and contact with blood or bodily fluid via an open wound or bite.
For people with hemophilia and another condition, such as HIV and/or hepatitis C, a hepatitis A or B infection can be devastating. “If the patient has underlying liver damage from hepatitis C, he should be vaccinated to prevent getting acute hepatitis A or B on top of that,” says Sherman. This combination of insults to the liver can result in fulminant hepatic failure, a very serious condition that can be fatal. The chronic form of hepatitis B also causes severe liver damage. Left undiagnosed or untreated, it sets the stage for cirrhosis, cancer and, eventually, acute liver failure. (See “In for the Long Haul,” HemAware, May/June 2009, page 20.)
The CDC recommends that children receive the hepatitis A vaccine between the ages of 12 and 23 months, with a second vaccination six months later. In Recommendation #128, “MASAC Recommendations for Hepatitis A and B Immunization of Individuals with Bleeding Disorders,” the council urges all individuals with bleeding disorders, and especially people with hepatitis C infection, to receive the immunization, too. The hepatitis B vaccine, on the other hand, is typically given in a series of three doses—within the first week after birth, one month later and, finally, six months after that.
The vaccines are made from inactivated viruses treated with chemicals, heat or radiation to render them unable to cause disease. Although safer than live attenuated (weakened) viruses, used in the influenza vaccine, for example, they produce a weaker immune response. That’s why a booster or a series of shots is needed. A combination vaccine is available that protects against both hepatitis A and B.
To avoid the risk of muscle bleeds or bruises, these vaccines can be given subcutaneously (under the skin), rather than intramuscularly. According to NHF’s Nurses’ Guide to Bleeding Disorders, “excellent results” have been achieved in people with hemophilia, including those who are HIV-positive. After one injection of the hepatitis A vaccine, more than 95% of patients developed immunity.
With that kind of success rate, further testing might seem unnecessary. However, that is not the case in the bleeding disorders community. Post-vaccination testing is recommended by MASAC to ensure that the immune response is high enough to confer protection. A blood test reveals whether the antibody level is above the threshold of 10 milli international units per milliliter (10 mIU/ml). “If the anti-HBs (hepatitis B surface antigen) titer is greater than 10 with a quantitative test, that person is protected from being infected with hepatitis B,” says Sherman. According to the CDC, hepatitis vaccines can be given at the same time as other vaccines.
As with any vaccine, side effects can occur. Mild reactions to the hepatitis A vaccine include soreness at the injection site, headache, decreased appetite and fatigue. Muscle soreness and a low-grade fever are common after hepatitis B vaccination. Serious allergic reactions to either vaccine are indicated by trouble breathing, wheezing, hives, rapid heartbeat or dizziness. These symptoms, though rare, require immediate treatment.
Although hepatitis B vaccines are compulsory for school-age children, hepatitis A vaccines are optional. “A lot of times parents think they’re up-to-date on their children’s vaccines, but they’re not,” say Eiss. “They get behind in the series and have to go to a catch-up schedule. It’s not a perfect system.”
Similarly, catch-up schedules for adults are recommended, but not universally followed, says Sherman. “A lot of healthcare professionals don’t do catch-up vaccinations. Many insurers balk at covering them. They have not caught on.” That may explain why the hepatologist continues to see older men with liver damage who have not been vaccinated for hepatitis A and B. “They haven’t heard the message yet,” Sherman says.
Vaccination delinquency is both a consumer and provider problem. While pediatricians tend to be diligent about vaccinations, adults’ physicians can be somewhat lax. “Some adult providers will look at the list of vaccines and say, ‘You can get this, this and that. Do you want to get these?’ ” says Eiss. Leaving the decision to patients, though, may encourage procrastination. “Lots of adults have fallen through the cracks in getting vaccinated,” Eiss observes.
Risks abound when vaccine recommendations are ignored. Sherman uses the examples of a college student heading to Cozumel for spring break or a business traveler going to developing countries. “Hepatitis A is endemic in many countries, including parts of Mexico,” he warns. Healthcare workers also have to be proactive about prevention, because they are more exposed to patients with active cases of hepatitis A and B. Having sex with an infected partner is yet another concern. “I see a fair number of young women with chronic hepatitis B, which puts their sexual partners at risk,” says Sherman. Typically, they emigrated to the US from a country where the virus is endemic, or they contracted it from their mother during birth.
Delaying or avoiding vaccination for hepatitis A and B can be harmful to your liver. “MASAC’s viewpoint is that in patients at high risk, there is a reason to be very concerned about secondary liver infections, which include both hepatitis A and B,” Sherman says. “It’s better to try to vaccinate when you have a good immune system.”
MASAC recommends revaccination for nonresponders to the hepatitis B vaccination series—those without detectable antibodies in their bloodstream. “If you have HIV or end-stage liver disease, the take rates are not 90% or 95% for the vaccine. They drop to as low as 40% to 60%,” Sherman says. Up to three additional doses are necessary to jump-start the immune system. Studies have shown this second series of vaccines improved the response rate in 30% to 50% of nonresponders.
Waxing or Waning
Being vaccinated against a disease would seem to guarantee lifelong protection. After all, once your body has detected the antigens on inactivated hepatitis A or B viruses, it produces antibodies to protect you against future infection. But it’s not that straightforward. “After a period of time without natural exposure or booster shots, you lose antibody,” says Sherman. “This is true of every antigen-antibody interaction.”
Separate studies of boys in Taiwan, Alaska and Micronesia up to 15 years after routine vaccination for hepatitis B showed that their immune response two weeks after a booster shot of hepatitis B waned dramatically. In the Alaskan teens, only 60% showed a sustained response vs. 97% of 5-year-olds in a comparable group. In the Micronesian group, fewer than half showed such a response two weeks later. Several explanations for these results are possible. Since some of the children were not tested after the initial series at birth, they may have been nonresponders. In addition, their bodies may respond appropriately to the actual virus rather than a booster. Because some people are protected through “memory cells,” it’s difficult to discern who would benefit from a booster vaccination. Further studies are needed to determine whether boosters should be given to teens and adults.
If you are unsure of your vaccination history, contact your primary care physician. “For anyone who is concerned, it would always be an option to have the titer levels drawn,” says Eiss. “If the results show no detectable antibody, vaccines are in order,” she says.
“Everyone with hemophilia is recommended to be vaccinated against hepatitis A and B,” says Eiss. Ignoring that advice could be dangerous, even deadly. Eiss ticks off the ramifications: “Really bad food-borne illness, hospitalization for several weeks at time, liver failure, need for liver transplant—where do you want to draw the line?”