Hepatitis A Vaccination

The hepatitis A vaccination was first approved by the FDA in 1995. Originally manufactured by SmithKline Beecham ( now GlaxoSmith Kline) , this vaccination is called HAVRIX. In 1996, the FDA approved VAQTA, a hepatitis A vaccination manufactured by Merck and Company, Inc. As such, there are currently two hepatitis A vaccinations available, and they are equally effective. The hepatitis A vaccination is made by growing the hepatitis A virus (HAV) in a cell culture, and then killing the virus with a toxic substance known as formalin. A vaccine manufactured in this method is known as a formalin-inactivated vaccine.

The hepatitis A vaccination is given via an injection into the shoulder muscle. This is known as an intramuscular (IM) deltoid injection. Side effects from the vaccination are rare. If experienced, they may include mild soreness at the site of the injection, a headache, and a low-grade fever. When a person receives the vaccination, her body’s immune system will manufacture protective antibodies that guard her against a future hepatitis A infection. Because the HAV in the vaccination is dead and, therefore, is incapable of multiplying or causing disease, inoculation with the hepatitis A vaccination cannot possibly cause a person to become infected with HAV nor can it make one capable of transmitting HAV to others.

Within two weeks of receiving the hepatitis A vaccination, 80 percent of people develop the hepatitis A antibody (HAV Ab). And within one month of receiving the vaccination, 95 to 99 percent of people develop immunity to hepatitis A. A additional dose of the hepatitis A vaccination is given six to twelve months after the initial injection. This second injection has the effect of extending the duration of protection. After receiving both doses of the hepatitis A vaccination, a person is totally protected against future hepatitis A infections. This protection lasts at least ten years, if not longer.

Although HAV does not cause chronic liver disease, infection with this virus can make a person quite ill (see Chapter 8). In fact, some people are ill for as long as six months. Moreover, approximately 100 to 150 people die each year from fulminant liver failure caused by hepatitis A. It has been recognized that older people are especially likely to suffer a poor outcome when infected with HAV.  In fact, as compared with people under the age of 50, those over 50 years old are 5 – 10 times more likely to die if infected with hepatitis A. In addition, people with chronic liver disease, particularly those with hepatitis B or C, may be more likely to  experience a poor or fatal outcome when additionally infected with hepatitis A. Therefore, it is essential that all people with chronic liver disease, especially those over fifty years old, receive the hepatitis A vaccination. The hepatitis A vaccine should be administered to all people with chronic liver disease as early as possible, and prior to the development of cirrhosis and liver failure – since among people with advanced liver disease the efficacy of the hepatitis A vaccine is diminished. It is further recommended that all people who are awaiting a liver transplant or who have received a transplant be vaccinated. The vaccination of food handlers and day-care-center workers should also be considered.

Other groups of people who are at increased risk for hepatitis A and who should therefore receive the hepatitis A vaccination include:

• People traveling to, or working in, areas of the world where hepatitis A infection is common.

• Men who have sex with men.

• People who use intravenous drugs.

• People with blood clotting factor disorders.

• People who work with nonhuman primates.

• Laboratory workers handling hepatitis A-contaminated blood or stools.

Children have the highest rate of hepatitis A, and they typically have a silent course of disease.  This makes children a hidden reservoir for infection to adults who are not immune. Therefore, routine inoculation of children older than two years old with the hepatitis A vaccination was approved in 1999 for states with a consistently high incidence of hepatitis A (20 people per 100,000 population). Known as “high rate communities,” they include Arizona, Alaska, Oregon, New Mexico, Utah, Washington, Oklahoma, South Dakota, Nevada, California, and Idaho. “Intermediate rate communities,” in­cluding Missouri, Texas, Colorado, Arkansas, Montana, and Wyoming, where the incidence of hepatitis A falls between 10 people per 100,000 population (the national average), and 20 people per 100,000 do not mandate childhood hepatitis A ­vaccination, but would be wise to enact such a mandate. Certain states have enacted immunization programs on a targeted basis. Texas, for example, requires vaccination in high-rate counties or when an outbreak has occurred.  Mandatory hepatitis A vaccination for all children could make hepatitis A a disease of the past, or at least it would significantly decrease the incidence of hepatitis A in the United States. Hopefully, future policy changes will be directed toward accomplishing this goal.

If a person has already had hepatitis A or has been exposed ( contact with the hepatitis A virus to a degree sufficient to cause the body to produce the hepatitis A antibody ( HAVAb)) to HAV at any time in the past, she is protected from reinfection lifelong. Past exposure can be detected by obtaining a blood test for the hepatitis A antibody (HAV Ab). If a person tests positive for HAV Ab, there is no reason to get the vaccination because it will not provide any additional benefit. ( If the hepatitis A vaccine is administered to a person positive for HAV Ab no harm will be done, however).The hepatitis A vaccination will not protect a person from hepatitis B or C or from any form of hepatitis or liver disease other than hepatitis A.

Immune Globulin (IG) for Hepatitis A

Prior to 1995, when the hepatitis A vaccination first became available in the United States, an injection of immune globulin (IG) was the only way to protect a person who had been exposed to someone with acute hepatitis A. IG is a preparation composed of multiple antibodies (immunoglobulins). It is made from human plasma that has been pooled from many people. This plasma is sterilized and must test negative for other infectious diseases. (All IG administered in the United States has tested negative for hepatitis B, hepatitis C, and HIV.)

Since the hepatitis A vaccine does not provide immediate protection against acute hepatitis A, IG continues to be an important form of protection for people who have recently been exposed to HAV. IG is typically given as a single intramuscular injection and is effective only if it is administered within two weeks of one’s exposure to HAV. While IG provides immediate protection against hepatitis A, its beneficial effects are strictly short-term. The protection from HAV that IG provides usually lasts no more than three to five months. Therefore, a person who received IG more than five months ago and is exposed to someone with acute hepatitis A again, will be at risk for infection. Although IG cannot prevent infection in a person who already has acute hepatitis A, it may reduce the severity of the disease.

Hepatitis B Vaccination

The development of the hepatitis B vaccine represents one of the most important advances in medicine. This is the first and only vaccine in history that can simultaneously prevent liver cancer, cirrhosis, and a sexually transmitted disease—namely hepatitis B. The FDA approved the hepatitis B vaccine in 1981, and it became commercially available in 1982. The original hepatitis B vaccine was made from the plasma of people chronically infected with hepatitis B. While this version of the vaccine is still available, it has been phased out in the United States beginning in 1986, when the FDA approved Recombivax, an improved version of the vaccine. Recombivax, which is manufactured by Merck, Sharp and Dohme, is made from common baker’s yeast.

There are currently two separate hepatitis B vaccines in use, Recombivax and Engerix-B. Engerix-B, which is manufactured by GlaxoSmithKline ( now GlaxoSmithKline), was approved by the FDA in 1989. A person cannot develop hepatitis B infection as a result of receiving the hepatitis B vaccine, nor can he transmit the virus to others by receiving the vaccine. The vaccination is administered via an intramuscular injection in the shoulder muscle, and it rarely produces side effects., Side effects when experienced can include mild soreness at the site of injection, headache, and low-grade fever.

Adults are given three separate injections- the initial injection, a second injection one month after the initial one, and a third one, six months after the initial one. Approximately 95 to 99 percent of adults are protected against hepatitis B as a re­sult of receiving the three injections. Protection is manifested on blood work by a hepatitis B surface antibody (HBsAb) titer of greater than 10 IU/ml (international units per milliliter). When such a lab value appears on blood work, this signi­fies that a person is completely protected against a future hepatitis B infection for at least ten years and possibly lifelong. Additional hepatitis B injections are normally not necessary, with the exception of two circumstances – for people with poor immune systems, such as people with AIDS, and for  people whose HBsAb levels are lower than 10 IU/ml.

Hepatitis B can lead to cirrhosis, liver failure, and liver cancer. Since the hepatitis B vaccine prevents hepatitis B infection from occurring, it is crucial for all people at risk for hepatitis B to obtain this vaccination. In fact, the hepatitis B vaccine has now been incorporated into the immunization programs of more than eighty countries.  In 1991, the Advisory Committee on Immunization Practices (ACIP) mandated routine universal hepatitis B vaccination of all newborns in the United States. Routine prenatal screening of all pregnant women for HBsAg is now the standard of care. It is safe to administer the hepatitis B vaccine to a pregnant women if needed. Infants born to HBsAg positive mothers should receive both the hepatitis B vaccination and the hepatitis B immune globulin (HBIG; see below) within twelve hours of birth.

It is currently recommended that children receive the vaccination at age eleven or twelve if they did not receive it at birth. Many states have laws or regulations requiring the administration of the hepatitis B vaccination to children prior to their beginning daycare or school.

Other groups of people who are at increased risk for hepatitis B, and who therefore should receive the hepatitis B vaccination include:

• People of any age who have multiple sexual partners ( more than one sex partner within a 6 –month period).

-   People with a sexually transmitted disease

-   Immigrants from geographic areas in which high HBV is endemic – Asia, Sub-saharan Africa, Middle East, Amazon basin

-  Children born in the United States to a person from an  HBV endemic area

-  Adopted children from HBV- endemic areas

• Men who have sex with other men.

• People who use intravenous drugs as well as their sex partners.

• People with blood clotting factor disorders.

• Those who have intimate or household contact with a person who is a hepatitis B carrier (HBsAg positive).

• People who work in health care.

• Public safety workers who may come into contact with blood.

• People receiving hemodialysis.

• People who live or work in an institution for the developmentally disadvantaged.

• Prison inmates.

• Alaskan Natives and Pacific Islanders.

It is also advisable for any person with chronic liver disease to obtain the hepatitis B vaccination. These patients should receive the vaccine upon diagnosis, as the efficacy of the hepatitis B vaccine is decreased in people who have already progressed to advanced cirrhosis. Successful immunity to hepatitis B after receipt of the hepatitis B vaccination will eliminate the risk of acquiring hepatitis B through a liver transplant. It will also increase the number of potential donor livers available to a person awaiting transplant, because it will enable the use of a liver from a HBcAb positive donor. Finally, since it appears that coinfection with both HBV and HCV greatly increases a person’s chance of developing liver cancer, obtaining the hepatitis B vaccination is crucial for people with chronic hepatitis C. Patients with chronic hepatitis C may have some difficulty attaining immunity ( becoming HBsAb positive) from the hepatitis B vaccine.  Thus, some experts suggest that the HBsAb titer be tested in patients with chronic hepatitis C. For those with an HBsAb titer of less than 10, an additional booster is recommended.

If a person has been exposed to hepatitis B at some time in the past, the vaccination will not afford them any benefit. Therefore, there is no reason for a person who is HBcAb or HBsAb positive to receive the hepatitis B vaccination, although it will not cause them any harmful effects if received. The hepatitis B vaccine will not protect a person against hepatitis A or C, and it will not protect a person against any form of hepatitis or liver disease other than hepatitis B.

Hepatitis B Immune Globulin (HBIG)

Hepatitis B immune globulin (HBIG) is made from plasma that has been pooled from  people with high levels of the hepatitis B surface antibody (HBsAb). HBIG provides immediate, but temporary protection, to people who have been exposed to someone with infectious hepatitis B and to those who have accidentally been exposed to the blood or body fluids (for example, in a needle stick injury or blood splashing accident) of someone with infectious hepatitis B. Therefore, within two weeks of contact, HBIG should be administered to any person who has had exposure to hepatitis B-infected blood or who has had close or intimate contact with someone with infectious hepatitis B. As previously noted, infants born to mothers who are HBsAg positive should receive HBIG within twelve hours of birth. These infants must also obtain the hepatitis B vaccination. The hepatitis B vaccination may be obtained at the same time as HBIG. However, when the two are administered at the same time, they should not be injected into the same shoulder.

Combination Hepatitis A and B Vaccination

In May of 2001, the FDA approved a hepatitis A and B vaccination.  The vaccine, known as  Twinrex, (GlaxoSmithKline) consists of the inactivated hepatitis A virus, and the recombinant hepatitis B surface antigen.  As with the individual hepatitis A and B vaccines, it is impossible for a person to develop either hepatitis A or B infection, or to transmit these infections to others, as a result of receiving Twinrex. While Twinrex can prevent infection from the hepatitis A, B and D viruses, it cannot prevent infection from the hepatitis C virus.

     Approximately 95-99 percent of adults will be protected against both hepatitis A and B as a result of receiving this combined vaccine.  It is recommended to administer Twinrex on a 0, 1, and 6 month schedule ( like that of the hepatitis B vaccine).  Side effects are rare.  When they do occur they include soreness at the injection site, headache and fatigue.

   Now that Twinrex is available, it will simplify the vaccination process and will further the important goal of routinely immunizing the population against hepatitis A and B. The combined vaccination requires  fewer total injections (three versus five), to achieve protection against these two viruses, compared with giving two separate vaccines. As such, it seems certain that a greater  number of people will be getting immunized.

   If a person has been exposed to hepatitis A and  B at some time in the past, Twinrex  will not afford them any benefit.  Therefore, there is no reason for such a person to receive Twinrex, although it will not cause them any harmful effects if received.

Hepatitis C Vaccination

The development of a vaccination against HCV is being doggedly researched. Yet this challenging quest faces some considerable obstacles. One of the major barriers to the development of a vaccine involves the complex population of mutant strains of the hepatitis C virus, known as quasispecies, that can exist in a person infected with hepatitis C. The existence of quasispecies is also a factor responsible for the failure of so many people to respond to antiviral therapy. And it is one of the reasons why so many people relapse after initially responding to antiviral therapy. During treatment, mutant strains that are resistant to further therapy often emerge. Thus, to be effective, a vaccine would need to protect a person against many different HCV variants.  Preliminary research on insect cells which are capable of generating “hepatitis C –like particles” (HCV-LPs), has some promise and may be helpful in creating a vaccine.  The results of further research are being anxiously awaited.  Indeed, if and when an effective, safe vaccination against HCV is produced, it would rank as one of the all-time great advances in the annals of medicine.

Immune Globulin for Hepatitis C

It has not been convincingly demonstrated that immune globulin can protect a person who has been exposed to hepatitis C from getting infected with the virus. Therefore, it is not recommended that a person in this situation obtain an immune globulin injection.

Hepatitis D Vaccination

There is presently no vaccine available against the hepatitis delta virus (HDV), nor is there an immune globulin available that can combat this virus. However, the hepatitis B vaccination will effectively prevent the occurrence of hepatitis D in a person who did not have hepatitis B at the time she was vaccinated. For people who already have chronic hepatitis B, obtaining the hepatitis B vaccination will not provide any protection against becoming additionally infected with HDV.  Research being conducted on animals has shown some promising results as to the creation of a vaccine.  In those animals experimentally vaccinated, although infection with HDV was not prevented, the resultant liver disease was less severe than usual. Further investigation needs to be conducted in this area.

All contents of this article are Copyright © Melissa Palmer, MD

Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).

Dr. Palmer is an internationally renowned hepatologist who has been practicing medicine since 1985. Prior to 2012, she maintained perhaps the largest medical practice devoted to liver disease in the United States. Dr. Palmer is Clinical Professor of Medicine at New York University Medical Center. Dr. Palmer graduated from Columbia University with a B.A. and was trained in hepatology (as well as medical school) at the Mount Sinai School of Medicine in New York City.

Dr. Palmer is Board Certified in Gastroenterology and in Internal Medicine.

She has authored numerous scientific publications in the field of hepatology in such peer-reviewed journals as Hepatology, Gastroenterology, Seminars of Liver Disease, Transplantation and Archives of Internal Medicine.

She is frequently called upon by the media for her opinion on various topics related to liver disease. Dr. Palmer has appeared many times on television as a liver disease expert and has been quoted in such publications as TIME magazine, Cosmopolitan magazine, Prevention magazine, the Los Angeles Times, and Newsday. She also has appeared in numerous videos and CD-Roms aimed at educating doctors and the public about hepatitis C and other liver diseases, such as primary biliary cirrhosis. Dr. Palmer lectures to the medical and general public on liver disease-related topics on a regular basis.

Dr. Palmer has performed numerous clinical trials on various experimental medications for the treatment of hepatitis.

Dr. Palmer is currently available for lecturing, investor and hedge-fund consultations, consultations to industry, and media interviews and appearances-- including television. For such matters, she can be contacted through hepatitismedia@gmail.com.

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