Hepatitis A Overview

Hepatitis A: The Disease

 

What is Hepatitis A?

Hepatitis A is viral disease of the liver caused by the hepatitis A virus (HAV). The hepatitis A virus is a nonenveloped RNA virus and considered to be a picornavirus. Humans are the only natural host of this virus.  The hepatitis A virus is very stable and can remain present for several months in most environments. The virus, however, can be killed by high temperatures (temperatures greater than 85C/185F), or by solutions such as chlorine, or formalin.   

Hepatitis A is contracted orally and typically acquired by coming into contact with human fecal waste, generally through the consumption of contaminated food and/or water.  Source of contamination may include raw shellfish, fruits and vegetables and ice. 

Hepatitis A replicates in the liver and can be found in the blood stream within 10 to 12 days following exposure. The virus is excreted by the biliary system into the feces of a contaminated individual.  An infected individual can spread hepatitis A to others for one to two weeks prior to becoming symptomatic.    Excretion of the virus may persist longer in children than adults, however, by the third week of the illness, most infected individuals no longer excrete the virus in their feces. 

It generally takes an average of four weeks (range of two to seven weeks) following exposure to hepatitis A for symptoms to develop. Symptoms often occur suddenly and include fatigue, abdominal and/or joint pain, loss of appetite, fever, nausea, jaundice, dark urine, clay-colored bowel movements, and diarrhea. Young children are often asymptomatic and show no clinical signs of infection.  Most infected individuals recover fully within two months, however, approximately 10 to 15 percent of infected individuals can have lingering symptoms for up to six months. 

Hepatitis A infection does not result in chronic liver disease  and persons who recover from the illness develop lifelong immunity. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Is Hepatitis A contagious?

Hepatitis A is contagious and spread from person to person by exposure through oral contact with the feces of an infected person.  Infection can occur from exposure to water or foods that are contaminated with the virus. Contamination sources may include raw shellfish, vegetables, fruits, and even contaminated ice.  Transmission of the virus through blood is very rare.  Hepatitis A thrives in areas that lack proper sanitation and where personal hygiene habits are poor.  Contaminated water sources can also be a source of transmission. Hepatitis A may infect drinking water through several sources including malfunctioning sewage systems, pollution from storm runoff, and through the overflow of sewage.  Wells may also become contaminated if they are shallow or if floodwaters have submerged them for long periods of time. 

Hepatitis A is endemic in many areas of the world including Africa, the Middle East, the Western Pacific, Asia, and Central and South America.  Individuals traveling to developing countries with high or intermediate levels of hepatitis A are at higher risk for contracting the virus and developing infection. 

In the United States, outbreaks are often traced to contaminated food sources and may affect restaurants, grocery stores, and work places. In the U.S., between 1971 and 2020, nearly 58,000 reported outbreaks of hepatitis A have been reported. These outbreaks have been associated with over two million illnesses, over 41,000 hospitalizations, and 2,205 deaths. 

Since 2016, multiple states have reported hepatitis A outbreaks linked primarily to persons experiencing homelessness and among individuals who use drugs.  Between late 2016 and January 6, 2023 over 44,700 cases have been reported, resulting in 27,332 hospitalizations, and 421 deaths.  It is believed that the higher number of hospitalizations and deaths that have occurred during this ongoing outbreak may be attributed to cofactors such as pre-existing health conditions, hepatitis B and hepatitis C co-infections, age, and additional risk behaviors found within this particular population. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

What is the history of Hepatitis A in America and other countries?

Hippocrates described outbreaks of jaundice in 5^th Century B.C. and medical historians believe this is likely the first reported cases of hepatitis A infections.   Throughout more recent history, reports of the disease were often associated with wars, and descriptions of outbreaks, often referred to in medical literature as infectious hepatitis or epidemic jaundice, have been documented since the Napoleonic Wars. 

By the early part of the 20^th century, physicians believed that transmission of infectious hepatitis occurred through food and water sources and from person to person.  By 1931, it was hypothesized that outbreaks of this epidemic jaundice were caused by an “ultra-microscopic virus which is pathogenic only to man.” 

In the 1940’s, experiments on the transmission of hepatitis A were conducted in Germany, the United States, and the Middle East. In Germany, human subjects involved in these experiments were fed duodenal juice. In the United States, researchers fed hepatitis A contaminated stool or serum filtrate to 12 conscientious objectors who volunteered for the experiment in lieu of military service. In the Middle East, volunteers were injected with blood or serum from patients with jaundice. From these experiments, researchers were able to determine the incubation period of infectious hepatitis, as well as the difference in the incubation periods between infectious hepatitis, now referred to as hepatitis A, and serum hepatitis, now hepatitis B. 

In the mid 1940’s, researchers discovered that gamma globulins (immunoglobulins) could help in the prevention of illness, including hepatitis A. Small amounts of hepatitis A gamma globulins were found to prevent illness for up to nine months.  This treatment continues to be an option for hepatitis A prevention even today. 

Human experimentation with Hepatitis A continued in the United States in the 1950’s, most notably at the Willowbrook State School on Staten Island, New York. In 1956, Dr. Saul Krugman began experimenting on children with developmental and intellectual disabilities residing at the state run school. Krugman wanted to learn more about the hepatitis virus as well as the available gamma globulin’s ability to reduce the risk of infection. As high rates of infectious hepatitis were well documented at Willowbrook, the institution was considered to be the perfect environment for Krugman to conduct further research. Krugman’s hepatitis experiments lasted for 14 years, and involved exposing new residents to the current circulating strain of infectious hepatitis found at the state school. Krugman, along with his assistant, Dr. Joan Giles, intentionally exposed intellectually disabled residents to the feces and serum of children who were known to have had the infection and proceeded to monitor their health status in an attempt to learn more information about the virus. Experiments performed by Krugman and Giles were not focused on treating the infection, but rather on observing the symptoms of hepatitis A infection for scientific gain. Krugman justified the experiments by reporting that the children of Willowbrook would most likely be exposed to the virus anyway due to the high rates of infection at the school, and that all children participating in the experiments would receive proper care and monitoring on a special hepatitis unit. Parental consent for participation was obtained, however, in many cases, parents who applied to have their children admitted to Willowbrook were informed that openings were only available for the particular unit where hepatitis experiments were taking place.     

Willowbrook was an overcrowded and unsanitary facility and few attempts were made to improve the living conditions of the residents. The facility lacked adequate staffing and residents often came from poor and minority families, most of whom had no other housing alternatives available for their children due to their financial situation or as a result of racial discrimination.  Robert Kennedy visited Willowbrook in 1965 and called it a “snakepit,”   noting that children were living in filth. He recommended that changes be implemented to improve the living conditions, however, no improvements were ever made to the facility. 

In 1971, several physicians publicly condemned the ongoing experiments on intellectually disabled children and voiced serious ethical concerns. In letters published by The Lancet in 1971, concerns expressed by physicians critical of the study included the ethics of experimentation on intellectually disabled children, the fact that the experiments would offer no improvement to the health of the child, the lack of any attempt to control the outbreak of infectious hepatitis by improving sanitation within the school, and more.      In 1972, investigative reporter Geraldo Rivera exposed the horrors of Willowbrook in an award winning documentary aired on ABC news. Rivera’s news report prompted the families of Willowbrook’s residents to take action and file a class action lawsuit against the State of New York. The hepatitis experiments were halted following public outcry and eventually federal laws were passed to protect the rights of individuals living in institutions. 

While the experiments that took place at Willowbrook resulted in a gain in scientific knowledge about the hepatitis virus, including the confirmation of a distinction between infectious hepatitis, now known as hepatitis A, and serum hepatitis, or hepatitis B, as well as the differentiation between their modes of transmission,  the ethics of Krugman’s experiments continue to be questioned today. 

In 1973, the hepatitis A virus was finally detected and isolated in the feces  and additional techniques to adequately test samples to definitively determine a diagnosis of hepatitis A infection and differentiate it between hepatitis B were also developed during this time.  Hepatitis A vaccine development began following virus isolation, and by 1991, the first published research on the use of an inactivated hepatitis A vaccine in humans appeared in medical literature. 

Hepatitis became a reportable disease in the early 1950’s  and in 1961, there were 72,651 reported cases of both infectious and serum hepatitis reported to the CDC.  In 1961, the CDC reported on an increase in the number of cases, noted it to be “the largest number reported since hepatitis was added to the list of notifiable diseases ten years ago.”  It was also reported that there was a seven year interval between high rates of hepatitis infection, and most cases were reported in the later part of the winter and the early part of spring. 

In 1966, the CDC began differentiating between infectious hepatitis, now referred to as hepatitis A, and serum hepatitis, or hepatitis B. Prior to 1966, the CDC collected data on the rates of both types of hepatitis infection, however, no distinction was made between the two. In 1966, there were 32,859 reported cases of hepatitis A and 1,497 reported cases of hepatitis B, an over 50 percent decrease from the number of reported cases five years earlier. 

Between 1966 and 1995, the year prior to the Food and Drug Administration’s (FDA) approval of the inactivated hepatitis A vaccine (1996), reported rates of hepatitis A infection varied between a high of 59,606 in 1971, and a low of 21,532 in 1983,  with higher numbers of outbreaks occurring in the U.S. approximately every 10 years.  Hepatitis A infection rates were noted to be highest among Alaskan Natives and American Indians and more prevalent in the western part of the United States. Children under the age of fifteen were found to have the highest rates of infection, with 30 percent of cases occurring within this population.  Outbreaks occurred most frequently between family members or sexual contacts, daycare workers, and international travelers. Only between two and three percent of all hepatitis A infections were the result of an identified water or food source and 50 percent of all reported cases had no identified source of infection. 

It was also reported in 1996 that one third of all Americans had lifelong hepatitis A immunity due to previous exposure to the virus and exposure to hepatitis A directly correlated to age. 75 percent of adults over the age of 70 were found to be immune to hepatitis A, whereas only 10 percent of children under the age of 10 had previous exposure to the virus and determined to be immune. 

At the time of the CDC’s Advisory Committee on Immunization Practices (ACIP) recommendation of the newly available hepatitis A vaccines, VAQTA, and HAVRIX in 1996, ACIP acknowledged that the number of cases of hepatitis A had declined over the past several decades primarily as a result of an improvement in sanitation and hygiene practices.  In 1996, there were 31,032 cases of hepatitis A infection reported to the CDC. 

In 2007, one year following the ACIP’s recommendation for routine administration of two doses of hepatitis A vaccine for all children beginning at 12 months of age,  there were 2,979 reported cases of hepatitis A infections reported. At this time, it was noted that hepatitis A infections were highest among adults between the ages of 25 and 39 and lowest in children under the age of five. However, as children under the age of five are often asymptomatic when exposed to hepatitis A, infection rates in young children may have actually been much higher than reported. 18 percent of all cases of hepatitis A were attributable to international travel with approximately 85 percent of all travel-related cases associated with trips to Mexico and Central or South America. Six percent of cases occurred in men who had sex with other men, and one percent of cases involved injectable drug users. Information on risk factors for hepatitis A infection were absent from nearly half of the reported cases. 

The number of reported hepatitis A infections steadily decreased until 2013, when a large multistate outbreak occurred in association with imported pomegranate arils from Turkey resulted in 165 reported infections,  and put the total number of reported cases for the year at 1,781.  In 2016, reported rates of hepatitis A infection increased yet again as a result of two separate outbreaks associated with contaminated food, with one in Hawaii linked to raw scallops imported from the Philippines  and a second multi-state outbreak linked to frozen strawberries imported from Egypt.  There were 2,007 reported cases of hepatitis A infections in 2016.  The CDC reported that only 1,026 of the 2,007 reported cases of hepatitis A infection included clinical data pertaining to death, and from these reported cases, seven deaths were associated with hepatitis A. 

In the United States, risk factors for acquiring hepatitis A infection include international travel, exposure to a person with hepatitis A infection, employment at a day care center, being a man who has sex with another man, being an injection drug user, or becoming exposed from a contaminated food or water source. It is important to note that in 2014, only 7 percent of reported cases of hepatitis A infection listed a risk factor, with the overwhelming majority of cases missing information or reporting no known etiology for the infection.  

Since 2016, multiple states have reported hepatitis A infections that have primarily impacting persons who use drugs or who are experiencing homelessness. As of January 6, 2023, there have been 44,768 cases, 27,332 hospitalizations, and 421 deaths attributed to this outbreak.  In October of 2018, the CDC added homelessness as a risk factor for developing hepatitis A and recommended hepatitis A vaccination for this particular population. 

What Is the Incidence of Hepatitis A in the Rest of the World?

Globally, hepatitis A is the most common form of acute hepatitis, with an estimated 1.5 million clinical cases occurring each year.  Hepatitis A infections are often cyclical and closely associated with sanitation and hygiene practices. In developing countries that lack adequate sanitation and where hygiene habits are poor, most children become infected with hepatitis A prior to the age of ten. As infection in most young children tends to be asymptomatic, outbreaks are uncommon as most individuals have been exposed to the virus early in life and have lifelong immunity. 

In countries that are developing and may have varying conditions of sanitation and personal hygiene, hepatitis A exposure may be avoided in childhood and delayed until an older age during which infection will often be symptomatic. As a result, these countries are noted to have higher rates of hepatitis A infection. 

In developed countries, such as the United States, Canada, Western Europe, Japan, and Australia, where good hygiene and sanitation practices exist, rates of hepatitis A infection are very low, and occur mainly as a result of international travel, exposure in residential or childcare centers, or by water or food borne contamination. Risk factors for hepatitis A infection in developed countries include men who have sex with other men, drug users, international travelers, and persons experiencing homelessness.   

Hepatitis A infection does not result in chronic liver disease and rarely results in death. When death occurs, it is often a result of fulminant hepatitis or acute liver failure. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Can Hepatitis A cause injury and/or death?

Complications from hepatitis A are extremely uncommon. In rare cases, severe clinical symptoms of hepatitis A can result in neurological, immunological, and hematological impairments and the virus can also affect the kidneys and the pancreas. Additional complications that have been reported include autoimmune hepatitis, relapsing hepatitis, cholestatic hepatitis, subfulminant and fulminant hepatitis. Fulminant hepatitis is the most severe complication resulting in a nearly 80 percent fatality rate. 

While hepatitis A complications have historically been rare, the ongoing hepatitis A outbreak among persons who use drugs and who are experiencing homelessness has resulted in a higher number of hospitalizations and deaths than what was previously reported. Public health officials have speculated that this may be the result of age, pre-existing illnesses, including hepatitis B and hepatitis C co-infections, and high risk activities such as heavy alcohol consumption and drug use that tend to be found among persons within this population.  As of January 6, 2023, over 44,700 cases of hepatitis A have been reported, resulting in 27,332 hospitalizations and 421 deaths. 

Most infected individuals recover fully from hepatitis A within two months, however, approximately 10 to 15 percent of infected individuals can have lingering symptoms for up to six months. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Who is at highest risk for getting Hepatitis A?

United States public health officials state that, while anyone can become infected with hepatitis A, those most at risk include:   

• Men who have sexual relations with other men
• Persons having sexual relations with an infected individual
• Individuals using recreational drugs, whether they are injected or not
• Persons residing in or traveling to countries where Hepatitis A is endemic
• Caregivers or household members who are living with someone who is infected with hepatitis A
• Hemophiliacs or persons with a similar blood clotting disorder
• HIV-positive individuals
• Families who may be adopting a child from countries considered to have intermediate or high hepatitis A infection rates
• Persons working with the hepatitis A virus including those working with hepatitis A infected primates
• Homeless individuals

A 2015 published study found that adults, rather than children, were at a higher risk of developing hepatitis A infection and that infections were not limited to high risk groups, primarily due to the increasing number of foods imported to the United States as some have been found to be the source of hepatitis A infections.    Infection rates in the United States and other developed countries are considered to be very low due to proper sanitation and hygiene practices.  However, since 2016, many U.S. states have experienced hepatitis A outbreaks, primarily among persons who use drug or who are experiencing homelessness and as of January 2023, multiple states continue to be impacted by the ongoing outbreaks.   

In developing countries, however, 90 percent of children will develop hepatitis A prior to the age of ten due to poor personal hygiene practices and inadequate sanitation. The majority of these infected children will show no clinical symptoms of disease and exposure to the virus will result in lifelong hepatitis A immunity. As a result, the rates of symptomatic disease in developing countries are very low and epidemics are rare. In developing countries where personal hygiene practices and proper sanitation are variable, symptomatic outbreaks may be much more common. In these countries, children may not become exposed to the hepatitis A virus at a young age and this may result in a higher rate of adults without immunity to the illness. In these countries, hepatitis A disease rates may be much higher. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Who is at highest risk for suffering complications from Hepatitis A?

Complication from hepatitis A are very rare. Persons most at risk from developing complications as a result of hepatitis A include adults over the age of forty  and persons previous diagnosed with chronic liver disease. 

In 2017, however, public health officials noted an increase in the rate of hospitalizations and deaths from hepatitis A among persons experiencing homelessness and those who use drugs in comparison to data from 2016. Health officials have speculated that the elevated risk of complications within this particular population may be related to additional pre-existing illnesses such as hepatitis B, hepatitis C, in addition to participating in high risk activities, such as increased alcohol consumption and drug use. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Can Hepatitis A be prevented and are there treatment options?

Prevention strategies to decrease the risk of hepatitis A infection include the following: 

• Consistent thorough handwashing with soap and water after using the restroom or following contact with an infected person’s bodily fluids such as blood, urine and feces.
• Washing of hands before and after diaper changes
• Thoroughly handwashing before cooking or serving food
• Avoiding the consumption of contaminated food and water, especially when traveling

When traveling to areas where the risk of hepatitis A infection may be high, avoidance of unclean water and food is important. Strategies to prevent hepatitis A while traveling include the following: 

• Avoiding undercooked and raw fish and meat
• Avoiding dairy products
• Drinking carbonated bottle water
• Using only carbonated bottle water to brush teeth
• Avoiding the use of ice in beverages
• Promptly consuming food that is hot to the touch
• Refraining from purchasing food from street vendors
• Boiling water at full boil for at least one minute if bottled water sources are unavailable.

If a person has been exposed to hepatitis A virus, it may be possible to prevent infection with hepatitis A immune globulin within 2 weeks of exposure to the virus.  Hepatitis A immune globulin can also be administered prior to traveling to countries where rates of hepatitis A virus may be high.   

As hepatitis A is a viral infection, there are no specific treatment options for the infection itself. Treatments are targeted towards the management the symptoms. These treatment options may include assuring adequate nutritional status, maintaining comfort, and replacing fluids that may be lost as a result of diarrhea or vomiting. The use of acetaminophen or medications to prevent emesis are not recommended.  It is, however, recommended that affected persons avoid alcohol, ensure adequate water intake and consume a healthy diet. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

What is Hepatitis A vaccine?

The CDC’s Advisory Committee on Immunization Practices currently recommends that all children receive the first dose of hepatitis A vaccine between 12 and 23 months of age and the second dose is recommended 6 months or longer following the first dose of the vaccine. Additionally, hepatitis A vaccination is recommended for person considered at high risk for developing hepatitis A related to travel, employment, pre-existing health issues, lifestyle and in the event of an outbreak situation. 

Read the Product Information Insert

NVIC strongly recommends reading the vaccine manufacturer product information insert before you or your child receives any vaccine, including a shot containing hepatitis A vaccine. Product inserts are published by drug companies making vaccines and list important information about vaccine ingredients, reported health problems (adverse events) associated with the vaccine, and directions for who should and should not get the vaccine.

Links to hepatitis A vaccine product inserts are available below or you can ask your doctor to give you a copy of the vaccine product insert to read before you or your child is vaccinated. It is best to ask your doctor for a copy of the product inserts for the vaccines you or your child is scheduled to receive well in advance of the vaccination appointment.

Hepatitis A Vaccines Licensed for Use in the U.S.

The U.S. Food and Drug Administration and U.S. Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control (CDC) has approved three different hepatitis A containing shots. There are different rules for use of these vaccines by different aged groups.

VAQTA: a vaccine containing inactivated hepatitis A vaccine virus approved for use in adults and children 12 months of age and older. This vaccine is manufactured by Merck. Two doses of VAQTA vaccine are recommended and doses should be given at least six months apart or longer. 

VAQTA vaccine is made from hepatitis A virus grown in human MRC-5 diploid fibroblasts. Human MRC-5 cells are derived from a cell line that was developed in 1966 from lung tissue taken from a 14 week aborted fetus and contains viral antigens.  The inactivated strain is derived by the further processing of an attenuated strain that has been grown, selected, purified and inactivated by formalin. Following inactivation, the virus is combined with amorphous aluminum hydroxyphosphate sulfate, an aluminum adjuvant with the potential to cause autoimmune/auto inflammatory conditions and noted to be linked to adverse events. 

Each adult dose of VAQTA contains 50U of hepatitis A virus antigen and 450mcg of aluminum in the form of amorphous aluminum hydroxyphosphate sulfate. Each pediatric dose of VAQTA contains 25U of hepatitis A virus antigen and 225 mcg of aluminum. VAQTA also contains DNA, non-viral protein, bovine albumin, formaldehyde, neomycin, sodium borate, and sodium chloride.   

The vial stopper, the syringe plunger stopper, and the tip cap contain dry natural latex rubber that may cause allergic reactions in latex-sensitive persons. 

HAVRIX: a vaccine containing inactivated hepatitis A vaccine virus approved for use in adults and children 12 months of age and older. This vaccine is manufactured by GlaxoSmithKline. Two doses of HAVRIX vaccine are recommended and doses should be given at least six months apart or longer. 

HAVRIX vaccine is manufactured by propagating the hepatitis A virus in MRC-5 human diploid cells. Human MRC-5 cells are derived from a cell line that was developed from lung tissue taken from a 14 week aborted fetus in 1966 and contains viral antigens.  The cells are lysed to form a suspension and purified. It is inactivated by formalin and absorbed into aluminum hydroxide. 

Each 1-ml adult dose of the vaccine contains 500mcg of aluminum and each 0.5ml pediatric dose contains 250mcg of aluminum, both in the form of aluminum hydroxide. 

Additional ingredients in the vaccine include MRC-5 human diploid cells, polysorbate 20, formalin, neomycin sulfate, amino acid supplement in a phosphate-buffered saline solution, and an aminoglycoside antibiotic.   

TWINRIX: a vaccine containing both inactivated hepatitis A vaccine (HAVRIX) and hepatitis B recombinant vaccine (ENGERIX-B) approved for use in adults 18 years of age and older. This vaccine is manufactured by GlaxoSmithKline. There are two different dosing options for TWINRIX vaccine. The most common dosing schedule of TWINRIX vaccine involves the administration of three vaccine doses, with the second dose administered one month following the initial dose, and the third dose administered six months after the first dose was administered. An accelerated dosing option has also been approved and involves three doses administered within three weeks, with the second dose at Day 7 and the third dose at Day 21, followed by a fourth dose at 12 months. 

TWINRIX vaccine is bivalent vaccine containing the HAVRIX vaccine (see above) and the ENGERIX-B (hepatitis B vaccine). ENGERIX-B is comprised of a suspension of hepatitis B virus surface antigen (HBsAg) and contains purified surface antigen of the hepatitis B virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells (yeast cells), which carry the surface antigen gene of the hepatitis B virus. The HBsAg expressed in the cells is purified and adsorbed on aluminum hydroxide. ENGERIX-B should contain no more than 5 percent yeast protein. 

Each 1-ml dose of TWINRIX contains 450mcg of aluminum, in the form of aluminum hydroxide and aluminum phosphate, as an adjuvant. Additional ingredients in the vaccine include formalin, amino acids, phosphate buffer, polysorbate 20, sodium chloride, neomycin sulfate, yeast protein, and MRC-5 human diploid cells (residual DNA).   

The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions. 

Is the Hepatitis Vaccine Mandated?

Federal health officials make recommendations for vaccine use and states enact laws that require vaccine use. Currently, 23 states and the District of Columbia require hepatitis A vaccine for either childcare enrollment, K-12 school enrollment, or both.  Medical exemptions to vaccination are allowed in every state but few medical conditions qualify for a medical exemption, which must be written by a medical doctor (M.D.) or Doctor of Osteopathy (D.O.) or other licensed professional approved by the state.

Depending upon which state you live in, you may be legally allowed to exercise a religious or philosophical/conscientious belief exemption to vaccination, including hepatitis A vaccination. For more information about which vaccines your state requires and exemptions, go here on NVIC’s website.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

What is the history of Hepatitis A vaccine use in America?

Research involving the use of formalin-inactivated hepatitis A vaccine in human subjects was first published in 1991 by a group of scientists from Walter Reed Army Institute of Research. According to the published study, scientists were able to show that the inactivated vaccine could produce antibodies against hepatitis A.  Additionally in 1991, research was also published on the use of a live attenuated hepatitis A vaccine capable of producing hepatitis A antibodies in humans.  While no live hepatitis A vaccine has ever received FDA approval for use in the United States, live attenuated hepatitis A vaccines are currently in use in both India and China. 

Merck and GlaxoSmithKline continued independently to develop their inactivated hepatitis A vaccines and in 1992, Merck scientists published research on the VAQTA hepatitis A vaccine. The published paper reported on a study involving approximately 1000 children between the ages of two and 16 living in a Hasidic Jewish community in upstate New York. 519 children were administered the vaccine that contained 300mcg of aluminum hydroxide and thimerosal at a 1:20,000 dilution, while 518 children received a “placebo” dose of 300mcg of aluminum hydroxide along with a 1:20,000 dilution of thimerosal. The published study reported on the vaccine’s ability to prevent clinical cases of hepatitis A infection, however, it also stated that researchers were not able to prove that the vaccine could prevent subclinical infections.  GlaxoSmithKline published research in 1994 on its HAVRIX hepatitis A vaccine, reporting the vaccine to be 94 percent effective in preventing cases of hepatitis A infections. This particular vaccine was tested on over 40,000 children between the ages of one and 16 living in Thailand. 

On February 22, 1995, HAVRIX received FDA approval for use in adults and children two years of age and older.  One year later, Merck’s hepatitis A vaccine, VAQTA, received FDA approval for use in persons aged 2 and older. 

In December of 1996, the CDC’s Advisory Committee on Immunization Practices (ACIP) released its first recommendations on the use of hepatitis A vaccine. ACIP recommended hepatitis A vaccination for all persons traveling to or residing in countries noted to have intermediate or high rates of hepatitis A infections, with the first dose recommended at least four weeks prior to departure. It was, however, suggested that pre-vaccination testing for the presence of hepatitis A antibodies be performed in older persons, due to the likelihood of previous exposure and current immunity to hepatitis A. Hepatitis A vaccination was also recommended for all children ages 2 and older residing in communities with high rates of hepatitis A infection or where periodic outbreaks occurred. The CDC, however, noted that children aged 10 to 15 years who resided in these high risk communities would probably not require vaccination due to the likelihood of previous exposure and current immunity to hepatitis A. 

Additionally, the CDC recommended the vaccine for use in populations consider at high risk for hepatitis A infection. These groups included illegal drug users, both injection and non-injection users, men who had sex with other men, persons with chronic liver disease, including those who were liver transplant recipients or awaiting transplant, persons working with hepatitis A exposed primates in laboratory settings, and those with clotting factor disorders. As well, it was suggested that vaccination of food handlers be considered should it be deemed cost effective by local or state regulators or by private employers. Further guidelines were issued on the use of hepatitis A vaccine in response to outbreaks, however, the CDC admitted that the ease and cost of vaccination, as well as the ability to continually sustain high rates of vaccination in young children may factor into the decision on how to proceed in the event of an outbreak. The CDC declined to recommend routine vaccination of persons residing or working in potentially high risk settings such as daycare centers, prisons, and institutions for developmentally disabled, but recommended the use of hepatitis A immune globulin in these particular populations in event of an outbreak. 

In 1999, ACIP updated recommendations for the use of the hepatitis A vaccine to include routine vaccination of all children two and older living in areas where hepatitis A infection rates were twice or more the 1987 to 1997 national average rates. The CDC also suggested that routine vaccination be considered as a tool to decrease the number of hepatitis A infections in areas found to be above the 1987-1997 national average. Recommendations for travelers and persons considered high risk for exposure to hepatitis A as defined in the 1996 ACIP recommendations remained unchanged. 

On May 11, 2001, GlaxoSmithKline’s TWINRIX vaccine, a bivalent vaccine containing HAVRIX hepatitis A vaccine, and ENGERIX-B hepatitis B vaccine, received approval for use in adults ages 18 and older, following clinical studies involving less than 2,200 healthy adults. TWINRIX, containing both aluminum phosphate and aluminum hydroxide, thimerosal, neomycin, formalin, yeast as well as 2-phenoxyethanol as a preservative, was reported by GlaxoSmithKline to be as effective as separate doses of HAVRIX and ENGERIX-B.   

Hepatitis A infection rates dropped from 17,047 reported cases in 1999 to 4,488 reported cases in 2005 despite low hepatitis A vaccination rates. In 2004, the National Immunization Survey found that only 54 percent of children between the ages of 24 and 35 months residing in states where hepatitis A vaccination was recommended had received the hepatitis A vaccine. As well, only 27 percent of children in states where vaccination should be considered were vaccinated. Vaccination rates of children in the remaining states were reported to be at only 2 percent. 

In 2005, both Merck’s VAQTA and GlaxoSmithKline’s HAVRIX received FDA approval for use in children beginning at one year of age, instead of two years.    Merck’s VAQTA received approval for use in children at one year of age and older following clinical trials involving only 706 children  while GlaxoSmithKline’s HAVRIX received their approval following clinical trials that involved 723 children younger than two years.  In early 2006, following the FDA’s approval to lower the age of administration of both hepatitis A vaccines, ACIP recommended routine hepatitis A vaccination of all children, with the first dose to be administered between 12 and 23 months of age, and the second dose at least six month later.  In 2007, the CDC updated hepatitis A vaccine recommendations for post-exposure to hepatitis A and for international travelers  and in 2009, the vaccine was recommended for families and close contacts of newly adopted international adoptees. 

Since the 2006 CDC recommendation for routine vaccination of all children with two doses of hepatitis A vaccine beginning at 12 months, vaccination rates have remained low. A 2010 CDC published survey found that by 2009, only 15 percent of children between the ages of 12 and 35 months had received the recommended two doses of hepatitis A vaccine.  By 2014, this number had only increased to 57.5 percent. 

In 2018, a published report found that less than 65 percent of adolescents between the ages of 13 and 17 had received the recommended two doses of hepatitis A vaccine.  Adult vaccination rates have also remained low, with a 2015 study reporting that only 9 percent of adults ages 19 and older to be vaccinated with the hepatitis A vaccine. 

Currently, only 18 states and the District of Columbia require hepatitis A vaccination for school entry and only 23 states and the District of Columbia require hepatitis A vaccination for children enrolled in childcare. 

At the October 2018 CDC ACIP meeting, committee members voted to recommend routine vaccination of hepatitis A vaccine for all persons 12 months of age and older who were experiencing homelessness.  This recommendation was made in response to the multi-state outbreak of hepatitis A first identified in 2016 among persons who use drugs and those experiencing homelessness.  In this recommendation, committee members reported that alternative strategies to prevent exposure to hepatitis A such as adequate handwashing, access to sanitary toilet facilities, and avoidance of crowded living spaces would be difficult to implement, therefore vaccination would likely be the best strategy to prevent hepatitis A among homeless individuals. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

How effective Is Hepatitis A vaccine?

Vaccine acquired immunity is only temporary and, in some cases, vaccines may also fail to provide even temporary immunity for some individuals.

A systematic review on the efficacy of the hepatitis A vaccine completed in 2003 reported the inactivated hepatitis A vaccine to be 86 percent effective at preventing hepatitis A. 

The duration of immunity following hepatitis A vaccine is unknown. A 2017 published study reviewing the antibody levels of 52 hepatitis A vaccine recipients found that 88.5 percent had measurable antibody levels after 20 years.  It is important to note that while protection from hepatitis A infection may be related to the presence of antibodies, the lowest levels of antibody protection is not known.   

According to GlaxoSmithKline’s package insert for TWINRIX (bivalent vaccine containing both Hepatitis A and Hepatitis B vaccine), when blood antibody levels were tested in 264 healthy adults in the U.S. one month after the completion of three doses of TWINRIX vaccine, 99.6 percent of individuals developed hepatitis A antibodies and 95.1 percent developed hepatitis B antibodies. When the blood antibody levels were tested one month following completion of the accelerated dosing schedule in 194-204 healthy adults, 100 percent of people developed hepatitis A antibodies and 96.4 percent developed hepatitis B antibodies. GlaxoSmithKline reports that TWINRIX vaccine acquired antibodies for both hepatitis A and hepatitis B persist for at least 4 years. 

Persons who are immunocompromised may not develop antibodies against hepatitis A following vaccination. The package inserts for Merck’s VAQTA vaccine, and GlaxoSmithKline’s HAVRIX and TWINRIX vaccines state that vaccination may not result in protective antibodies against hepatitis A.      Published studies on the use of hepatitis A vaccine in HIV positive individuals determined the vaccine to be effective approximately 50 percent of the time.   

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Can Hepatitis A vaccine cause injury & death?

The Institute of Medicine (IOM) has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons, but that vaccine providers cannot accurately predict prior to a vaccine’s administration who will suffer complications, injury or death from vaccination.  However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving a hepatitis A vaccine or any other vaccine.

According to the CDC, possible side effects from the hepatitis A vaccine include: 

• Redness or pain at the injection site
• Headache
• Fatigue
• Fever
• Loss of appetite
• Fainting
• Dizziness
• Allergic reaction
• Death

VAQTA: Adverse events reported to have occurred during pre-licensing clinical trials of Merck’s VAQTA hepatitis A vaccine included: injection site warmth, bruising, pain, redness, and swelling; headache; fever; bronchial constriction; asthma; wheezing; swelling/edema; generalized redness; rash; eye irritation; itching; dermatitis; irritability; diaper dermatitis; upper respiratory infection; diarrhea; teething; rhinorrhea; vomiting; constipation; otitis media; insomnia; nasopharyngitis; rhinitis; viral infection; croup; Streptococcal pharyngitis; laryngotracheobronchitis; viral exanthema; viral gastroenteritis; roseola; anorexia; febrile seizure; dehydration; cellulitis and insomnia. 

Serious complications reported by Merck in the VAQTA product insert during vaccine post-marketing surveillance have included: Diarrhea/gastroenteritis; thrombocytopenia; Guillain-Barre Syndrome; encephalitis and cerebellar ataxia. 

In all of Merck’s pre-licensing clinical safety trials involving children under the age of 2, VAQTA vaccine was administered either alone, or in combination with additional vaccines. No pre-clinical safety studies were ever completed to compare the health outcomes of VAQTA against a true placebo or even against another previously licensed vaccine. In one study, vaccine recipients received either VAQTA vaccine alone or else VAQTA vaccine in combination with Merck’s ProQuad (Measles-Mumps-Rubella-Varicella) vaccine, a vaccine found to be associated with an increased risk of febrile seizures,    along with Wyeth’s Prevnar vaccine, for the first dose of the vaccine. For the second dose of the vaccine, pre-licensure clinical trials compared the safety of VAQTA vaccine against the safety of VAQTA vaccine administered in combination with Merck’s highly reactive ProQuad vaccine. An additional clinical safety trial compared health outcomes of children who received either VAQTA alone or else VAQTA in combination with Merck’s Haemophilus B Conjugate Vaccine, PedvaxHIB or both PedvaxHIB and GlaxoSmithKline’s Infanrix, a diphtheria, tetanus and acellular pertussis vaccine. Health outcomes of clinical trial vaccine recipients were monitored for only 2 weeks. 

In pre-licensing clinical trials involving children between the ages of 2 and 18 years of age, clinical trial participants received either VAQTA or a dose of amorphous aluminum hydroxyphosphate sulfate, an aluminum adjuvant linked to adverse events and associated with autoimmune/autoinflammatory conditions.  In this particular clinical trial, the second dose of the aluminum adjuvant was not administered to the control group because “code for the trial was broken.”  As with pre-licensing clinical trials involving children under the age of two years, the health outcomes of the clinical trial participants were limited to 14 days. 

Only 240 healthy adults ages 19 and older were studied in the initial VAQTA vaccine pre-licensing clinical trials and participants received either VAQTA alone, or VAQTA in combination with the Typhoid Vi polysaccharide vaccine and the yellow fever vaccine. Four additional clinical trials involving 1,645 healthy adults compared VAQTA against differing amounts of viral antigens of hepatitis A and/or aluminum, VAQTA when administered alone or in combination with hepatitis A immune globulin, three different lots of VAQTA vaccine, and VAQTA against differing amounts of the hepatitis A viral antigens. Again, the evaluation of health outcomes of the pre-licensing clinical trial participants was limited to 14 days. 

HAVRIX: Adverse events reported to have occurred during pre-licensing clinical trials of GlaxoSmithKline (GSK) HAVRIX hepatitis A vaccine included: injection site warmth, bruising, pain, redness, induration, and swelling; headache; fever; anorexia; nausea; fatigue; malaise; vertigo; photophobia; lymphadenopathy; dysgeusia; hypertonia; rash; urticaria; pruritus; abdominal pain; diarrhea; vomiting; insomnia; muscle and joint pain; pharyngitis; upper respiratory infections; seizure; bronchial hyper-reactivity and respiratory distress. 

Serious complications reported by GlaxoSmithKline (GSK) in the HAVRIX product insert during vaccine post-marketing surveillance have included: rhinitis; vasculitis; hepatitis; jaundice; anaphylaxis and anaphylactoid reactions; serum sickness-like syndrome; thrombocytopenia; shortness of breath; dizziness; vasculitis; shortness of breath; multiple sclerosis; Guillain-Barre Syndrome; musculoskeletal stiffness; injection site reaction; local swelling; paresthesia; encephalopathy, syncope, myelitis, neuropathy, angioedema, erythema multiforme, hyperhidrosis, chills, influenza-like symptoms and congenital anomaly. 

The HAVRIX vaccine package insert reports that clinical trials involving the vaccine have occurred in over 37,000 individuals, however, GSK provides very limited information on these trials in their vaccine product insert. The only study detailed as part of its package insert, HAVRIX Study 231, involved 1,241 healthy children between the ages of 11 and 25 months.  Safety studies in this clinical trial compared the health outcomes of individuals receiving HAVRIX alone, HAVRIX in combination with Merck’s MMR vaccine and Merck’s varicella vaccine, or MMR and Varicella vaccine followed by a dose of HAVRIX vaccine 42 days later. Solicited adverse events such as fever, irritability, drowsiness, loss of appetite, redness, pain, and swelling were recorded by parents on diary cards for 3 days following vaccination and submitted to clinical trial monitors. Information on unsolicited adverse events occurring between Day 4 and Day 31 post vaccination were collected from the parents of trial participants and a telephone follow up occurred 6 months later. While the vaccine product insert provides limited information on health outcomes of the 1,241 trial participants, further data on this particular study was released in February of 2013 as part of GSK’s “commitment to further clinical transparency through public disclosure of GSK Clinical Study Reports (CSRs) on the GSK Clinical Study Register.” 

According to the clinical trial documents of HAVRIX Study 231 released by GSK in 2013, over 62 percent of trial participants receiving HAVRIX alone, nearly 58 percent of trial participants receiving HAVRIX in combination with MMR and varicella vaccine, and over 66 percent of participants receiving MMR and varicella vaccine followed by HAVRIX at Day 42, experienced an adverse reaction in the first 30 days following vaccination.  Of the 1,241 children who participated in this clinical trial, 51, or four percent, experienced a serious adverse event following vaccination, with half of those serious reactions occurring in children who received HAVRIX in combination with the MMR and varicella vaccine.  In the United States, the hepatitis A vaccine is routinely administered with the MMR, varicella, and pneumococcal vaccines, in accordance to the CDC’s recommended vaccine schedule. 

Details on the serious adverse events that occurred during HAVRIX Study 231 remain unknown, as the information was redacted by GSK prior to release. The document, however, reports that one serious adverse reaction, a diagnosis of autism following vaccination with HAVRIX in combination with the MMR and varicella vaccine, “was considered by the investigator to have a possible causal relationship to vaccination.” 

The HAVRIX Study 231 document released by GSK also noted that a diagnosis of or suspected immunodeficient condition such as HIV or a newly diagnosed neurologic disorder, in addition to other possible medical events that occurred during the clinical trial, would result in the removal of the individual’s results from the study’s final outcome.  1,474 children were initially enrolled in the study; however, final data includes the outcomes of only 1,241 children. In the Study 231 document, GSK states that four children who suffered adverse events were removed from the study and that seven others were eliminated for “other reasons”, with further details redacted by GSK. 

TWINRIX: Adverse events reported to have occurred during pre-licensing clinical trials of GlaxoSmithKline (GSK)’s TWINRIX hepatitis A/ hepatitis B vaccine included: injection site redness, pain, induration, and swelling; headache; fatigue; nausea; diarrhea; vomiting; upper respiratory infections; insomnia; anorexia; dizziness; migraine; paresthesia; somnolence; syncope; vertigo; muscle and joint pain; back pain; constipation; weakness; agitation; irritability, abdominal pain; influenza-like illness; erythema; petechiae; rash; sweating; urticaria; lymphadenopathy; dysgeusia; hypertonia; tingling; migraine; flushing; photophobia and hypotension. 

Serious complications reported by GSK in the TWINRIX product insert during vaccine post-marketing surveillance have included: meningitis, herpes zoster; allergic reaction, anaphylactoid reaction, anaphylaxis, serum sickness–like syndrome days to weeks after vaccination (including arthralgia/arthritis; fever; urticaria; erythema multiforme; ecchymoses; and erythema nodosum) thrombocytopenia; thrombocytopenic purpura; Bell's palsy; convulsions; encephalitis; encephalopathy; Guillain-Barré Syndrome; myelitis; multiple sclerosis; neuritis; neuropathy; optic neuritis; paralysis; paresis; transverse myelitis; hepatitis; jaundice; shortness of breath; bronchospasm, including asthma-like symptoms; conjunctivitis; visual disturbances; earache; tinnitus; palpitations; tachycardia; vasculitis; dyspepsia; arthritis; alopecia; eczema; erythema multiforme; erythema nodosum; hyperhidrosis; lichen planus and muscular weakness. 

Pre-licensure clinical trials of TWINRIX, a bivalent vaccine combining HAVRIX (inactivated Hepatitis A vaccine) and ENGERIX-B (recombinant Hepatitis B vaccine), were limited to approximately 2,500 trial participants. In the United States, TWINRIX was studied for use in only 773 healthy adults between the ages of 18 and 70. In this U.S. pre-clinical vaccine trial, study participants received either TWINRIX, a dose of HAVRIX (hepatitis A vaccine), a dose ENGERIX-B (Hepatitis B vaccine), or a dose of both HAVRIX and ENGERIX-B. Adverse events such as fever, irritability, and drowsiness, loss of appetite, redness, pain, and swelling were actively solicited by clinical trial monitors for only 3 days following vaccination. Data on unsolicited adverse reactions were collected between Day 4 and Day 31 following vaccine administration. GSK reports that the data collected from U.S. clinical trials were comparable to those reported from other clinical trials, however, this data has not been published. Adverse events reported during the pre-licensure clinical trials included injection site redness, swelling, and induration, agitation, insomnia, abdominal pain, vomiting, anorexia, respiratory tract infections, vertigo, dizziness, migraine, rash, weakness, and more. 

In the comprehensive report evaluating scientific evidence, Adverse Effects of Vaccines: Evidence and Causality,  published in 2012 by the Institute of Medicine (IOM), eight reported vaccine adverse events following the hepatitis A vaccine were evaluated by a physician committee.  These adverse events included acute disseminated encephalomyelitis, transverse myelitis, multiple sclerosis, Guillain Barre Syndrome, chronic inflammatory disseminated polyneuropathy, Bell’s palsy, anaphylaxis, and autoimmune hepatitis.

Of the eight vaccine-related adverse events evaluated, the IOM committee concluded that there was inadequate evidence to support or reject a causal relationship between the hepatitis A vaccine and all eight vaccine related adverse events, because of the complete absence of methodologically sound published studies required to make a determination. 

A 2011 published study linked hepatitis A vaccination to Henoch-Schönlein purpura, a disorder that causes bleeding and swelling of the small blood vessels.  In 2012, an epidemiological study examining the risk of immune thrombocytopenic purpura (ITP), a blood disorder causing unusually low levels of platelets in the body, following vaccination found a significantly higher number of reported cases in individuals between the ages of 7 and 17 following vaccination with the hepatitis A vaccine. The study authors recommended further research on this association, however, no additional studies have been published. 

Acute disseminated encephalomyelitis (ADEM) combined with acute motor axonal neuropathy following the hepatitis A vaccine and an infection with Campylobacter jejuni, a bacteria commonly associated with food poisoning, was documented in a 1999 published case study.  In 2009, doctors from Singapore submitted a case report of retrobulbar optic neuritis in an HIV positive man following vaccination with the hepatitis A vaccine. 

Using the MedAlerts search engine, as of June 30, 2023, there have been more than 49,616 reports of hepatitis A vaccine reactions, with over 25 percent (12,705) of reaction occurring in children under 3 years of age. Reports made to the federal Vaccine Adverse Events Reporting System (VAERS) note hospitalizations, injuries and deaths following hepatitis A vaccinations, including 172 related deaths, 3,680 hospitalizations, and 1,019 related disabilities. However, the numbers of vaccine-related injuries and deaths reported to VAERS may not reflect the true number of serious health problems that occur after hepatitis A vaccination.

Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to federal health agencies (VAERS), many doctors and other medical workers giving vaccines to children and adults fail to report vaccine-related health problem to VAERS. There is evidence that only between one and 10 percent of serious health problems that occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials, who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.       

On December 1, 2004, hepatitis A vaccine was added to the National Vaccine Injury Compensation Program's (VICP) Vaccine Injury Table, as published in the Federal Register. As of August 1, 2023, there had been 199 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following hepatitis A vaccination, including 7 deaths and 192 serious injuries. Of that number, the U.S. Court of Claims administering the VICP has compensated 95 children and adults, who have filed for hepatitis A vaccine injury.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Who is at highest risk for complications from Hepatitis A vaccine?

There is a gap in medical knowledge in terms of doctors being able to predict who will have an adverse reaction to hepatitis A vaccination, and who will not.

In the clinical trials of children receiving HAVRIX, higher rates of serious adverse reactions occurred in children who received HAVRIX in combination with MMR and varicella vaccine, in comparison to children who received HAVRIX alone or in children who received MMR and varicella vaccine followed by HAVRIX vaccine at Day 42 of the clinical trial. 

According to the CDC, most serious adverse reactions following hepatitis A vaccination occur in adults, with one-third of those reported reactions occurring when hepatitis A vaccine was administered in combination with other vaccines. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Who should not get Hepatitis A vaccine?

According to the CDC, certain persons should not get hepatitis A vaccine, or should postpone getting it. Those persons are: 

• Anyone who has ever had a severe (life-threatening) allergic reaction to a previous dose of hepatitis A vaccine or to any component of the hepatitis A vaccine. It is important to tell your doctor if you have any severe allergies.
• Anyone who is moderately or severely ill at the time the shot is scheduled should wait until they recover before receiving hepatitis A vaccine.

While the CDC recommends that infants 6 to 11 months of age traveling outside the United States receive a dose of hepatitis A vaccine,  both VAQTA and HAVRIX are not FDA approved for use in children under the age of 12 months. Further, product inserts for both VAQTA and HAVRIX state that the safety and effectiveness of their products have not been established in children younger than 12 months of age.   

VAQTA: Contraindications to receiving the VAQTA (hepatitis A inactivated) vaccine documented in Merck’s product insert include persons who have experienced a severe allergic reaction or anaphylaxis to any component of VAQTA, including neomycin, or to a previous dose of any hepatitis A vaccine. As well, both the syringe plunger and vial stopper of VAQTA contain latex that may cause an allergic reaction in persons who are sensitive to latex. 

Merck also cautions that immunocompromised individuals and persons receiving immunosuppressive therapy may have a decreased immune response to vaccination with VAQTA. 

VAQTA is approved for use in children and adults 12 months and older. Children under the age of 12 months should not receive VAQTA. 

There are no adequate and well-controlled studies designed to evaluate VAQTA in pregnant women. It is also unknown whether VAQTA is excreted in human milk. 

HAVRIX: Contraindications to receiving the HAVRIX (hepatitis A inactivated) vaccine documented in GlaxoSmithKline’s insert include persons who have experienced anaphylaxis or a severe allergic reaction to a previous dose of any hepatitis A vaccine or to any component of HAVRIX, including neomycin. The tip caps of the prefilled HAVRIX vaccine syringes contain latex and may cause an allergic reaction in individuals who are sensitive to latex. 

GlaxoSmithKline also cautions that fainting may occur following administration with HAVRIX and can include symptoms such as paresthesia, tonic-clonic limb movements, and visual disturbances. Immunocompromised individuals and persons receiving immunosuppressive therapy may have a decreased immune response to HAVRIX. 

HAVRIX is approved for use in children and adults 12 months and older and children under the age of 12 months should not receive HAVRIX.

There are no adequate and well-controlled studies of HAVRIX in pregnant women in the United States and no animal studies have ever been completed to guide the use of HAVRIX during pregnancy. There is no information regarding HAVRIX in human milk, the effects of HAVRIX on the breastfeeding child, or the impact that the vaccine may have on milk production.   

Clinical trials of HAVRIX vaccine did not include a sufficient number of persons above the age of 65 years and it is unknown whether this population responds to HAVRIX in a similar manner as the younger population. 

TWINRIX: Contraindications to receiving the TWINRIX (hepatitis A inactivated/hepatitis B Recombinant) vaccine documented in GlaxoSmithKline’s insert include persons who have experienced a severe allergic reaction to a previous dose of any hepatitis A or hepatitis B vaccine or to any component of TWINRIX, including yeast and neomycin. The tip caps of the prefilled TWINRIX vaccine syringes contain latex and may cause an allergic reaction in individuals who are sensitive to latex. 

GlaxoSmithKline also cautions that syncope can occur following administration of TWINRIX and can include symptoms such as tonic-clonic limb movements, visual disturbances and paresthesia. GlaxoSmithKline recommends postponing vaccination with TWINRIX in persons who are exhibiting signs of moderate or severe acute illness to avoid any confusion between a possible reaction to the vaccine and signs of an impending acute infection. 

Immunocompromised individuals and persons receiving immunosuppressive therapy may have a decreased immune response to TWINRIX. In clinical trials, TWINRIX was not studied for use with any other vaccine and no information on safety or effectiveness of giving TWINRIX simultaneously with any other vaccine is available. 

TWINRIX is approved for use in persons 18 years of age and older. Persons under the age of 18 should not receive TWINRIX. Clinical trials of TWINRIX did not include a sufficient number of persons over the age of 65 years of age and it is unknown whether this population responds to TWINRIX in a similar manner as the younger population. 

There are no well-controlled and adequate studies of TWINRIX in pregnant women in the United States. There is no information regarding TWINRIX in human milk, the effects of TWINRIX on the breastfeeding child, or the impact that the vaccine may have on milk production. 

NVIC Note: Some doctors only vaccinate children who are healthy and are not sick at the time of vaccination with a coinciding viral or bacterial infection. If you do not want your acutely ill child vaccinated and your doctor disagrees with you, you may want to consider consulting one or more other trusted health care professionals before vaccinating.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

What questions should I ask my doctor about the Hepatitis A vaccine?

NVIC’s If You Vaccinate, Ask 8! Webpage downloadable brochure suggests asking eight questions before you make a vaccination decision for yourself, or for your child. If you review these questions before your appointment, you will be better prepared to ask your doctor questions. Also make sure that the nurse or doctor gives you the relevant Vaccine Information Statement (VIS) for the vaccine or vaccines you are considering well ahead of time to allow you to review it before you or your child gets vaccinated. Copies of VIS for each vaccine are also available on the CDC's website and there is a link to the VIS for hepatitis A and hepatitis A & hepatitis B combination vaccine on NVIC's “Quick Facts”.

It is also a good idea to read the vaccine manufacturer product insert that can be obtained from your doctor or public health clinic because federal law requires drug companies marketing vaccines to include certain kinds of vaccine benefit, risk and use information in product information inserts that may not be available in other published information. Vaccine package inserts for hepatitis A and hepatitis A & hepatitis B combination vaccine are located on the NVIC’s “Quick Facts” page.

Other questions that may be useful to discuss with your doctor before getting the hepatitis A (or hepatitis A & hepatitis B combination) vaccine are: 

• If other vaccines in addition to hepatitis A vaccine are scheduled for my child at this office visit, am I allowed to modify the schedule so fewer vaccines are given at once?
• What should I do if my child has a high fever or appears very ill after vaccination?
• What other kinds of reaction symptoms should I call to report after hepatitis A vaccination?
• If the hepatitis A vaccine doesn’t protect my child, do I have any other options for preventing hepatitis A infection?

Under the National Childhood Vaccine Injury Act of 1986, doctors and all vaccine providers are legally required to give you vaccine benefit and risk information before vaccination; record serious health problems following vaccination in the permanent medical record; keep a permanent record of all vaccines given, including the manufacturer’s name and lot number; and report serious health problems, injuries and deaths that follow vaccination to VAERS.

Remember, if you choose to vaccinate, always keep a written record of exactly which shots/vaccines you or your child have received, including the manufacturer’s name and vaccine lot number. Write down and describe in detail any serious health problems that develop after vaccination, and keep vaccination records in a file you can access easily.

It also is important to be able to recognize a vaccine reaction and seek immediate medical attention if the reaction appears serious, as well as know how to make a vaccine reaction report to federal health officials at the Vaccine Adverse Reporting System (VAERS). NVIC’s Report Vaccine Reactions—It’s the Law webpage can help you file a vaccine reaction report yourself to VAERS if your doctor fails or refuses to make a report. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

NVIC Press Releases, Statements, and Commentaries Related to Hepatitis A

The Vaccine Reaction

• Parpia R, Fisher BL All Homeless People to Get Hepatitis A Vaccine The Vaccine Reaction Mar. 7, 2019.
• TVR Staff CDC Approves Adult and Childhood Vaccine Schedules for 2019 The Vaccine Reaction Feb. 27, 2019.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Additional Bibliography of References

Manufacturer Product Information Inserts:

• Merck: VAQTA – Hepatitis A Vaccine, inactivated
• GlaxoSmithKline: HAVRIX – Hepatitis A Vaccine, inactivated
• GlaxoSmithKline: Twinrix – Hepatitis A Vaccine, inactivated & Hepatitis B (Recombinant) Vaccine

World Health Organization

• Hepatitis A

Centers for Disease Control (CDC)

• Hepatitis A Outbreaks in the United States
• Hepatitis A

Medical Literature

• Gould L, Kline J, Monahan C, Vierk K. Outbreaks of Disease Associated with Food Imported into the United States, 1996–2014. Emerg Infect Dis. 2017;23(3):525-528.
• Ly KN, Klevens, RM. Trends in disease and complications of hepatitis A virus infection in the United States, 1999-2011: a new concern for adults. J Infect Dis.Jul 15, 2015;212(2):176-82.
• Jariwala S, Vernon N, Shliozberg J. Henoch-Schönlein purpura after hepatitis A vaccination. Ann Allergy Asthma Immunol Aug 2011;107(2):180-1.
• O'Leary ST, Glanz JM, McClure DL et al. The risk of immune thrombocytopenic purpura after vaccination in children and adolescents. Pediatrics 2012;129(2):248-55.
• Huber S, Kappos L, Fuhr P, et al. Combined acute disseminated encephalomyelitis and acute motor axonal neuropathy after vaccination for hepatitis A and infection with Campylobacter jejuni. J Neurol Dec 1999;246(12):1204-6.
• Huang EHZ , Lim SA, Lim PL et al. Retrobulbar optic neuritis after Hepatitis A vaccination in a HIV-infected patient Eye (Lond) 2009;23(12):2267-71.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

Hepatitis A & Hepatitis A Vaccine Quick Facts

Hepatitis A

• Hepatitis A is a viral disease of the liver that is contracted through contact with, or by swallowing human fecal waste, generally through eating or drinking contaminated food and/or water.  The virus is typically spread when people eat or drink something that has been contaminated with the virus; 
• Hepatitis A thrives in areas that lack proper sanitation, clean drinking water or where personal hygiene habits are poor.  The virus can remain in the environment for several months. Formalin, chlorine, and high temperatures can kill the virus.    Hepatitis A can be found in all areas of the world but is often endemic in Africa, Asia, the Western Pacific, the Middle East, and Central and South America; 
• Symptoms of hepatitis A generally appear between two and seven weeks following exposure to the virus and infected individuals can spread the virus to others for up to two weeks before showing symptoms.  Symptoms often occur suddenly and may include fatigue, abdominal and/or joint pain, loss of appetite, fever, nausea, jaundice, dark urine, clay-colored bowel movements, and diarrhea. Younger children often show no clinical symptoms of infection. Only lab testing can confirm a diagnosis of hepatitis A; 
• Complications and deaths from hepatitis A are rare  and most infected individuals recover fully within two months. In approximately 10 to 15 percent of individuals, symptoms may last up to six months. 

Hepatitis A Vaccine

• There are three hepatitis A containing vaccines available for use in the United States. VAQTA,  an inactivated hepatitis A virus vaccine, manufactured by Merck; HAVRIX,  an inactivated hepatitis A virus vaccine manufactured by GlaxoSmithKline; and TWINRIX,  a combination vaccine containing both inactivated hepatitis A virus vaccine (HAVRIX) and recombinant hepatitis B vaccine (ENGERIX-B), manufactured by GlaxoSmithKline. VAQTA, HAVRIX, and TWINRIX were developed using aborted fetal cells.     
• Common side effects from the hepatitis A vaccine include soreness around injection site, headache, low-grade fever, and fatigue.  Reported serious side effects following hepatitis A (VAQTA, HAVRIX, & TWINRIX) vaccination include anaphylaxis, thrombocytopenia, encephalopathy, multiple sclerosis, Guillain-Barre Syndrome, and more.     
• Adequate and well-controlled studies on the use of hepatitis A vaccine during pregnancy have not been conducted and it is not known whether the vaccine is present in breastmilk. Studies have not been conducted to determine whether hepatitis A vaccine can impair fertility, or whether the vaccine is carcinogenic or mutagenic.     
• Using the MedAlerts search engine, as June 30, 2023, there have been 49,616 reports of hepatitis A vaccine reactions, hospitalizations, injuries and deaths following hepatitis A vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS), with over 25 percent (12,705) of reactions occurring in children under 3 years of age. VAERS reports note 172 related deaths, 3,680 hospitalizations, and 1,019 related disabilities;
• On December 1, 2004, hepatitis A vaccine was added to the National Vaccine Injury Compensation Program's (VICP) Vaccine Injury Table, as published in the Federal Register. As of August 1, 2023, there had been 199 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following hepatitis A vaccination, including 7 deaths and 192 serious injuries.

Food & Drug Administration (FDA)

• Hepatitis A Vaccine, Inactivated, Product Inserts & Licensing Information
• Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine Product Inserts & Licensing Information

 

Centers for Disease Control (CDC)

• CDC on Hepatitis A
• CDC on Hepatitis A Vaccination
• Hepatitis A Vaccine Information Statement (VIS)

Vaccine Reaction Symptoms & Ingredients

Our Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and more. 

Search for Vaccine Reactions

NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts examines symptoms, reactions, vaccines, dates, places, and more.

Reporting a Vaccine Reaction

Since 1982 NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is the law. If your doctor will not report a reaction, you have the right to report a suspected vaccine reaction to VAERS is the law.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis A and the Hepatitis A vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

 

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