Hepatitis A Vaccine

Number: 0048

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses hepatitis A vaccine.

1. Medical Necessity

   1. Aetna considers hepatitis A (HepA) vaccine a medically necessary preventive service according to the recommendations of the Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) for the following at-risk groups:
      
      
      1. All children 12 to 23 months of age;
      2. Children and adolescents aged 2 to 18 years who have not previously received HepA vaccine;
      3. Immunocompromised persons who are at increased risk for severe disease from HepA virus infection:
         
         
         1. Hematopoietic cell transplant (HCT) recipients who received vaccines before their HCT may be vaccinated or revaccinated routinely after HCT, regardless of the source of the transplanted stem cells;
         2. Human immunodeficiency virus (HIV) infection in persons 1 year of age or older regardless of their level of immune suppression;
         3. Liver transplant candidates aged 12 months or older;
      4. Individuals aged 1 year and older who are homeless;
      5. Individuals who anticipate close personal contact (e.g., household contact, caretaker, or regular babysitting) with an international adoptee from a country with high or intermediate endemicity during the first 60 days after arrival of the adoptee in the United States;
      6. Individuals with chronic liver disease, including but not limited to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, or an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level persistently greater than twice the upper limit of normal;
      7. Individuals with occupational risk for exposure (i.e., primate-animal handlers, working with clinical or nonclinical material containing HAV in a research laboratory setting)Footnote1*;
      8. Injection or non-injection drugs (i.e., individual who use illicit drugs);
      9. International travelers (e.g., tourists, nonimmune immigrants, military personnel, missionaries) to areas where hepatitis A is endemicFootnote1*; 
      10. Men who have sex with men (MSM);
      11. Pregnant women who are identified to be at risk for hepatitis A virus (HAV) infection during pregnancy (e.g., international travelers, injection or illegal drug users, have occupational risk for infection, anticipate close personal contact with an international adoptee, or experiencing homelessness) or for having a severe outcome from HAV infection (e.g., persons with chronic liver disease or persons with HIV infection);
      12. Unvaccinated adults 19 years of age or older in settings considered to have risk factors for HAV infection (e.g., group homes and nonresidential day care facilities for persons with developmental disabilities, homeless shelters, syringe services programs).

      Footnote1* Note: Most Aetna HMO plans exclude coverage of immunizations required for travel or work. Please check benefit plan descriptions for details.

   2. Aetna considers hepatitis A vaccine medically necessary for prophylaxis when initiated within 2 weeks after hepatitis A exposure.

2. Policy Limitations and Exclusions

   Note: Disclosure of a risk factor for HAV infection or complication is not necessary for HepA vaccination. Because a person might not disclose a risk factor to the provider, ACIP recommends that any person who has not previously completed the HepA vaccine series may receive HepA vaccine (Nelson et al, 2020).

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
90632	Hepatitis A vaccine (Hep A), adult dosage, for intramuscular use
90633	Hepatitis A vaccine (Hep A), pediatric/adolescent dosage-2 dose schedule, for intramuscular use
90634	Hepatitis A vaccine (Hep A), pediatric/adolescent dosage-3 dose schedule, for intramuscular use
90636	Hepatitis A and hepatitis B vaccine (HepA-HepB), adult dosage, for intramuscular use
Other CPT codes related to the CPB:
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
38241	Hematopoietic progenitor cell (HPC); autologous transplantation
84450	Transferase; aspartate amino (AST) (SGOT)
84466	Transferase; alanine amino (ALT) (SGPT)
Other HCPCS codes related to the CPB:
S2150	Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency services, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition
ICD-10 codes covered if selection criteria are met:
B15.0-B15.9	Acute hepatitis A
B16.0-B16.9	Acute hepatitis B
B17.0	Acute delta-(super) infection of hepatitis B carrier
B17.10	Acute hepatitis C without hepatic coma
B17.11	Acute hepatitis C with hepatic coma
B18.0	Chronic viral hepatitis B with delta-agent
B18.1	Chronic viral hepatitis B without delta-agent
B18.2	Chronic viral hepatitis C
B19.10 - B19.11	Unspecified viral hepatitis B
B19.20	Unspecified viral hepatitis C without hepatic coma
B19.21	Unspecified viral hepatitis C with hepatic coma
B20	Human immunodeficiency virus [HIV] disease
B97.35	Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere
F11.10 - F19.99	Drug dependence and nondependent abuse of drugs
K70.0 - K70.9	Alcoholic liver disease
K73.0 - K74.69	Fibrosis and cirrhosis of liver
K75.4	Autoimmune hepatitis
K75.81	Nonalcoholic steatohepatitis (NASH)
K76.0	Fatty (change of) liver, not elsewhere classified
K76.89 - K76.9	Other specified and unspecified diseases of liver
O98.411 - O98.419	Viral hepatitis complicating pregnancy
O98.711 - O98.719	Human immunodeficiency virus [HIV] disease complicating pregnancy
Z20.828	Contact with and (suspected) exposure to other viral communicable diseases
Z21	Asymptomatic human immunodeficiency virus [HIV] infection status
Z23	Encounter for immunization
Z57.0 - Z57.9	Occupational exposure to risk factors
Z59.00 - Z59.02	Homelessness
Z76.82	Awaiting organ transplant status Liver [covered for age 12 months or older]
Z94.0 - Z94.9	Transplanted organ and tissue status

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Background

Hepatitis A virus (HAV) is a non-enveloped RNA virus transmitted primarily via the fecal–oral route through contaminated food, water, or close contact. Infection is usually self-limited, with symptoms such as jaundice, fatigue, and gastrointestinal upset, though severe cases are rare. In the U.S., widespread vaccination since the mid-1990s has reduced HAV incidence by over 90%, though outbreaks have occurred among people who use drugs, those experiencing homelessness, and travelers. The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for all children at 12–23 months, catch-up for unvaccinated youth, and adults at risk (e.g., travelers, MSM, chronic liver disease). Inactivated vaccines (Havrix, Vaqta, Twinrix) are highly effective, providing long-term immunity after a two-dose series, and are safe with minimal adverse effects.

The hepatitis A vaccine is approved for individuals aged 12 months and older and is administered in a 2-dose schedule, with doses given at least 6 months apart. The currently licensed vaccines, Havrix and Vaqta, are delivered intramuscularly. Additionally, a combination hepatitis A and hepatitis B vaccine, Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium), is approved for those aged 18 years and older, offered in either a 3-dose schedule (0, 1, and 6 months) or an accelerated 4-dose schedule (0, 7, and 21 to 30 days, with a fourth dose at 1 year). The first three doses of the 4-dose schedule provide protection comparable to the first two doses of the original schedule, making it useful for individuals expecting travel or potential exposure before the second dose. The annual immunization schedule recommended by the American Academy of Pediatrics (AAP), the Advisory Committee on Immunization Practices (ACIP) of the CDC, and the American Academy of Family Physicians advises universal vaccination for all children at 1 year of age (12 to 23 months), with the two doses separated by at least 6 months. Children who miss vaccination by age 2 can receive it at later pediatric visits.

While either vaccine can be used for both doses, it is preferable to use the same vaccine. The recommended interval between doses is 6 to 18 months for Vaqta and 6 to 12 months for Havrix. All three vaccines—Havrix, Twinrix, and Vaqta—are preservative-free and administered intramuscularly. Vaqta is available in two formulations: individuals aged 12 months to 18 years receive 25 units of HAV antigen per dose in a 2-dose schedule, while those aged 19 years and older receive 50 units per dose. Similarly, Havrix is also available in two formulations, with individuals aged 12 months to 18 years receiving 720 ELISA units per dose and those aged 19 years and older receiving 1,440 ELISA units per dose. Twinrix, licensed for adults aged 18 years and older, contains 720 ELISA units of HAV antigen (half the adult dose of Havrix) and 20 μg of recombinant HBV surface antigen protein (equivalent to the adult dose of Engerix-B). The primary vaccination schedule for Twinrix consists of three doses administered at 0, 1, and 6 months, which is the same as the schedule for the single-antigen hepatitis B vaccine. After completing the three doses of Twinrix, antibody responses to both HAV and HBV surface antigens are comparable to those achieved with the separate single-antigen vaccines. Twinrix can also be administered on an accelerated schedule of three doses at 0, 7, and 21–30 days, followed by a booster dose at 12 months for long-term protection.

The American Academy of Pediatrics (AAP) advises that regions with immunization programs for children aged 2 to 18 years should maintain and expand these programs to include children aged 12 to 23 months. In areas lacking hepatitis A immunization programs, catch-up vaccinations for unvaccinated children aged 2 to 18 years should be considered. Additionally, previously unvaccinated children who will be living in or traveling to regions with intermediate or high endemicity of hepatitis A should receive the vaccine prior to departure. The AAP also recommends vaccinating children with immunocompromising conditions, as the hepatitis A vaccines do not contain live organisms. However, hypersensitivity to components such as aluminum hydroxide and phenoxyethanol is a contraindication for the use of these vaccines. Hepatitis A vaccination can be co-administered with other vaccines in the childhood immunization schedule.

The ACIP of the CDC recommends post-exposure prophylaxis with hepatitis A vaccine for healthy individuals between the ages of 1 and 40 years (CDC, 2007). Persons who have recently been exposed to hepatitis A virus and who have not been vaccinated previously should be administered a single dose of single-antigen hepatitis A vaccine or immune globulin (0.02 ml/kg) as soon as possible, within 2 weeks after exposure. All others should receive immune globulin, if possible.

The guidelines vary by age and health status (CDC, 2007). For healthy persons aged 12 months to 40 years, single-antigen hepatitis A vaccine at the age-appropriate dose is preferred to immune globulin because of vaccine’s advantages, including long-term protection and ease of administration, as well as the equivalent efficacy of vaccine to immune globulin. For persons aged more than 40 years, immune globulin is preferred because of the absence of information regarding vaccine performance in this age group and because of the more severe manifestations of hepatitis A in older adults. Vaccine can be used if immune globulin can not be obtained. The magnitude of the risk of hepatitis A virus transmission from the exposure should be considered in decisions to use vaccine or immune globulin in this age group. For children aged less than 12 months, immunocompromised persons, persons with chronic liver disease, and persons who are allergic to the vaccine or a vaccine component, immune globulin should be used.

The ACIP recommendation is based upon evidence that hepatitis A vaccine is as effective as immune globulin in preventing transmission. Researchers randomized 1,090 susceptible household or day-care contacts of patients in Kazakhstan to prophylaxis with either hepatitis A vaccine or immune globulin within 2 weeks of exposure (Victor et al, 2007). The investigators found that the effect of the vaccine would be similar to immune globulin. Between 2 and 8 weeks after exposure, vaccine recipients showed a 1.35 relative risk (95 % confidence interval: 0.70 to 2.67) for developing symptomatic infection as compared with those receiving immune globulin.

The ACIP annually reviews the recommended adult immunization schedule to ensure that the schedule reflects current recommendations for the licensed vaccines. 

Rowe et al. (2012) reported that super-infection with hepatitis A virus (HAV) in individuals with hepatitis C virus (HCV) infection is associated with a high mortality rate, leading to a recommendation for vaccination. Although the incidence of HAV is low, the study aimed to assess the mortality risk associated with HAV super-infection and the implications of routine vaccination for those with HCV. A meta-analysis was conducted, including studies that reported mortality in HCV-infected individuals. Data were independently extracted by two investigators and recorded on a standardized spreadsheet. The pooled mortality estimate was used to calculate the number needed to vaccinate (NNV) to prevent one death from HAV super-infection, along with the total vaccine cost. Out of 239 studies identified through a defined search strategy, 11 were deemed relevant, and 10 were suitable for inclusion in the meta-analysis. The pooled odds ratio (OR) for mortality risk from HAV super-infection in HCV-infected individuals was found to be 7.23 (95% confidence interval: 1.24 to 42.12), with significant heterogeneity (I² = 56%; p = 0.03) among the studies. This translates to an estimated 1.4 deaths per 1,000,000 susceptible HCV-infected individuals annually. Consequently, the NNV to prevent one death per year is 814,849, assuming a 90% vaccine uptake and 94.3% vaccine efficacy, resulting in a total vaccine cost of $162 million, or $80.1 million per death prevented annually. The authors concluded that these findings challenge the routine use of HAV vaccination in HCV-infected individuals and its integration into clinical practice guidelines, as it may expose many to an intervention that offers no direct benefit.

Gutierrez Domingo et al. (2012) emphasized that in the absence of immunity, vaccination against HAV and hepatitis B virus (HBV) is recommended for patients with chronic liver disease and those being evaluated for liver transplantation (OLT). HAV and HBV infections post-OLT, which are common in this population, are linked to poorer prognoses. The researchers estimated the need for vaccination against HBV and HAV among cirrhotic patients who were candidates for OLT, considering factors such as gender, age, and etiology. They investigated HBV and HAV serological markers (HBsAg, anti-HBc, anti-HBs, and immunoglobulin G [IgG]-anti-HAV) among 568 patients, of whom 75% were men. The mean age was 53.6 ± 8.9 years (ranging from 17 to 69), and 20% were diabetic. The etiologies included alcohol (68%), hepatitis C virus (35%), and other causes (10.4%). Child-Pugh classifications were A (26%), B (44%), and C (30%). Among the patients, 359 (63.2%) had negative HBV markers, while 209 (36.8%) were positive: HBsAg (+) in 43 (7.6%), isolated anti-HBc (+) in 57 (10%), isolated anti-HBs (+) in 19 (3.3%), and anti-HBc (+)/anti-HBs (+) in 90 (15.8%). HBV vaccination was indicated for 416 patients (73.2%) who had negative HBV markers or isolated anti-HBc (+), with a higher frequency in women (82.3% vs. 70.3%, p = 0.005), but no differences based on age or etiology. Only 8.2% (44/538) were IgG-anti-HAV-negative, indicating a need for HAV vaccination, which was more common among younger patients (≤ 45 years: 27.6%; 46 to 55: 7.2%; > 55: 2.6%; p < 0.0001), non-diabetics (9.5% vs. 2.8%, p = 0.023), non-alcoholics (11.4% vs. 6.6%, p = 0.056), and those with negative HBV markers (10.2% vs. 4.6%, p = 0.023). Only three patients with IgG-anti-HAV (-) were over 60 years old. The authors concluded that there is a frequent indication for HBV vaccination among cirrhotic patients, particularly for HAV vaccination in those under 45 years undergoing evaluation for OLT.

Andersson et al. (2013) highlighted that liver transplant recipients face an increased risk of liver failure when infected with HAV and HBV, making vaccination essential. This study evaluated the protection against HAV and HBV infection in liver transplant patients at their unit, as well as the vaccination rates and antibody responses to vaccination. The study included patients who underwent liver transplantation from January 2007 to August 2010 and had a post-transplant check-up between March and November 2010 (n = 51). Data on diagnosis, transplantation date, Child-Pugh score, and vaccination status were collected from patient records. Serum samples were analyzed for anti-HAV IgG and anti-HBs titers, with protective levels recorded. The results showed that 45% of patients were protected against hepatitis A infection and 29% against hepatitis B infection post-transplant. Only 26% had completed the vaccination schedule, with these patients showing a vaccine response of 50% for HAV and 31% for HBV. An additional 31% received at least one dose of the vaccine but did not complete the schedule, resulting in a significantly lower vaccine response, underscoring the importance of completing the vaccination regimen. The authors concluded that even fully vaccinated patients did not respond as robustly as healthy individuals, suggesting that vaccination should occur as early as possible in the course of liver disease, particularly for those with lower Child-Pugh scores.

Young (2018) reported that earlier in 2018, the CDC identified hepatitis A outbreaks among high-risk populations, including the homeless, in states such as California, Indiana, Kentucky, Michigan, Missouri, Utah, and West Virginia. According to an unpublished study cited by CNN, homeless individuals are 2 to 3 times more likely to contract hepatitis A and 2 to 4 times more likely to experience severe outcomes if infected. On February 14, 2019, the CDC recommended hepatitis A vaccination for individuals aged 1 year and older who are homeless. The routine vaccination schedule consists of either a 2-dose or a 3-dose series when combined with the hepatitis A and B vaccine. The CDC noted that "persons experiencing homelessness might have difficulty implementing recommended non-vaccine strategies to protect themselves from exposure (e.g., access to clean toilet facilities, regular hand-washing, and avoidance of crowded living conditions)." Therefore, vaccination is considered the most reliable means of protection against HAV infection for this population. Vaccination of homeless individuals not only provides individual protection but also contributes to herd immunity over time, reducing the risk of large-scale person-to-person outbreaks. The recommendation facilitates routine HepA vaccination for homeless individuals through healthcare facilities that already serve this population.

Nelson et al. (2018) provided an update to the ACIP recommendations for the use of the Hepatitis A vaccine for post-exposure prophylaxis (PEP) and pre-exposure prophylaxis for international travel. The authors indicated that the HepA vaccine is recommended for individuals aged 12 months and older for PEP. Additionally, immune globulin (IG) may be administered to adults over 40 years of age if indicated. The simultaneous administration of the MMR and HepA vaccines is recommended for infants aged 6–11 months traveling internationally. For individuals who are immunocompromised or have chronic liver disease and have been exposed to HAV within the past 14 days without having completed the 2-dose HepA vaccination series, both IG (0.1 mL/kg) and the HepA vaccine should be given simultaneously at different anatomical sites (e.g., separate limbs) as soon as possible after exposure. To ensure long-term immunity, the HepA vaccination series should be completed with a second dose at least 6 months after the first dose; however, this second dose is not required for PEP. It is important to note that the second dose should not be administered sooner than 6 months after the first dose, regardless of the risk of HAV exposure.

Freedman and colleagues (2020) noted that in June 2019, the ACIP recommended routine hepatitis A vaccination for all individuals with HIV aged 1 year and older. The list of other populations at risk for hepatitis A infection or severe disease has not changed significantly and includes individuals with chronic liver disease, travelers to countries with high or intermediate endemic hepatitis A, those with close personal contact with international adoptees within the first 60 days of their arrival from such countries, men who have sex with men, individuals who use injection or non-injection drugs, persons experiencing homelessness, and laboratory workers handling the hepatitis A virus or nonhuman primates infected with it. Notably, individuals with clotting factor disorders have been removed from this list. The definition of chronic liver disease has been broadened to encompass individuals with hepatitis B, hepatitis C, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and those with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than twice the upper limit of normal. A 2-dose series of the HepA vaccine (or a 3-dose series of the HepA-HepB vaccine) is recommended for pregnant women at risk of infection or severe outcomes during pregnancy. Additionally, hepatitis A vaccination is advised for individuals working in exposure settings, such as healthcare environments for injection or non-injection drug users, group homes, and nonresidential daycare facilities for developmentally disabled persons. Finally, anyone not at risk for hepatitis A virus infection who desires protection against it may also receive the vaccine.

The July 2020 recommendations from the Advisory Committee on Immunization Practices (ACIP) advocate for routine vaccination against Hepatitis A for all children and adolescents aged 2 to 18 years who have not previously received the vaccine. Additionally, vaccination is recommended for individuals aged 1 year or older who are infected with HIV, those with chronic liver disease, and pregnant women at risk for HAV infection. During outbreaks, it is important to extend vaccination to at-risk populations, including individuals who use drugs or are experiencing homelessness. Furthermore, vaccination is advised in settings where adults are likely to have risk factors for HAV infection, such as group homes and health care facilities.

For travelers, the HepA vaccine should be administered to infants aged 6–11 months when traveling to areas with high or intermediate HAV endemicity, although this dose does not count toward the routine vaccination series. Healthy individuals aged 12 months to 40 years planning travel should receive a single dose of the vaccine as soon as travel is considered. Those over 40, immunocompromised individuals, and those with chronic liver disease should also receive the vaccine promptly before travel. Overall, the ACIP emphasizes the importance of vaccination for anyone who has not completed the HepA vaccine series, regardless of whether they disclose risk factors for HAV infection.

Certain adult populations are at increased risk for Hepatitis A virus (HAV) infection or severe disease resulting from HAV. These groups include international travelers, particularly unvaccinated individuals from developed countries visiting areas with high or intermediate HAV endemicity. This risk extends to tourists, nonimmune immigrants, military personnel, and others who may work or study abroad. Travelers, especially those in rural areas or those consuming food and water in settings with poor sanitation, are particularly vulnerable. Even those with low-risk travel itineraries can contract HAV and potentially transmit it upon returning home.

Other at-risk groups include men who have sex with men, individuals who use injection or non-injection drugs, and those with occupational exposure to HAV, such as workers handling nonhuman primates or clinical materials containing the virus. Additionally, individuals anticipating close personal contact with international adoptees, persons experiencing homelessness, and those with chronic liver disease or HIV infection are also recommended for vaccination. The risk of severe outcomes from HAV infection increases with age, making older adults, particularly those over 40, a priority for vaccination.

Conversely, certain groups are considered to have a low risk for Hepatitis A. For instance, individuals with blood clotting disorders, such as hemophilia, are generally not at increased risk due to the sterilization processes used for clotting factor concentrates. Food service workers and child care centers have also seen a decline in hepatitis A outbreaks, largely due to the implementation of universal childhood vaccination. Health care personnel and workers exposed to sewage are not considered at elevated risk for HAV infection, and public water systems have effective treatment processes that prevent HAV transmission.

The humoral response to the Hepatitis A vaccine (HAV) may be diminished in immunocompromised individuals, including children and adults such as hematopoietic cell transplant (HCT) recipients, chemotherapy patients, and those with HIV infection. Limited evidence indicates that adjusting dosing regimens—such as doubling the standard antigen dose or providing additional doses—could enhance response rates. According to ACIP best practice guidelines, HCT recipients who were vaccinated prior to their transplant should receive routine vaccinations or revaccinations after the procedure, regardless of the stem cell source, with specific recommendations for HepA revaccination. Additionally, the Infectious Disease Society of America advises that solid organ transplant candidates who are unvaccinated, undervaccinated, or seronegative for hepatitis A, particularly liver transplant candidates aged 12–23 months and those aged 2 years and older, should receive a complete HepA vaccine series based on strong recommendations supported by moderate-quality evidence (Nelson, 2020).

Settings in which a high proportion of persons have risk factors for HAV infection include health care settings that focus on persons who use injection or non-injection drugs, as well as group homes and non-residential day care facilities for persons with developmental disabilities. Health care providers may assume that unvaccinated adults aged 19 years or older in these settings are at risk for HAV infection and offer HepA vaccination to those who have not previously completed vaccination. HepA vaccination may be offered in outreach and other settings in which services are provided to persons at risk for HAV infection (e.g., homeless shelters and syringe services programs). HepA vaccination should be considered for persons (e.g., residents and staff) in facilities where hygiene is difficult to maintain (e.g., group homes for persons with development disabilities, and homeless shelters) (Nelson et al, 2020).

Havrix

Havrix (GlaxoSmithKline) is a vaccine designed for the active immunization against diseases caused by the hepatitis A virus (HAV). It is approved by the Food and Drug Administration (FDA) for individuals aged 12 months and older. For effective protection, primary immunization should be administered at least two weeks prior to any expected exposure to HAV, and the vaccine is given via intramuscular injection. For children and adolescents, a single 0.5-mL dose is administered, followed by a booster dose of 0.5 mL given between 6 to 12 months later. Adults receive a single 1-mL dose, with a subsequent 1-mL booster dose also administered within the same 6 to 12-month timeframe.

There are specific contraindications associated with Havrix. Individuals who have experienced a severe allergic reaction, such as anaphylaxis, after a previous dose of any hepatitis A-containing vaccine or to any component of Havrix, including neomycin, should not receive this vaccine.

Warnings and precautions are also important to consider when administering Havrix. Syncope, or fainting, can occur following the injection of vaccines, including Havrix. It is essential to have procedures in place to prevent injuries from falls and to ensure proper restoration of cerebral perfusion in the event of syncope. Adverse reactions reported in studies of adults and children aged 2 years and older include injection-site soreness, which affected 56% of adults and 21% of children, as well as headaches reported by 14% of adults and less than 9% of children. In studies involving children aged 11 to 25 months, the most common local reactions were pain (32%) and redness (29%), while general adverse reactions included irritability (42%), drowsiness (28%), and loss of appetite (28%).

Twinrix

Twinrix (GlaxoSmithKline) is a vaccine designed for the active immunization against diseases caused by the hepatitis A virus and infections from all known subtypes of the hepatitis B virus. It is approved for individuals aged 18 years and older and is administered via intramuscular injection. The standard dosing schedule consists of three doses, each 1 mL, given at 0, 1, and 6 months. Alternatively, an accelerated dosing schedule is available, which includes four doses of 1 mL each, administered on Days 0, 7, and 21 to 30, followed by a booster dose at Month 12.

There are specific contraindications for Twinrix. Individuals who have experienced a severe allergic reaction, such as anaphylaxis, after receiving any hepatitis A- or hepatitis B-containing vaccine, or who are allergic to any component of Twinrix, including yeast and neomycin, should not receive this vaccine.

Warnings and precautions are important when administering Twinrix, as syncope, or fainting, can occur following the injection of vaccines, including Twinrix. It is crucial to have procedures in place to prevent injuries from falls and to ensure proper restoration of cerebral perfusion in the event of syncope. Common adverse reactions reported after any dose of Twinrix include injection site soreness (35% to 41%) and redness (8% to 11%), with systemic reactions such as headache (13% to 22%) and fatigue (11% to 14%) also frequently observed.

Vaqta

Vaqta (Merck Sharp & Dohme LLC) is an inactivated hepatitis A vaccine designed to prevent diseases caused by the hepatitis A virus (HAV) in individuals aged 12 months and older. To ensure effective protection, the primary dose should be administered at least two weeks prior to any anticipated exposure to HAV. The vaccine is intended for intramuscular administration only.

For children and adolescents, the vaccination regimen includes a 0.5-mL primary dose given intramuscularly, followed by a 0.5-mL booster dose administered 6 to 18 months later. In adults, the vaccination consists of a 1-mL primary dose, also given intramuscularly, with a subsequent 1-mL booster dose administered within the same 6 to 18-month timeframe.

There are specific contraindications for Vaqta; it should not be given to individuals with a history of immediate or severe allergic reactions, such as anaphylaxis, following a previous dose of any hepatitis A vaccine or to those who have experienced an anaphylactic reaction to neomycin. Additionally, the vial stopper contains dry natural latex rubber, which may trigger allergic reactions in individuals sensitive to latex. Common adverse reactions reported in clinical trials across various age groups include injection-site pain or tenderness (37.0% in children aged 12 to 23 months), injection-site erythema (21.2%), and fever (16.4% when administered alone, and 27.0% when given with other vaccines). In older children and adolescents (ages 2 to 18), injection-site pain was reported in 18.7% of cases, while in adults (19 years and older), injection-site pain, tenderness, or soreness occurred in 67.0% of recipients, along with injection-site warmth (18.2%) and headache (16.1%).

One or Two Doses of Hepatitis A Vaccine

Andani et al. (2022) stated that HAV is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved 2-dose schedules. Other countries have implemented 1-dose UV programs since 2005; the long-term impact of this schedule is unclear. In a systematic review, these investigators examined available evidence in 4 electronic databases for data published between January 2000 and July 2019 to evaluate scientific literature on 1-dose and 2-dose UV of children with non-live HAV vaccines and described their global impact on incidence, mortality, severity of hepatitis A, vaccine effectiveness, and antibody persistence. A total of 3,739 records were screened, and 33 peer-reviewed articles and 1 conference abstract were included. Rapid declines in the incidence of hepatitis A and related outcomes were observed in all age groups following the introduction of UV programs, which persisted for at least 14 years for 2-dose and 6 years for 1-dose programs, according to respective study durations. Vaccine effectiveness was 95% or more over 3 to 5 years for 2-dose programs. Vaccine effectiveness was 98% or more over 0.1 to 7.5 years for 1-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (90% or more) and 10 years (74% or more) for 2-dose and 1-dose schedules, respectively. The authors concluded that experience with 2-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for 1-dose UV, these investigators were unable to draw conclusions on immune response persistence beyond 10 years or the need for booster doses later in life. These researchers stated that ongoing epidemiological monitoring is essential in countries implementing 1-dose UV against HAV. Based on current evidence, 2 doses of non-live HAV vaccines are needed to ensure long-term protection.

Hepatitis A Vaccine Immunogenicity and Boostability in Adults Receiving Immunosuppressive Therapy and Adults living with HIV

Schnyder et al. (2025) found that while hepatitis A virus (HAV) is highly immunogenic in healthy individuals, there is uncertainty regarding its immunogenicity in immune-compromised populations (ICPs). In a prospective study, individuals living with HIV (PLWH), patients undergoing immunosuppressive mono- and combination therapy, and healthy controls received either two doses of HAV at months 0 and 6 to 12 or three doses of a combined hepatitis A and B vaccine at months 0, 1, and 6 to 12. Antibody levels were measured before vaccination and at various time points post-vaccination (T2, 6, 8, and 12 months), with the primary endpoint being the sero-conversion rate (SCR) at T8, defined as HAV antibodies of 20 mIU/ml or higher. To assess boostability, an additional vaccine dose was given 1 to 5 years after T12 to those with antibody levels below 50 mIU/ml, with measurements taken before and 7 days after the booster. The trial included 150 subjects, and at T2, SCRs ranged from 35% to 58% in ICPs compared to 94% in controls. Among PLWH, the SCRs at T8 were 33/34 (97%) for patients on monotherapy, 32/34 (94%) for those on combination therapy, 25/30 (83%) for controls, and 28/28 (100%) for healthy individuals. The booster dose led to an additional 71% sero-conversion (17/24), with only patients on combination therapy showing no response. The authors concluded that HAV was highly immunogenic in virologically suppressed PLWH and patients on immunosuppressive monotherapy, with SCRs after the complete HAV schedule comparable to controls and adequate booster responses in cases of waning immunity. However, patients on immunosuppressive combination therapy and all ICPs who did not complete the HAV schedule were at risk of non-response to vaccination, highlighting the need for post-vaccination antibody measurements.

Hepatitis A Vaccine Immunogenicity Among Seronegative Liver Transplanted Children

Sintusek et al. (2024) reported that while the hepatitis A virus (HAV) vaccine is generally highly immunogenic, there is limited data on its effectiveness in liver-transplanted (LT) children. The researchers investigated sero-immunity to HAV in all LT children and assessed the immunogenicity of an inactivated HAV vaccine in seronegative LT children at King Chulalongkorn Memorial Hospital. Seronegative LT children received the inactivated HAV vaccine at 0 and 6 to 8 months, with adverse events (AEs) monitored for three days post-immunization. Among 105 LT children, vaccination records were available for 81%, revealing that 7.1% and 16.5% had received one and two doses of the HAV vaccine prior to transplantation, respectively. Post-transplantation, 20.1% were seropositive for HAV, with 9.5% attributed to pre-transplant immunization. A total of 83 seronegative LT children (mean age 7.25 ± 4.40 years; 48.6% male) received two vaccine doses, resulting in an increase in seropositivity rates after the first and second doses, reaching 51.5% and 92.9%, respectively (p < 0.001), with no serious AEs reported. The study identified age at vaccination and the interval from transplantation to vaccination as risk factors for non-responsiveness (p < 0.001). The authors concluded that the findings underscored inadequate HAV vaccination coverage, leaving many LT children vulnerable to infection. They emphasized that the HAV vaccine is both highly immunogenic and safe, highlighting the need for improved vaccination strategies before and after liver transplantation.

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