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Clinical Policy Bulletin:
Hepatitis A Vaccine
Number: 0048


Policy

Aetna considers hepatitis A 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:

  • Children 12 to 23 months of age.  Children who are not vaccinated by age of 2 years can be vaccinated at subsequent visits
  • Ethnic and geographic populations with high endemic rates or periodic outbreaks of hepatitis A infection, such as Native Americans and Alaskan Natives
  • Hemophiliacs
  • Homosexual and bisexual men
  • Individuals who anticipate close personal contact (e.g., household contact or regular babysitting) with an international adoptee from a country of high or intermediate endemicity during the first 60 days after arrival of the adoptee in the United States
  • Individuals with chronic liver disease
  • Individuals with occupational risk of exposure, such as child-care and institutional workers, as well as primate-animal handlers*
  • Injection and illicit drug users
  • Laboratory workers who handle live hepatitis A virus*
  • Liver transplant recipients
  • Migrant Hispanics
  • Military personnel*
  • Travelers to areas where hepatitis A is endemic*

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

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



Background

Hepatitis A vaccine is approved for people 12 months of age and older and is given in a 2-dose schedule at least 6 months apart (AAP, 2003).  Currently licensed vaccines (Havrix and Vaqta) are given intra-muscularly.

A combination hepatitis A/hepatitis B vaccine (Twinrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) is approved for people 18 years of age and older and is given in a 3-dose schedule (0, 1, and 6 months) or an accelerated 4-dose schedule (0, 7, and 21 to 30 days, and a 4th dose at 1 year).  The first 3 doses of the 4-dose schedule are intended to provide protection equivalent to the first 2 doses of the original schedule.  The new schedule is useful if travel or potential exposure is expected before the 2nd dose (at 1 month) on the original schedule.

The annual recommended childhood and adolescent immunization schedule for approved by the American Academy of Pediatrics (AAP), the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), and the American Academy of Family Physicians (Fiore et al, 2006) recommends universal administration to all children at 1 year (12 to 23 months) of age.  Furthermore, the 2 doses in the series should be separated by at least 6 months.  Children who are not vaccinated by age 2 years can be vaccinated at subsequent visits to their pediatricians.

Either vaccine can be used for either dose, but use of the same vaccine for both doses is preferable.  The recommended dose interval is 6 to 18 months for Vaqta and 6 to 12 months for Havrix.

The AAP recommends that regions with immunization programs for 2- to 18-year old children should continue them and expand them to include 12- to 23-month olds.  In areas without existing hepatitis A immunization programs, catch-up immunization of unvaccinated 2- to 18-year old children should be considered.  In addition, previously unvaccinated children who will be living in, or traveling to, areas with intermediate or high hepatitis A endemicity should be immunized before departure.

Immunization is especially recommended for adolescent and adult males who have sex with males, users of injectable or non-injectable illicit drugs, recipients of clotting factors, and individuals who work with hepatitis A virus in the laboratory setting.

The AAP recommends vaccinating children with immunocompromising conditions, as the vaccines do not contain living organisms.  Hypersensitivity to vaccine components such as aluminum hydroxide and phenoxyethanol are contraindications to use of hepatitis A vaccines.  Hepatitis A vaccine may be co-administered with other vaccines in the childhood immunization series.

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 recommends hepatitis A vaccination for unvaccinated individuals who anticipate close personal contact (e.g., household contact or regular babysitting) with an international adoptee from a country of high or intermediate endemicity during the first 60 days after arrival of the adoptee in the United States.  The first dose of the 2-dose hepatitis A vaccine series should be administered as soon as adoption is planned, preferably 2 weeks or more before the arrival of the adoptee.

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) stated that hepatitis A virus (HAV) super-infection in persons with hepatitis C virus (HCV) infection has been associated with a high mortality rate, and vaccination is recommended.  The incidence of HAV is low, and the aim of this study was to determine the mortality risk of HAV super-infection and the consequences of routine vaccination in persons with HCV infection.  To determine the mortality risk of HAV super-infection, a meta-analysis including studies reporting mortality in HCV-infected persons was performed.  Data were extracted independently by 2 investigators and recorded on a standardized spread-sheet.  The pooled mortality estimate was used to determine the number needed to vaccinate (NNV) to prevent mortality from HAV super-infection.  The total vaccine cost was also calculated.  A total of 239 studies were identified using a defined search strategy.  Of these, 11 appeared to be relevant, and of these, 10 were suitable for inclusion in the meta-analysis.  The pooled odds ratio (OR) for mortality risk in HAV super-infection of HCV-infected persons was 7.23 (95 % confidence interval: 1.24 to 42.12) with significant heterogeneity (I(2) = 56 %; p = 0.03) between studies.  Using the pooled OR for mortality, this translates to 1.4 deaths per 1,000,000 susceptible persons with HCV per year.  The NNV to prevent 1 death per year is therefore 814,849, assuming 90 % vaccine uptake and 94.3 % vaccine efficiency.  The vaccine cost for this totals $162 million, or $80.1 million per death prevented per year.  The authors concluded that these data challenge the use of routine HAV vaccination in HCV-infected persons and its incorporation into clinical practice guidelines.  HAV vaccination of all HCV-infected persons is costly and likely to expose many individuals to an intervention that is of no direct benefit.

Gutierrez Domingo et al (2012) noted that in the absence of immunity, vaccination against HAV and hepatitis B virus (HBV) is recommended for patients with chronic liver disease and those evaluated for liver transplantation (OLT).  HAV and HBV infections after OLT, which are frequent in this setting, are associated with a worse prognosis.  These researchers estimated the need for vaccination against HBV and HAV among cirrhotic patients who were candidates for OLT and associations with gender, age, and etiologic factors.  HBV and HAV serological markers HBsAg, anti-HBc, antiHBs, immunoglobulin G (IgG)-anti-HAV were investigated among 568 patients, including 75 % men.  The overall mean age was 53.6 ± 8.9 years (range of 17 to 69) and 20 % were diabetic.  The etiologies were alcohol (68 %), hepatitis C virus (35 %) or other causes (10.4 %).  Child-Pugh classes were: A (26 %), B (44 %), and C (30 %).  In contrast with 359 patients (63.2 %) who had negative HBV markers, 209 (36.8 %) were positive: HBsAg (+), 43 (7.6 %), isolated anti-HBc (+), 57 (10 %), isolated anti-HBs (+), 19 (3.3 %), anti-HBc (+)/anti-HBs (+), 90 (15.8 %).  HBV vaccine indication was performed in 416 patients (73.2 %) who either had negative HBV markers or isolated anti-HBc (+).  It was more frequently performed in women (82.3 % versus 70.3 %, p = 0.005), albeit with no differences according to age or etiology.  There were only 8.2 % (44/538) IgG-anti-HAV-negative, an indication for vaccination against HAV, which was more frequent affecting patients who were younger [less than or equal to 45 years (27.6 %), 46 to 55 (7.2 %), greater than 55 (2.6 %); p < 0.0001)]; non-diabetic (9.5 % versus 2.8 %, p = 0.023); non-alcoholic (11.4 % versus 6.6 %, p = 0.056); and displayed negative HBV markers (10.2 % versus 4.6 %, p = 0.023).  Only t3 patients with IgG-anti- HAV (-) were over 60 years.  The authors concluded that there is a frequent indication for HBV vaccination among cirrhotic and especially HAV vaccine for under 45-year old patients undergoing evaluation for OLT.

Andersson et al (2013) stated that liver transplant recipients are at an increased risk for liver failure when infected with HAV and HBV.  Therefore, it is important to vaccinate these individuals.  These investigators evaluated how well liver transplanted patients in their unit were protected against HAV and HBV infection.  Furthermore, they investigated the vaccination rate and the antibody response to vaccination in these liver transplanted patients.  Patients liver transplanted from January 2007 until August 2010 with a post-transplant check-up during the period March to November 2010 were included (n = 51).  Information considering diagnosis, date of transplantation, Child-Pugh score, and vaccination were collected from the patient records.  Anti-HAV IgG and anti-HBs titers in serum samples were analyzed and protective levels were registered.  Of the patients, 45% were protected against hepatitis A infection and 29 % against hepatitis B infection after transplantation.  Only 26 % were vaccinated according to a complete vaccination schedule and these patients had a vaccine response for HAV and HBV of 50 % and 31 %, respectively.  An additional 31 % received greater than or equal to 1 doses of vaccine, but not a complete vaccination and the vaccine response was much lower among these patients, stressing the importance of completing the vaccination schedule.  The authors concluded that even when patients were fully vaccinated, they did not respond to the same degree as healthy individuals.  They stated that patients seemed to be more likely to respond to a vaccination if they had a lower Child-Pugh score, suggesting that patients should be vaccinated as early as possible in the course of their liver disease.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
90632
90633
90634
90636
ICD-9 codes covered if selection criteria are met:
286.0 - 286.2 Congenital factor VIII, IX disorder and XI deficiency
286.52 Other fetal abnormality causing disproportion, antepartum
304.00 - 304.93 Drug dependence
305.00 - 305.93 Nondependent abuse of drugs
571.0 - 571.9 Chronic liver disease and cirrhosis
V05.3 Prophylactic vaccination and inoculation against viral hepatitis
V01.79 Contact with or exposure to other viral diseases
V42.7 Liver replaced by transplant
V83.01 - V83.02 Asymptomatic and symptomatic hemophilia A carrier
Other ICD-9 codes related to the CPB:
070.0 - 070.1 Viral hepatitis A with hepatic coma or without mention of hepatic coma
286.3 - 286.9 Coagulation defects
304.00 - 305.93 Drug dependence and nondependent abuse of drugs
571.0 - 571.9 Chronic liver disease and cirrhosis


The above policy is based on the following references:
  1. No authors listed. Hepatitis A vaccine. Med Lett Drugs Ther. 1995;37(950):51-52.
  2. van Doorslaer E, Torman G, van Damme P, et al. Cost effectiveness of alternative hepatitis A immunisation strategies. Pharmacoeconomics. 1995;8(1):5-8.
  3. Centers for Disease Control and Prevention. Licensure of inactivated hepatitis A vaccine and recommendations for use among international travelers. MMWR Morb Mortal Wkly Rep. 1995;44(29):559-560.
  4. American Academy of Pediatrics. 2003 Red Book. Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003.
  5. Centers for Disease Control and Prevention (CDC). Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1996;45(RR-15):1-30.
  6. Centers for Disease Control and Prevention (CDC). Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1999;48(RR-12):1-37.
  7. Mawhorter SD. Who should receive hepatitis A vaccine? Cleve Clin J Med. 2001;68(10):825-827.
  8. National Advisory Committee on Immunisation (NACI). An Advisory Committee Statement (ACS). Update on hepatitis A vaccine (Avaxim, Aventis Pasteur). Can Commun Dis Rep. 2001;27:1-2.
  9. Bell BP. Hepatitis A vaccine. Semin Pediatr Infect Dis. 2002;13(3):165-173.
  10. Rosenthal P. Cost-effectiveness of hepatitis A vaccination in children, adolescents, and adults. Hepatology. 2003;37(1):44-51.
  11. Miller KE, Ruiz DE, Graves JC. Update on the prevention and treatment of sexually transmitted diseases. Am Fam Physician. 2003;67(9):1915-1922.
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  14. Van Damme P, Van Herck K. A review of the efficacy, immunogenicity and tolerability of a combined hepatitis A and B vaccine. Expert Rev Vaccines. 2004;3(3):249-267.
  15. Centers for Disease Control and Prevention (CDC), Office of Communications. CDC's Advisory Committee on Immunization Practices expands hepatitis A vaccination for children. Press Release. Atlanta, GA: CDC; October 28, 2005. Available at: http://www.cdc.gov/od/oc/media/pressrel/r051028.htm. Accessed November 4, 2005.
  16. American Academy of Pediatrics Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule--United States, 2006. Pediatrics. 2006;117(1):239-240.
  17. Centers for Disease Control and Prevention (CDC). Recommended childhood and adolescent immunization schedule - United States, 2006. MMWR Morbid Mortal Wkly Rep. 2006;54(52):Q1-Q4. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5451-Immunizationa1.htm. Accessed May 15, 2006.
  18. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-7):1-23. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm?s_cid=rr5507a1_e. Accessed May 18, 2006.
  19. American Academy of Pediatrics Committee on Infectious Diseases. Hepatitis A vaccine recommendations. Pediatrics. 2007;120(1):189-199.
  20. Victor JC, Monto AS, Surdina TY, et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med. 2007;357(17):1685-1694.
  21. Baker CJ. Another success for hepatitis A vaccine. N Engl J Med. 2007;357(17):1757-1759.
  22. Centers for Disease Control and Prevention (CDC). Notice to readers: FDA approval of an alternate dosing schedule for a combined hepatitis A and B vaccine (Twinrix). MMWR Morbid Mortal Wkly Rep. 2007;56(40):1057.
  23. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;56(41):1080-1084.
  24. Longworth DL. Update on infectious disease prevention: Human papillomavirus, hepatitis A. Cleve Clin J Med. 2008;75(6):402-403, 409-410.
  25. Beran J. Ten year's experience with combined hepatitis A and B vaccine. Klin Mikrobiol Infekc Lek. 2008;14(1):13-14, 16-23.
  26. Faridi MM, Shah N, Ghosh TK, et al. Immunogenicity and safety of live attenuated hepatitis A vaccine: A multicentric study. Indian Pediatr. 2009;46(1):29-34.
  27. Wolters B, Müller T, Ross RS, et al. Comparative evaluation of the immunogenicity of combined hepatitis A and B vaccine by a prospective and retrospective trial. Hum Vaccin. 2009;5(4):248-253.
  28. Centers for Disease Control and Prevention (CDC). Recommended adult immunization schedule – United States, 2010. MMWR Morbid Mortal Wkly Rep. 2010;59(01):1-4. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5901a5.htm. Accessed January 22, 2010.
  29. Marshall H, Nolan T, Díez Domingo J, et al. Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years. Vaccine. 2010;28(27):4411-4415.
  30. Tung J, Carlisle E, Smieja M, et al. A randomized clinical trial of immunization with combined hepatitis A and B versus hepatitis B alone for hepatitis B seroprotection in hemodialysis patients. Am J Kidney Dis. 2010;56(4):713-719.
  31. Crum-Cianflone NF, Wilkins K, Lee AW, et al; Infectious Disease Clinical Research Program HIV Working Group. Long-term durability of immune responses after hepatitis A vaccination among HIV-infected adults. J Infect Dis. 2011;203(12):1815-1823.
  32. Committee on Infectious Diseases. Recommendations for administering hepatitis A vaccine to contacts of international adoptees. Pediatrics. 2011;128(4):803-804.
  33. Irving GJ, Holden J, Yang R, Pope D. Hepatitis A immunisation in persons not previously exposed to hepatitis A. Cochrane Database Syst Rev. 2012;7:CD009051.
  34. Rowe IA, Parker R, Armstrong MJ, et al. Hepatitis A virus vaccination in persons with hepatitis C virus infection: Consequences of quality measure implementation. Hepatology. 2012;56(2):501-506.
  35. Gutierrez Domingo I, Pascasio Acevedo JM, Alcalde Vargas A, et al. Prevalence of hepatitis B and A virus markers and vaccination indication in cirrhotic patients evaluated for liver transplantation in Spain. Transplant Proc. 2012;44(6):1502-1504.
  36. Andersson D, Castedal M, Friman V. Are liver transplant recipients protected against hepatitis A and B? Transplant Proc. 2013;45(3):1193-1197.
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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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