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Hepatitis A Virus 

Updated July 2015

I. INTRODUCTION

Annually, the total number of reported cases of hepatitis A virus (HAV) in the United States has fallen consistently, from 13,397 in 2000 to 1,781 in 2013.1 Statewide in New York, the total number of reported HAV cases in 2013 was 165, with 93 cases in New York City and 75 in the rest of the state.2,3 Although actual acute cases are estimated to be two times the number of reported cases in any year,1 the overall decline of reported and actual cases corresponds with inclusion of HAV vaccination in the recommended pediatric immunization panels for those 2 to 18 years of age.

The modes of transmission are well established: ingestion of contaminated water and food, such as raw clams or oysters; oral-anal contact; person-to-person spread via fomites, such as shared utensils or bath towels; or, very rarely, blood or blood product transfusion. Approximately 40% of cases occur in individuals who have had known contact with a person with HAV; 10% of cases are related to food and/or waterborne disease outbreaks or international travel; and 50% of cases have no identified source. Men who have sex with men (MSM) are at increased risk for HAV infection, and limited data suggest low rates of HAV vaccination in this population,4-6 particularly among young MSM.4,5

Key Point:
Currently, no specific treatment is available for HAV, although infection can be prevented by both pre-exposure vaccination and post-exposure serum immune globulin administration.

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Severity of Disease
The incubation period of HAV infection averages 28 days (range, 15-50 days). Although HAV does not cause chronic hepatitis, it is not a benign disease; the morbidity in adults is substantial. Young children tend to have asymptomatic or minimally symptomatic disease, whereas older children and adults have more severe illness, with jaundice occurring in approximately 70% of cases.7 Adults with acute HAV lose an average of 30 workdays,8 and approximately 40.8% of patients with reported cases of acute HAV required hospitalization in 2013.1 Overall case fatality is low (0.3%) but increases to 2.7% in individuals >50 years of age,9 11.7% in those with concomitant chronic hepatitis B infection,9 and 35% in those with chronic hepatitis C infection.10

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HIV/HAV Co-Infection

RECOMMENDATION:
Whenever possible, ART should not be interrupted in HIV/HAV co-infected patients; when interruption of ART is indicated for management of severe or fulminant liver disease, clinicians should consult with a provider experienced in the treatment of hepatitis and HIV. (AIII)

HAV does not cause more severe clinical illness in HIV-infected individuals. HIV-infected patients may have significantly higher HAV viral load levels and significantly prolonged durations of HAV viremia compared with non-HIV-infected individuals,11 which may result in a prolonged duration of risk of HAV transmission to others.

HIV-infected patients with acute HAV infection rarely require even temporary interruption of ART. Cessation of ART should be avoided whenever possible because of the potential long-term consequences, such as reduced viral suppression when ART is reinstituted.12,13 In the rare instances when interruption of ART is indicated for management of fulminant liver disease, clinicians should consult with a provider experienced in the treatment of hepatitis and HIV.

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II. PREVENTION OF HAV INFECTION

A. Pre-Exposure Vaccination

RECOMMENDATIONS:
Clinicians should obtain HAV IgG for the HIV-infected populations indicated in Table 1 and should administer the HAV vaccine to those who are HAV antibody-negative.

When performing vaccination in HIV-infected patients, clinicians should:

  • Administer the full HAV vaccination series, consisting of an initial dose and a second dose 6 to 12 months later, to ensure maximal antibody response (AI)
  • Administer the HAV vaccine early in the course of HIV infection for patients with CD4 counts ≥200 cells/mm3 (AI)
  • Defer vaccination for patients with counts CD4 counts <200 cells/mm3 or who have symptomatic HIV disease until immune reconstitution after initiation of ART in an attempt to maximize the antibody response (BII)
  • Obtain a post-vaccination antibody measurement in patients who are at increased risk for HAV-related morbidity and mortality (see Table 1) (BIII)

Table 1: Patients Who Should Receive Hepatitis A Vaccination
  • Persons with chronic liver disease or conditions that can lead to chronic liver disease (e.g., chronic HBV, chronic HCV, alcohol abuse, or genetic liver diseases)a (AIII)
  • MSM (AIII)
  • Travelers to countries with high or intermediate endemicity of infectionb,c (AII)
  • Illicit drug users, particularly injection drug users (AIII)
  • Persons who live in a community identified by the local health department as experiencing an outbreak of HAV infection (BIII)
  • Persons who have clotting-factor disorders (BIII)
  • Persons who want to reduce their risk for HAV infection (BIII)
  • Persons at occupational risk who are not otherwise required to receive HAV vaccination (CIII)
a Persons with chronic liver disease are at increased risk for severe infection if they become co-infected with HAV.
b Hepatitis A vaccine at the age-appropriate dose is preferred over immune globulin; however, for optimal protection, adults aged >40 years, immunocompromised people, and people with chronic liver disease or other chronic medical conditions planning to depart to an area in <2 weeks should receive the initial dose of vaccine along with immune globulin (0.02 mL/kg) at a separate injection site. For additional information regarding HAV vaccination for travelers, see Centers for Disease Control and Prevention’s CDC Health Information for International Travel, Chapter 3: Infectious diseases related to travel: Hepatitis A. Available at: wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/hepatitis-a.
c Because of the complexity involved in interpreting travel-associated HAV infection risk, some expert travel clinicians advise people traveling outside the United States to consider HAV vaccination regardless of their destination.

 

Infection with HAV can be prevented by active immunization prior to exposure with either of the two currently licensed vaccines, which are considered equivalent in efficacy. HAV vaccines are highly immunogenic in immunocompetent adults, with >95% seroconversion. However, the seroconversion rates and the geometric mean serum antibodies in HIV-infected individuals are lower than in non-HIV-infected populations, with response rates from 50% to 95%.14-19 HAV vaccine appears to have no effect on the course of HIV infection or on plasma HIV viral load. A combined hepatitis A and B vaccine is also available and can be used in persons susceptible to both hepatitis A and B. It is given in three total doses at 0, 1, and 6 months.

Administration of HAV vaccine is preferred when CD4 counts are ≥200 cells/mm3 to maximize response to the vaccine. An effective antibody response may not occur in up to 15% of immunocompromised patients.16,19 This Committee recommends follow-up HAV antibody testing for patients who are at increased risk for HAV-related morbidity and mortality (see Table 1) to verify vaccine efficacy and to identify those who should be counseled to avoid infection because of continued susceptibility.

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B. Post-Exposure Immune Globulin

RECOMMENDATION:
Clinicians should administer a single dose of immune serum globulin (0.02 mL/kg IM) as HAV post-exposure prophylaxis to susceptible HIV-infected patients within 2 weeks of an exposure to close personal contacts with serologically confirmed HAV infection (i.e., through a blood test), including:

  • Household and sexual contacts (AII)
  • Individuals who have shared illicit drugs with someone with HAV (AII)

Patients for whom HAV vaccination is also indicated should receive the HAV vaccine concurrently with immune serum globulin to protect against future infection (see Table 1).

Clinicians must report all suspected or confirmed hepatitis A infections to the local health department of the area where the patient resides according to NYS requirements (also see Communicable Disease Reporting Requirements). Infections that occur among food-handlers or in other settings that pose a high risk of transmission are immediately reportable by telephone to the local health department.

Immune serum globulin is the recommended HAV post-exposure prophylaxis for HIV-infected patients and should be given to individuals who are susceptible to HAV infection within 2 weeks after an exposure to an HAV-infected household contact, sexual partner, or needle-sharing partner.20 Consideration should also be given to HIV-infected patients providing other types of ongoing, close personal contact with a person with HAV (e.g., a regular babysitter or caretaker).20,21 A single intramuscular dose of 0.02 mL/kg is effective in preventing infection or attenuating HAV infection that might result from such an exposure. Concurrent administration of HAV vaccine with immune serum globulin is indicated for individuals at risk for future infection (see Table 1).

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REFERENCES

1. Centers for Disease Control and Prevention. Surveillance for Viral Hepatitis – United States, 2013. Atlanta, GA: National Center for HIV/AIDS, Viral Hepatitis, STD & TB Preventions. Available at: http://www.cdc.gov/hepatitis/statistics/2013surveillance/index.htm.

2. New York State Department of Health. Reported Cases of Selected Diseases – 2004-2013: New York State Exclusive of New York City. September, 2013. Available at: http://www.health.ny.gov/statistics/diseases/communicable/2013/new_york_state/by_year.htm.

3. New York State Department of Health. Reported Cases of Selected Diseases – 2004-2013: New York City. September, 2013. Available at http://www.health.ny.gov/statistics/diseases/communicable/2013/new_york_city/by_year.htm.

4. Diamond C, Thiede H, Perdue T, et al. Viral hepatitis among young men who have sex with men: Prevalence of infection, risk behaviors, and vaccination. Sex Transm Dis 2003;30:425-432. [PubMed]

5. Urbanus AT, et al. Viral hepatitis among men who have sex with men, epidemiology and public health consequences. Euro Surveill. 2009;14:pii: 19421. [PubMed]

6. Cotter SM, Sansom S, Long T, et al. Outbreak of hepatitis A among men who have sex with men: Implications for hepatitis A vaccination strategies. J Infect Dis 2003;187:1235-1240. [PubMed]

7. Cuthbert JA. Hepatitis A: Old and new. Clin Microbiol Rev 2001;14:38-58. [PubMed]

8. World Health Organization. Hepatitis A. Department of Communicable Disease Surveillance and Response, 2000. Available at: http://www.who.int/csr/disease/hepatitis/HepatitisA_whocdscsredc2000_7.pdf

9. Keeffe EB. Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases? Am J Gastroenterol 1995;90:201-205. [PubMed]

10. Vento S, Garofano T, Renzini C, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 1998;338:286-290. [PubMed]

11. Gallego M, Robles M, Palacios R, et al. Impact of acute hepatitis A virus (HAV) infection on HIV viral load in HIV-infected patients and influence of HIV infection on acute HAV infection. J Int Assoc Physicians AIDS Care (Chic) 2011;10:40-42. [PubMed]

12. SMART Study Group, El-Sadr WM, Grund B, et al. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: A randomized trial. Ann Intern Med 2008;149:289-299. [PubMed]

13. Lutwick L. Clinical interactions between human immunodeficiency virus and the human hepatitis viruses. Infect Dis Clin Prac 1999;8:9-20.

14. Weissman S, Feucht C, Moore BA. Response to hepatitis A vaccine in HIV-positive patients. J Viral Hepat 2006;13:81-86. [PubMed]

15. Shire NJ, Welge JA, Sherman KE. Efficacy of inactivated hepatitis A vaccine in HIV-infected patients: A hierarchical bayesian meta-analysis. Vaccine 2006;24:272-279. [PubMed]

16. Wallace MR, Brandt CJ, Earhart KC, et al. Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV-infected subjects. Clin Infect Dis 2004;39:1207-1213. [PubMed]

17. Kemper CA, Haubrich R, Frank I. Safety and immunogenicity of hepatitis A vaccine in human immunodeficiency virus-infected patients: A double-blind, randomized, placebo-controlled trial. J Infect Dis 2003;187:1327-1331. [PubMed]

18. Rimland D, Guest JL. Response to hepatitis A vaccine in HIV patients in the HAART era.  AIDS 2005;19:1702-1704. [PubMed]

19. Mena G, García-Basteiro AL, Llupià A, et al. Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy. Vaccine 2013;31:3668-3674. [PubMed]

20. Centers for Disease Control and Prevention. Hepatitis A FAQs for Health Professionals: Postexposure Prophylaxis for Hepatitis A. Page last reviewed: April 1, 2008. Available at: http://www.cdc.gov/hepatitis/HAV/HAVfaq.htm#D2

21. Centers for Disease Control and Prevention. 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. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5641a3.htm

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FURTHER READING

Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2006;55(No. RR-7):1-23. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm

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. [PubMed]

Laurence JC. Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus. Am J Med 2005;118(Suppl 10A):75S-83S. [PubMed]

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