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JAMA Insights
July 6, 2020

Management of Hepatitis A in 2020-2021

Author Affiliations
  • 1Fishbein Fellow, JAMA, Chicago, Illinois
  • 2Division of Infectious Diseases, Massachusetts General Hospital, Boston
  • 3Harvard Medical School, Boston, Massachusetts
JAMA. 2020;324(4):383-384. doi:10.1001/jama.2020.4017

Hepatitis A virus (HAV) is a common cause of viral hepatitis.1 Following decades of improved sanitation and hygiene measures and the introduction of HAV vaccination in 1995, the number of infections in the US declined by nearly 95% between 1996 and 2011, from 31 032 to 1398 reported cases yearly. However, HAV infections increased between 2016 and 2018 with an estimated 15 000 reported cases over this period, largely associated with outbreaks related to drug use and homelessness.1 Other recent infections in the US have occurred among men who have sex with men and during large foodborne outbreaks.1 These outbreaks have signaled an epidemiological shift in the US from small events typically associated with consumption of contaminated food, childcare centers, or unvaccinated travelers returning from endemic settings, to large outbreaks in networks characterized by person-to-person transmission.1,2

Diagnosis

HAV is primarily transmitted via the fecal-oral route and is acquired through ingestion of contaminated food or water (indirect transmission) or through sexual or other direct contact with an infected individual. Symptoms from HAV infection are indistinguishable from other causes of acute viral hepatitis, so diagnosis must be established by serological testing, typically during the acute or early convalescent phase. Anti-HAV IgM establishes the diagnosis of acute hepatitis A and appears in symptomatic patients 5 to 10 days before symptom onset. Anti-HAV IgM can remain elevated for 3 to 12 months following infection.2 Testing asymptomatic persons without evidence of clinical hepatitis or exposure to known HAV with an IgM assay is not recommended.3 Indeterminate anti-HAV IgM results should be followed by repeat testing. Anti-HAV IgG generally persists for the duration of a patient’s life following infection or vaccination and presents right before or at the time of symptom onset in cases of acute infection. Peak infectivity, as determined by viral shedding in the stool, occurs approximately 2 weeks prior to the development of clinical symptoms, although prolonged shedding can occur, especially in children.4 HAV nucleic acid amplification testing for viral RNA (including polymerase chain reaction) is also available to detect the virus in blood or feces but is rarely required to establish a diagnosis.2

Treatment and Prevention

HAV infection is generally self-limited, although symptoms can range from asymptomatic to fulminant hepatitis, which occurs more rarely. Acute hepatitis A tends to be more symptomatic and severe in older children and adults, and some patients can develop prolonged and cholestatic patterns of hepatitis following infection. Clinical relapse can also occur within 6 months of initial infection.4 Treatment relies on supportive management, underscoring the importance of prevention. Vaccination is the most important preventive measure against acquiring HAV infection. The Centers for Disease Control and Prevention (CDC) 2020 Advisory Committee on Immunization Practices (ACIP) recommends vaccination for all children aged 1 year and older; men who have sex with men; and people who use injection and noninjection drugs, have occupational risk factors for infection, travel to high-endemicity areas, have increased risk for complication from hepatitis A (eg, chronic liver disease, HIV infection, and pregnancy if at risk for infection), or have an otherwise increased risk of infection.5,6 In response to large community outbreaks and observational data surrounding HAV-related hospitalization and death rates, persons experiencing homelessness or unstable housing should be immunized1,5 (Table). While food service workers are not routinely recommended to receive hepatitis A vaccination, the decision to vaccinate this population can be considered in the setting of large-scale outbreaks.4,5

Table.  Indications for Hepatitis A Vaccination in the USa
Indications for Hepatitis A Vaccination in the USa

In the US, there are currently 2 single-antigen inactivated vaccines, Havrix and Vaqta, and 1 inactivated combination vaccine, Twinrix, that are licensed for use.4 Havrix and Vaqta, if administered alone, consist of a 2-dose schedule typically given at age 12 to 18 months. Following the initial dose, the second dose is given 6 to 12 months later with Havrix or 6 to 18 months later with Vaqta. Twinrix is given on a 3-dose schedule and is a combined hepatitis A and hepatitis B vaccine typically administered at 1 and 6 months following the initial dose. The inactivated combination vaccine is approved for use in persons aged 18 years or older.4 All 3 vaccines can be administered safely to immunocompromised individuals.

HAV infection and vaccination are presumed to confer lifelong immunity to hepatitis A. Current CDC ACIP recommendations note that while vaccinating an individual who is already immune does not increase the risk of adverse events, serologic testing prior to vaccination can be considered in select scenarios, such as with adults from high-prevalence settings for HAV (both geographically and per epidemiological risk), when the cost of testing and follow-up visits does not eclipse the cost of vaccination, and in adults older than 40 years of age.4 Serologic testing is not recommended in children with a low likelihood of prior infection.4 Individuals who have received 1 dose of vaccine in the past do not need to restart the series but should be administered the second dose as indicated. Postvaccination serological testing is not indicated due to high response in most adults and children to the vaccine.5 Rapid vaccination and contact tracing have been used as part of outbreak control strategies in the past, particularly when implemented among household members. One dose of single-antigen vaccine can be effective in controlling an outbreak.7 One study conducted in the midst of a US outbreak demonstrated that vaccination rates must be high (>80%) to effectively limit progression of the epidemic.7

Immunoglobulin is used for both preexposure and postexposure prophylaxis of HAV. Due to the declining prevalence of HAV antibodies in the US donor pool for immunoglobulin, the recommended doses for preexposure and postexposure prophylaxis were changed in 2017.8 Preexposure prophylaxis for travelers to intermediate- or high-endemicity areas is typically reserved for individuals who are immunocompromised, vaccine allergic, or children younger than 6 months prior to travel. The recommended dosages of immunoglobulin are 0.1 mL/kg for travel up to 1 month in duration, 0.2 mL/kg for up to 2 months of travel, and repeat dosing of 0.2 mL/kg every 2 months if traveling for longer than 2 months.8 After exposure, children younger than 12 months old, adults with chronic liver disease, adults older than 40 years of age, and immunocompromised individuals should receive a single dose of intramuscular HAV immunoglobulin (0.1 mL/kg) in addition to vaccine, unless either is contraindicated. When administered within 2 weeks of exposure, HAV immunoglobulin is 80% to 90% effective in preventing acquisition of disease.9 A noninferiority, randomized clinical trial that compared the efficacy of hepatitis A vaccine with immunoglobulin for postexposure prophylaxis found that both provided adequate protection less than 14 days after exposure, although there were slightly higher rates of hepatitis A among vaccine recipients compared with those who received immunoglobulin.10 Immunoglobulin continues to be recommended in clinical practice; however, if immunoglobulin is not readily available, hepatitis A vaccine may be administered alone.

Conclusions

Hepatitis A is an important cause of acute viral hepatitis worldwide. Recent large-scale outbreaks in the US have prompted guideline changes and expanded indications for vaccination, which remains the cornerstone of disease prevention.

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Article Information

Corresponding Author: Angel N. Desai, MD, MPH, Fishbein Fellow, JAMA, 330 N Wabash Ave, Chicago, IL 60654 (angel.n.desai@gmail.com).

Published Online: July 6, 2020. doi:10.1001/jama.2020.4017

Conflict of Interest Disclosures: Dr Kim reported receiving personal fees from Biomarin and other fees from UpToDate. No other disclosures were reported.

References
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Lemon  SM, Ott  JJ, Van Damme  P, Shouval  D.  Type A viral hepatitis: a summary and update on the molecular virology, epidemiology, pathogenesis and prevention.   J Hepatol. 2017;S0168-8278(17)32278-X.PubMedGoogle Scholar
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Centers for Disease Control and Prevention.  Hepatitis A questions and answers for health professionals. Accessed December 19, 2019. https://www.cdc.gov/hepatitis/hav/havfaq.htm
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Nelson  NP, Link-Gelles  R, Hofmeister  MG,  et al.  Update: recommendations of the Advisory Committee on Immunization Practices for use of hepatitis A vaccine for postexposure prophylaxis and for preexposure prophylaxis for international travel.   MMWR Morb Mortal Wkly Rep. 2018;67(43):1216-1220. doi:10.15585/mmwr.mm6743a5PubMedGoogle ScholarCrossref
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Centers for Disease Control and Prevention.  Immunization schedules: recommended adult immunization schedule for ages 19 and older, United States, 2020. Accessed March 2, 2020. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html
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McMahon  BJ, Beller  M, Williams  J, Schloss  M, Tanttila  H, Bulkow  L.  A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine.   Arch Pediatr Adolesc Med. 1996;150(7):733-739. doi:10.1001/archpedi.1996.02170320079014PubMedGoogle ScholarCrossref
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Nelson  NP.  Updated dosing instructions for immune globulin (human) GamaSTAN S/D for hepatitis A virus prophylaxis.   MMWR Morb Mortal Wkly Rep. 2017;66(36):959-960. doi:10.15585/mmwr.mm6636a5PubMedGoogle ScholarCrossref
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Winokur  PL, Stapleton  JT.  Immunoglobulin prophylaxis for hepatitis A.   Clin Infect Dis. 1992;14(2):580-586. doi:10.1093/clinids/14.2.580PubMedGoogle ScholarCrossref
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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. doi:10.1056/NEJMoa070546PubMedGoogle ScholarCrossref
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