Hepatitis A Virus (HAV)

OVERVIEW: What every clinician needs to know

Pathogen name and classification

Hepatitis A virus (HAV) is a positive-stranded RNA virus of the Herpavirus genus of Picornaviridae that is 27 nm, nonenveloped, and icosahedral.

What is the best treatment?

  • Supportive treatment only, but if the infection is fulminant, the patient should be cared for in a center that performs liver transplantation. Best treatment is vaccination prior to exposure, which decreases incidence by more than 90%. Immunity lasts approximately 6 months.

  • Vaccine is not universal, as there is a low exposure risk in the United States, and it only lasts 6 months. Hepatitis A vaccine is usually not associated with morbidity/mortality, painful injection, or high expense. Those individuals that do not respond to vaccination have been found to have a lower expression of HAVcr-1 (receptors) on CD4 T.

  • Vaccine has been used to prevent secondary cases of HAV in persons exposed to hepatitis A.

  • The standard preventive measure for hepatitis A post -exposure is immune globulin administration. A randomized study that took place in Kazakhstan noted similar results with vaccine or immune globulin given within 14 days of exposure.

How do patients contract this infection, and how do I prevent spread to other patients?

  • Infection is passed via fecal-oral route, and the majority of infections are related to socio-economic conditions. Risk factors include contact with infected food/water, sexual contact with infected individuals, daycare workers, military service, blood transfusions, and intravenous (IV) drug use. Well water is the most common source, as well as food, usually shell fish.

  • Prevalence in United States went from 12 to 1 case per 100,000 from 1995 to 2007 after wide spread use of vaccination. Currently, the highest rates of HAV are in the poorest countries in which sanitation is subpar.

  • Worldwide, there are 1.4 million reported cases of infection. Individuals living in third world countries have greater than 90% lifetime risk of contracting illness, but outbreaks are rare, as most older individuals are immune (Figure 1).

Figure 1.

Worldwide distribution of Hepatitis A.

Infection control issues

The best route to decrease transmission is oral hygiene. Gloves are recommended; gown and masks are unnecessary.


Vaccination is recommended for:

  • Persons with clotting-factor disorders or chronic liver disease

  • Men who have sex with men (MSM) or illegal drug users

  • Those with 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 following arrival of the adoptee in the United State

  • Persons working with HAV infected primates or with HAV in a research laboratory

  • Persons traveling to countries with high or intermediate endemicity

What host factors protect against this infection?

  • Replication of the virus occurs in the cytoplasm of the hepatocytes, and hepatocellular damage occurs via immune response largely mediated by T killer and natural killer cells. Interferon gamma plays a central role in clearing damaged hepatocytes and limiting immune response. Of note, once a patient has had hepatitis A, this confers life-long immunity.

  • Hepatitis A almost is always self-limited, but patients with chronic hepatitis C (HCV) have a small, but increased chance of developing fulminant hepatitis.

What are the clinical manifestations of infection with this organism?

  • Cholestatic jaundice develops in 30% of individuals who are infected; this normally decreases within 2 weeks with supportive care. On rare occasions, patients can get prolonged cholestatic jaundice with clinical manifestations, including jaundice, pruritus, diarrhea, and malaise. Even these prolonged symptoms resolve within 12 weeks.

  • There is no good prediction rule as to which individuals will experience prolonged symptoms, but liver biopsy done on individuals who experienced this prolonged picture showed a predominance of centrilobular cholestasis. Ultrasound is recommended in these patients to rule out biliary obstruction, but no biopsy is needed.

  • Relapsing hepatitis occurs in below 20% of patients, and usually occurs within 3 months. The course is usually milder but may present with different clinical manifestations, including:

    Extrahepatic manifestations such as arthralgias (most common), glomerulonephritis, toxic epidermal necrolysis, optic neuritis, multiple cell line aplasia, transverse, myelitis, myocarditis, and leukocytoclastic vasculitis.

  • Hepatitis A h as also been described as an uncommon trigger for autoimmune hepatitis.

How should I identify the organism?

HAV is diagnosed most commonly with serologic testing. IgM to HAV is present with recent infection, whereas IgG is present with past infection/immunization. IgM is usually not detected after 6 months and is greater than 99% sensitive. Biopsy, culturing, and electron microscopy are not performed for this virus (Figure 2).

Figure 2.

Serological course of hepatitis A infection.

How does this organism cause disease?

  • Intracellular hepatocyte death occurs as an immune response to the infected cells. Therefore, it is largely the host’s immunity that causes the clinical manifestation, and the virus serves as an antigen.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Daniels, D, Grytdal, S, Wasley, A. “Surveillance for acute viral hepatitis – United States, 2007”. MMWR Surveill Summ. vol. 58. 2009. pp. 1-27. (Recent summary of rates of hepatitis A in the U.S.)

Ilan, Y, Hillman, M, Oren, R. “Vasculitis and cryoglobulinemia associated with persisting cholestatic hepatitis A virus infection”. Am J Gastroenterol. vol. 85. 1990. pp. 586(Description of an unusual complication of hepatitis A infection.)

Sagliocca, L, Amoroso, P, Stroffolini, T. “Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomized trial”. Lancet. vol. 353. 1999. pp. 1136-1139. (Showed efficacy of giving hepatitis A vaccine after exposure to hepatitis A in the group receiving vaccine vs the group receiving no vaccine.)

Shenoy, R, Nair, S, Kamath, N. “Thrombocytopenia in hepatitis A–an atypical presentation”. J Trop Pediatr. vol. 50. 2004. pp. 241(Another unusual complication of hepatitis A infection.)

Skoog, SM, Rivard, RE, Batts, KP, Smith, CI. “Autoimmune hepatitis preceded by acute hepatitis A infection”. Am J Gastroenterol. vol. 97. 2002. pp. 1568-1569. (Case report of triggering of autoimmune hepatitis following hepatitis A infection.)

Vento, S, Garofano, T, Renzini, C. “Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C”. N Engl J Med. vol. 338. 1998. pp. 286-290. (Important paper detailing fulminant hepatitis A infection among patients who have chronic hepatitis C infection.)

Victor, JC, Monto, AS, Surdina, TY. “Hepatitis A vaccine versus immune globulin for postexposure prophylaxis”. N Engl J Med. vol. 357. 2007. pp. 1685-1694. (Compared vaccine with immunoglobulin in persons exposed to hepatitis A and found no difference in the protection afforded.)

Winokur, PL, Stapleton, JT. “Immunoglobulin prophylaxis for hepatitis A”. Clin Infect Dis. vol. 14. 1992. pp. 580-586. (Review of use of immunoglobulin prophylaxis for persons exposed to hepatitis A.)