Viral hepatitis is a major global public health problem affecting hundreds of millions of people and is associated with significant morbidity and mortality. Five biologically unrelated hepatotropic viruses cause most of the global burden of viral hepatitis: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), and hepatitis E virus (HEV). HBV, HCV, HDV, and, occasionally, HEV can produce chronic infections, whereas HAV does not.
Hepatitis A is a communicable (or contagious) disease that often spreads from person to person.[1] Person-to-person transmission occurs via the “fecal-oral route,” while all other exposure is generally attributable to contaminated food or water.[2] Food-related outbreaks are usually associated with contamination of food during preparation by a HAV-infected food handler.[3] The food handler is generally not ill because the peak time of infectivity—that is, when the most virus is present in the stool of an infected individual—occurs two weeks before illness begins.[4]
Fresh produce contaminated during cultivation, harvesting, processing, and distribution has also been a source of hepatitis A.[5] In 1997, frozen strawberries were the source of a hepatitis A outbreak in five states.[6] Six years later, in 2003, fresh green onions were identified as the source of a HAV outbreak traced to consumption of food at a Pennsylvania restaurant.[7] Other fruits and vegetables, such as blueberries and lettuce, have also been associated with HAV outbreaks in the U.S. as well as in other developed countries.[8] HAV is relatively stable and can survive for several hours on fingertips and hands and up to two months on dry surfaces.[9] The virus can be inactivated by heating to 185°F (85°C) or higher for one minute, or disinfecting surfaces with a 1:100 dilution of household bleach in tap water.[10] HAV can still be spread from cooked food if it is contaminated after cooking.[11]
Although ingestion of contaminated food is a common means of spread for HAV, it may also be spread by household contact among families or roommates, sexual contact, or by direct inoculation from persons sharing illicit drugs.[12] Children are often asymptomatic, or have unrecognized infections, and can pass the virus through ordinary play, unknown to their parents, who may later become infected from contact with their children.[13]
What are the Symptoms of Hepatitis A?
Hepatitis A may cause no symptoms at all when it is contracted, especially in children.[14] Asymptomatic individuals will only know they were infected (and have become immune, given that you can only get hepatitis A once) by getting a blood test later in life.[15] Approximately 10 to 12 days after exposure, HAV is present in blood and is excreted via the biliary system into the feces.[16] Although the virus is present in the blood, its concentration is much higher in feces.[17] HAV excretion begins to decline at the onset of clinical illness, and decreases significantly by 7 to 10 days after onset of symptoms.[18] Most infected persons no longer excrete virus in the feces by the third week of illness. Children may excrete HAV longer than adults.[19]
Seventy percent of HAV infections in children younger than six years of age are asymptomatic; in older children and adults, infection tends to be symptomatic with more than 70% of those infected developing jaundice.[20] Symptoms typically begin about 28 days after contracting HAV, but can begin as early as 15 days or as late as 50 days after exposure.[21] The symptoms include muscle aches, headache, anorexia (loss of appetite), abdominal discomfort, fever, and malaise.[22]
After a few days of typical symptoms, jaundice (also termed “icterus”) sets in.[23] Jaundice is a yellowing of the skin, eyes, and mucous membranes that occurs because bile flows poorly through the liver and backs up into the blood.[24] The urine will also turn dark with bile and the stool light or clay-colored from lack of bile.[25] When jaundice sets in, initial symptoms such as fever and headache begin to subside.[26]
In general, symptoms usually last less than two months, although 10% to 15% of symptomatic persons have prolonged or relapsing disease for up to 6 months.[27] It is not unusual, however, for blood tests to remain abnormal for six months or more.[28] The jaundice so commonly associated with HAV can also linger for a prolonged period in some infected persons, sometimes as long as eight months or more.[29] Additionally, pruritus, or severe “itchiness” of the skin, can persist for several months after the onset of symptoms. These conditions are frequently accompanied by diarrhea, anorexia, and fatigue.[30]
Relapse is possible with hepatitis A, typically within three months of the initial onset of symptoms.[31] Although relapse is more common in children, it does occur with some regularity in adults.[32] The vast majority of persons who are infected with hepatitis A fully recover, and do not develop chronic hepatitis.[33] Persons do not carry HAV long-term as with hepatitis B and C.[34]
Fulminant Hepatitis A
Fulminant hepatitis A, or acute liver failure, is a rare but devastating complication of HAV infection.[35] As many as 50% of individuals with acute liver failure may die or require emergency liver transplantation.[36] Elderly patients and patients with chronic liver disease are at higher risk for fulminant hepatitis A.[37] In parallel with a declining incidence of acute HAV infection in the general population, however, the incidence of fulminant HAV appears to be decreasing.[38]
HAV infects the liver’s parenchymal cells (internal liver cells).[39] Once a cell has been penetrated by the viral particles, the hepatitis A releases its own toxins that cause, in essence, a hostile takeover of the host’s cellular system.[40]The cell then produces new viral components that are released into the bile capillaries or tubes that run between the liver’s parenchymal cells.[41] This process results in the death of liver cells, called hepatic necrosis.[42]
The fulminant form of hepatitis occurs when this necrotic process kills so many liver cells—upwards of three-quarters of the liver’s total cell count—that the liver can no longer perform its job.[43] Aside from the loss of liver function, fulminant hepatic failure can lead to encephalopathy and cerebral edema.[44] Encephalopathy is a brain disorder that causes central nervous system depression and abnormal neuromuscular function.[45] Cerebral edema is a swelling of the brain that can result in dangerous intracranial pressure.[46] Intracranial hypertension leading to brainstem herniation and sepsis with multiple organ failure are the leading causes of death in individuals with fulminant hepatic failure.[47]
Hepatitis A is much more common in countries with underdeveloped sanitation systems and, thus, is a risk in most of the world.[48] An increased transmission rate is seen in all countries other than the United States, Canada, Japan, Australia, New Zealand, and the countries of Western Europe.[49] Nevertheless, infections continue to occur in the United States, where approximately one-third of the population has been previously infected with HAV.[50]
Incidence of Hepatitis A
Each year, approximately 1,600 to 4,500 cases of hepatitis A occur in the United States.[51] Historically, acute hepatitis A rates have varied cyclically, with nationwide increases every 10 to 15 years.[52] The national rate of HAV infections has declined steadily since the last peak in 1995.[53] After a surge peaking at 18,846 reported cases in 2019 due to widespread person-to-person outbreaks, cases have declined substantially. In 2023, there were 1,648 reported cases and approximately 3,300 estimated infections after adjusting for underreporting—a 91% decrease from the 2019 peak.[54]
In 2023, the CDC reported 1,648 new confirmed cases of hepatitis A, with an estimated 3,300 actual infections after adjusting for underascertainment and underreporting.[55] After annual increases from 2015 through 2019—driven by widespread outbreaks among people who use drugs and people experiencing homelessness—reported cases declined sharply. From 2019 to 2023, the rate of newly reported cases decreased by 91%.[56][57]
Hepatitis A outbreaks associated with fresh, frozen, and minimally processed produce, worldwide, from 1983 to 2016. Adapted and expanded from Sivapalasingam et al., 2004 and Fiore, 2004. Italics indicate instances where the food was locally sourced with respect to the cases. The implicated foods were raw unless listed otherwise.
The economic burden of hepatitis A in the United States remains substantial. A retrospective analysis of privately insured patients (2012–2018) found that the average cost of hepatitis A-related care was $2,520 per patient (in 2020 dollars), rising to $17,373 for hospitalized patients.[58] During the 2016–2020 outbreak period, hospitalization costs associated with person-to-person outbreaks across 32 states exceeded $306.8 million.[59] In a 2007 Ohio study, each case of HAV infection attributable to contaminated food was estimated to cost at least $10,000, including medical and other non-economic costs.[60] Nationwide, adults who become ill miss an average of 27 workdays per illness, and 11 to 22 percent of those infected are hospitalized.[61] All of these costs are entirely preventable given the effectiveness of a vaccination in providing immunity from infection.[62]
Prevention
Hepatitis A can be spread by eating food that was touched by a person with the disease. People should get the vaccine within 14 days of exposure (the date they ate food from the restaurant) for the vaccine to be most effective at protecting against hepatitis A. The earlier the vaccine is given, the more effective it is in preventing the disease. In some cases, a dose of immune globulin (antibodies) is also needed, depending on the person’s age and health. People who ate food from the restaurant and have previously received two doses of hepatitis A vaccine or have already had hepatitis A infection, do not need another dose of the vaccine. People who were exposed but only received one dose in the past should get a second dose.
[1] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1.
[2] Id.; See also Jaykus Lee Ann, “Epidemiology and Detection as Options for Control of Viral and Parasitic Foodborne Disease,” Emerging Infectious Diseases, Vol. 3, No. 4, pp. 529-39 (October-December 1997). Full text of the article is available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640072/pdf/9366607.pdf
[3] Fiore, Anthony, supra note 7; CDC, “Hepatitis A,” supra note 5; See also CDC, “Surveillance for Acute Viral Hepatitis – United States, 2007, Morbidity and Mortality Weekly Report, Surveillance Summaries, Vol. 58, No. SS03 (May 22, 2009) at http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5803a1.htm.
[4] Fiore, Anthony, Division of Viral Hepatitis, CDC, “Hepatitis A Transmitted by Food,” supra note 7.
[5] Id.; See also, Wheeler, C, et al., “An Outbreak of Hepatitis A Associated with Green Onions,” New England Journal of Medicine, Vol. 353, 890-97 (2005). Full text of article available at http://www.nejm.org/doi/full/10.1056/NEJMoa050855.
[6] Hutin YJF, et al., “A Multistate, Foodborne Outbreak of Hepatitis A,” New England Journal of Medicine, Vol. 340, pp. 595-602 (1999). Full text of article is online at http://nejm.org/doi/full/10.1056/NEJM199902253400802.
[7] Wheeler, C, et al., “An Outbreak of Hepatitis A Associated with Green Onions,” supra note 15.
[8] Butot S, et al., “Effects of Sanitation, Freezing and Frozen Storage on Enteric Viruses in Berries and Herbs,” Intentional Journal of Food Microbiology, Vol. 126, No. 4, pp. 233-246 (2003). Full text of article is available at http://www.prograd.uff.br/virologia/sites/default/files/bulot_et_al_2008_inactivation.pdf.; Calder, L, et al., An Outbreak of Hepatitis A Associated with Consumption of Raw Blueberries,” Epidemiology and Infection, Vol. 131, No. 1 745-51 (2003) at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870016/pdf/12948375.pdf.
[9] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[10] CDC, “Updated recommendations from Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees,” Morbidity and Mortality Weekly Report, Vol. 58, No. 36, (Sept. 18, 2006), http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a4.htm; Fiore, Anthony, et al., Advisory Committee on Immunization Practices (ACIP), Prevention of Hepatitis-A Through Active or Passive Immunization: Recommendations, Morbidity & Mortality Weekly Review, Vol. 55, Report 407, (May 29, 2006) at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm; Todd, Ewan C.D., et al., “Outbreaks Where Food Workers Have Been Implicated in the Spread of Foodborne Disease. Part 6. Transmission and Survival of Pathogens in the Food Processing and Preparation-environment,” Journal of Food Protection, Vol. 72, 202-19 (2009). Full text of the article is available online at http://courses.washington.edu/eh451/articles/Todd_2009_food%20processing.pdf.
[11] Fiore, Anthony, Division of Viral Hepatitis, CDC, “Hepatitis A Transmitted by Food,” supra note 7.
[12] Id.; See also, Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[13] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Piazza, M, et al., “Safety and Immunogenicity of Hepatitis A Vaccine in Infants: A Candidate for Inclusion in Childhood Vaccination Program,” Vol. 17, pp. 585-588 (1999). Abstract at http://www.ncbi.nlm.nih.gov/pubmed/10075165; Schiff, E.R., “Atypical Manifestations of hepatitis-A,” Vaccine, Vol. 10, Suppl. 1, pp. 18-20 (1992). Abstract at http://www.ncbi.nlm.nih.gov/pubmed/1475999.
[14] Fiore, Anthony, Division of Viral Hepatitis, CDC, “Hepatitis A Transmitted by Food,” supra note 7
[15] Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[16] CDC, “Hepatitis A,” supra note 5; Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1
[17] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1
[18] Id.
[19] Id.; See also Sagliocca, Luciano, et al., “Efficacy of Hepatitis A Vaccine in Prevention of Secondary Hepatitis A Infection: A Randomized Trial,” Lancet, Vol. 353, 1136-39 (1999). Abstract at http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)08139-2/abstract.
[20] CDC, “Hepatitis A,” supra note 5.
[21] Id.; See also Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Fiore, Anthony, Division of Viral Hepatitis, CDC, “Hepatitis A Transmitted by Food,” supra note 7.
[22] CDC, “Hepatitis A,” supra note 5; Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[23] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[24] Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[25] CDC, “Hepatitis A,” supra note 5; Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[26] Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[27] Fiore, Anthony, et al., Advisory Committee on Immunization Practices (ACIP), Prevention of Hepatitis-A Through Active or Passive Immunization: Recommendations,” supra note 20; Gilkson Miryam, et al., “Relapsing Hepatitis A. Review of 14 cases and literature survey,” Medicine, Vol. 71, No. 1, 14-23 (Jan. 1992). Abstract of article online at http://www.ncbi.nlm.nih.gov/pubmed/1312659.
[28] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1.
[29] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[30] CDC, “Hepatitis A,” supra note 5; Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[31] Gilkson Miryam, et al., “Relapsing Hepatitis A. Review of 14 cases and literature survey,” supra note 37.
[32] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Gilkson Miryam, et al., “Relapsing Hepatitis A. Review of 14 cases and literature survey,” supra note 37.
[33] Mayo Clinic Staff, “Hepatitis A,” supra note 1.
[34] CDC Summary, “Disease Burden from Viral Hepatitis A, B and C in the United States, 2004-2009, at http://www.cdc.gov/hepatitis/pdfs/disease_burden.pdf; CDC, “Hepatitis A,” supra note 5.
[35] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” World Journal of Gastroenterology, Vol. 12, No. 46 pp. 7405-7412 (Dec. 14, 2006). Full article is available online at http://www.wjgnet.com/1007-9327/12/7405.pdf.
[36] Taylor, Ryan, et al., “Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes,” Hepatology, Vol. 44, 1589-1597. Full text http://deepblue.lib.umich.edu/bitstream/2027.42/55879/1/21349_ftp.pdf.
[37] Id.; See also Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1.
[38] Taylor, Ryan, et. al., “Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes,” supra note 46.
[39] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45; Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1.
[40] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Schiff, E.R., “Atypical Manifestations of hepatitis-A,” supra note 23.
[41] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45.
[42] Id.; See also Taylor, Ryan, et. al., “Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes,” supra note 46.
[43] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45; Taylor, Ryan, et. al., “Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes,” supra note 46.
[44] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45.
[45] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45; Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1.
[46] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45.
[47] Detry, Oliver, et al., “Brain Edema and Intracranial Hypertension in Fulminant Hepatic Failure: Pathophysiology and Management,” supra note 45; Taylor, Ryan, et. al., “Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes,” supra note 46.
[48] Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” supra note 1; Jaykus Lee Ann, “Epidemiology and Detection as Options for Control of Viral and Parasitic Foodborne Disease,” supra note 12.
[49] CDC, “Update: Prevention of Hepatitis A after Exposure to Hepatitis A Virus and in International Travelers, Updated ACIP Recommendations,” Morbidity and Mortality Weekly Report, Vol. 56, No. 41, pp. 1080-84 (Oct. 19, 2007), online at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5641a3.htm.
[50] CDC, “Surveillance for Acute Viral Hepatitis – United States 2007,” supra note 13; Fiore, Anthony, Division of Viral Hepatitis, CDC, “Hepatitis A Transmitted by Food,” supra note 7.
[51] CDC, Hepatitis A Surveillance, 2023 Viral Hepatitis Surveillance Report, available at https://www.cdc.gov/hepatitis-surveillance-2023/hepatitis-a/index.html (reporting 1,648 confirmed cases and an estimated 3,300 infections in 2023).
[52] Hutin YJF, et al., “A Multistate, Foodborne Outbreak of Hepatitis A,” supra note 16.
[53] CDC, Hepatitis A Outbreaks, available at https://www.cdc.gov/hepatitis-a/outbreaks/ (reporting a 91% decrease in newly reported cases from 2019 to 2023); CDC, Hepatitis A Surveillance, 2023 Viral Hepatitis Surveillance Report, available at https://www.cdc.gov/hepatitis-surveillance-2023/hepatitis-a/index.html.
[54] CDC, Hepatitis A Surveillance, 2023 Viral Hepatitis Surveillance Report, available at https://www.cdc.gov/hepatitis-surveillance-2023/hepatitis-a/index.html.
[55] CDC, Hepatitis A Surveillance, 2023 Viral Hepatitis Surveillance Report, available at https://www.cdc.gov/hepatitis-surveillance-2023/hepatitis-a/index.html; CDC, Hepatitis A Outbreaks, available at https://www.cdc.gov/hepatitis-a/outbreaks/.
[56] Id.
[57] Id.
[58] Swart E, et al., “Healthcare resource utilization and costs associated with hepatitis A in the United States: a retrospective database analysis,” J Med Econ. (2024), available at https://pubmed.ncbi.nlm.nih.gov/39092467/ (mean cost $2,520 per patient in 2020 USD; $17,373 for hospitalized patients); Welch C, et al., “Hepatitis A Hospitalization Costs, United States, 2017,” Emerg. Infect. Dis., Vol. 26, No. 5 (May 2020), available at https://wwwnc.cdc.gov/eid/article/26/5/19-1224_article (estimating outbreak hospitalization costs exceeded $306.8 million as of Feb. 2020).
[59] Bownds, Lynne, et al., “Economic Impact of a Hepatitis A Epidemic in a Mid-Sized Urban Community: The Case of Spokane, Washington,” Journal of Community Health, Vol. 28, No. 4, pp. 233-46 (2003). Abstract at http://www.ncbi.nlm.nih.gov/pubmed/12856793; Fiore, Anthony, et al., Advisory Committee on Immunization Practices (ACIP), Prevention of Hepatitis-A Through Active or Passive Immunization: Recommendations,” supra note 20.
[60] Scharff, RL, et al., “Economic Cost of Foodborne Illness in Ohio,” Journal of Food Protection, Vol. 72, No. 1, pp. 128-36 (2009). Abstract available online at http://www.ingentaconnect.com/content/iafp/jfp/2009/00000072/00000001/art00018.
[61] CDC, “Surveillance for Acute Viral Hepatitis – United States 2007,” supra note 13; CDC, “Hepatitis A,” supra note 5.
[62] CDC, “Hepatitis A,” supra note 5; Fiore, Anthony, et al., Advisory Committee on Immunization Practices (ACIP), Prevention of Hepatitis-A Through Active or Passive Immunization: Recommendations,” supra note 20.