An Introduction to Hepatitis A
Exposure to the hepatitis A virus can cause an acute infection of the liver that is typically mild and resolves on its own. [11, 17] The symptoms and duration of illness vary a great deal, with many persons showing no symptoms at all.  Fever and jaundice are two of the symptoms most commonly associated with a hepatitis A infection. 
It has been written that the “earliest accounts of contagious jaundice are found in ancient China.”  According to the CDC,
The first descriptions of hepatitis (epidemic jaundice) are generally attributed to Hippocrates. Outbreaks of jaundice, probably hepatitis A, were reported in the 17th and 18th centuries, particularly in association with military campaigns. Hepatitis A (formerly called infectious hepatitis) was first differentiated epidemiologically from hepatitis B, which has a long incubation period, in the 1940s. Development of serologic tests allowed definitive diagnosis of hepatitis B. In the 1970s, identification of the virus, and development of serologic tests helped differentiate hepatitis A from other types of non-B hepatitis.
Until 2004, hepatitis A was the most frequently reported type of hepatitis in the United States. In the pre-vaccine era, the primary methods used for preventing hepatitis A were hygienic measures and passive protection with immune globulin (IG). Hepatitis A vaccines were licensed in 1995 and 1996. These vaccines provide long-term protection against hepatitis A virus (HAV) infection. 
Consequently, hepatitis A is the only common vaccine-preventable foodborne disease in the United States. [7, 12] This virus is one of five human hepatitis viruses that primarily infect the human liver and cause human illness.  Unlike hepatitis B and C, hepatitis A does not develop into chronic hepatitis or cirrhosis, which are both potentially fatal conditions, [7, 11, 17] Nonetheless, infection with the hepatitis A virus (HAV) can lead to acute liver failure and death. [12, 17]
The Incidence of Hepatitis A Infections
Hepatitis A is much more common in countries with underdeveloped sanitation systems and, thus, is a risk in most of the world. [11, 16] 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.  Nevertheless, infections continue to occur in the United States, where approximately one-third of the population has been previously infected with HAV. [6, 12]
Each year, approximately 30,000 to 50,000 cases of hepatitis A occur in the United States. [5, 7] Historically, acute hepatitis A rates have varied cyclically, with nationwide increases every 10 to 15 years.  The national rate of HAV infections has declined steadily since the last peak in 1995. [5, 6] Although the national incidence—1.0 case per 100,000 population—of hepatitis A was the lowest ever recorded in 2007, it is estimated that asymptomatic infections and underreporting kept the documented incidence-rate lower than it actually is. In fact, it is estimated that there were 25,000 new infections in 2007. [6, 22]
Although the rates of HAV infection have declined over the years, rates are twice as high among American Indians and Alaskan Natives.  Hispanics are also twice as likely to be infected compared to non-Hispanic Whites in the United States. . Rates among American Indians and Alaskan Natives have decreased dramatically, largely as a result of increased vaccination of children in both urban and rural communities. 
In 2007, the CDC reported a total of 2,979 acute symptomatic cases of hepatitis A.  Of these, information about food and water exposure was known for 1,047 cases, leading to an estimate that 6.5% of all infections were caused by exposure to contaminated water or food.  In 2,500 of the cases, no known risk factor was identified. 
Estimates of the annual costs (direct and indirect) of hepatitis A in the United States have ranged from $300 million to $488.8 million in 1997 dollars.  In one study conducted in Spokane, Washington, the combined direct and indirect costs for each case of hepatitis A from all sources ranged from $2892 to $3837. [2, 13] 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.  Nationwide, adults who become ill miss an average of 27 workdays per illness, and 11-to-22 percent of those infected are hospitalized. [6, 7] All of these costs are entirely preventable given the effectiveness of a vaccination in providing immunity from infection. [7, 13]
How is Hepatitis A transmitted?
Hepatitis A is a communicable (or contagious) disease that often spreads from person to person.  Person-to-person transmission occurs via the “fecal-oral route,” while all other exposure is generally attributable to contaminated food or water. [11, 16] Food-related outbreaks are usually associated with contamination of food during preparation by a HAV-infected food handler. [6, 7, 12] 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. 
Fresh produce contaminated during cultivation, harvesting, processing, and distribution has also been a source of hepatitis A. [12, 25] In 1997, frozen strawberries were the source of a hepatitis A outbreak in five states.  Six years later, in 2003, fresh green onions were identified as the source of a hepatitis A outbreak traced to consumption of food at a Pennsylvania restaurant.  Other produce, such as blueberries and lettuce, has been associated with hepatitis A outbreaks in the U.S. as well as other developed countries. [3, 4]
HAV is relatively stable and can survive for several hours on fingertips and hands and up to two months on dry surfaces. [11, 17] 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 sodium hypochlorite (household bleach) in tap water. [8, 13, 24] It must be noted, however, that HAV can still be spread from cooked food if it is contaminated after cooking. 
Although ingestion of contaminated food is a common means of spread for hepatitis A, it may also be spread by household contact among families or roommates, sexual contact, or by direct inoculation from persons sharing illicit drugs. [12, 17] 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. [11, 18, 22]
Symptoms of Hepatitis A Infection
Hepatitis A may cause no symptoms at all when it is contracted, especially in children.  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.  Approximately 10 to 12 days after exposure, HAV is present in blood and is excreted via the biliary system into the feces. [7, 11] Although the virus is present in the blood, its concentration is much higher in feces.  HAV excretion begins to decline at the onset of clinical illness, and decreases significantly by 7 to 10 days after onset of symptoms.  Most infected persons no longer excrete virus in the feces by the third week of illness; children may excrete HAV longer than adults. [11, 20]
Seventy percent of hepatitis A 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.  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. [7, 11, 12] The symptoms include muscle aches, headache, anorexia (loss of appetite), abdominal discomfort, fever, and malaise. [[7, 11, 17]
After a few days of typical symptoms, jaundice (also termed “icterus”) sets in. [11, 17] 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.  The urine will also turn dark with bile and the stool light or clay-colored from lack of bile. [7, 11, 17] When jaundice sets in, initial symptoms such as fever and headache begin to subside. 
In general, symptoms usually last less than 2 months, although 10% to 15% of symptomatic persons have prolonged or relapsing disease for up to 6 months. [13, 14] It is not unusual, however, for blood tests to remain abnormal for six months or more.  The jaundice so commonly associated with hepatitis A can also linger for a prolonged period in some infected persons—sometimes as long as eight months or more. [11, 17] 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. [7, 17]
Relapse is possible with hepatitis A, typically within three months of the initial onset of symptoms.  Although relapse is more common in children, it does occur with some regularity in adults. [11, 14] The vast majority of persons who are infected with hepatitis A fully recover, and do not develop chronic hepatitis.  Persons do not carry hepatitis A long-term as with hepatitis B and C. [5, 7]
Fulminant Hepatitis A
Fulminant hepatitis A is a rare but devastating complication of HAV infection.  As many as 50% of individuals with acute liver failure may die or require emergency liver transplantation.  Elderly patients and patients with chronic liver disease are at higher risk for fulminant hepatitis A. [11, 23] In parallel with a declining incidence of acute HAV infection in the general population, however, the incidence of fulminant HAV appears to be decreasing. 
HAV infects the liver’s parenchymal cells (internal liver cells). [10, 11] Once a cell has been penetrated by the viral particles, the hepatitis A virus releases its own toxins that cause, in essence, a hostile takeover of the host’s cellular system. [11, 22] The cell then produces new viral components that are released into the bile capillaries or tubes that run between the liver’s parenchymal cells.  This process results in the death of liver cells, called hepatic necrosis. [11, 23]
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. [10, 23] Aside from the loss of liver function, fulminant hepatic failure can lead to encephalopathy and cerebral edema.  Encephalopathy is a brain disorder that causes central nervous system depression and abnormal neuromuscular function. [10, 11] Cerebral edema is a swelling of the brain that can result in dangerous intracranial pressure.  Intracranial hypertensions leading to brain stem death and sepsis with multiple organ failure are the leading causes of death in individuals with fulminant hepatic failure. [10, 23]
How is Hepatitis A Infection Diagnosed?
The various human hepatitis viruses cause very similar illnesses.  Therefore, neither the individual nor the healthcare provider can tell by symptoms or signs if a given individual is suffering from hepatitis A unless laboratory tests are performed. [7, 17]
Fortunately, blood tests are widely available to accurately diagnose hepatitis A, including tests for antibodies, or the affected person’s immune response to hepatitis A proteins.  This immune response is conclusively demonstrated by the presence of Immunoglobulin M (IgM) antibodies, indicating acute disease, and immunoglobulin G (IgG), indicating a past infection. [11, 13] The IgG antibodies are present for life, indicating immunity.  Following is some guidance for the interpretation of the test results:
- IgM negative / IgG negative: Most persons with these results have never contracted hepatitis A. Antibodies of the IgM variety develop five to ten days prior to the onset of symptoms.
- IgM positive / IgG negative: This result indicates acute hepatitis A.
- IgM positive / IgG positive: This result indicates that acute hepatitis A occurred within the last six months. By six months, the IgM reverts to negative.
- IgM negative / IgG positive: Persons with this result are immune to hepatitis A. They have either been infected with the virus months or years in the past (with or without symptoms), or they have been vaccinated for hepatitis A. However, if they are currently ill, it is not likely to be due to hepatitis A.
Treatment for Acute Hepatitis A Infection
Once a clinical infection is established, there is no specific treatment for hepatitis A. Affected individuals generally suffer from loss of appetite, so the main concern is ensuring a patient receives adequate nutrition and avoids permanent liver damage. [7, 17] An individual’s perception of the severity of fatigue or malaise is the best determinant of the need for rest. 
Treatment of those suffering from fulminant hepatic failure depends largely on the affected person’s status. [23, 26] Those who have not become encephalopathic generally undergo an intense course of supportive treatment. [10, 23] But for those whose liver failure is so complete that it has lead to encephalopathy or cerebral edema, timely liver transplantation is often the only option. [10, 14] Unfortunately, many individuals with irreversible liver failure do not receive a transplant because of contraindications or the unavailability of donor livers. [11, 23]
Real Life Impacts
The number of acute hepatitis A infections in the U.S. drastically fell in the first part of the 21st Century, largely in part because hepatitis A vaccination was recommended for persons in groups shown to be at high risk for infection and children living in communities with high rates of disease beginning in 1996. By 2006, hepatitis A vaccine had been incorporated into the Advisory Committee on Immunization Practices’ recommended childhood vaccination schedule. 
Despite a decrease in the number of hepatitis A cases reported annually, anyone who has not been vaccinated is at increased risk for contracting hepatitis A infection. Persons over the age of 50, those with chronic liver disease, and immunocompromised individuals who have not been vaccinated against hepatitis A remain most at risk for developing fulminant hepatitis, a rare but devastating complication of a hepatitis A infection that can lead to the need for a liver transplant, or death. See, 27 year history of Hepatitis A outbreaks at Outbreak Database.
How to Prevent Hepatitis A Infection
Hepatitis A is totally and completely preventable.  Although outbreaks continue to occur in the United States, no one should ever get infected if preventive measures are taken. [7, 12] For example, food handlers must always wash their hands with soap and water after using the bathroom, changing a diaper, and certainly before preparing food. [12, 24] Food handlers should always wear gloves when handling or preparing ready-to-eat foods, although gloves are not a substitute for good hand washing. Ill food-handlers should be excluded from work. [14, 24]
After exposure, immune globulin (IG) is 80% to 90% effective in preventing clinical hepatitis A when administered within 2 weeks of last exposure.  Although efficacy is greatest when IG is administered early in the incubation period, when administered later, IG is still likely to make the symptoms less severe. [9, 11] Given the lack of appropriately designed studies comparing the post exposure efficacy of vaccine with that of IG, the Advisory Committee on Immunization Practices (ACIP) recommends IG exclusively for post-exposure.  Hepatitis A vaccine, if recommended for other reasons, could be given at the same time. [9, 13]
In 2006, the ACIP recommended routine hepatitis A vaccination for all children ages 12-23 months, that hepatitis A vaccination be integrated into the routine childhood vaccination schedule, and that children not vaccinated by two years of age be vaccinated subsequently. [9, 13] The vaccine is recommended for the following persons:
- Travelers to areas with increased rates of hepatitis A
- Men who have sex with men
- Injecting and non-injecting drug users
- Persons with clotting factor disorders (e.g. hemophilia)
- Persons with chronic liver disease
- Persons with occupational risk of infection (e.g. those who work with hepatitis A-infected primates or with hepatitis A virus in a laboratory setting)
- Children living in regions of the U.S. with increased rates of hepatitis A
- Household members and other close personal contacts (such as regular babysitters) of adopted children newly arriving from countries with high or intermediate rates of hepatitis A. 
The vaccine may also help protect household contacts of those persons infected with hepatitis A. [9, 20] Although generally not a legal requirement at this time, vaccination of food handlers would be expected to substantially diminish the incidence of hepatitis A outbreaks.  Persons traveling to a high-risk area less than four weeks after receiving the initial dose of hepatitis A vaccine, or travelers who choose not to be vaccinated against hepatitis A should receive a single dose of Immune Globulin, which provides protection against hepatitis A infection for up to three months. [9, 11, 18]
1. Bialek, Stephanie, et al., “Hepatitis A Incidence and Hepatitis A Vaccination among American Indians and Alaska Natives, 1990–2001,” American Journal of Public Health.Vol. 94, No. 6, pp. 996-1001 (2004). Full text of article is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1448379/pdf/0940996.pdf.
2. 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. 233-246 (2003). Abstract available online at http://www.ncbi.nlm.nih.gov/pubmed/12856793
3. Butot S, et al., “Effects of Sanitation, Freezing and Frozen Storage on Enteric Viruses in Berries and Herbs,” International Journal of Food Microbiology, Vol. 126, pp. 30-35 (2008). Full text of article is available at http://www.prograd.uff.br/virologia/sites/default/files/bulot_et_al_2008_inactivation.pdf
4. Calder, L, et al., “An Outbreak of Hepatitis A Associated with Consumption of Raw Blueberries,” Epidemiology and Infection, Vol. 131, No. 1, 745-751 (2003) at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870016/pdf/12948375.pdf
5. 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
6. 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
7. CDC, “Hepatitis A,” in EPIDEMIOLOGY AND PREVENTION OF VACCINE-PREVENTABLE DISEASES (also known as “The Pink Book”), Atkinson W, Wolfe S, Hamborsky J, McIntyre L, editors, 12th edition. Chapter available online at http://www.cdc.gov/vaccines/pubs/pinkbook/hepa.html
8. 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, 2009), http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a4.htm
9. 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.
10. 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
11. Feinstone, Stephen and Gust, Ian, “Hepatitis A Virus,” in Mandell, Douglas, & Bennett’s PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES, Fifth Edition, Chap. 161, pp. 1920-40 (2000).
12. Fiore, Anthony, Division of Viral Hepatitis, CDC, “Hepatitis A Transmitted by Food,” Clinical Infectious Diseases, Vol. 38, 705-715 (March 1, 2004). Full text online at http://www.cdc.gov/hepatitis/PDFs/fiore_ha_transmitted_by_food.pdf
13. 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 19, 2006) at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm
14. 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
15. Hutin YJF, et al., “A Multistate, Foodborne Outbreak of Hepatitis A,” New England Journal of Medincine, Vol. 340, pp. 595–602 (1999). Full text of article is online at http://www.nejm.org/doi/full/10.1056/NEJM199902253400802
16. 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
17. Mayo Clinic Staff, “Hepatitis A,” (last updated Sept. 1, 2011). Articles available online at http://www.mayoclinic.com/health/hepatitis-a/DS00397 .
18. Piazza, M, et al., “Safety and Immunogenicity of Hepatitis A Vaccine in Infants: A Candidate for Inclusion in Childhood Vaccination Program,” Vaccine. Vol. 17, pp. 585-588 (1999). Abstract at http://www.ncbi.nlm.nih.gov/pubmed/10075165
19. Rawls, R.A. and Vega, K.J., “Viral Hepatitis in Minority America,” Journal of Clinical Gastroenterology, Vol. 39, No. 2, pp. 144–151 (Feb. 2005). Abstract is at http://www.ncbi.nlm.nih.gov/pubmed/15681912
20. 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
21. Scharff, RL, et al., “Economic Cost of Foodborne Illness in Ohio,” Journal of Food Protection, Vol. 72, No. 1, pp. 128-136 (2009). Abstract available online at http://www.ingentaconnect.com/content/iafp/jfp/2009/00000072/00000001/art00018
22. 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
23. Taylor, Ryan, et al., “Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes,” Hepatology, Vol. 44, 1589-1597 (2006). Full text http://deepblue.lib.umich.edu/bitstream/2027.42/55879/1/21439_ftp.pdf
24. 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, 202-219 (2009). Full text of the article is available online at http://courses.washington.edu/eh451/articles/Todd_2009_food%20processing.pdf
25. Wheeler, C, et al., “An Outbreak of Hepatitis A Associated with Green Onions,” New England Journal of Medicine, Vol. 353, 890-897 (2005). Full text of article available at http://www.nejm.org/doi/full/10.1056/NEJMoa050855
26. Willner, IR, et al., “Serious Hepatitis A: An Analysis of Patients Hospitalized During an Urban Epidemic in the United States,” Annals of Internal Medicine, Vol. 128, No. 2, pp. 111-114 (Jan. 15, 1998). Full text of the article is available at http://www.annals.org/content/128/2/111.full.pdf+html
27. CDC. “Prevention of Hepatitis A through Active or Passive Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP),” Morbidity and Mortality Weekly Report, Vol. 55, (RR07), pp. 1-23 (May 29, 2006) online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm