Hepatitis A – HAV – Pathogenesis, Epidemiology, Caces and Diagnosis

Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus (HAV), which is most commonly transmitted by the fecal-oral route via contaminated food or drinking water. Every year, approximately 10 million people worldwide are infected with the virus. The time between infection and the appearance of the symptoms, (the incubation period), is between two and six weeks and the average incubation period is 28 days.

In developing countries, and in regions with poor hygiene standards, the incidence of infection with this virus is high and the illness is usually contracted in early childhood. HAV has also been found in samples taken to study ocean water quality. Hepatitis A infection causes no clinical signs and symptoms in over 90% of these children and since the infection confers lifelong immunity, the disease is of no special significance to the indigenous population. In Europe, the United States and other industrialized countries, on the other hand, the infection is contracted primarily by susceptible young adults, most of whom are infected with the virus during trips to countries with a high incidence of the disease.

Hepatitis A does not HAVe a chronic stage and does not cause permanent liver damage. Following infection, the immune system makes antibodies against HAV that confer immunity against future infection. The disease can be prevented by vaccination and hepatitis A vaccine has been proven effective in controlling outbreaks worldwide.


Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine. The blood carries the virus to its target, the liver, and multiplies within hepatocytes and Kupffer cells (i.e., liver macrophages). There is no apparent virus-mediated cytotoxicity, and liver pathology is likely immune-mediated. Virions are secreted into the bile and released in stool. HAV is excreted in large quantities approximately 11 days prior to appearance of symptoms or anti-HAV IgM antibodies in the blood. The incubation period is 15-50 days, and mortality is less than 0.5%.


The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and contains a single-stranded RNA packaged in a protein shell. There is only one type of the virus.



Hepatitis A Distribution 2005

HAV is found in the feces of infected persons and those who are at higher risk include travelers to developing countries where there is a higher incidence rate, and those HAVing sexual contact or drug use with infected persons. There were 30,000 cases of Hepatitis A reported to the CDC in the U.S. in 1997. The agency estimates that there were as many as 270,000 cases each year from 1980 through 2000.


The virus spreads by the fecal-oral route and infections often occur in conditions of poor sanitation and overcrowding. Hepatitis A can be transmitted by the parenteral route but very rarely by blood and blood products. Food-borne outbreaks are not uncommon, and ingestion of shellfish cultivated in polluted water is associated with a high risk of infection. Approximately 40% of all acute viral hepatitis is caused by HAV. Infected individuals are infectious prior to onset of symptoms, roughly 10 days following infection. The virus is resistant to detergent, acid (pH 1), solvents (e.g., ether, chloroform), drying, and temperatures up to 60oC. It can survive for months in fresh and salt water. Common-source (e.g., water, restaurant) outbreaks are typical. Infection is common in children in developing countries, reaching 100% incidence, but following infection there is life-long immunity. HAV can be inactivated by: chlorine treatment (drinking water), formalin (0.35%, 37oC, 72 hours), peracetic acid (2%, 4 hours), beta-propiolactone (0.25%, 1 hour), and UV radiation (2 μW/cm2/min).


The most widespread hepatitis A outbreak in the United States afflicted at least 640 people (killing four) in north-eastern Ohio and south-western Pennsylvania in late 2003. The outbreak was blamed on tainted green onions at a restaurant in Monaca, Pennsylvania. In 1988, 300,000 people in Shanghai, China were infected with HAV after eating clams from a contaminated river.

Medical aspects


For about the vaccine, its properties, and its application, see Hepatitis A vaccine.

Hepatitis A can be prevented by vaccination, good hygiene and sanitation. Hepatitis A is also one of the main reasons not to surf or go in the ocean after rains in coastal areas that are known to HAVe bad runoff.

The vaccine protects against HAV in more than 95% of cases for 10 years. It contains inactivated Hepatitis A virus providing active immunity against a future infection. The vaccine was first phased in 1996 for children in high-risk areas, and in 1999 it was spread to areas with elevating levels of infection.

The vaccine is given in two doses in the muscle of the upper arm. The first dose provides protection two to four weeks after initial vaccination; the second booster dose, given six to twelve months later, provides protection for up to twenty years.


Serum IgG, IgM and ALT following Hepatitis A virus infection

Although HAV is excreted in the feces towards the end of the incubation period, specific diagnosis is made by the detection of HAV-specific IgM antibodies in the blood. IgM antibody is only present in the blood following an acute hepatitis A infection. It is detectable from one to two weeks after the initial infection and persists for up to 14 weeks. The presence of IgG antibody in the blood means that the acute stage of the illness is past and the person is immune to further infection. IgG antibody to HAV is also found in the blood following vaccination and tests for immunity to the virus are based on the detection of this antibody.

During the acute stage of the infection, the liver enzyme alanine transferase (ALT) is present in the blood at levels much higher than is normal. The enzyme comes from the liver cells that HAVe been damaged by the virus.

Hepatitis A virus is present in the blood, (viremia), and feces of infected people up to two weeks before clinical illness develops.


The United States Centers for Disease Control and Prevention (CDC) in 1991 reported a low mortality rate for hepatitis A of 4 deaths per 1000 cases for the general population but a higher rate of 17.5 per 1000, in those aged 50 and over. Death usually occurs when the patient contracts Hepatitis A while already suffering from another form of Hepatitis, such as Hepatitis B or Hepatitis C or AIDS.

Young children who are infected with hepatitis A typically HAVe a milder form of the disease, usually lasting from 1-3 weeks, whereas adults tend to experience a much more severe form of the disease.