HEPATITIS A

Hepatitis A, also known as infectious or epidemic hepatitis is worldwide in distribution, occurring mainly in children and young adults. 

Etiology: 
The disease is caused by Hepatitis A virus, which was previously classified as Enterovirus 72 under the family picrornaviridae. It was discovered in 1973 by immunoelectronmicroscopy from feces. Genomic analysis has revealed that it is sufficiently different from enteroviruses, hence it has been assigned a new genus hepatovirus. There is only one serotype of Hepatitis A virus. It is a non-enveloped virus with icosahedral symmetry that measures 27 nm. The nucleic acid is a single stranded positive sense RNA. It is rapidly destroyed by heating at temperatures above 85^oC and is stable at low pH.

Mode of infection: 
Hepatitis A virus is spread by the fecal-oral route, person-to-person contact; and under conditions of poor sanitation and overcrowding. Person-to-person transmission of hepatitis A virus from one individual to another by hand contact is also known to occur. Many outbreaks are most frequently initiated by fecal contamination of water and food. Infection may occur by eating raw or partially cooked contaminated shellfish grown in polluted waters. Transmission has been documented to have occurred from infected food handlers. There are no known carriers or animal reservoirs.

Pathogenesis:
The incubation period of hepatitis A is 3-5 weeks, with a mean of 28 days. 

Symptoms develop gradually. Clinical presentation of HAV infection varies from subclinical and mild in children to jaundice in adults. The severity of illness ranges from the asymptomatic to anicteric or icteric hepatitis. The virus usually enters by intestinal infection, replicates in the intestinal epithelium, viremia transports the virus to the liver where secondary virus multiplication in the hepatocytes and Kupffer cells results in infectious hepatitis A. Pathogenesis involves necrosis of parenchymal cells and histiocytic periportal inflammation, may be mediated by cellular immune responses.

Symptoms include loss of appetite, malaise, fever and vomiting, followed by jaundice. Illness usually lasts a few weeks but may last several months, and is usually more severe in adults than in children. Death may occur, particularly in the elderly, but is very rare. Large numbers of virus particles may be shed in the urine and feces during the latter part of the long incubation, before jaundice is apparent, but may be absent one week after the onset of jaundice. There is no evidence that hepatitis A causes persistent infections. Hepatitis A usually heals spontaneously with no complications. 

Immune Response:
The onset of clinical symptoms coincides with the development of antibodies. Antibody to hepatitis A virus develops late in the incubation period. Specific hepatitis A IgM is found in the serum within 1 week from the onset of dark urine, reaching maximum levels after 1 week and declining slowly during the next 40-60 days. Specific IgG antibody appears shortly after IgM is detectable, reaching a maximum titer after 60-80 days. This antibody is protective and persists for many years. Antibodies help to clear virus from the body via complement and antibody-dependent cell-mediated cytotoxicity, which may account for some of the liver damage.

Laboratory Diagnosis:

• Specimens collected are serum for liver enzymes and serology and feces for detection of viruses.

• HAV is detectible in the feces during the incubation period, preceding a rise in serum levels of aminotransferase enzymes. Hepatitis A virus can be detected in faeces by electron microscopy, but is usually not possible; because by the time jaundice occurs the peak of excretion of virus particles has passed.

• Diagnosis is based on detection of specific IgM and IgG antibodies in the blood serum or saliva. The detection of IgM or rising titres of IgG in the serum of the patient would indicate active disease. Various serologic tests are available for hepatitis A, including immune electron microscopy, complement-fixation, immune adherence hemagglutination, radioimmunoassay, and enzyme immunoassay.

• Isolation of virus in tissue culture requires prolonged adaptation and it is, therefore, not suitable for diagnosis.

Prophylaxis:

• Passive protection may be obtained by the administration of pooled normal human immunoglobulin, containing at least 100 IU/ml of anti-HAV given intramuscularly at a dose of 2 IU/kg body weight.

• The hepatitis A vaccine (Havrix) consists of killed formalin-inactivated virus that is adsorbed to aluminum hydroxide and given intramuscularly. Immunization requires an initial IM injection followed by a booster shot 6 to 12 months later.

• Control can be achieved via public education on transmission modes and personal hygiene. Adequate sewage disposal and uncontaminated water supplies are critical for prevention of Hepatitis A infections. Sufficient chlorination of water (1 ppm of total residual chlorine or 0.4 ppm of free residual chlorine) can inactivate the virus.