Hepatitis A Virus

The most common causative organism of acute hepatitis in tropical countries is Hepatitis A virus. Hepatitis A viral infection may be asymptomatic or may present as acute hepatitis, which is a self limiting disease. Fulminant hepatitis is very uncommon and chronic liver disease is almost never seen, unlike Hepatitis B and Hepatitis C infections.

Classification

Hepatitis A virus (HAV) belongs to the family Picornaviridae along with the human Rhinoviruses and Enteroviruses. Though it was orginally called Enterovirus 72, it has recently been reclassified and now has  its own genus known as Heparnavirus, within the family Picornaviridae. It is a spherical, 27 to 28 nm in size, non-enveloped virus with a single stranded RNA genome.

Resistance to disinfectants

Unlike other picornaviruses, HAV is more heat resistant but can be completely destroyed by heat at 60°C after exposure for 10 to 12 hours. In food, it can be rendered harmless when exposed to temperatures > 85°C for 1 minute. HAV is capable of surviving on shellfish, water and soil for many days. Outbreaks of HAV induced hepatitis following ingestion of steamed shellfish have proven the survival potential of the virus under such conditions. Autoclaving at 121°C for 30 minutes is the most reliable method of destroying the virus.

Since HAV is a non-enveloped virus it is resistant to the majority of organic solvents and detergents utilized for the purpose of surface disinfection. It can even survive at a pH of 3. Additionally, it can be deactivated by using hypochlorite (bleach) and quaternary ammonium compounds containing 23 % hydrochloric acid.

Host range

Humans are the only crucial reservoirs for HAV, though studies have shown that disease can be introduced in other primates such as chimpanzees or tamarins. Studies have proved that the disease can be spread from infected primates to humans even though the primates might be contained. Screening of nonhuman primates like orangutans, chimpanzees, tamarins, gibbons, etc., have shown antibodies to HAV. This is indicative that these animals may serve either as reservoirs or transient hosts after exposure to HAV from infected human sources.

Transmission of HAV

The virus multiplies in the liver and is excreted via the bile. The maximum concentration of the virus can be found in the feces from which it can readily be shed. This is the primary source of the virus. Experimental studies have demonstrated fecal shedding to take place 14 to 21 days prior to the appearance of jaundice and up to 8 days after the onset of jaundice. Maximum shedding has been observed to occur 2 weeks before the onset of jaundice. Also, children tend to shed the virus for a much longer time than adults.  This can be up to 3 months after clinical illness. No chronic shedding of the virus is notable.  Other modes of transmission follow:

• Person to person: This is the primary mode of transmission of HAV. Children have the highest incidence of infection and also become an important source of infection for further spread of the disease.
• Food: Contaminated food has been an important source of large scale outbreaks. The virus is known to survive in uncooked or partially cooked food for an extended period of time. This mode of transmission is common in the acquisition of infection among travelers. People visiting developing countries must be diligent about the food and water they ingest in order to prevent infection.
• Transfusion associated HAV infections: This is a very rare occurrence, however outbreaks have been reported in Europe and United States due to blood transfusion from donors in the viremic phase.
• Vertical transmission: There have been two reported cases of vertical transmission during the first trimester of pregnancy with involvement of fetal meconium peritonitis. The newborns were diagnosed with perforated ileum in both the cases. The risk of transmission during the third trimester is low and newborns acquiring infection during this time are often asymptomatic.

Clinical features

The oro-fecal route is the primary mode of transmission while age is the most important determinant of presentation of clinical illness. Asymptomatic infection is frequently noted in children under than 5 years of age. The incubation period ranges from 1 to 4 weeks.  A mild flu-like prodromal illness is observed preceding the onset of jaundice. The patient complains of malaise, fever associated with chills and pain in the upper abdomen. Loss of appetite is a common symptom and the patient experiences extreme nausea when presented with the smell of fatty foods. The patient seeks medical advice after the onset of high colored urine and yellow discoloration of sclera, skin and mucous membranes. Clay colored stools and itching are the features of cholecystitis. There is a rise in the specific liver enzymes and bilirubin levels, which takes about 3 to 4 weeks to return to normal. This corresponds to the period of clinical recovery.

Prevention of HAV infections

The most crucial method for the prevention and control of hepatitis A is improvement in the standards of sanitation and hygiene and provision of clean, safe drinking water. The standard to prevent traveler’s diarrhea ‘boil it, cook it, peel it or forget it’ also applies to prevention of Hepatitis A infections.

Immunization

• Passive: Before the vaccines for HAV were licensed, the mainstay of prophylaxis was passive immunization with pooled IgG of infected patients. Several studies have shown the efficacy of immunoglobulins for pre- exposure prophylaxis. The recommended dose is 0.2 ml/kg.
• Active: There are two killed vaccines (Havrix, GSK and Vaqta, Merck) licensed by the US FDA for use. They are grown in MRC – 5 cells, inactivated with formalin and formulated with the addition of alum as an adjuvant. The vaccines become effective after 2 weeks of intramuscular dosing. For individuals who are likely to be exposed repeatedly, a booster dose is recommended 6 to 12 months after the first dose. Various clinical trials have shown that the deactivated virus vaccines are safe, effective and provide protection for a minimum of 10 years if the booster is also taken.  A protective level of antibodies for preventing hepatitis is 10 to 20 mIU/ml. The deactivated virus induces protective antibody levels within 2 weeks of vaccination. 
• Live candidate vaccines CR326 and HM 175 have been tested in primates and, to a limited extent, in humans. It has been discovered that very high inoculating doses are required for inducing antibody response with the live virus candidate vaccine. The remaining challenge is to produce live strains which will be attenuated as well as highly immunogenic in order to protect against hepatitis A infections.