Hepatitis A Virus

Sample

1. Venous blood is needed to prepare the serum.
2. Random sampling can be used.
3. The serum can be stored at 4 °C for 5 days.
4. Feces can be taken for immuno-electron microscopy.

Purpose of the test (Indications)

• To diagnose viral hepatitis A (HAV) infection.

Definition of Hepatitis A Virus (HAV)

1. Hepatitis A viral infection is also called Infectious hepatitis or short incubation hepatitis.
2. Hepatitis virus A is a non-enveloped virus that belongs to the hepatotropic virus family and is 27 nm in diameter.
3. HAV belongs to the Picornaviridae family.
   1. It is a picornavirus.
   2. Genus is a hapatovirus.
4. There is no cross-reactivity with HBV or other hepatotropic viruses.

Structure of the virus:

1. It consists of a linear single-stranded RNA virus (ssRNA) genome with 7.5 kb.
2. It measures 27 to 32 nm spherical particles with cubic symmetry.
3. VPg is a Viral protein genome-linked. It is a protein attached to the positive strand of viral RNA.
   1. VPg acts as a primer during RNA synthesis.
4. HAV is a self-limiting acute liver disease.
   

   Hepatitis A virus (HAV) structure

The incubation period of HAV infection:

1. The incubation period is short, 3 to 4 weeks (range is 2 to 6 weeks).
2. It is highly infective during active infection and is excreted in the stool.
3. It will spread through contaminated water or food.
4. Urine and alive are less infective than the stool.
5. A great number of virus appears in the stool before the symptoms appear.
6. The number of viruses decreases as the symptoms appear.
7. Complete recovery in1 to 3 weeks and no carrier state.
8. An occasional patient may have the longer disease for almost one year.

Mode of the spread of HAV infection:

1. Initially, it was found in the stool and liver by E/M.
2. It is a highly contagious viral infection and is most common in children.
   1. Most children recover from the disease and develop lifelong immunity.
   2. It is common in daycares and orphanages.
3. In the active stage, this virus is excreted in the stool.
4. So there is an oro-fecal spread because of the contamination of food and drinks.
5. Sexual transmission between male homosexuals has been reported.
6. Transmission via blood transfusion and I/V drug use is rare.
7. It is most common in the third world, almost 90% to 100%.
   

   Hepatitis A virus (HAV) spread

The clinical course of Hepatitis A virus (HAV):

1. Mostly asymptomatic.
2. >50% cases are subclinical, anicteric hepatitis.
3. The most common age group is children.
4. There may be a prodromal period of fever, chills, fatigue, malaise, and headache.
   1. The above symptoms will be followed by nausea and vomiting.
5. There is anorexia.
6. Sometimes there may be abdominal pain which is usually in the upper quadrant.
7. Sometimes there may be gastroenteritis.
8. When jaundice appears, then there is rapid improvement in the clinical symptoms.
   1. Jaundice may last for a few days to 12 weeks.
   2. Usually not infective after the appearance of jaundice.

Outcome HAV infection:

1. There is mild to severe disease.
2. Mostly recovered from the HAV infection and gets life-long immunity.
3. Very few die of HAV infection with fulminant hepatitis.

Summary of the HAV infection:

Parameters	Characteristic features
Family	Picronaviridae
Genus	Hepatotropic virus
Transmission	Oro-fecal route
Size	27 nm
Genome	ssRNA Virus
Genome size	7.5 kb
Envelop	Absent
Stability	Heat stable = 60°C for one hour Acid stable = pH 1.0 for 2 hours Ether 20% When dried can survive for one month at 25 °C For years at -20°C
Destroyed	By autoclave at 121°C for 20 minutes Boiling water for 5 minutes Dry heat = 180 °V for one hour Ultraviolet radiation for one minute Heating food >85 °C for one minute Formaline at 37 °C for 3 days Sodium hypochlorite  1:10 dilution
Acute infection	Anti-HAV-IgM
Immune status	Anti-HAV-IgG
Fulminant hepatitis	Rarely seen
Chronicity	Never seen
Oncogenicity	It is not oncogenic

High-risk group:

1. Child-care centers.
2. The family members who are in close contact with the patient.
3. In the summer camps.
4. People are working in correctional centers.
5. In homosexual peoples.

Immunology:

1. The first antibody in acute infection is IgM type (HAV-IgM)
2. IgM appears 3 to 4 weeks after exposure to the virus or before the liver function tests are raised.
   1. IgM returns to normal in roughly 8 weeks or disappears in 3 to 4 months. It is not detectable after 12 months.
3. HAV-IgG appears after 2 weeks when IgM is increasing.
   1. Now IgM slowly comes to normal, and IgG will be present in the blood.
   2. HAV-IgG will be detectable in the blood even after 10 years.

      1. Disease stage	IgM	IgG
         Acute infection	Positive	Negative
         Later on	Positive	Positive
         Immunity	Negative	Positive
         Repeat test 2 weeks later	Not done	Negative

Diagnosis:

1. SGPT and SGOT have raised the varying range to hundreds of the normal, which may remain for 1 to 3 weeks.
2. Blood show relative lymphocytosis.
3. HAV-IgM
   1. IgM is macroglobulin and it indicates acute infection.
   2. It appears in the blood 3 to 4 weeks after the exposure to HAV virus.
   3. Or it appears just before the rise in SGPT.
   4. The peak level reaches in one week after the rise begins.
   5. It appears simultaneously when symptoms appear.
   6. It becomes normal in about 2 months after the clinical symptoms become normal,
   7. It is non-detectable by 12 months. In few cases may be detected in 12 to 14 months.
4. HAV-IgG
   1. It appears after 2 weeks of the beginning of IgM increase.
   2. It is seen in the middle stage of the symptoms.
   3. It reaches a peak in about 1 to 2 months after it begins to rise.
   4. Now its titer will fall and remain low titer at least for 10 years.
   5. The rising titer is needed in only IgG-positive cases.
5. HAV-IgG positive and HAV-IgM negative indicate convalescent or chronic stage.
   1. Anti-HAV- IgG is present throughout life. It is positive in 50% of the USA population, indicating past infection and immune status.
   2. HAV total antibody indicates present or past infection.
   3. HAV total antibody also indicates vaccination.
6. PCR: In the early stage, antibodies are not detectable then only PCR for RNA can be found in the stool and blood.
   1. PCR for RNA may be found in the saliva as well.
   2. PCR is rarely needed.
7. The fecal HAV virus is positive 2 weeks before the symptoms appear.
   1. In the stool HAV  virus can be detected as early as 1 to 2 weeks after the exposure.
   2. This period ends about 1 to 4 days after the appearance of the symptoms.
   3. At admission in 40% to 64% of the patient, the HAV virus in stool is negative.
8. Summary of HAV virus diagnosis:
   1. For acute infection (current or recent HAV infection) = HAV-IgM.
   2. Past HAV infection/immunity = HAV-antbody total
      

      Hepatitis A virus (HAV) profile

Preventions:

1. The best is to give the vaccine in epidemic areas and to the children.
2. Improve:
   1. Safe water supply.
   2. Safe food supply, which is the best hygienically.
   3. Have good sanitation.
   4. Washing of the hands before taking the foods.

Treatment:

• These patients recover without any treatment.
• Mainly there is a need for supportive treatment.

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