Hepatitis A virus - Pathogenesis, Host immunity, Clinical syndrome
Pathogenesis of Hepatitis A virus
Natural infection of Hepatitis A virus usually follows ingestion of the virus from materially contaminated feces containing Hepatitis A virus. The virus first replicates in the gastrointestinal tract and then spreads to the liver.
In the liver, the viruses infect and damage hepatocytes but the mechanism of Hepatitis A virus causing the cytopathic effect is not known. Tc cells cause damage to hepatocytes. Hence, when infections clear, cell damage is repaired and no chronic infection occurs.
Clinical findings in hepatocytes include mononuclear infiltrate, ballooning, degeneration, and acidophilic bodies. Liver pathology is not distinguishable from that caused by other hepatitis viruses.
Host immunity of Hepatitis A virus
Host immunity is mediated primarily by circulating antibodies.
IgM anti-HAV is detectable at the time of the appearance of jaundice in the initial stage of infection. It remains detectable for several months after jaundice.
IgG antibody appears 1-3 weeks after the appearance of IgM antibodies. IgG provides lifelong immunity against recurrent Hepatitis A virus infection.
The initial non-cytopathic phase, during which the virus replicates and is released is followed by decreased virus replication and inflammatory cell infiltration, suggesting that immune mechanisms are involved in the pathogenesis.
NK (Natural Killer) cells are mobilized and activated. The Liver cell injury in acute HAV infection is mediated by human leukocyte antigen (HLA)- restricted, HAV, specific, CD8+, cytotoxic t-cells and is not entirely due to an intrinsic cytopathic effect of the virus itself.
Clinical syndrome/manifestation of Hepatitis A virus
(Acute hepatitis occurs; chronic hepatitis does not occur)
The majority of young patients with Hepatitis A virus are symptomless or have mild general symptoms. The incubation period of Hepatitis A virus is usually 4 weeks (2-6 weeks) and has 3 stages:
prodromal phase (stage at which symptoms begin)
icteric (acute) phage
posticteric
Prodromal phase
The prodromal phase is a short prodromal phase varying from 2-7 days, usually preceded by the icteric phase lasting usually 1-2 weeks, often longer in adults.
Prodromal phase (preicteric)
Symptoms of Prodromal phase (preicteric): Malaise, weakness, mild fever, nausea and vomiting, anorexia, headache, abdominal discomfort
Icteric phase
Symptoms of Icteric phase: jaundice, itching, dark urine, pale stool
The liver is usually enlarged and LFT (Liver Function Test) is abnormal with highly elevated levels of serum alanine aminotransaminase (ALT) and serum aspartate aminotransaminase (AST).
Hepatitis A virus infection is usually a self-limiting mild disease. In most cases resolves spontaneously in 2-4 weeks. Fulminant hepatitis and cholestatic hepatitis are some of the rare complications with a high mortality rate. The case fatality is 0.01%.