HAV usually is a benign self-limited infection that does not cause chronic hepatitis and rarely (in about 0.1% of cases) produces fulminant hepatitis. HAV has an incubation period of 3-6 weeks. It is typically cleared by the host immune response, so it does not establish a carrier state. The infection occurs throughout the world and is endemic in countries with poor hygiene and sanitation.
Fig. 16.8 TemporalchangesinserologicmarkersinacutehepatitisAinfec-tion.HAV, HepatitisAvirus.
Table 16.2 The Hepatitis Viruses ssRNA, Single-strandedRNA;dsDNA, double-strandedDNA;HBcAg, hepatitisBcoreantigen;HBsAg, hepatitisBsurfaceantigen;HDAg, hepatitisDantigen;ELISA, enzyme-linkedimmunosorbentassay.FromWashingtonK:Inflammatoryandinfectiousdiseasesoftheliver.InIacobuzio-DonahueCA,MontgomeryEA,editors:Gastrointestinal and liver pathology, Philadelphia,2005,ChurchillLivingstone.
Acute HAV tends to cause a febrile illness associated with jaundice and nonspecific symptoms such as fatigue and loss of appetite. Overall, HAV accounts for about 25% of clinically evident acute hepatitis worldwide.
HAV is a small, nonenveloped, positive-strand RNA picornavirus that occupies its own genus, Hepatovirus. Ultrastructurally, HAV is an icosahedral capsid 27 nm in diameter. The receptor for HAV is HAVcr-1, a membrane glycoprotein that also may serve as a receptor for Ebola virus. HAV is spread by ingestion of contaminated water and food and is shed in the stool for 2 to 3 weeks before and 1 week after the onset of jaundice. Thus, close personal contact with an infected individual or fecal-oral contamination accounts for most cases and explains outbreaks in institutional settings such as schools and nurseries, as well as water-borne epidemics in places where people live in overcrowded, unsanitary conditions. HAV can also be detected in serum and saliva of infected individuals.
In developed countries, sporadic infections may be contracted by the consumption of raw or steamed shellfish that have concentrated the virus from seawater contaminated with human sewage. Infected workers in the food industry are another source of outbreaks. HAV itself does not seem to be cytopathic. The cellular immune response, particularly that involving cytotoxic CD8+ T cells, plays a key role in HAV-mediated hepatocellular injury.
Because HAV viremia is transient, blood-borne transmission is very rare; therefore, donated blood is not specifically screened for this virus. IgM antibody against HAV appears in blood at the onset of symptoms and is a reliable marker of acute infection (
Fig. 16.8 ). Fecal shedding of the virus ends as the IgM titer rises. The IgM response usually declines in a few months followed by the appearance of IgG anti-HAV that persists for years, often conferring lifelong immunity. However, there are no routinely available tests for IgG anti-HAV; the presence of IgG anti-HAV is inferred from the difference between total and IgM anti-HAV. The HAV vaccine, available since 1992, is effective in preventing infection.