Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine. The blood carries the virus to its target, the liver, where it multiplies within hepatocytes and Kupffer cells (liver macrophages). Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the virus to host receptors, which mediates endocytosis. Replication follows the positive-stranded RNA virus replication model. Translation takes place by viral initiation. The virus exits the host cell by lysis and viroporins. Virions are secreted into the bile and released in stool. HAV is excreted in large numbers about 11 days prior to the appearance of symptoms or anti-HAV IgM antibodies in the blood. The incubation period is 15–50 days and risk of death in those infected is less than 0.5%.