Although limited, findings from nonhuman primate and human volunteer studies have elucidated aspects of hepatitis E pathogenesis and pathophysiology. Enterically transmitted virus enters the host via the oral route and begins replicating in the intestinal tract. Presumably, the portal veins transport the virus to the liver where it replicates in the cytoplasm of hepatocyes and induces histologic changes.
Characteristic tissue alterations include focal necrosis throughout the hexagonal liver lobules as well as inflammation and accumulation of phagocytotic Kupffer cells and polymorphonuclear leukocytes. As seen in other viral hepatitis infections, cholestatic hepatitis—suppression of biliary secretion—is another indicator of HEV. Ballooning of hepatocytes may occur, and some epidemics present an unusual pseudoglandular reorganization of hepatocytes.
RT-PCR confirms viremia at 22 days post-exposure and over one week before the onset of illness. HEV antigen can be detected in the liver and bile. Shedding of virus-like particles begins 4 weeks after oral ingestion. Alanine aminotransferase (ALT) indicates liver damage and peaks between days 42 and 46 (CDC; Knipe et al. 3056-7). Enzyme immunoassays (EIA) and Western blots begin to detect HEV antibodies (anti-HEV) at this time. IgM, IgG, and IgA titers rise rapidly and persist for two weeks after infection. IgM levels dwindle within several months. The extent of IgG anti-HEV immunity is unknown. Serum titers plateau then decrease shortly after illness, but antibodies endure 14 years post-infection. The hypothesis that immunopathology may play a role in liver damage and pathogenesis is currently under investigation (Knipe et al. 3057).
