Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis E Virus Genotype 1 and 2 Infections

Infection with genotype 1 or 2 hepatitis E virus (HEV) results primarily from human-to-human transmission through the fecal-oral route in low-resource countries. It presents primarily as "acute viral hepatitis" syndrome, usually a self-limiting illness. A few cases progress to acute liver failure, a serious illness with high fatality. Clinical disease is infrequent among children. Infection during pregnancy is associated with a higher risk of symptomatic disease, severe liver injury, and mortality. Severe disease is also encountered in persons with preexisting chronic liver disease. Some cases have associated extrahepatic features, particularly acute pancreatitis and neurological manifestations. Chronic infection appears to be extremely infrequent with these HEV genotypes. The exact pathogenesis of liver injury remains unknown, although the host immune response appears to be important for viral clearance as well as for induction of liver injury. Hormonal and immune factors appear to be responsible for the severe disease during pregnancy.