Evidence for a Virus in Non-A, Non-B Hepatitis Transmitted via the Fecal-Oral Route

TLDR

The study reproduced acute hepatitis by orally administering pooled stool extracts from epidemic non‑A, non‑B hepatitis cases to a HAV‑immune volunteer and by intravenously inoculating cynomolgus monkeys with the same extracts, demonstrating infection and immune response. Virus‑like particles 27–30 nm in diameter were visualized in stool, banded at 1.35 g cm⁻³, reacted with sera from non‑B hepatitis patients but not HAV‑positive sera, and caused hepatitis and antibody production in monkeys, with no HBV or HAV markers detected in the volunteer.

Abstract

Typical acute hepatitis was reproduced in a human volunteer immune to hepatitis A virus (HAV) after oral administration of pooled stool extracts from presumed cases of epidemic non-A, non-B hepatitis. Markers of hepatitis B infection, anti-HAV IgM, and increase in total anti-HAV level were not detectable in the volunteer's sera during the course of infection. Spherical 27- to 30-nm virus-like particles were visualized by immune electron microscopy (IEM) in stool samples collected during preclinical and early postclinical phases. These particles banded in CsCl at a buoyant density of 1.35 g/cm3. They reacted in the IEM test with sera from individuals who had experienced two non-B hepatitis episodes but did not react with sera from routine anti-HAV IgM-positive hepatitis patients. Intravenous inoculation of cynomolgus monkeys with the virus-containing stool extract resulted in histopathologically and enzymatically confirmed hepatitis, excretion of virus-like particles, and antibody response to them.