Occurrence and character of a putative causative virus of enterically-transmitted non-A, non-B hepatitis in bile

The present investigation confirms the possibility that the etiological agent of enterically-transmitted non-A, non-B (ET-NANB) hepatitis (type E hepatitis), multiplied in hepatocytes, is excreted into the feces via bile. The fecal extract was inoculated into 7 cynomolgus monkeys. Bile juice was collected directly from the gallbladder by needle puncture after abdominal operation 3 to 6 times during the experimental course. All 7 monkeys developed elevated serum aminotransferases, which began gradually approximately 2 weeks postinoculation and reached a peak at 3 to 5 weeks. In parallel with this elevation, both in time and magnitude, necroinflammation was observed in the livers. The virus-like particles (VLPs) were found in the bile juice of all 7 monkeys and the serial occurrence of VLPs was typified as follows: the VLPs were negative on day 7, appeared on day 10 after inoculation, and were present until the 3rd week when the subjects were sacrificed. While the particles were individually dispersed on day 10, they started to exhibit spontaneous aggregation on and after week 2. Also, empty particles were very rare at first, but increased in ratio compared to full ones over time. Thus, the putative causative virus of ET-NANB hepatitis was demonstrated to be excreted through bile. The spontaneous aggregation of VLPs might be due to the specific antibody secreted into the bile juice and was closely correlated with hepatitis activity. The increase in empty particles might indicate an increase in disorganized assembly of the nucleic acid and protein during virus proliferation.