To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 ؋ 10 3 to 1.7 ؋ 10 7 copies/ml, and HEV viremia lasted until days 17 to 48 (mean, 28.3) after the onset of hepatitis. Even at the initial examination on days 10 to 29 (mean, 17.6), the HEV load in fecal supernatant was less than 5.7 ؋ 10 4 copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 ؋ 10 7 copies/ml on day 22. In addition, although HEV RNA in fecal supernatant continued to be positive until days 14 to 33 (mean, 22.4) for patients 2 to 11, that for patient 1 was detectable even on day 121. HEVs in fecal specimens obtained on days 22, 24, 26, 28, and 30, but not day 121, from patient 1 grew efficiently in PLC/PRF/5 cells, reaching the highest titer of up to 10 7 copies/ml in culture medium on day 50 postinoculation. The HEV genome recovered from patient 1 had 29 unique nucleotides that were not seen in any of the 25 reported HEV isolates of the same genotype over the entire genome, with six amino acid substitutions in the ORF1 protein.Hepatitis E is an enterically transmitted viral disease caused by hepatitis E virus (HEV). The disease occurs in epidemic and sporadic forms in most developing countries of Asia, Africa, and Latin America (43). Sporadic cases of locally acquired hepatitis E also have been identified in industrialized countries, including the United States, European countries, and Japan (3,7,11,19,20,24,27,32,33,39,42,62,64,69). A significant proportion of healthy individuals in industrialized countries are seropositive for antibodies to HEV (anti-HEV), and a high prevalence of anti-HEV of over 20% has been reported in some areas of the United States (57). Anti-HEV also has been detected in many animal species, and HEV has been isolated from domestic pigs and wild animals, including boars, a deer, and a mongoose (30,34,50,51,56). Accumulating lines of evidence indicate that hepatitis E is a zoonosis (19, 28-30, 37, 38, 47, 56, 68). HEV infection runs an acute course, normally resulting in resolution within a few weeks after onset. Although only a minority of HEV infections induce overt hepatitis, the contribution of HEV to the development of fulminant hepatitis is known not only in developing countries (35) but also in industrialized countries (42,49). The presence of a chronic or persistent HEV infection, however, has not been described.HEV is a nonenveloped RNA virus and is classified as the sole member of the genus Hepevirus in the family Hepeviridae (13). Its genome is a single-stranded, positive-sense RNA of approximately 7.2 kb. It contains a short 5Ј-untranslated region (5ЈUTR) followed by three open reading frames (ORFs; ORF1, ORF2, and ORF3) and then a short 3ЈUTR w...