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Journal of Clinical Microbiology, November 2007, p. 3671-3679, Vol. 45, No. 11
0095-1137/07/$08.00+0     doi:10.1128/JCM.01086-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prolonged Fecal Shedding of Hepatitis E Virus (HEV) during Sporadic Acute Hepatitis E: Evaluation of Infectivity of HEV in Fecal Specimens in a Cell Culture System

Masaharu Takahashi,¹ Toshinori Tanaka,¹ Masahiro Azuma,² Eiji Kusano,² Tatsuya Aikawa,³ Takao Shibayama,⁴ Yasuyuki Yazaki,⁵ Hitoshi Mizuo,⁶ Jun Inoue,^1, and Hiroaki Okamoto^1*

Division of Virology, Department of Infection and Immunity,¹ Department of Nephrology, Jichi Medical University School of Medicine, Tochigi-Ken, Japan,² Aikawa Internal Medicine Hospital, Ibaraki-Ken, Japan,³ Department of Internal Medicine, Metropolitan Toshima Hospital, Tokyo, Japan,⁴ Center for Gastroenterology, Kobayashi Hospital, Hokkaido, Japan,⁵ Department of Internal Medicine, Kin-ikyo Chuo Hospital, Hokkaido, Japan⁶

Received 29 May 2007/ Returned for modification 6 August 2007/ Accepted 20 August 2007

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 x 10³ to 1.7 x 10⁷ 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 x 10⁴ copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 x 10⁷ 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 10⁷ 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.

Published ahead of print on 29 August 2007.

Present address: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.