Lack of infectivity of HBV in feces from patients with chronic hepatitis B virus infection, and infection using chimeric mice.
BACKGROUND
Body fluids such as saliva and tears from patients with hepatitis B virus (HBV) infection are known as infectious agents. The infectivity of feces from patients with HBV infection has not been established. The aim of this study was to determine whether feces from HBV carriers can be a source of HBV infection.


METHODS
Thirty-three children and 17 adults (ages 0-49 years, median age 13 years) who were chronically infected with HBV were enrolled. The levels of HBV DNA in the feces from these patients were quantified by real-time PCR, and the levels of fecal HBsAg were measured. Isolated human hepatocytes from chimeric mice with humanized livers were co-cultured with serum, tears and feces from the HBV carriers. Four chimeric mice were inoculated intravenously with sterilized feces from HBV carriers.


RESULTS
HBV DNA was detected in the feces of 37 (74%) of the 50 patients. The fecal HBV DNA levels ranged from 2.8 to 8.4 log copies/mL (mean ± SD  =  5.6 ± 1.2 log copies/mL). A significant correlation was observed in the levels of HBV DNA between serum and feces (r  =  0.54, p < 0.05). Of the 13 HBV carries, 7 (54%) were positive for fecal HBsAg. The fecal HBsAg levels ranged from 0.06 to 1.0 IU/mL (median 0.28 IU/mL). Immunogold electron microscopy showed Dane particles in feces. HBV DNA was detected in the human hepatocytes co-cultured with serum and tears, but not in those co-cultured with feces. HBV DNA was not detected in the serum of the chimeric mice after oral or intravenous inoculation with sterilized fecal samples, which contained 5 log copies/mL of HBV DNA levels.


CONCLUSIONS
Although the positive rate of fecal HBV DNA was high, the fecal HBsAg levels were extremely low. The chimeric mice were not infected with HBV after oral or intravenous inoculation with sterilized fecal samples. Therefore, feces from HBV carriers seem not to serve as an infectious vehicle for the transmission of HBV.
Department of Pediatrics, Toho University Sakura Medical Center, 564-1 Shimoshizu Sakura, Chiba, Japan. haruki-komatsu@chive.ocn.ne.jp.|Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan. haruki-komatsu@chive.ocn.ne.jp.
Haruki
H
Komatsu
Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan. a_inui@tobu.saiseikai.or.jp.
Ayano
A
Inui
Department of Research and Development, Toho University Sakura Medical Center, Chiba, Japan. murano@sakura.med.toho-u.ac.jp.
Takeyoshi
T
Murano
Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan. t_tsunoda@tobu.saiseikai.or.jp.
Tomoyuki
T
Tsunoda
Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan. t_Sogo@tobu.saiseikai.or.jp.
Tsuyoshi
T
Sogo
Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan. t_fujisawa@tobu.saiseikai.or.jp.
Tomoo
T
Fujisawa
D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification*; D005243:Feces / Q000821:virology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000302:isolation & purification*; D006515:Hepatitis B virus / Q000254:growth & development* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000097:blood / Q000635:transmission* / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D013666:Tears / Q000821:virology
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens