title: Evidence for viral infection as a causative factor of human biliary atresia.
abstract: OBJECTIVE
  To explore the evidence for viral infections triggering human biliary atresia (BA) by reviewing archival original articles that analyzed human samples via polymerase chain reaction (PCR) experiments, considering the recent experimental trend of extensive use of rotaviral BA animal models.
  
  
  METHODS
  A PubMed search retrieved original articles that reported the results of PCR experiments for detecting viral DNA or RNA in patient samples as proof of past infection. Search terms included the often-debated DNA or RNA viruses and BA. Special focus was directed toward PCR analyses that targeted reovirus and rotavirus, where PCR accuracy, specimen characteristics and their interpretations were compared.
  
  
  RESULTS
  Nineteen studies were conducted on 16 different kinds of viruses using PCR, with 5 studies on reovirus, 3 on rotavirus, 10 on cytomegalovirus, 5 on Epstein-Barr virus, 4 on parvovirus B19, and so on. Among the papers suggesting a possible viral link to only BA, there was no study on reovirus, 1 on rotavirus, 3 on cytomegalovirus, 1 on EB virus, and 1 on papillomavirus. Of the 6 PCR studies on Reoviridae, 3 on reovirus and 2 on rotavirus were evaluated rigorously for experimental accuracy, including their sensitivity. Two research groups analyzed preoperative stool samples in addition to generic hepatobiliary tissue obtained at surgery. Sample collection timing varied widely, with storage period prior to PCR experimentation not revealed in most reports on Reoviridae.
  
  
  CONCLUSIONS
  Although a considerable number of PCR studies have sought to clarify a viral role in the pathogenesis of BA using human samples, the findings have been contradictory and have not succeeded in achieving an obvious differentiation between causative and accidental infection of the focused virus. Reproducible and convincing evidence for a causative Reoviridae infection has been lacking based on objective data from highly sensitive PCR experiments. Even though the possibility remains of viral disappearance at the timing of collection, to avoid further ambiguous interpretations of PCR results, rigorous and meticulous collection of large numbers of specimens at carefully planned timing, along with a strictly adjusted and finely tuned PCR system, is strongly recommended for obtaining more reliable and consistent results.
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: takk@faculty.chiba-u.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Terui
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsunaga
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mise
authors.affiliation: Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
mesh_terms: D001656:Biliary Atresia / Q000821:virology*; D006801:Humans; D016133:Polymerase Chain Reaction; D012088:Reoviridae Infections / Q000150:complications / Q000175:diagnosis; D014777:Virus Diseases / Q000150:complications* / Q000175:diagnosis
keywords: Choledochal cyst; Cytomegalovirus; Etiology; Mouse model; Reovirus; Rotavirus