Saito Takeshi, Terui Keita, Mitsunaga Tetsuya, Nakata Mitsuyuki, Ono Sachie, Mise Naoko, Yoshida Hideo
Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Pediatric Surgery (E6), Graduate School of Medicine, Chiba University, Chiba, Japan.
J Pediatr Surg. 2015 Aug;50(8):1398-404. doi: 10.1016/j.jpedsurg.2015.04.006. Epub 2015 Apr 25.
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.
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.
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.
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.
通过回顾那些通过聚合酶链反应（PCR）实验分析人类样本的存档原始文章，探讨病毒感染引发人类胆道闭锁（BA）的证据，同时考虑到近期广泛使用轮状病毒BA动物模型的实验趋势。
在PubMed上进行检索，获取报告了用于检测患者样本中病毒DNA或RNA的PCR实验结果以证明既往感染的原始文章。检索词包括经常被讨论的DNA或RNA病毒以及BA。特别关注针对呼肠孤病毒和轮状病毒的PCR分析，并比较了PCR准确性、样本特征及其解读。
使用PCR对16种不同病毒进行了19项研究，其中对呼肠孤病毒进行了5项研究，对轮状病毒进行了3项研究，对巨细胞病毒进行了10项研究，对爱泼斯坦 - 巴尔病毒进行了5项研究，对细小病毒B19进行了4项研究等等。在仅提示病毒与BA可能存在关联的论文中，没有关于呼肠孤病毒的研究，有1项关于轮状病毒的研究，3项关于巨细胞病毒的研究，1项关于EB病毒的研究，以及1项关于乳头瘤病毒的研究。在对呼肠孤病毒科的6项PCR研究中，对3项呼肠孤病毒研究和2项轮状病毒研究的实验准确性（包括敏感性）进行了严格评估。两个研究小组除了分析手术时获取的一般肝胆组织外，还分析了术前粪便样本。样本采集时间差异很大，大多数关于呼肠孤病毒科的报告未提及PCR实验前的储存时间。
尽管大量PCR研究试图利用人类样本阐明病毒在BA发病机制中的作用，但研究结果相互矛盾，未能成功明确所关注病毒的致病性感染与偶然感染之间的明显区别。基于高灵敏度PCR实验的客观数据，一直缺乏关于呼肠孤病毒科致病性感染的可重复且令人信服的确凿证据。尽管在采集时病毒仍有可能消失，但为避免对PCR结果进行进一步模糊的解读，强烈建议在精心规划的时间严格且细致地采集大量样本，并采用严格调整和精细校准的PCR系统，以获得更可靠和一致的数据。
