In this study, theliver of 74 human patients with BA were tested by the nested reversetranscriptase polymerase chain reaction (RT-PCR) to detect for RNA viruses (e.g. rotavirus and reovirus)(9).
The goal of this study was to find RNA strains in BA Patients. Only 64samples were extracted for RNA detection, and 24 biopsies were positive for atleast one hepatotropic virus and 4 liver biopsies were positive for doubleinfection (9). One constraint that lead to these outcomes were that viruses arequickly cleared from the liver and the rest of the biliary system in the firstfew weeks after child birth (1). Another constraint could have been the age ofthe patient at the time of analysis because most of these viruses are found ininfants (1).In this next study,liver tissue samples were obtained from human patients with biliary atresia,and from patients with total parenteral nutrition (TPN)–related cholestasis.The patients with TPN-related cholestasis, were chosen for this experiment becausethis disease have similar symptoms to BA, therefore these patients acted asdisease control subjects for comparison. Fluorescent-tagged cytokine-specific(IL-2, IFN-?, TNF-?) probes were applied to the liver tissue samples (11). Insitu hybridization revealed that all biliary atresia patients had Th1cytokine–producing cells around the portal tracts of the bile ducts (11).
Whereas total parenteral nutrition (TPN)-related cholestasis patients werenegative for Th1 cytokine–producing cells around the portal tracts (11). Inconclusion, this study provides evidence that Th1 cytokine-producing cells areonly found in the portal tracts of BA patients, and not present in TPN-related cholestasispatients. More research on other similarliver disorders is required to support the conclusions made in this case study.In this study,liver samples were obtained from human infants with BA. Controls were liversamples obtained from organ transplant donors.
Some sections of liver sampleswere stained with antibodies against CD56 to detect NK (natural killer) cells (4).Cytokeratin was used to detect changiocytes (4). Immunofluorescence revealedthat NK cells did surround the portal tract of the bile ducts of the BApatients (4). Conversely, NK cells rarely surrounded the portal tracts of thebile ducts of the control samples (4). The same procedure was applied to mice,and immunofluorescence reveled similar results. Thanks to the rotavirus-inducedmice models of BA, it was concluded that NK cells indeed engage thecholangiocytes, and NK cells do play a role in the initiation of bile ductinjury. More research is required to understand what the role exactly is.
In this nextstudy, it was hypothesized that the production of the cytokine IFN-? is animportant factor in the mechanism of this disease. In this experiment rhesusrotavirus was inoculated into mice with an active form of the IFN-y gene (10). Thesemice showed BA symptoms by day 7 and the symptoms persisted in most of thesemice (10).
The rotavirus was also inoculated into mice with the inactive formof the INF-y gene (10). Even though BAsymptoms were present in the first days of these mice, the symptoms wereresolved between days 8-13 (10). In conclusion, the loss of IFN-? prevented thedestruction of the bile ducts which was observed by not showing any symptoms ofBA. Therefore, IFN-y may be used as a target to block disease progression inbiliary atresia patients.
In this final casestudy, the controls were mice injected with saline. The other mice wereinjected with five different strains of rotavirus, which were the following:RRV (simian), SA11-FM (simian/bovine), SA11-SM (simian), EDIM (murine), and Wa(human) (13). The histologic appearances of the mice inoculated with the RRVand SA11-FM showed inflammatory cells in the portal tracts, which was a signfor bile duct destruction (13).
In contrast, there was little to noinflammatory cells in the portal tract of the mice injected with the otherstrains. The study also revealed that the mice inoculated with any simianstrain had a higher injury score, which meant that there was more bile ductinjury (13). In conclusion, the simian strain was more likely to induce BA inthe mice. More research is required to understand what strain of the rotavirusis what induces BA in us humans.
