{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T16:35:34Z","timestamp":1771864534014,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,10,31]],"date-time":"2014-10-31T00:00:00Z","timestamp":1414713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000145","name":"Alberta Innovates Health Solutions","doi-asserted-by":"crossref","award":["200800252"],"award-info":[{"award-number":["200800252"]}],"id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000264","name":"Canadian Liver Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000264","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. This model for primary biliary cirrhosis (<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>) has evidence of biliary infection with mouse mammary tumour virus (<jats:styled-content style=\"fixed-case\">MMTV<\/jats:styled-content>), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. We tested the hypothesis that <jats:styled-content style=\"fixed-case\">MMTV<\/jats:styled-content> infection is associated with cholangitis in the <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>.c3c4 mouse model by investigating whether antiretroviral therapy impacts on viral levels and liver disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>.c3c4 mice were treated with combination antiretroviral therapy. Response to treatment was studied by measuring <jats:styled-content style=\"fixed-case\">MMTV RNA<\/jats:styled-content> in the liver, liver enzyme levels in serum and liver histology using a modified Ishak score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combination therapy with the reverse transcriptase inhibitors, tenofovir and emtricitabine, resulted in a significant reduction in serum liver enzyme levels, attenuation of cholangitis and decreased <jats:styled-content style=\"fixed-case\">MMTV<\/jats:styled-content> levels in the livers of <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>.c3c4 mice. Furthermore, treatment with the retroviral protease inhibitors, lopinavir and ritonavir, in addition to the reverse transcriptase inhibitors, resulted in further decrease in <jats:styled-content style=\"fixed-case\">MMTV<\/jats:styled-content> levels and attenuation of liver disease in this model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The attenuation of cholangitis with regimens containing the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the protease inhibitors, lopinavir and ritonavir, suggests that retroviral infection may play a role in the development of cholangitis in this model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12699","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T12:22:26Z","timestamp":1412943746000},"page":"1442-1450","source":"Crossref","is-referenced-by-count":22,"title":["Impact of combination antiretroviral therapy in the <scp>NOD<\/scp>.c3c4 mouse model of autoimmune biliary disease"],"prefix":"10.1111","volume":"35","author":[{"given":"David","family":"Sharon","sequence":"first","affiliation":[{"name":"Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safwat","family":"Girgis","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banu","family":"Sis","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alberta 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