{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:40:51Z","timestamp":1791351651066,"version":"4.3.1"},"reference-count":232,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1038\/s41575-019-0226-7","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T14:03:08Z","timestamp":1575900188000},"page":"93-110","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":276,"title":["Primary biliary cholangitis: pathogenesis and therapeutic opportunities"],"prefix":"10.1038","volume":"17","author":[{"given":"Aliya F.","family":"Gulamhusein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M.","family":"Hirschfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"226_CR1","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1053\/j.gastro.2010.09.004","volume":"139","author":"GM Hirschfield","year":"2010","unstructured":"Hirschfield, G. M., Heathcote, E. J. & Gershwin, M. E. Pathogenesis of cholestatic liver disease and therapeutic approaches. Gastroenterology 139, 1481\u20131496 (2010).","journal-title":"Gastroenterology"},{"key":"226_CR2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nrgastro.2016.201","volume":"14","author":"GJ Webb","year":"2017","unstructured":"Webb, G. J. & Hirschfield, G. M. Primary biliary cholangitis in 2016: high-definition PBC: biology, models and therapeutic advances. Nat. Rev. Gastroenterol. Hepatol. 14, 76\u201378 (2017).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"226_CR3","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-pathol-020712-164014","volume":"8","author":"GM Hirschfield","year":"2013","unstructured":"Hirschfield, G. M. & Gershwin, M. E. The immunobiology and pathophysiology of primary biliary cirrhosis. Annu. Rev. Pathol. 8, 303\u2013330 (2013).","journal-title":"Annu. Rev. Pathol."},{"key":"226_CR4","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2014.08.029","volume":"147","author":"WJ Lammers","year":"2014","unstructured":"Lammers, W. J. et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology 147,\u00a01338\u20131349.e5 quiz e15, (2014).","journal-title":"Gastroenterology"},{"key":"226_CR5","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1053\/j.gastro.2004.05.005","volume":"127","author":"C Selmi","year":"2004","unstructured":"Selmi, C. et al. Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment. Gastroenterology 127, 485\u2013492 (2004).","journal-title":"Gastroenterology"},{"key":"226_CR6","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/S0168-8278(99)80097-X","volume":"30","author":"DE Jones","year":"1999","unstructured":"Jones, D. E., Watt, F. E., Metcalf, J. V., Bassendine, M.\u00a0F. & James, O. F. Familial primary biliary cirrhosis reassessed: a geographically-based population study. J. Hepatol. 30, 402\u2013407 (1999).","journal-title":"J. Hepatol."},{"key":"226_CR7","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/hep.21749","volume":"46","author":"KN Lazaridis","year":"2007","unstructured":"Lazaridis, K. N. et al. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology 46, 785\u2013792 (2007).","journal-title":"Hepatology"},{"key":"226_CR8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/hep.29783","volume":"68","author":"AF Gulamhusein","year":"2018","unstructured":"Gulamhusein, A. F. & Lazaridis, K. N. Primary biliary cholangitis, DNA, and beyond: the relative contribution of genes. Hepatology 68, 19\u201321 (2018).","journal-title":"Hepatology"},{"key":"226_CR9","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1055\/s-0035-1567831","volume":"35","author":"AF Gulamhusein","year":"2015","unstructured":"Gulamhusein, A. F., Juran, B. D. & Lazaridis, K. N. Genome-wide association studies in primary biliary cirrhosis. Semin. Liver Dis. 35, 392\u2013401 (2015).","journal-title":"Semin. Liver Dis."},{"key":"226_CR10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cld.2015.08.002","volume":"20","author":"PJ Trivedi","year":"2016","unstructured":"Trivedi, P. J. & Hirschfield, G. M. The immunogenetics of autoimmune cholestasis. Clin. Liver Dis. 20, 15\u201331 (2016).","journal-title":"Clin. Liver Dis."},{"key":"226_CR11","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/ng2068","volume":"39","author":"JA Todd","year":"2007","unstructured":"Todd, J. A. et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat. Genet. 39, 857\u2013864 (2007).","journal-title":"Nat. Genet."},{"key":"226_CR12","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1399-0039.1994.tb02303.x","volume":"43","author":"AB Begovich","year":"1994","unstructured":"Begovich, A. B. et al. Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis. Tissue Antigens 43, 71\u201377 (1994).","journal-title":"Tissue Antigens"},{"key":"226_CR13","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0168-8278(05)80617-8","volume":"21","author":"S Onishi","year":"1994","unstructured":"Onishi, S. et al. DNA typing of HLA class II genes; DRB1*0803 increases the susceptibility of Japanese to primary biliary cirrhosis. J. Hepatol. 21, 1053\u20131060 (1994).","journal-title":"J. Hepatol."},{"key":"226_CR14","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1002\/hep.22567","volume":"48","author":"P Invernizzi","year":"2008","unstructured":"Invernizzi, P. et al. Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls. Hepatology 48, 1906\u20131912 (2008).","journal-title":"Hepatology"},{"key":"226_CR15","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-11148-6","volume":"7","author":"M Yasunami","year":"2017","unstructured":"Yasunami, M. et al. Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population. Sci. Rep. 7, 11093 (2017).","journal-title":"Sci. Rep."},{"key":"226_CR16","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/hep.24414","volume":"54","author":"P Invernizzi","year":"2011","unstructured":"Invernizzi, P. Human leukocyte antigen in primary biliary cirrhosis: an old story now reviving. Hepatology 54, 714\u2013723 (2011).","journal-title":"Hepatology"},{"key":"226_CR17","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jhep.2018.06.027","volume":"69","author":"PM Probert","year":"2018","unstructured":"Probert, P. M. et al. Identification of a xenobiotic as a potential environmental trigger in primary biliary cholangitis. J. Hepatol. 69, 1123\u20131135 (2018).","journal-title":"J. Hepatol."},{"key":"226_CR18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1055\/s-0034-1383726","volume":"34","author":"BD Juran","year":"2014","unstructured":"Juran, B. D. & Lazaridis, K. N. Environmental factors in primary biliary cirrhosis. Semin. Liver Dis. 34, 265\u2013272 (2014).","journal-title":"Semin. Liver Dis."},{"key":"226_CR19","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/gut.24.10.940","volume":"24","author":"AN Hamlyn","year":"1983","unstructured":"Hamlyn, A. N., Macklon, A. F. & James, O. Primary biliary cirrhosis: geographical clustering and symptomatic onset seasonality. Gut 24, 940\u2013945 (1983).","journal-title":"Gut"},{"key":"226_CR20","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jhep.2010.02.019","volume":"53","author":"C Corpechot","year":"2010","unstructured":"Corpechot, C., Chretien, Y., Chazouilleres, O. & Poupon, R. Demographic, lifestyle, medical and familial factors associated with primary biliary cirrhosis. J. Hepatol. 53, 162\u2013169 (2010).","journal-title":"J. Hepatol."},{"key":"226_CR21","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1002\/hep.20907","volume":"42","author":"ME Gershwin","year":"2005","unstructured":"Gershwin, M. E. et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology 42, 1194\u20131202 (2005).","journal-title":"Hepatology"},{"key":"226_CR22","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/cei.12224","volume":"175","author":"JJ Wang","year":"2014","unstructured":"Wang, J. J. et al. Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrial antibodies in non-obese diabetic (NOD).B6 (Idd10\/Idd18) mice. Clin. Exp. Immunol. 175, 192\u2013201 (2014).","journal-title":"Clin. Exp. Immunol."},{"key":"226_CR23","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.chom.2008.03.009","volume":"3","author":"J Mattner","year":"2008","unstructured":"Mattner, J. et al. Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe 3, 304\u2013315 (2008).","journal-title":"Cell Host Microbe"},{"key":"226_CR24","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1084\/jem.181.5.1835","volume":"181","author":"S Shimoda","year":"1995","unstructured":"Shimoda, S., Nakamura, M., Ishibashi, H., Hayashida, K. & Niho, Y. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases. J. Exp. Med. 181, 1835\u20131845 (1995).","journal-title":"J. Exp. Med."},{"key":"226_CR25","doi-asserted-by":"crossref","first-page":"5874","DOI":"10.4049\/jimmunol.174.9.5874","volume":"174","author":"K Amano","year":"2005","unstructured":"Amano, K. et al. Chemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis: identification of antibodies against a common environmental, cosmetic, and food additive, 2-octynoic acid. J. Immunol. 174, 5874\u20135883 (2005).","journal-title":"J. Immunol."},{"key":"226_CR26","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/hep.22390","volume":"48","author":"K Wakabayashi","year":"2008","unstructured":"Wakabayashi, K. et al. Loss of tolerance in C57BL\/6 mice to the autoantigen E2 subunit of pyruvate dehydrogenase by a xenobiotic with ensuing biliary ductular disease. Hepatology 48, 531\u2013540 (2008).","journal-title":"Hepatology"},{"key":"226_CR27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jaut.2006.06.002","volume":"27","author":"R Rieger","year":"2006","unstructured":"Rieger, R. et al. Identification of 2-nonynoic acid, a cosmetic component, as a potential trigger of primary biliary cirrhosis. J. Autoimmun. 27, 7\u201316 (2006).","journal-title":"J. Autoimmun."},{"key":"226_CR28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/gene.2013.1","volume":"14","author":"SP Kar","year":"2013","unstructured":"Kar, S. P. et al. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies. Genes Immun. 14, 179\u2013186 (2013).","journal-title":"Genes Immun."},{"key":"226_CR29","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1056\/NEJMoa0810440","volume":"360","author":"GM Hirschfield","year":"2009","unstructured":"Hirschfield, G. M. et al. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N. Engl. J. Med. 360, 2544\u20132555 (2009).","journal-title":"N. Engl. J. Med."},{"key":"226_CR30","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ng.627","volume":"42","author":"X Liu","year":"2010","unstructured":"Liu, X. et al. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat. Genet. 42, 658\u2013660 (2010).","journal-title":"Nat. Genet."},{"key":"226_CR31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/ng.789","volume":"43","author":"GF Mells","year":"2011","unstructured":"Mells, G. F. et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 43, 329\u2013332 (2011).","journal-title":"Nat. Genet."},{"key":"226_CR32","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jaut.2012.06.002","volume":"39","author":"RL van Wanrooij","year":"2012","unstructured":"van Wanrooij, R. L., Zwiers, A., Kraal, G. & Bouma, G. Genetic variations in interleukin-12 related genes in immune-mediated diseases. J. Autoimmun. 39, 359\u2013368 (2012).","journal-title":"J. Autoimmun."},{"key":"226_CR33","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jhep.2011.05.040","volume":"56","author":"A Lleo","year":"2012","unstructured":"Lleo, A., Gershwin, M. E., Mantovani, A. & Invernizzi,\u00a0P. Towards common denominators in primary biliary cirrhosis: the role of IL-12. J. Hepatol. 56, 731\u2013733 (2012).","journal-title":"J. Hepatol."},{"key":"226_CR34","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1055\/s-0034-1383729","volume":"34","author":"L Wang","year":"2014","unstructured":"Wang, L., Wang, F. S., Chang, C. & Gershwin, M. E. Breach of tolerance: primary biliary cirrhosis. Semin. Liver Dis. 34, 297\u2013317 (2014).","journal-title":"Semin. Liver Dis."},{"key":"226_CR35","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/hep.28641","volume":"64","author":"HR Bae","year":"2016","unstructured":"Bae, H. R. et al. Chronic expression of interferon-\u03b3 leads to murine autoimmune cholangitis with a female predominance. Hepatology 64, 1189\u20131201 (2016).","journal-title":"Hepatology"},{"key":"226_CR36","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms9019","volume":"6","author":"HJ Cordell","year":"2015","unstructured":"Cordell, H. J. et al. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nat. Commun. 6, 8019 (2015).","journal-title":"Nat. Commun."},{"key":"226_CR37","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.1038\/ncomms9019","volume":"6","author":"HJ Cordell","year":"2015","unstructured":"Cordell, H. J. et al. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nat. Commun. 6, 8019 (2015).","journal-title":"Nat. Commun."},{"key":"226_CR38","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.jhep.2012.07.008","volume":"57","author":"YH Oo","year":"2012","unstructured":"Oo, Y. H. et al. CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver. J. Hepatol. 57, 1044\u20131051 (2012).","journal-title":"J. Hepatol."},{"key":"226_CR39","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jaut.2009.02.022","volume":"32","author":"KA Padgett","year":"2009","unstructured":"Padgett, K. A. et al. Primary biliary cirrhosis is associated with altered hepatic microRNA expression. J. Autoimmun. 32, 246\u2013253 (2009).","journal-title":"J. Autoimmun."},{"key":"226_CR40","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/hep.25691","volume":"56","author":"JM Banales","year":"2012","unstructured":"Banales, J. M. et al. Up-regulation of microRNA 506 leads to decreased Cl\u2013\/HCO3 \u2013 anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology 56, 687\u2013697 (2012).","journal-title":"Hepatology"},{"key":"226_CR41","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jhep.2018.08.020","volume":"69","author":"PM Rodrigues","year":"2018","unstructured":"Rodrigues, P. M. et al. Primary biliary cholangitis: a tale of epigenetically-induced secretory failure? J. Hepatol 69, 1371\u20131383 (2018).","journal-title":"J. Hepatol"},{"key":"226_CR42","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/hep.29533","volume":"67","author":"O Erice","year":"2018","unstructured":"Erice, O. et al. miRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation. Hepatology 67, 1420\u20131440 (2018).","journal-title":"Hepatology"},{"key":"226_CR43","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1074\/jbc.M114.587030","volume":"290","author":"M Ananthanarayanan","year":"2015","unstructured":"Ananthanarayanan, M. et al. Post-translational regulation of the type III inositol 1,4,5-trisphosphate receptor by miRNA-506. J. Biol. Chem. 290, 184\u2013196 (2015).","journal-title":"J. Biol. Chem."},{"key":"226_CR44","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.jhep.2017.02.002","volume":"66","author":"R Nakagawa","year":"2017","unstructured":"Nakagawa, R. et al. miR-425 regulates inflammatory cytokine production in CD4+ T cells via N-Ras upregulation in primary biliary cholangitis. J. Hepatol. 66, 1223\u20131230 (2017).","journal-title":"J. Hepatol."},{"key":"226_CR45","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41418-017-0019-x","volume":"25","author":"MB Afonso","year":"2018","unstructured":"Afonso, M. B. et al. miRNA-21 ablation protects against liver injury and necroptosis in cholestasis. Cell Death Differ. 25, 857\u2013872 (2018).","journal-title":"Cell Death Differ."},{"key":"226_CR46","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2016.280","volume":"7","author":"MB Afonso","year":"2016","unstructured":"Afonso, M. B. et al. Activation of necroptosis in human and experimental cholestasis. Cell Death Dis. 7, e2390 (2016).","journal-title":"Cell Death Dis."},{"key":"226_CR47","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jaut.2012.12.013","volume":"41","author":"Y Ando","year":"2013","unstructured":"Ando, Y. et al. Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-\u03b2 receptor type II mouse. J. Autoimmun. 41, 111\u2013119 (2013).","journal-title":"J. Autoimmun."},{"key":"226_CR48","volume":"8","author":"H Arora","year":"2013","unstructured":"Arora, H., Qureshi, R. & Park, W. Y. miR-506 regulates epithelial mesenchymal transition in breast cancer cell lines. PLOS ONE 8, e64273 (2013).","journal-title":"PLOS ONE"},{"key":"226_CR49","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.4049\/jimmunol.1001597","volume":"186","author":"GX Yang","year":"2011","unstructured":"Yang, G. X. et al. CD8 T cells mediate direct biliary ductule damage in nonobese diabetic autoimmune biliary disease. J. Immunol. 186, 1259\u20131267 (2011).","journal-title":"J. Immunol."},{"key":"226_CR50","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1002\/hep.29524","volume":"67","author":"HR Bae","year":"2018","unstructured":"Bae, H. R. et al. The interplay of type I and type II interferons in murine autoimmune cholangitis as a basis for sex-biased autoimmunity. Hepatology 67, 1408\u20131419 (2018).","journal-title":"Hepatology"},{"key":"226_CR51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jaut.2005.01.012","volume":"24","author":"KA Padgett","year":"2005","unstructured":"Padgett, K. A. et al. Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis. J. Autoimmun. 24, 209\u2013219 (2005).","journal-title":"J. Autoimmun."},{"key":"226_CR52","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1055\/s-0034-1383728","volume":"34","author":"J Wang","year":"2014","unstructured":"Wang, J. et al. Animal models of primary biliary cirrhosis. Semin. Liver Dis. 34, 285\u2013296 (2014).","journal-title":"Semin. Liver Dis."},{"key":"226_CR53","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1055\/s-2007-979469","volume":"27","author":"P Invernizzi","year":"2007","unstructured":"Invernizzi, P., Lleo, A. & Podda, M. Interpreting serological tests in diagnosing autoimmune liver diseases. Semin. Liver Dis. 27, 161\u2013172 (2007).","journal-title":"Semin. Liver Dis."},{"key":"226_CR54","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/hep.22736","volume":"49","author":"A Lleo","year":"2009","unstructured":"Lleo, A. et al. Apotopes and the biliary specificity of primary biliary cirrhosis. Hepatology 49, 871\u2013879 (2009).","journal-title":"Hepatology"},{"key":"226_CR55","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0140-6736(88)91894-6","volume":"1","author":"SJ Yeaman","year":"1988","unstructured":"Yeaman, S. J. et al. Primary biliary cirrhosis: identification of two major M2 mitochondrial autoantigens. Lancet 1, 1067\u20131070 (1988).","journal-title":"Lancet"},{"key":"226_CR56","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1084\/jem.20010956","volume":"195","author":"H Kita","year":"2002","unstructured":"Kita, H. et al. Identification of HLA-A2-restricted CD8+ cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross-presented by dendritic cells. J. Exp. Med. 195, 113\u2013123 (2002).","journal-title":"J. Exp. Med."},{"key":"226_CR57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00535-010-0303-8","volume":"46","author":"A Lleo","year":"2011","unstructured":"Lleo, A., Shimoda, S., Ishibashi, H. & Gershwin, M. E. Primary biliary cirrhosis and autoimmune hepatitis: apotopes and epitopes. J. Gastroenterol. 46, 29\u201338 (2011).","journal-title":"J. Gastroenterol."},{"key":"226_CR58","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/hep.23783","volume":"52","author":"A Lleo","year":"2010","unstructured":"Lleo, A. et al. Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis. Hepatology 52, 987\u2013998 (2010).","journal-title":"Hepatology"},{"key":"226_CR59","doi-asserted-by":"crossref","first-page":"10895","DOI":"10.1073\/pnas.0802702105","volume":"105","author":"K Takeda","year":"2008","unstructured":"Takeda, K. et al. Death receptor 5 mediated-apoptosis contributes to cholestatic liver disease. Proc. Natl Acad. Sci. USA 105, 10895\u201310900 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"226_CR60","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nri957","volume":"2","author":"J Savill","year":"2002","unstructured":"Savill, J., Dransfield, I., Gregory, C. & Haslett, C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat. Rev. Immunol. 2, 965\u2013975 (2002).","journal-title":"Nat. Rev. Immunol."},{"key":"226_CR61","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaut.2008.05.003","volume":"31","author":"S Shimoda","year":"2008","unstructured":"Shimoda, S. et al. CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. J. Autoimmun. 31, 110\u2013115 (2008).","journal-title":"J. Autoimmun."},{"key":"226_CR62","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ni0407-345","volume":"8","author":"E Bettelli","year":"2007","unstructured":"Bettelli, E., Oukka, M. & Kuchroo, V. K. TH17 cells in the circle of immunity and autoimmunity. Nat. Immunol. 8, 345\u2013350 (2007).","journal-title":"Nat. Immunol."},{"key":"226_CR63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.coi.2016.08.003","volume":"43","author":"H Ueno","year":"2016","unstructured":"Ueno, H. T follicular helper cells in human autoimmunity. Curr. Opin. Immunol. 43, 24\u201331 (2016).","journal-title":"Curr. Opin. Immunol."},{"key":"226_CR64","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jaut.2016.12.012","volume":"78","author":"HD Ma","year":"2017","unstructured":"Ma, H. D. et al. Chemokine receptor CXCR3 deficiency exacerbates murine autoimmune cholangitis by promoting pathogenic CD8+ T cell activation. J. Autoimmun. 78, 19\u201328 (2017).","journal-title":"J. Autoimmun."},{"key":"226_CR65","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1002\/hep.24526","volume":"54","author":"M Tsuda","year":"2011","unstructured":"Tsuda, M. et al. Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis. Hepatology 54, 1293\u20131302 (2011).","journal-title":"Hepatology"},{"key":"226_CR66","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/MOG.0b013e32833755aa","volume":"26","author":"Y Ueno","year":"2010","unstructured":"Ueno, Y., Ambrosini, Y. M., Moritoki, Y., Ridgway, W.\u00a0M. & Gershwin, M. E. Murine models of autoimmune cholangitis. Curr. Opin. Gastroenterol. 26, 274\u2013279 (2010).","journal-title":"Curr. Opin. Gastroenterol."},{"key":"226_CR67","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1365-2249.2009.03898.x","volume":"156","author":"G Rong","year":"2009","unstructured":"Rong, G. et al. Imbalance between T helper type 17 and T regulatory cells in patients with primary biliary cirrhosis: the serum cytokine profile and peripheral cell population. Clin. Exp. Immunol. 156, 217\u2013225 (2009).","journal-title":"Clin. Exp. Immunol."},{"key":"226_CR68","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1749-6632.2009.05133.x","volume":"1183","author":"JM Damsker","year":"2010","unstructured":"Damsker, J. M., Hansen, A. M. & Caspi, R. R. Th1 and Th17 cells: adversaries and collaborators. Ann. NY Acad. Sci. 1183, 211\u2013221 (2010).","journal-title":"Ann. NY Acad. Sci."},{"key":"226_CR69","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1002\/hep.26979","volume":"59","author":"CY Yang","year":"2014","unstructured":"Yang, C. Y. et al. IL-12\/Th1 and IL-23\/Th17 biliary microenvironment in primary biliary cirrhosis: implications for therapy. Hepatology 59, 1944\u20131953 (2014).","journal-title":"Hepatology"},{"key":"226_CR70","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/hep.27306","volume":"61","author":"L Wang","year":"2015","unstructured":"Wang, L. et al. CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis. Hepatology 61, 627\u2013638 (2015).","journal-title":"Hepatology"},{"key":"226_CR71","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/hep.27552","volume":"61","author":"GJ Webb","year":"2015","unstructured":"Webb, G. J. & Hirschfield, G. M. Follicles, germinal centers, and immune mechanisms in primary biliary cirrhosis. Hepatology 61, 424\u2013427 (2015).","journal-title":"Hepatology"},{"key":"226_CR72","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/sji.12616","volume":"86","author":"J Zheng","year":"2017","unstructured":"Zheng, J., Wang, T., Zhang, L. & Cui, L. Dysregulation of circulating Tfr\/Tfh ratio in primary biliary cholangitis. Scand. J. Immunol. 86, 452\u2013461 (2017).","journal-title":"Scand. J. Immunol."},{"key":"226_CR73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2174\/156652409787314525","volume":"9","author":"C Selmi","year":"2009","unstructured":"Selmi, C., Lleo, A., Pasini, S., Zuin, M. & Gershwin, M.\u00a0E. Innate immunity and primary biliary cirrhosis. Curr. Mol. Med. 9, 45\u201351 (2009).","journal-title":"Curr. Mol. Med."},{"key":"226_CR74","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/hep.23318","volume":"51","author":"S Shimoda","year":"2010","unstructured":"Shimoda, S. et al. CX3CL1 (fractalkine): a signpost for biliary inflammation in primary biliary cirrhosis. Hepatology 51, 567\u2013575 (2010).","journal-title":"Hepatology"},{"key":"226_CR75","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1136\/jcp.2004.023507","volume":"59","author":"K Harada","year":"2006","unstructured":"Harada, K., Isse, K. & Nakanuma, Y. Interferon \u03b3 accelerates NF-\u03baB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction. J. Clin. Pathol. 59, 184\u2013190 (2006).","journal-title":"J. Clin. Pathol."},{"key":"226_CR76","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1478-3231.2006.01254.x","volume":"26","author":"T Yokoyama","year":"2006","unstructured":"Yokoyama, T. et al. Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-\u03baB and -MAPK signaling pathways. Liver. Int. 26, 467\u2013476 (2006).","journal-title":"Liver. Int."},{"key":"226_CR77","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/hep.29418","volume":"67","author":"H Zhang","year":"2018","unstructured":"Zhang, H. et al. A functional characteristic of cysteine-rich protein 61: modulation of myeloid-derived suppressor cells in liver inflammation. Hepatology 67, 232\u2013246 (2018).","journal-title":"Hepatology"},{"key":"226_CR78","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.dld.2013.01.005","volume":"45","author":"A Lleo","year":"2013","unstructured":"Lleo, A. & Invernizzi, P. Apotopes and innate immune system: novel players in the primary biliary cirrhosis scenario. Dig. Liver Dis. 45, 630\u2013636 (2013).","journal-title":"Dig. Liver Dis."},{"key":"226_CR79","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nature01433","volume":"422","author":"E Treiner","year":"2003","unstructured":"Treiner, E. et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422, 164\u2013169 (2003).","journal-title":"Nature"},{"key":"226_CR80","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jaut.2006.04.001","volume":"26","author":"YH Chuang","year":"2006","unstructured":"Chuang, Y. H. et al. Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis. J. Autoimmun. 26, 232\u2013240 (2006).","journal-title":"J. Autoimmun."},{"key":"226_CR81","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/hep.22052","volume":"47","author":"YH Chuang","year":"2008","unstructured":"Chuang, Y. H. et al. Natural killer T cells exacerbate liver injury in a transforming growth factor \u03b2 receptor II dominant-negative mouse model of primary biliary cirrhosis. Hepatology 47, 571\u2013580 (2008).","journal-title":"Hepatology"},{"key":"226_CR82","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1002\/hep.28122","volume":"62","author":"S Shimoda","year":"2015","unstructured":"Shimoda, S. et al. Natural killer cells regulate T cell immune responses in primary biliary cirrhosis. Hepatology 62, 1817\u20131827 (2015).","journal-title":"Hepatology"},{"key":"226_CR83","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1111\/jgh.14076","volume":"33","author":"T Setsu","year":"2018","unstructured":"Setsu, T. et al. Persistent reduction of mucosal-associated invariant T cells in primary biliary cholangitis. J. Gastroenterol. Hepatol 33, 1286\u20131294 (2018).","journal-title":"J. Gastroenterol. Hepatol"},{"key":"226_CR84","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.bbadis.2017.09.022","volume":"1864","author":"JC Chang","year":"2018","unstructured":"Chang, J. C., Go, S., Verhoeven, A. J., Beuers, U. & Oude Elferink, R. P. J. Role of the bicarbonate-responsive soluble adenylyl cyclase in cholangiocyte apoptosis in primary biliary cholangitis; a new hypothesis. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 1232\u20131239 (2018).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis"},{"key":"226_CR85","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1242\/jeb.029454","volume":"212","author":"SL Alper","year":"2009","unstructured":"Alper, S. L. Molecular physiology and genetics of Na+-independent SLC4 anion exchangers. J. Exp. Biol. 212, 1672\u20131683 (2009).","journal-title":"J. Exp. Biol."},{"key":"226_CR86","doi-asserted-by":"crossref","first-page":"C1305","DOI":"10.1152\/ajpcell.00584.2004","volume":"288","author":"W Geng","year":"2005","unstructured":"Geng, W. et al. Cloning and characterization of the human soluble adenylyl cyclase. Am. J. Physiol. Cell Physiol. 288, C1305\u2013C1316 (2005).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"226_CR87","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1073\/pnas.1322778111","volume":"111","author":"S Kleinboelting","year":"2014","unstructured":"Kleinboelting, S. et al. Crystal structures of human soluble adenylyl cyclase reveal mechanisms of catalysis and of its activation through bicarbonate. Proc. Natl Acad. Sci. USA 111, 3727\u20133732 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"226_CR88","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/hep.28550","volume":"64","author":"JC Chang","year":"2016","unstructured":"Chang, J. C. et al. Soluble adenylyl cyclase regulates bile salt-induced apoptosis in human cholangiocytes. Hepatology 64, 522\u2013534 (2016).","journal-title":"Hepatology"},{"key":"226_CR89","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1053\/j.gastro.2008.02.020","volume":"134","author":"JT Salas","year":"2008","unstructured":"Salas, J. T. et al. Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis. Gastroenterology 134, 1482\u20131493 (2008).","journal-title":"Gastroenterology"},{"key":"226_CR90","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/hep.22348","volume":"48","author":"M Sasaki","year":"2008","unstructured":"Sasaki, M., Ikeda, H., Yamaguchi, J., Nakada, S. & Nakanuma, Y. Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence. Hepatology 48, 186\u2013195 (2008).","journal-title":"Hepatology"},{"key":"226_CR91","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jhep.2010.03.008","volume":"53","author":"M Sasaki","year":"2010","unstructured":"Sasaki, M., Miyakoshi, M., Sato, Y. & Nakanuma, Y. Modulation of the microenvironment by senescent biliary epithelial cells may be involved in the pathogenesis of primary biliary cirrhosis. J. Hepatol. 53, 318\u2013325 (2010).","journal-title":"J. Hepatol."},{"key":"226_CR92","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1016\/j.jhep.2015.02.023","volume":"62","author":"U Beuers","year":"2015","unstructured":"Beuers, U., Trauner, M., Jansen, P. & Poupon, R. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J. Hepatol. 62, S25\u2013S37 (2015).","journal-title":"J. Hepatol."},{"key":"226_CR93","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jhep.2003.11.006","volume":"40","author":"JY Chiang","year":"2004","unstructured":"Chiang, J. Y. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J. Hepatol. 40, 539\u2013551 (2004).","journal-title":"J. Hepatol."},{"key":"226_CR94","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1194\/jlr.R900012-JLR200","volume":"50","author":"PA Dawson","year":"2009","unstructured":"Dawson, P. A., Lan, T. & Rao, A. Bile acid transporters. J. Lipid Res. 50, 2340\u20132357 (2009).","journal-title":"J. Lipid Res."},{"key":"226_CR95","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0005-2736(00)00355-2","volume":"1511","author":"H Akita","year":"2001","unstructured":"Akita, H. et al. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. Biochim. Biophys. Acta 1511, 7\u201316 (2001).","journal-title":"Biochim. Biophys. Acta"},{"key":"226_CR96","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00424-006-0109-y","volume":"453","author":"AT Nies","year":"2007","unstructured":"Nies, A. T. & Keppler, D. The apical conjugate efflux pump ABCC2 (MRP2). Pflug. Arch. 453, 643\u2013659 (2007).","journal-title":"Pflug. Arch."},{"key":"226_CR97","doi-asserted-by":"crossref","first-page":"12598","DOI":"10.1021\/bi050943e","volume":"44","author":"P Lam","year":"2005","unstructured":"Lam, P., Wang, R. & Ling, V. Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Biochemistry 44, 12598\u201312605 (2005).","journal-title":"Biochemistry"},{"key":"226_CR98","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/13543776.2018.1459569","volume":"28","author":"V Sepe","year":"2018","unstructured":"Sepe, V., Distrutti, E., Fiorucci, S. & Zampella, A. Farnesoid X receptor modulators 2014\u2013present: a patent review. Expert Opin. Ther. Pat. 28, 351\u2013364 (2018).","journal-title":"Expert Opin. Ther. Pat."},{"key":"226_CR99","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jhep.2012.08.002","volume":"58","author":"E Halilbasic","year":"2013","unstructured":"Halilbasic, E., Claudel, T. & Trauner, M. Bile acid transporters and regulatory nuclear receptors in the liver and beyond. J. Hepatol. 58, 155\u2013168 (2013).","journal-title":"J. Hepatol."},{"key":"226_CR100","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1053\/j.gastro.2003.06.005","volume":"126","author":"GA Kullak-Ublick","year":"2004","unstructured":"Kullak-Ublick, G. A., Stieger, B. & Meier, P. J. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126, 322\u2013342 (2004).","journal-title":"Gastroenterology"},{"key":"226_CR101","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0076-6879(05)00028-5","volume":"400","author":"JJ Eloranta","year":"2005","unstructured":"Eloranta, J. J., Meier, P. J. & Kullak-Ublick, G. A. Coordinate transcriptional regulation of transport and metabolism. Methods Enzymol. 400, 511\u2013530 (2005).","journal-title":"Methods Enzymol."},{"key":"226_CR102","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1097-2765(00)80348-2","volume":"3","author":"H Wang","year":"1999","unstructured":"Wang, H., Chen, J., Hollister, K., Sowers, L. C. & Forman, B. M. Endogenous bile acids are ligands for the nuclear receptor FXR\/BAR. Mol. Cell 3, 543\u2013553 (1999).","journal-title":"Mol. Cell"},{"key":"226_CR103","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","volume":"284","author":"M Makishima","year":"1999","unstructured":"Makishima, M. et al. Identification of a nuclear receptor for bile acids. Science 284, 1362\u20131365 (1999).","journal-title":"Science"},{"key":"226_CR104","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1073\/pnas.051551698","volume":"98","author":"JL Staudinger","year":"2001","unstructured":"Staudinger, J. L. et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl Acad. Sci. USA 98, 3369\u20133374 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"226_CR105","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1126\/science.1070477","volume":"296","author":"M Makishima","year":"2002","unstructured":"Makishima, M. et al. Vitamin D receptor as an intestinal bile acid sensor. Science 296, 1313\u20131316 (2002).","journal-title":"Science"},{"key":"226_CR106","first-page":"649","volume":"20","author":"B Desvergne","year":"1999","unstructured":"Desvergne, B. & Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. 20, 649\u2013688 (1999).","journal-title":"Endocr. Rev."},{"key":"226_CR107","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1124\/mol.112.082503","volume":"83","author":"M Thomas","year":"2013","unstructured":"Thomas, M. et al. Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1). Mol. Pharmacol. 83, 709\u2013718 (2013).","journal-title":"Mol. Pharmacol."},{"key":"226_CR108","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/hep.27744","volume":"62","author":"NS Ghonem","year":"2015","unstructured":"Ghonem, N. S., Assis, D. N. & Boyer, J. L. Fibrates and cholestasis. Hepatology 62, 635\u2013643 (2015).","journal-title":"Hepatology"},{"key":"226_CR109","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0006-291X(02)02550-0","volume":"298","author":"T Maruyama","year":"2002","unstructured":"Maruyama, T. et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun. 298, 714\u2013719 (2002).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"226_CR110","doi-asserted-by":"crossref","first-page":"9435","DOI":"10.1074\/jbc.M209706200","volume":"278","author":"Y Kawamata","year":"2003","unstructured":"Kawamata, Y. et al. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278, 9435\u20139440 (2003).","journal-title":"J. Biol. Chem."},{"key":"226_CR111","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bbrc.2008.04.171","volume":"372","author":"V Keitel","year":"2008","unstructured":"Keitel, V., Donner, M., Winandy, S., Kubitz, R. & Haussinger, D. Expression and function of the bile acid receptor TGR5 in Kupffer cells. Biochem. Biophys. Res. Commun. 372, 78\u201384 (2008).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"226_CR112","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/hep.24525","volume":"54","author":"YD Wang","year":"2011","unstructured":"Wang, Y. D., Chen, W. D., Yu, D., Forman, B. M. & Huang, W. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor \u03ba light-chain enhancer of activated B cells (NF-\u03baB) in mice. Hepatology 54, 1421\u20131432 (2011).","journal-title":"Hepatology"},{"key":"226_CR113","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s00424-003-1130-z","volume":"447","author":"B Hagenbuch","year":"2004","unstructured":"Hagenbuch, B. & Dawson, P. The sodium bile salt cotransport family SLC10. Pflug. Arch. 447, 566\u2013570 (2004).","journal-title":"Pflug. Arch."},{"key":"226_CR114","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/0092-8674(95)90530-8","volume":"81","author":"BM Forman","year":"1995","unstructured":"Forman, B. M. et al. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81, 687\u2013693 (1995).","journal-title":"Cell"},{"key":"226_CR115","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S1097-2765(00)00051-4","volume":"6","author":"B Goodwin","year":"2000","unstructured":"Goodwin, B. et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell 6, 517\u2013526 (2000).","journal-title":"Mol. Cell"},{"key":"226_CR116","doi-asserted-by":"crossref","first-page":"28857","DOI":"10.1074\/jbc.M011610200","volume":"276","author":"M Ananthanarayanan","year":"2001","unstructured":"Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J. & Suchy, F. J. Human bile salt export pump promoter is transactivated by the farnesoid X receptor\/bile acid receptor. J. Biol. Chem. 276, 28857\u201328865 (2001).","journal-title":"J. Biol. Chem."},{"key":"226_CR117","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1161\/01.ATV.0000178994.21828.a7","volume":"25","author":"T Claudel","year":"2005","unstructured":"Claudel, T., Staels, B. & Kuipers, F. The farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler. Thromb. Vasc. Biol. 25, 2020\u20132030 (2005).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"226_CR118","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2005.09.001","volume":"2","author":"T Inagaki","year":"2005","unstructured":"Inagaki, T. et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2, 217\u2013225 (2005).","journal-title":"Cell Metab."},{"key":"226_CR119","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1194\/jlr.M700330-JLR200","volume":"48","author":"I Kim","year":"2007","unstructured":"Kim, I. et al. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J. Lipid Res. 48, 2664\u20132672 (2007).","journal-title":"J. Lipid Res."},{"key":"226_CR120","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/hep.23708","volume":"52","author":"V Triantis","year":"2010","unstructured":"Triantis, V., Saeland, E., Bijl, N., Oude-Elferink, R. P. & Jansen, P. L. Glycosylation of fibroblast growth factor receptor 4 is a key regulator of fibroblast growth factor 19-mediated down-regulation of cytochrome P450 7A1. Hepatology 52, 656\u2013666 (2010).","journal-title":"Hepatology"},{"key":"226_CR121","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1074\/jbc.M109326200","volume":"277","author":"HR Kast","year":"2002","unstructured":"Kast, H. R. et al. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J. Biol. Chem. 277, 2908\u20132915 (2002).","journal-title":"J. Biol. Chem."},{"key":"226_CR122","doi-asserted-by":"crossref","first-page":"29749","DOI":"10.1074\/jbc.274.42.29749","volume":"274","author":"J Grober","year":"1999","unstructured":"Grober, J. et al. Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid X receptor\/9-cis-retinoic acid receptor heterodimer. J. Biol. Chem. 274, 29749\u201329754 (1999).","journal-title":"J. Biol. Chem."},{"key":"226_CR123","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1053\/gast.2001.25503","volume":"121","author":"LA Denson","year":"2001","unstructured":"Denson, L. A. et al. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 121, 140\u2013147 (2001).","journal-title":"Gastroenterology"},{"key":"226_CR124","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","volume":"62","author":"M Pawlak","year":"2015","unstructured":"Pawlak, M., Lefebvre, P. & Staels, B. Molecular mechanism of PPAR\u03b1 action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 62, 720\u2013733 (2015).","journal-title":"J. Hepatol."},{"key":"226_CR125","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S2468-1253(17)30246-7","volume":"2","author":"D Jones","year":"2017","unstructured":"Jones, D. et al. Seladelpar (MBX-8025), a selective PPAR-\u03b4 agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. Lancet Gastroenterol. Hepatol. 2, 716\u2013726 (2017).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"226_CR126","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1021\/jm990554g","volume":"43","author":"TM Willson","year":"2000","unstructured":"Willson, T. M., Brown, P. J., Sternbach, D. D. & Henke, B. R. The PPARs: from orphan receptors to drug discovery. J. Med. Chem. 43, 527\u2013550 (2000).","journal-title":"J. Med. Chem."},{"key":"226_CR127","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1161\/hq1101.098228","volume":"21","author":"SM Post","year":"2001","unstructured":"Post, S. M. et al. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-\u03b1-mediated downregulation of cholesterol 7\u03b1-hydroxylase and sterol 27-hydroxylase expression. Arterioscler. Thromb. Vasc. Biol. 21, 1840\u20131845 (2001).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"226_CR128","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0022-2275(20)32398-1","volume":"41","author":"M Marrapodi","year":"2000","unstructured":"Marrapodi, M. & Chiang, J. Y. Peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) and agonist inhibit cholesterol 7\u03b1-hydroxylase gene (CYP7A1) transcription. J. Lipid Res. 41, 514\u2013520 (2000).","journal-title":"J. Lipid Res."},{"key":"226_CR129","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1194\/jlr.M800579-JLR200","volume":"50","author":"CL Vrins","year":"2009","unstructured":"Vrins, C. L. et al. Peroxisome proliferator-activated receptor \u03b4 activation leads to increased transintestinal cholesterol efflux. J. Lipid Res. 50, 2046\u20132054 (2009).","journal-title":"J. Lipid Res."},{"key":"226_CR130","doi-asserted-by":"crossref","first-page":"32852","DOI":"10.1074\/jbc.M305361200","volume":"278","author":"O Barbier","year":"2003","unstructured":"Barbier, O. et al. Peroxisome proliferator-activated receptor \u03b1 induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. J. Biol. Chem. 278, 32852\u201332860 (2003).","journal-title":"J. Biol. Chem."},{"key":"226_CR131","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1124\/dmd.106.013243","volume":"35","author":"K Senekeo-Effenberger","year":"2007","unstructured":"Senekeo-Effenberger, K. et al. Expression of the human UGT1 locus in transgenic mice by 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY-14643) and implications on drug metabolism through peroxisome proliferator-activated receptor \u03b1 activation. Drug Metab. Dispos. 35, 419\u2013427 (2007).","journal-title":"Drug Metab. Dispos."},{"key":"226_CR132","doi-asserted-by":"crossref","first-page":"30559","DOI":"10.1074\/jbc.M203511200","volume":"277","author":"D Jung","year":"2002","unstructured":"Jung, D., Fried, M. & Kullak-Ublick, G. A. Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor \u03b1. J. Biol. Chem. 277, 30559\u201330566 (2002).","journal-title":"J. Biol. Chem."},{"key":"226_CR133","doi-asserted-by":"crossref","first-page":"17838","DOI":"10.1074\/jbc.M210634200","volume":"278","author":"H Kitada","year":"2003","unstructured":"Kitada, H. et al. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. J. Biol. Chem. 278, 17838\u201317844 (2003).","journal-title":"J. Biol. Chem."},{"key":"226_CR134","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1172\/JCI117658","volume":"95","author":"RP Oude Elferink","year":"1995","unstructured":"Oude Elferink, R. P. et al. Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse. J. Clin. Invest. 95, 31\u201338 (1995).","journal-title":"J. Clin. Invest."},{"key":"226_CR135","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/hep.26894","volume":"59","author":"NS Ghonem","year":"2014","unstructured":"Ghonem, N. S., Ananthanarayanan, M., Soroka, C. J. & Boyer, J. L. Peroxisome proliferator-activated receptor \u03b1 activates human multidrug resistance transporter 3\/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion. Hepatology 59, 1030\u20131042 (2014).","journal-title":"Hepatology"},{"key":"226_CR136","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1194\/jlr.M400132-JLR200","volume":"45","author":"J Shoda","year":"2004","unstructured":"Shoda, J. et al. Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPAR\u03b1-mediated redistribution of ABCB4. J. Lipid Res. 45, 1813\u20131825 (2004).","journal-title":"J. Lipid Res."},{"key":"226_CR137","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/hep.27297","volume":"60","author":"M Pawlak","year":"2014","unstructured":"Pawlak, M. et al. The transrepressive activity of peroxisome proliferator-activated receptor \u03b1 is necessary and sufficient to prevent liver fibrosis in mice. Hepatology 60, 1593\u20131606 (2014).","journal-title":"Hepatology"},{"key":"226_CR138","doi-asserted-by":"crossref","first-page":"549627","DOI":"10.1155\/2013\/549627","volume":"2013","author":"FA Monsalve","year":"2013","unstructured":"Monsalve, F. A., Pyarasani, R. D., Delgado-Lopez, F. & Moore-Carrasco, R. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm. 2013, 549627 (2013).","journal-title":"Mediators Inflamm."},{"key":"226_CR139","doi-asserted-by":"crossref","first-page":"578","DOI":"10.3858\/emm.2012.44.10.066","volume":"44","author":"MY Lee","year":"2012","unstructured":"Lee, M. Y. et al. Peroxisome proliferator-activated receptor \u03b4 agonist attenuates hepatic steatosis by anti-inflammatory mechanism. Exp. Mol. Med. 44, 578\u2013585 (2012).","journal-title":"Exp. Mol. Med."},{"key":"226_CR140","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/hep4.1072","volume":"1","author":"F Haczeyni","year":"2017","unstructured":"Haczeyni, F. et al. The selective peroxisome proliferator-activated receptor-\u03b4 agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. Hepatol. Commun. 1, 663\u2013674 (2017).","journal-title":"Hepatol. Commun."},{"key":"226_CR141","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.bbadis.2011.01.014","volume":"1812","author":"CA Ihunnah","year":"2011","unstructured":"Ihunnah, C. A., Jiang, M. & Xie, W. Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochim. Biophys. Acta 1812, 956\u2013963 (2011).","journal-title":"Biochim. Biophys. Acta"},{"key":"226_CR142","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/sj.bjp.0707235","volume":"151","author":"S Teng","year":"2007","unstructured":"Teng, S. & Piquette-Miller, M. Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced cholestasis. Br. J. Pharmacol. 151, 367\u2013376 (2007).","journal-title":"Br. J. Pharmacol."},{"key":"226_CR143","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/j.1478-3231.2006.01326.x","volume":"26","author":"S Khurana","year":"2006","unstructured":"Khurana, S. & Singh, P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int. 26, 943\u2013948 (2006).","journal-title":"Liver Int."},{"key":"226_CR144","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jhep.2009.04.009","volume":"51","author":"European Association for the Study of the Liver.","year":"2009","unstructured":"European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J. Hepatol. 51, 237\u2013267 (2009).","journal-title":"J. Hepatol."},{"key":"226_CR145","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.gastro.2005.05.009","volume":"129","author":"HU Marschall","year":"2005","unstructured":"Marschall, H. U. et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 129, 476\u2013485 (2005).","journal-title":"Gastroenterology"},{"key":"226_CR146","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/0016-5085(92)90335-V","volume":"102","author":"L Bachs","year":"1992","unstructured":"Bachs, L., Pares, A., Elena, M., Piera, C. & Rodes, J. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology 102, 2077\u20132080 (1992).","journal-title":"Gastroenterology"},{"key":"226_CR147","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1053\/j.gastro.2012.08.029","volume":"143","author":"Y Lu","year":"2012","unstructured":"Lu, Y. et al. Glucocorticoids promote hepatic cholestasis in mice by inhibiting the transcriptional activity of the farnesoid X receptor. Gastroenterology 143, 1630\u20131640.e8 (2012).","journal-title":"Gastroenterology"},{"key":"226_CR148","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/gut.53.1.78","volume":"53","author":"D Jung","year":"2004","unstructured":"Jung, D., Fantin, A. C., Scheurer, U., Fried, M. & Kullak-Ublick, G. A. Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 53, 78\u201384 (2004).","journal-title":"Gut"},{"key":"226_CR149","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.abb.2004.09.019","volume":"433","author":"JJ Eloranta","year":"2005","unstructured":"Eloranta, J. J. & Kullak-Ublick, G. A. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch. Biochem. Biophys. 433, 397\u2013412 (2005).","journal-title":"Arch. Biochem. Biophys."},{"key":"226_CR150","doi-asserted-by":"crossref","first-page":"G427","DOI":"10.1152\/ajpgi.00205.2012","volume":"305","author":"T Takigawa","year":"2013","unstructured":"Takigawa, T. et al. Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid on liver lymphocytes in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G427\u2013G438 (2013).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"226_CR151","first-page":"695","volume":"118","author":"F Arenas","year":"2008","unstructured":"Arenas, F. et al. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J. Clin. Invest. 118, 695\u2013709 (2008).","journal-title":"J. Clin. Invest."},{"key":"226_CR152","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/S0168-8278(18)30293-9","volume":"68","author":"G Hirschfield","year":"2018","unstructured":"Hirschfield, G. et al. Results of a randomised controlled trial of budesonide add-on therapy in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid. J. Hepatol. 68, S38 (2018).","journal-title":"J. Hepatol."},{"key":"226_CR153","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1053\/j.gastro.2008.12.040","volume":"136","author":"E D'Aldebert","year":"2009","unstructured":"D\u2019Aldebert, E. et al. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology 136, 1435\u20131443 (2009).","journal-title":"Gastroenterology"},{"key":"226_CR154","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1194\/jlr.M044420","volume":"55","author":"J Cheng","year":"2014","unstructured":"Cheng, J. et al. Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in intestine-specific VDR-deficient mice. J. Lipid Res. 55, 455\u2013465 (2014).","journal-title":"J. Lipid Res."},{"key":"226_CR155","doi-asserted-by":"crossref","first-page":"14486","DOI":"10.1074\/jbc.M110.116004","volume":"285","author":"DR Schmidt","year":"2010","unstructured":"Schmidt, D. R. et al. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J. Biol. Chem. 285, 14486\u201314494 (2010).","journal-title":"J. Biol. Chem."},{"key":"226_CR156","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1136\/gut.2010.234666","volume":"60","author":"S Abramovitch","year":"2011","unstructured":"Abramovitch, S. et al. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut 60, 1728\u20131737 (2011).","journal-title":"Gut"},{"key":"226_CR157","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s12072-014-9548-2","volume":"8","author":"K Hochrath","year":"2014","unstructured":"Hochrath, K. et al. Vitamin D modulates biliary fibrosis in ABCB4-deficient mice. Hepatol. Int. 8, 443\u2013452 (2014).","journal-title":"Hepatol. Int."},{"key":"226_CR158","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.cell.2013.03.028","volume":"153","author":"N Ding","year":"2013","unstructured":"Ding, N. et al. A vitamin D receptor\/SMAD genomic circuit gates hepatic fibrotic response. Cell 153, 601\u2013613 (2013).","journal-title":"Cell"},{"key":"226_CR159","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.dld.2013.10.021","volume":"46","author":"H Duboc","year":"2014","unstructured":"Duboc, H., Tache, Y. & Hofmann, A. F. The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig. Liver Dis. 46, 302\u2013312 (2014).","journal-title":"Dig. Liver Dis."},{"key":"226_CR160","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1021\/jm7015864","volume":"51","author":"H Sato","year":"2008","unstructured":"Sato, H. et al. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure\u2013activity relationships, and molecular modeling studies. J. Med. Chem. 51, 1831\u20131841 (2008).","journal-title":"J. Med. Chem."},{"key":"226_CR161","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1677\/joe.1.06546","volume":"191","author":"T Maruyama","year":"2006","unstructured":"Maruyama, T. et al. Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1\/M-Bar) in mice. J. Endocrinol. 191, 197\u2013205 (2006).","journal-title":"J. Endocrinol."},{"key":"226_CR162","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/hep.26463","volume":"58","author":"N Pean","year":"2013","unstructured":"Pean, N. et al. The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice. Hepatology 58, 1451\u20131460 (2013).","journal-title":"Hepatology"},{"key":"226_CR163","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/hep.23032","volume":"50","author":"V Keitel","year":"2009","unstructured":"Keitel, V. et al. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology 50, 861\u2013870 (2009).","journal-title":"Hepatology"},{"key":"226_CR164","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s12016-014-8443-x","volume":"48","author":"V Keitel","year":"2015","unstructured":"Keitel, V., Reich, M. & Haussinger, D. TGR5: pathogenetic role and\/or therapeutic target in fibrosing cholangitis? Clin. Rev. Allergy Immunol. 48, 218\u2013225 (2015).","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"226_CR165","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/hep.24537","volume":"54","author":"A Baghdasaryan","year":"2011","unstructured":"Baghdasaryan, A. et al. Dual farnesoid X receptor\/TGR5 agonist INT-767 reduces liver injury in the Mdr2\u2013\/\u2013 (Abcb4\u2013\/\u2013) mouse cholangiopathy model by promoting biliary HCO3 \u2013 output. Hepatology 54, 1303\u20131312 (2011).","journal-title":"Hepatology"},{"key":"226_CR166","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1053\/j.gastro.2014.08.042","volume":"147","author":"T Lieu","year":"2014","unstructured":"Lieu, T. et al. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology 147, 1417\u20131428 (2014).","journal-title":"Gastroenterology"},{"key":"226_CR167","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.bbrc.2007.07.001","volume":"361","author":"JI Yang","year":"2007","unstructured":"Yang, J. I. et al. Bile acid-induced TGR5-dependent c-Jun-N terminal kinase activation leads to enhanced caspase 8 activation in hepatocytes. Biochem. Biophys. Res. Commun. 361, 156\u2013161 (2007).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"226_CR168","doi-asserted-by":"crossref","first-page":"G322","DOI":"10.1152\/ajpgi.00263.2012","volume":"304","author":"W Cao","year":"2013","unstructured":"Cao, W. et al. Expression of bile acid receptor TGR5 in gastric adenocarcinoma. Am. J. Physiol. Gastrointest. Liver Physiol. 304, G322\u2013G327 (2013).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"226_CR169","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/S0140-6736(17)30319-7","volume":"389","author":"VS Hegade","year":"2017","unstructured":"Hegade, V. S. et al. Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Lancet 389, 1114\u20131123 (2017).","journal-title":"Lancet"},{"key":"226_CR170","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/hep4.1305","volume":"3","author":"MJ Mayo","year":"2019","unstructured":"Mayo, M. J. et al. A randomized, controlled, phase 2 study of maralixibat in the treatment of itching associated with primary biliary cholangitis. Hepatol. Commun. 3, 365\u2013381 (2019).","journal-title":"Hepatol. Commun."},{"key":"226_CR171","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-25214-0","volume":"8","author":"S Al-Dury","year":"2018","unstructured":"Al-Dury, S. et al. Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis. Sci. Rep. 8, 6658 (2018).","journal-title":"Sci. Rep."},{"key":"226_CR172","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00394-017-1524-x","volume":"57","author":"F de Faria Ghetti","year":"2018","unstructured":"de Faria Ghetti, F. et al. Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis. Eur. J. Nutr. 57, 861\u2013876 (2018).","journal-title":"Eur. J. Nutr."},{"key":"226_CR173","doi-asserted-by":"crossref","first-page":"94416","DOI":"10.1172\/jci.insight.94416","volume":"2","author":"C Acharya","year":"2017","unstructured":"Acharya, C., Sahingur, S. E. & Bajaj, J. S. Microbiota, cirrhosis, and the emerging oral\u2013gut\u2013liver axis. JCI Insight 2, 94416 (2017).","journal-title":"JCI Insight"},{"key":"226_CR174","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1002\/hep.29676","volume":"67","author":"P Hartmann","year":"2018","unstructured":"Hartmann, P. et al. Modulation of the intestinal bile acid\/farnesoid X receptor\/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67, 2150\u20132166 (2018).","journal-title":"Hepatology"},{"key":"226_CR175","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1073\/pnas.0509592103","volume":"103","author":"T Inagaki","year":"2006","unstructured":"Inagaki, T. et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl Acad. Sci. USA 103, 3920\u20133925 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"226_CR176","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s00535-017-1400-8","volume":"53","author":"T Inamine","year":"2018","unstructured":"Inamine, T. & Schnabl, B. Immunoglobulin A and liver diseases. J. Gastroenterol. 53, 691\u2013700 (2018).","journal-title":"J. Gastroenterol."},{"key":"226_CR177","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12876-014-0189-7","volume":"14","author":"SC Bischoff","year":"2014","unstructured":"Bischoff, S. C. et al. Intestinal permeability \u2014 a new target for disease prevention and therapy. BMC Gastroenterol. 14, 189 (2014).","journal-title":"BMC Gastroenterol."},{"key":"226_CR178","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/hep4.1331","volume":"3","author":"N Ohtani","year":"2019","unstructured":"Ohtani, N. & Kawada, N. Role of the gut\u2013liver axis in liver inflammation, fibrosis, and cancer: a special focus on the gut microbiota relationship. Hepatol. Commun. 3, 456\u2013470 (2019).","journal-title":"Hepatol. Commun."},{"key":"226_CR179","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tem.2018.01.002","volume":"29","author":"AR Hamoud","year":"2018","unstructured":"Hamoud, A. R., Weaver, L., Stec, D. E. & Hinds, T. D. Jr. Bilirubin in the liver\u2013gut signaling axis. Trends Endocrinol. Metab. 29, 140\u2013150 (2018).","journal-title":"Trends Endocrinol. Metab."},{"key":"226_CR180","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1016\/j.ajpath.2016.06.003","volume":"186","author":"K Sato","year":"2016","unstructured":"Sato, K. et al. Pathogenesis of Kupffer cells in cholestatic liver injury. Am. J. Pathol. 186, 2238\u20132247 (2016).","journal-title":"Am. J. Pathol."},{"key":"226_CR181","first-page":"27","volume":"6","author":"E Treiner","year":"2015","unstructured":"Treiner, E. Mucosal-associated invariant T cells in inflammatory bowel diseases: bystanders, defenders, or offenders? Front. Immunol. 6, 27 (2015).","journal-title":"Front. Immunol."},{"key":"226_CR182","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jhep.2015.12.017","volume":"64","author":"HC Jeffery","year":"2016","unstructured":"Jeffery, H. C. et al. Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1. J. Hepatol. 64, 1118\u20131127 (2016).","journal-title":"J. Hepatol."},{"key":"226_CR183","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12072-018-9882-x","volume":"12","author":"M Atif","year":"2018","unstructured":"Atif, M., Warner, S. & Oo, Y. H. Linking the gut and liver: crosstalk between regulatory T cells and mucosa-associated invariant T cells. Hepatol. Int. 12, 305\u2013314 (2018).","journal-title":"Hepatol. Int."},{"key":"226_CR184","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/hep.29782","volume":"68","author":"K Bottcher","year":"2018","unstructured":"Bottcher, K. et al. MAIT cells are chronically activated in patients with autoimmune liver disease and promote profibrogenic hepatic stellate cell activation. Hepatology 68, 172\u2013186 (2018).","journal-title":"Hepatology"},{"key":"226_CR185","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jhep.2017.05.007","volume":"67","author":"R Wiest","year":"2017","unstructured":"Wiest, R., Albillos, A., Trauner, M., Bajaj, J. S. & Jalan, R. Targeting the gut\u2013liver axis in liver disease. J. Hepatol. 67, 1084\u20131103 (2017).","journal-title":"J. Hepatol."},{"key":"226_CR186","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1572-0241.2002.05521.x","volume":"97","author":"A Floreani","year":"2002","unstructured":"Floreani, A. et al. Mucosal IgA defect in primary biliary cirrhosis. Am. J. Gastroenterol. 97, 508\u2013510 (2002).","journal-title":"Am. J. Gastroenterol."},{"key":"226_CR187","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/cmi.2018.7","volume":"15","author":"B Li","year":"2018","unstructured":"Li, B., Selmi, C., Tang, R., Gershwin, M. E. & Ma, X. The microbiome and autoimmunity: a paradigm from the gut\u2013liver axis. Cell Mol. Immunol. 15, 595\u2013609 (2018).","journal-title":"Cell Mol. Immunol."},{"key":"226_CR188","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaut.2015.04.006","volume":"60","author":"N Isailovic","year":"2015","unstructured":"Isailovic, N., Daigo, K., Mantovani, A. & Selmi, C. Interleukin-17 and innate immunity in infections and chronic inflammation. J. Autoimmun. 60, 1\u201311 (2015).","journal-title":"J. Autoimmun."},{"key":"226_CR189","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/ni.3512","volume":"17","author":"L Campisi","year":"2016","unstructured":"Campisi, L. et al. Apoptosis in response to microbial infection induces autoreactive TH17 cells. Nat. Immunol. 17, 1084\u20131092 (2016).","journal-title":"Nat. Immunol."},{"key":"226_CR190","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/labinvest.2010.40","volume":"90","author":"I Haruta","year":"2010","unstructured":"Haruta, I. et al. Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation. Lab. Invest. 90, 577\u2013588 (2010).","journal-title":"Lab. Invest."},{"key":"226_CR191","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.immuni.2010.06.001","volume":"32","author":"HJ Wu","year":"2010","unstructured":"Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815\u2013827 (2010).","journal-title":"Immunity"},{"key":"226_CR192","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.jhep.2016.09.020","volume":"66","author":"E Schrumpf","year":"2017","unstructured":"Schrumpf, E. et al. The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation. J. Hepatol. 66, 382\u2013389 (2017).","journal-title":"J. Hepatol."},{"key":"226_CR193","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.27927","volume":"63","author":"JH Tabibian","year":"2016","unstructured":"Tabibian, J. H. et al. Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis. Hepatology 63, 185\u2013196 (2016).","journal-title":"Hepatology"},{"key":"226_CR194","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.1233521","volume":"339","author":"JG Markle","year":"2013","unstructured":"Markle, J. G. et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339, 1084\u20131088 (2013).","journal-title":"Science"},{"key":"226_CR195","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.immuni.2013.08.013","volume":"39","author":"L Yurkovetskiy","year":"2013","unstructured":"Yurkovetskiy, L. et al. Gender bias in autoimmunity is influenced by microbiota. Immunity 39, 400\u2013412 (2013).","journal-title":"Immunity"},{"key":"226_CR196","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.clim.2015.04.016","volume":"159","author":"A Gomez","year":"2015","unstructured":"Gomez, A., Luckey, D. & Taneja, V. The gut microbiome in autoimmunity: sex matters. Clin. Immunol. 159, 154\u2013162 (2015).","journal-title":"Clin. Immunol."},{"key":"226_CR197","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.4049\/jimmunol.1400076","volume":"194","author":"D Schwinge","year":"2015","unstructured":"Schwinge, D. et al. Testosterone suppresses hepatic inflammation by the downregulation of IL-17, CXCL-9, and CXCL-10 in a mouse model of experimental acute cholangitis. J. Immunol. 194, 2522\u20132530 (2015).","journal-title":"J. Immunol."},{"key":"226_CR198","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jhep.2019.04.001","volume":"71","author":"MH Harms","year":"2019","unstructured":"Harms, M. H. et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J. Hepatol. 71, 357\u2013365 (2019).","journal-title":"J. Hepatol."},{"key":"226_CR199","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S0016-5085(97)70183-5","volume":"113","author":"RE Poupon","year":"1997","unstructured":"Poupon, R. E. et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 113, 884\u2013890 (1997).","journal-title":"Gastroenterology"},{"key":"226_CR200","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0168-8278(01)00092-7","volume":"35","author":"KN Lazaridis","year":"2001","unstructured":"Lazaridis, K. N., Gores, G. J. & Lindor, K. D. Ursodeoxycholic acid \u2018mechanisms of action and clinical use in hepatobiliary disorders\u2019. J. Hepatol. 35, 134\u2013146 (2001).","journal-title":"J. Hepatol."},{"key":"226_CR201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/00365529409103618","volume":"204","author":"AF Hofmann","year":"1994","unstructured":"Hofmann, A. F. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand. J. Gastroenterol. Suppl. 204, 1\u201315 (1994).","journal-title":"Scand. J. Gastroenterol. Suppl."},{"key":"226_CR202","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2165\/00003495-198427020-00001","volume":"27","author":"A Ward","year":"1984","unstructured":"Ward, A., Brogden, R. N., Heel, R. C., Speight, T. M. & Avery, G. S. Ursodeoxycholic acid: a review of its pharmacological properties and therapeutic efficacy. Drugs 27, 95\u2013131 (1984).","journal-title":"Drugs"},{"key":"226_CR203","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0889-8553(05)70050-9","volume":"28","author":"A Stiehl","year":"1999","unstructured":"Stiehl, A., Benz, C. & Sauer, P. Mechanism of hepatoprotective action of bile salts in liver disease. Gastroenterol. Clin. North Am. 28, 195\u2013209 viii. (1999).","journal-title":"Gastroenterol. Clin. North Am."},{"key":"226_CR204","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1046\/j.1365-2036.1999.00596.x","volume":"13","author":"M Trauner","year":"1999","unstructured":"Trauner, M. & Graziadei, I. W. Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases. Aliment. Pharmacol. Ther. 13, 979\u2013996 (1999).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"226_CR205","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/0016-5085(93)90735-U","volume":"105","author":"J Prieto","year":"1993","unstructured":"Prieto, J., Qian, C., Garcia, N., Diez, J. & Medina, J. F. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Gastroenterology 105, 572\u2013578 (1993).","journal-title":"Gastroenterology"},{"key":"226_CR206","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/hep.510250104","volume":"25","author":"JF Medina","year":"1997","unstructured":"Medina, J. F., Martinez, A., Vazquez, J. J. & Prieto, J. Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis. Hepatology 25, 12\u201317 (1997).","journal-title":"Hepatology"},{"key":"226_CR207","first-page":"1194","volume":"86","author":"S Terasaki","year":"1991","unstructured":"Terasaki, S., Nakanuma, Y., Ogino, H., Unoura, M. & Kobayashi, K. Hepatocellular and biliary expression of HLA antigens in primary biliary cirrhosis before and after ursodeoxycholic acid therapy. Am. J. Gastroenterol. 86, 1194\u20131199 (1991).","journal-title":"Am. J. Gastroenterol."},{"key":"226_CR208","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S0022-2275(20)37599-4","volume":"37","author":"DM Heuman","year":"1996","unstructured":"Heuman, D. M., Bajaj, R. S. & Lin, Q. Adsorption of mixtures of bile salt taurine conjugates to lecithin\u2013cholesterol membranes: implications for bile salt toxicity and cytoprotection. J. Lipid Res. 37, 562\u2013573 (1996).","journal-title":"J. Lipid Res."},{"key":"226_CR209","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1159\/000450913","volume":"35","author":"M Sasaki","year":"2017","unstructured":"Sasaki, M. & Nakanuma, Y. Bile Acids and deregulated cholangiocyte autophagy in primary biliary cholangitis. Dig. Dis. 35, 210\u2013216 (2017).","journal-title":"Dig. Dis."},{"key":"226_CR210","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1007\/s00535-014-1033-0","volume":"50","author":"M Sasaki","year":"2015","unstructured":"Sasaki, M., Yoshimura-Miyakoshi, M., Sato, Y. & Nakanuma, Y. A possible involvement of endoplasmic reticulum stress in biliary epithelial autophagy and senescence in primary biliary cirrhosis. J. Gastroenterol. 50, 984\u2013995 (2015).","journal-title":"J. Gastroenterol."},{"key":"226_CR211","doi-asserted-by":"crossref","first-page":"7687","DOI":"10.1021\/jm500889f","volume":"57","author":"V Sepe","year":"2014","unstructured":"Sepe, V. et al. Modification on ursodeoxycholic acid (UDCA) scaffold. Discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1). J. Med. Chem. 57, 7687\u20137701 (2014).","journal-title":"J. Med. Chem."},{"key":"226_CR212","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1021\/jm025529g","volume":"45","author":"R Pellicciari","year":"2002","unstructured":"Pellicciari, R. et al. 6\u03b1-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J. Med. Chem. 45, 3569\u20133572 (2002).","journal-title":"J. Med. Chem."},{"key":"226_CR213","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","volume":"375","author":"F Nevens","year":"2016","unstructured":"Nevens, F. et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N. Engl. J. Med. 375, 631\u2013643 (2016).","journal-title":"N. Engl. J. Med."},{"key":"226_CR214","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.jhep.2017.01.013","volume":"66","author":"L Verbeke","year":"2017","unstructured":"Verbeke, L., Nevens, F. & Laleman, W. Steroidal or non-steroidal FXR agonists\u2014is that the question? J. Hepatol. 66, 680\u2013681 (2017).","journal-title":"J. Hepatol."},{"key":"226_CR215","doi-asserted-by":"crossref","first-page":"529","DOI":"10.2165\/11313370-000000000-00000","volume":"48","author":"T Lehr","year":"2009","unstructured":"Lehr, T. et al. A quantitative enterohepatic circulation model: development and evaluation with tesofensine and meloxicam. Clin. Pharmacokinet. 48, 529\u2013542 (2009).","journal-title":"Clin. Pharmacokinet."},{"key":"226_CR216","doi-asserted-by":"crossref","first-page":"9201","DOI":"10.1021\/acs.jmedchem.6b01126","volume":"59","author":"R Pellicciari","year":"2016","unstructured":"Pellicciari, R. et al. Discovery of 3\u03b1,7\u03b1,11\u03b2-trihydroxy-6\u03b1-ethyl-5\u03b2-cholan-24-oic acid (TC-100), a novel bile acid as potent and highly selective FXR agonist for enterohepatic disorders. J. Med. Chem. 59, 9201\u20139214 (2016).","journal-title":"J. Med. Chem."},{"key":"226_CR217","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/hepr.12373","volume":"45","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y. et al. Combination therapy of bezafibrate and ursodeoxycholic acid for primary biliary cirrhosis: a meta-analysis. Hepatol. Res. 45, 48\u201358 (2015).","journal-title":"Hepatol. Res."},{"key":"226_CR218","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.clinre.2015.02.011","volume":"39","author":"AY Grigorian","year":"2015","unstructured":"Grigorian, A. Y., Mardini, H. E., Corpechot, C., Poupon, R. & Levy, C. Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: a meta-analysis. Clin. Res. Hepatol. Gastroenterol. 39, 296\u2013306 (2015).","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"226_CR219","first-page":"985","volume":"379","author":"C Corpechot","year":"2018","unstructured":"Corpechot, C., Chazouilleres, O. & Rousseau, A. Bezafibrate in primary biliary cholangitis. N. Engl. J. Med. 379, 985 (2018).","journal-title":"N. Engl. J. Med."},{"key":"226_CR220","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/hep.30145","volume":"69","author":"KD Lindor","year":"2019","unstructured":"Lindor, K. D., Bowlus, C. L., Boyer, J., Levy, C. & Mayo, M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 69, 394\u2013419 (2019).","journal-title":"Hepatology"},{"key":"226_CR221","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0378-4274(98)00042-3","volume":"98","author":"AD Edgar","year":"1998","unstructured":"Edgar, A. D. et al. Fenofibrate modifies transaminase gene expression via a peroxisome proliferator activated receptor \u03b1-dependent pathway. Toxicol. Lett. 98, 13\u201323 (1998).","journal-title":"Toxicol. Lett."},{"key":"226_CR222","doi-asserted-by":"crossref","first-page":"4740","DOI":"10.1021\/jm300212s","volume":"55","author":"M Karlgren","year":"2012","unstructured":"Karlgren, M. et al. Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug\u2013drug interactions. J. Med. Chem. 55, 4740\u20134763 (2012).","journal-title":"J. Med. Chem."},{"key":"226_CR223","doi-asserted-by":"crossref","first-page":"3C","DOI":"10.1016\/j.amjcard.2006.11.016","volume":"99","author":"MH Davidson","year":"2007","unstructured":"Davidson, M. H., Armani, A., McKenney, J. M. & Jacobson, T. A. Safety considerations with fibrate therapy. Am. J. Cardiol. 99, 3C\u201318C (2007).","journal-title":"Am. J. Cardiol."},{"key":"226_CR224","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2165\/00003088-199834020-00003","volume":"34","author":"DB Miller","year":"1998","unstructured":"Miller, D. B. & Spence, J. D. Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin. Pharmacokinet. 34, 155\u2013162 (1998).","journal-title":"Clin. Pharmacokinet."},{"key":"226_CR225","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1345\/aph.17310","volume":"32","author":"KJ Ascah","year":"1998","unstructured":"Ascah, K. J., Rock, G. A. & Wells, P. S. Interaction between fenofibrate and warfarin. Ann. Pharmacother. 32, 765\u2013768 (1998).","journal-title":"Ann. Pharmacother."},{"key":"226_CR226","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1001\/jama.1990.03450010075034","volume":"264","author":"LR Pierce","year":"1990","unstructured":"Pierce, L. R., Wysowski, D. K. & Gross, T. P. Myopathy and rhabdomyolysis associated with lovastatin\u2013gemfibrozil combination therapy. JAMA 264, 71\u201375 (1990).","journal-title":"JAMA"},{"key":"226_CR227","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1161\/01.RES.0000143422.83209.be","volume":"95","author":"DS Ory","year":"2004","unstructured":"Ory, D. S. Nuclear receptor signaling in the control of cholesterol homeostasis: have the orphans found a home? Circ. Res. 95, 660\u2013670 (2004).","journal-title":"Circ. Res."},{"key":"226_CR228","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1101\/gad.1138104","volume":"18","author":"Y Zhang","year":"2004","unstructured":"Zhang, Y., Castellani, L. W., Sinal, C. J., Gonzalez, F. J. & Edwards, P. A. Peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev. 18, 157\u2013169 (2004).","journal-title":"Genes Dev."},{"key":"226_CR229","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1172\/JCI0215387","volume":"110","author":"CR Pullinger","year":"2002","unstructured":"Pullinger, C. R. et al. Human cholesterol 7\u03b1-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J. Clin. Invest. 110, 109\u2013117 (2002).","journal-title":"J. Clin. Invest."},{"key":"226_CR230","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1172\/JCI0216076","volume":"110","author":"A Beigneux","year":"2002","unstructured":"Beigneux, A., Hofmann, A. F. & Young, S. G. Human CYP7A1 deficiency: progress and enigmas. J. Clin. Invest. 110, 29\u201331 (2002).","journal-title":"J. Clin. Invest."},{"key":"226_CR231","doi-asserted-by":"crossref","first-page":"25123","DOI":"10.1074\/jbc.M112.375907","volume":"287","author":"HA Cyphert","year":"2012","unstructured":"Cyphert, H. A. et al. Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21. J. Biol. Chem. 287, 25123\u201325138 (2012).","journal-title":"J. Biol. Chem."},{"key":"226_CR232","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S2468-1253(18)30163-8","volume":"3","author":"M Carbone","year":"2018","unstructured":"Carbone, M. et al. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. Lancet Gastroenterol. Hepatol. 3, 626\u2013634 (2018).","journal-title":"Lancet Gastroenterol. Hepatol."}],"container-title":["Nature Reviews Gastroenterology & Hepatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41575-019-0226-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41575-019-0226-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41575-019-0226-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T20:04:38Z","timestamp":1695499478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41575-019-0226-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":232,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["226"],"URL":"https:\/\/doi.org\/10.1038\/s41575-019-0226-7","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]},"assertion":[{"value":"9 October 2019","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2019","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.F.G. has received consulting and\/or speaker fees in the last 3 years from Abbvie and Intercept. G.M.H. has received consulting and\/or speaker fees in the last 3 years from Blade, Cymabay, Falk, Genfit, Gilead, GSK, Intercept and Pliant. G.M.H. is supported by the Lily and Terry Horner Chair in Autoimmune Liver Disease Research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}