Advances in pharmacotherapy for primary biliary cirrhosis

Bibliography

• Ahrens EHJr, Payne MA, Kunkel HG, et al. Primary biliary cirrhosis. Medicine (Baltimore) 1950;29(4):299-364
   Google Scholar
• Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med 2005;353(12):1261-73
   PubMed Web of Science ®Google Scholar
• Dubel L, Tanaka A, Leung PS, et al. Autoepitope mapping and reactivity of autoantibodies to the dihydrolipoamide dehydrogenase-binding protein (E3BP) and the glycine cleavage proteins in primary biliary cirrhosis. Hepatology 1999;29(4):1013-18
   PubMed Web of Science ®Google Scholar
• Van de Water J, Fregeau D, Davis P, et al. Autoantibodies of primary biliary cirrhosis recognize dihydrolipoamide acetyltransferase and inhibit enzyme function. J Immunol 1988;141(7):2321-4
   PubMed Web of Science ®Google Scholar
• Leung PS, Chuang DT, Wynn RM, et al. Autoantibodies to BCOADC-E2 in patients with primary biliary cirrhosis recognize a conformational epitope. Hepatology 1995;22(2):505-13
   PubMed Web of Science ®Google Scholar
• Ichiki Y, Selmi C, Shimoda S, et al. Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis. Clin Rev Allergy Immunol 2005;28(2):83-91
   Google Scholar
• Kita H, Matsumura S, He XS, et al. Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis. J Clin Invest 2002;109(9):1231-40
   PubMed Web of Science ®Google Scholar
• Kita H, Naidenko OV, Kronenberg M, et al. Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer. Gastroenterology 2002;123(4):1031-43
   Google Scholar
• Shimoda S, Van de Water J, Ansari A, et al. Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis. J Clin Invest 1998;102(10):1831-40
   PubMed Web of Science ®Google Scholar
• Shimoda S, Harada K, Niiro H, et al. Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells. Hepatology 2008;47(3):958-65
   PubMed Web of Science ®Google Scholar
• Podda M, Selmi C, Lleo A, et al. The limitations and hidden gems of the epidemiology of primary biliary cirrhosis. J Autoimmun 2013;46:81-7
   PubMed Web of Science ®Google Scholar
• Gershwin ME, Selmi C, Worman HJ, et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology 2005;42(5):1194-202
   PubMed Web of Science ®Google Scholar
• Gershwin ME, Mackay IR, Sturgess A, Coppel RL. Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol 1987;138(10):3525-31
   PubMed Web of Science ®Google Scholar
• Zhang J, Zhang W, Leung PS, et al. Ongoing activation of autoantigen-specific B cells in primary biliary cirrhosis. Hepatology 2014;60(5):1708-16
   PubMed Web of Science ®Google Scholar
• Lleo A, Zhang W, McDonald WH, et al. Shotgun proteomics: identification of unique protein profiles of apoptotic bodies from biliary epithelial cells. Hepatology 2014;60(4):1314-23
   PubMed Web of Science ®Google Scholar
• Huang W, Kachapati K, Adams D, et al. Murine autoimmune cholangitis requires two hits: cytotoxic KLRG1(+) CD8 effector cells and defective T regulatory cells. J Autoimmun 2014;50:123-34
   PubMed Web of Science ®Google Scholar
• Yang CY, Ma X, Tsuneyama K, et al. IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis: implications for therapy. Hepatology 2014;59(5):1944-53
   PubMed Web of Science ®Google Scholar
• Hudspeth K, Pontarini E, Tentorio P, et al. The role of natural killer cells in autoimmune liver disease: a comprehensive review. J Autoimmun 2013;46:55-65
   PubMed Web of Science ®Google Scholar
• Gershwin ME, Mackay IR. The causes of primary biliary cirrhosis: convenient and inconvenient truths. Hepatology 2008;47(2):737-45
   Google Scholar
• Kuiper EM, Hansen BE, de Vries RA, et al. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology 2009;136(4):1281-7
   PubMed Web of Science ®Google Scholar
• Pares A, Caballeria L, Rodes J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology 2006;130(3):715-20
   PubMed Web of Science ®Google Scholar
• Zein CO, Angulo P, Lindor KD. When is liver biopsy needed in the diagnosis of primary biliary cirrhosis? Clin Gastroenterol Hepatol 2003;1(2):89-95
   PubMed Web of Science ®Google Scholar
• Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 2008;48(3):871-7
   PubMed Web of Science ®Google Scholar
• Kumagi T, Guindi M, Fischer SE, et al. Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol 2010;105(10):2186-94
   PubMed Web of Science ®Google Scholar
• Azemoto N, Kumagi T, Abe M, et al. Biochemical response to ursodeoxycholic acid predicts long-term outcome in Japanese patients with primary biliary cirrhosis. Hepatol Res 2011;41(4):310-17
   Google Scholar
• Zhang LN, Shi TY, Shi XH, et al. Early biochemical response to ursodeoxycholic acid and long-term prognosis of primary biliary cirrhosis: results of a 14-year cohort study. Hepatology 2013;58(1):264-72
   PubMed Web of Science ®Google Scholar
• Lammers WJ, van Buuren HR, Hirschfield GM, 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 2014;147(6):1338-49
   PubMed Web of Science ®Google Scholar
• Carbone M, Mells GF, Pells G, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 2013;144(3):560-69 e7; quiz e13-4
   PubMed Web of Science ®Google Scholar
• Lleo A, Bowlus CL, Yang GX, et al. Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis. Hepatology 2010;52(3):987-98
   PubMed Web of Science ®Google Scholar
• Lleo A, Gershwin ME, Mantovani A, Invernizzi P. Towards common denominators in primary biliary cirrhosis: the role of IL-12. J Hepatol 2012;56(3):731-3
   PubMed Web of Science ®Google Scholar
• Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 2002;36(3):525-31
   PubMed Web of Science ®Google Scholar
• Arenas F, Hervias I, Uriz M, et al. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest 2008;118(2):695-709
   PubMed Web of Science ®Google Scholar
• Serviddio G, Pereda J, Pallardo FV, et al. Ursodeoxycholic acid protects against secondary biliary cirrhosis in rats by preventing mitochondrial oxidative stress. Hepatology 2004;39(3):711-20
   Google Scholar
• Rodrigues CM, Fan G, Ma X, et al. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 1998;101(12):2790-9
   PubMed Web of Science ®Google Scholar
• Miura T, Ouchida R, Yoshikawa N, et al. Functional modulation of the glucocorticoid receptor and suppression of NF-kappaB-dependent transcription by ursodeoxycholic acid. J Biol Chem 2001;276(50):47371-8
   Google Scholar
• Invernizzi P, Setchell KD, Crosignani A, et al. Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. Hepatology 1999;29(2):320-7
   PubMed Web of Science ®Google Scholar
• Lindor KD, Gershwin ME, Poupon R, et al. Primary biliary cirrhosis. Hepatology 2009;50(1):291-308
   PubMed Web of Science ®Google Scholar
• European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol 2009;51(2):237-67
   PubMed Web of Science ®Google Scholar
• Gong Y, Huang Z, Christensen E, Gluud C. Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses. Am J Gastroenterol 2007;102(8):1799-807
   PubMedGoogle Scholar
• Goodwin B, Jones SA, Price RR, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 2000;6(3):517-26
   PubMed Web of Science ®Google Scholar
• Huang L, Zhao A, Lew JL, et al. Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J Biol Chem 2003;278(51):51085-90
   PubMed Web of Science ®Google Scholar
• Boyer JL, Trauner M, Mennone A, et al. Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol 2006;290(6):G1124-30
   PubMed Web of Science ®Google Scholar
• Denson LA, Sturm E, Echevarria W, et al. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 2001;121(1):140-7
   PubMed Web of Science ®Google Scholar
• Ananthanarayanan M, Balasubramanian N, Makishima M, et al. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 2001;276(31):28857-65
   PubMed Web of Science ®Google Scholar
• Kurosu H, Choi M, Ogawa Y, et al. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem 2007;282(37):26687-95
   PubMed Web of Science ®Google Scholar
• Wang YD, Chen WD, Wang M, et al. Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response. Hepatology 2008;48(5):1632-43
   PubMed Web of Science ®Google Scholar
• Wang YD, Chen WD, Yu D, et al. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB) in mice. Hepatology 2011;54(4):1421-32
   PubMed Web of Science ®Google Scholar
• Chen WD, Yu D, Forman BM, et al. Deficiency of G-protein-coupled bile acid receptor Gpbar1 (TGR5) enhances chemically induced liver carcinogenesis. Hepatology 2013;57(2):656-66
   Google Scholar
• Pellicciari R, Fiorucci S, Camaioni E, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem 2002;45(17):3569-72
   PubMed Web of Science ®Google Scholar
• Song KH, Li T, Owsley E, et al. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Hepatology 2009;49(1):297-305
   PubMed Web of Science ®Google Scholar
• Fiorucci S, Distrutti E, Ricci P, et al. Targeting FXR in cholestasis: hype or hope. Expert Opin Ther Targets 2014;1-11
   Google Scholar
• Gadaleta RM, van Erpecum KJ, Oldenburg B, et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 2011;60(4):463-72
   PubMed Web of Science ®Google Scholar
• Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol 2006;3(6):318-28
   PubMedGoogle Scholar
• Rizzo G, Passeri D, De Franco F, et al. Functional characterization of the semisynthetic bile acid derivative INT-767, a dual farnesoid X receptor and TGR5 agonist. Mol Pharmacol 2010;78(4):617-30
   PubMed Web of Science ®Google Scholar
• Miyazaki-Anzai S, Masuda M, Levi M, et al. Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis. PLoS One 2014;9(9):e108270
   PubMed Web of Science ®Google Scholar
• Baghdasaryan A, Claudel T, Gumhold J, et al. Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mouse cholangiopathy model by promoting biliary HCO(-)(3) output. Hepatology 2011;54(4):1303-12
   PubMed Web of Science ®Google Scholar
• Pellicciari R, Gioiello A, Macchiarulo A, et al. Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J Med Chem 2009;52(24):7958-61
   PubMed Web of Science ®Google Scholar
• Wu X, Ge H, Lemon B, et al. FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation. J Biol Chem 2010;285(8):5165-70
   PubMed Web of Science ®Google Scholar
• Honda A, Ikegami T, Nakamuta M, et al. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology 2013;57(5):1931-41
   PubMed Web of Science ®Google Scholar
• Lens S, Leoz M, Nazal L, et al. Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid. Liver Int 2014;34(2):197-203
   PubMed Web of Science ®Google Scholar
• Levy C, Peter JA, Nelson DR, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Aliment Pharmacol Ther 2011;33(2):235-42
   PubMed Web of Science ®Google Scholar
• Ghonem NS, Boyer JL. Fibrates as adjuvant therapy for chronic cholestatic liver disease: its time has come. Hepatology 2013;57(5):1691-3
   Google Scholar
• Kar SP, Seldin MF, Chen W, et al. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies. Genes Immun 2013;14(3):179-86
   Google Scholar
• Gershwin ME, Ansari AA, Mackay IR, et al. Primary biliary cirrhosis: an orchestrated immune response against epithelial cells. Immunol Rev 2000;174:210-25
   PubMed Web of Science ®Google Scholar
• Yoshida K, Yang GX, Zhang W, et al. Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor beta receptor type II mice. Hepatology 2009;50(5):1494-500
   PubMed Web of Science ®Google Scholar
• Hirschfield GM, Liu X, Xu C, et al. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med 2009;360(24):2544-55
   PubMed Web of Science ®Google Scholar
• Liu X, Invernizzi P, Lu Y, et al. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet 2010;42(8):658-60
   PubMed Web of Science ®Google Scholar
• Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421(6924):744-8
   PubMed Web of Science ®Google Scholar
• Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003;278(3):1910-14
   PubMed Web of Science ®Google Scholar
• Lan RY, Salunga TL, Tsuneyama K, et al. Hepatic IL-17 responses in human and murine primary biliary cirrhosis. J Autoimmun 2009;32(1):43-51
   Google Scholar
• Rong G, Zhou Y, Xiong Y, 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 2009;156(2):217-25
   Google Scholar
• Hirschfield GM. P367 phase 2 study evaluating the efficacy and safety of Ustekinumab in patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid. J Hepatol 2014;60(1):S189-S90
   Web of Science ®Google Scholar
• Dhirapong A, Yang GX, Nadler S, et al. Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine model of primary biliary cirrhosis. Hepatology 2013;57(2):708-15
   PubMed Web of Science ®Google Scholar
• Schoenberger SP, Toes RE, van der Voort EI, et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 1998;393(6684):480-3
   PubMed Web of Science ®Google Scholar
• Pessach IM, Notarangelo LD. X-linked primary immunodeficiencies as a bridge to better understanding X-chromosome related autoimmunity. J Autoimmun 2009;33(1):17-24
   PubMed Web of Science ®Google Scholar
• Goules A, Tzioufas AG, Manousakis MN, et al. Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases. J Autoimmun 2006;26(3):165-71
   PubMed Web of Science ®Google Scholar
• Afford SC, Ahmed-Choudhury J, Randhawa S, et al. CD40 activation-induced, Fas-dependent apoptosis and NF-kappaB/AP-1 signaling in human intrahepatic biliary epithelial cells. FASEB J 2001;15(13):2345-54
   PubMed Web of Science ®Google Scholar
• Lleo A, Liao J, Invernizzi P, et al. Immunoglobulin M levels inversely correlate with CD40 ligand promoter methylation in patients with primary biliary cirrhosis. Hepatology 2012;55(1):153-60
   PubMed Web of Science ®Google Scholar
• Law CL, Grewal IS. Therapeutic interventions targeting CD40L (CD154) and CD40: the opportunities and challenges. Adv Exp Med Biol 2009;647:8-36
   PubMed Web of Science ®Google Scholar
• Tanaka H, Yang GX, Iwakoshi N, et al. Anti-CD40 ligand monoclonal antibody delays the progression of murine autoimmune cholangitis. Clin Exp Immunol 2013;174(3):364-71
   PubMed Web of Science ®Google Scholar
• Borchers AT, Shimoda S, Bowlus C, et al. Lymphocyte recruitment and homing to the liver in primary biliary cirrhosis and primary sclerosing cholangitis. Semin Immunopathol 2009;31(3):309-22
   PubMed Web of Science ®Google Scholar
• Chuang YH, Lian ZX, Cheng CM, et al. Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives. J Autoimmun 2005;25(2):126-32
   PubMed Web of Science ®Google Scholar
• Bernuzzi F, Fenoglio D, Battaglia F, et al. Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis. J Autoimmun 2010;35(3):176-80
   Google Scholar
• Lan RY, Cheng C, Lian ZX, et al. Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology 2006;43(4):729-37
   PubMed Web of Science ®Google Scholar
• Wakabayashi K, Lian ZX, Moritoki Y, et al. IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. Hepatology 2006;44(5):1240-9
   PubMed Web of Science ®Google Scholar
• Aoki CA, Roifman CM, Lian ZX, et al. IL-2 receptor alpha deficiency and features of primary biliary cirrhosis. J Autoimmun 2006;27(1):50-3
   Google Scholar
• Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011;365(22):2067-77
   PubMed Web of Science ®Google Scholar
• Matsuoka K, Koreth J, Kim HT, et al. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med 2013;5(179):179ra43
   PubMed Web of Science ®Google Scholar
• Tanaka H, Zhang W, Yang GX, et al. Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells. Clin Exp Immunol 2014;178(2):253-61
   PubMed Web of Science ®Google Scholar
• Jeffery LE, Burke F, Mura M, et al. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol 2009;183(9):5458-67
   PubMed Web of Science ®Google Scholar
• Invernizzi P, Crosignani A, Battezzati PM, et al. Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology 1997;25(5):1090-5
   PubMed Web of Science ®Google Scholar
• Dhirapong A, Lleo A, Yang GX, et al. B cell depletion therapy exacerbates murine primary biliary cirrhosis. Hepatology 2011;53(2):527-35
   PubMed Web of Science ®Google Scholar
• Tsuda M, Moritoki Y, Lian ZX, et al. Biochemical and immunologic effects of rituximab in patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Hepatology 2012;55(2):512-21
   PubMed Web of Science ®Google Scholar
• Moritoki Y, Lian ZX, Lindor K, et al. B-cell depletion with anti-CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor-beta receptor II dominant negative mice. Hepatology 2009;50(6):1893-903
   Google Scholar
• Wang H, Shin DM, Abbasi S, et al. Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions. Proc Natl Acad Sci USA 2012;109(49):20077-82
   Google Scholar
• Leuschner M, Guldutuna S, You T, et al. Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis. J Hepatol 1996;25(1):49-57
   PubMed Web of Science ®Google Scholar
• Mitchison HC, Bassendine MF, Malcolm AJ, et al. A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss. Hepatology 1989;10(4):420-9
   PubMed Web of Science ®Google Scholar
• Wolfhagen FH, van Hoogstraten HJ, van Buuren HR, et al. Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study. J Hepatol 1998;29(5):736-42
   PubMed Web of Science ®Google Scholar
• Leuschner M, Maier KP, Schlichting J, et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 1999;117(4):918-25
   PubMed Web of Science ®Google Scholar
• Rautiainen H, Karkkainen P, Karvonen AL, et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology 2005;41(4):747-52
   PubMed Web of Science ®Google Scholar
• Hempfling W, Grunhage F, Dilger K, et al. Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis. Hepatology 2003;38(1):196-202
   PubMed Web of Science ®Google Scholar
• Combes B, Emerson SS, Flye NL, et al. Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis. Hepatology 2005;42(5):1184-93
   PubMed Web of Science ®Google Scholar
• Christensen E, Neuberger J, Crowe J, et al. Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial. Gastroenterology 1985;89(5):1084-91
   PubMed Web of Science ®Google Scholar
• Treiber G, Malfertheiner P. Mycophenolate mofetil for the treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. J Clin Gastroenterol 2005;39(9):837-8; author reply 38
   Google Scholar
• Charatcharoenwitthaya P, Talwalkar JA, Angulo P, et al. Moexipril for treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. Dig Dis Sci 2010;55(2):476-83
   PubMed Web of Science ®Google Scholar
• Mason AL, Wasilenko ST. Other potential medical therapies: the use of antiviral agents to investigate and treat primary ciliary cirrhosis. Clin Liver Dis 2008;12(2):445-60; xi
   Google Scholar
• Kaplan MM, Alling DW, Zimmerman HJ, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986;315(23):1448-54
   PubMed Web of Science ®Google Scholar
• Kaplan MM, Schmid C, Provenzale D, et al. A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis. Gastroenterology 1999;117(5):1173-80
   PubMedGoogle Scholar
• Bonis PA, Kaplan M. Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol. Gastroenterology 1999;117(2):395-9
   Google Scholar
• Askari F, Innis D, Dick RB, et al. Treatment of primary biliary cirrhosis with tetrathiomolybdate: results of a double-blind trial. Transl Res 2010;155(3):123-30
   Google Scholar
• Wang L, Han Q, Chen H, et al. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis. Stem Cells Dev 2014;23(20):2482-9
   PubMed Web of Science ®Google Scholar
• Eaton JE, Talwalkar JA, Lazaridis KN, et al. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology 2013;145(3):521-36
   PubMed Web of Science ®Google Scholar