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Lancet 1977;1:721-724."},{"key":"ref96","doi-asserted-by":"crossref","unstructured":"Bengoa JM, Sitrin MD, Meredith S, Kelly SE, Shah N, Baker AL, Rosenberg IH. Intestinal calcium absorption and vitamin D status in chronic cholestatic liver disease. Hepatology 1984;4:261-265.","DOI":"10.1002\/hep.1840040215"},{"key":"ref97","doi-asserted-by":"crossref","unstructured":"Heathcote EJ. Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology 2000;31:1005-1013.","DOI":"10.1053\/he.2000.5984"},{"key":"ref98","doi-asserted-by":"crossref","unstructured":"Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet 2003;362:53-61.","DOI":"10.1016\/S0140-6736(03)13808-1"},{"key":"ref99","doi-asserted-by":"crossref","unstructured":"Eastell R, Dickson ER, Hodgson SF, Wiesner RH, Porayko MK, Wahner HW, Cedel SL, Riggs BL, Krom RA. Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis. Hepatology 1991;14:296-300.","DOI":"10.1002\/hep.1840140215"},{"key":"ref100","doi-asserted-by":"crossref","unstructured":"Leslie WD, Bernstein CN, Leboff MS. AGA technical review on osteoporosis in hepatic disorders. Gastroenterology 2003;125:941-966.","DOI":"10.1016\/S0016-5085(03)01062-X"},{"key":"ref101","doi-asserted-by":"crossref","unstructured":"Benetti A, Crosignani A, Varenna M, Giussani CS, Allocca M, Zuin M, Podda M, Battezzati PM. Primary biliary cirrhosis is not an additional risk factor for bone loss in women receiving regular calcium and vitamin D supplementation: a controlled longitudinal study. J Clin Gastroenterol 2008;42:306-311.","DOI":"10.1097\/01.mcg.0000248017.31386.39"},{"key":"ref102","doi-asserted-by":"crossref","unstructured":"Hodgson SF, Dickson ER, Wahner HW, Johnson KA, Mann KG, Riggs BL. 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Hepatology 1985;5:837-842.","DOI":"10.1002\/hep.1840050522"},{"key":"ref109","doi-asserted-by":"crossref","unstructured":"Pares A, Rodes J. Natural history of primary biliary cirrhosis. Clin Liver Dis 2003;7:779-794.","DOI":"10.1016\/S1089-3261(03)00100-4"},{"key":"ref110","doi-asserted-by":"crossref","unstructured":"Allocca M, Crosignani A, Gritti A, Benetti A, Zuin M, Podda M, Battezzati PM. Inadequate dietary intake but not renal tubular acidosis is associated with bone demineralization in primary biliary cirrhosis. Aliment Pharmacol Ther 2007;25:219-227.","DOI":"10.1111\/j.1365-2036.2006.03181.x"},{"key":"ref111","doi-asserted-by":"crossref","unstructured":"Rigamonti C, Shand LM, Feudjo M, Bunn CC, Black CM, Denton CP, Burroughs AK. Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis. Gut 2006;55:388-394.","DOI":"10.1136\/gut.2005.075002"},{"key":"ref112","doi-asserted-by":"crossref","unstructured":"Lee YM, Kaplan MM. The natural history of PBC: has it changed? Semin Liver Dis 2005;25:321-326.","DOI":"10.1055\/s-2005-916323"},{"key":"ref113","doi-asserted-by":"crossref","unstructured":"Roll J, Boyer JL, Barry D, Klatskin G. The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis. N Engl J Med 1983;308:1-7.","DOI":"10.1056\/NEJM198301063080101"},{"key":"ref114","doi-asserted-by":"crossref","unstructured":"Mahl TC, Shockcor W, Boyer JL. Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years. J Hepatol 1994;20:707-713.","DOI":"10.1016\/S0168-8278(05)80139-4"},{"key":"ref115","doi-asserted-by":"crossref","unstructured":"Springer J, Cauch-Dudek K, O’Rourke K, Wanless IR, Heathcote EJ. Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis. 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Gastroenterology 1985;89:1084-1091.","DOI":"10.1016\/0016-5085(85)90213-6"},{"key":"ref122","doi-asserted-by":"crossref","unstructured":"Rydning A, Schrumpf E, Abdelnoor M, Elgjo K, Jenssen E. Factors of prognostic importance in primary biliary cirrhosis. Scand J Gastroenterol 1990;25:119-126.","DOI":"10.3109\/00365529009107932"},{"key":"ref123","doi-asserted-by":"crossref","unstructured":"Biagini MR, Guardascione M, Raskino C, McIntyre N, Surrenti C, Burroughs AK. Poor prognostication for survival in individual PBC patients with Cox models. J Hepatol 1990;11:S7.","DOI":"10.1016\/0168-8278(90)91362-Z"},{"key":"ref124","doi-asserted-by":"crossref","unstructured":"Hughes MD, Raskino CL, Pocock SJ, Biagini MR, Burroughs AK. Prediction of short-term survival with an application in primary biliary cirrhosis. 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Stimulation of bile acid 6 alpha-hydroxylation by rifampin. J Hepatol 1996;24:713-718.","DOI":"10.1016\/S0168-8278(96)80268-6"},{"key":"ref138","doi-asserted-by":"crossref","unstructured":"Marschall HU, Wagner M, Zollner G, Fickert P, Diczfalusy U, Gumhold J, Silbert D, Fuchsbichler A, Benthin L, Grundstrom R. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 2005;129:476-485.","DOI":"10.1016\/j.gastro.2005.05.009"},{"key":"ref139","doi-asserted-by":"crossref","unstructured":"Bachs L, Pares A, Elena M, Piera C, Rodes J. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology 1992;102:2077-2080.","DOI":"10.1016\/0016-5085(92)90335-V"},{"key":"ref140","doi-asserted-by":"crossref","unstructured":"Prince MI, Burt AD, Jones DE. Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut 2002;50:436-439.","DOI":"10.1136\/gut.50.3.436"},{"key":"ref141","doi-asserted-by":"crossref","unstructured":"Raderer M, Muller C, Scheithauer W. Ondansetron for pruritus due to cholestasis. N Engl J Med 1994;330:1540.","DOI":"10.1056\/NEJM199405263302117"},{"key":"ref142","doi-asserted-by":"crossref","unstructured":"Schworer H, Hartmann H, Ramadori G. Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. Pain 1995;61:33-37.","DOI":"10.1016\/0304-3959(94)00145-5"},{"key":"ref143","doi-asserted-by":"crossref","unstructured":"Schworer H, Ramadori G. Improvement of cholestatic pruritus by ondansetron. Lancet 1993;341:1277.","DOI":"10.1016\/0140-6736(93)91178-O"},{"key":"ref144","unstructured":"Jones EA, Molenaar HA, Oosting J. Ondansetron and pruritus in chronic liver disease: a controlled study. Hepato-gastroenterology 2007;54:1196-1199."},{"key":"ref145","doi-asserted-by":"crossref","unstructured":"Muller C, Pongratz S, Pidlich J, Penner E, Kaider A, Schemper M, Raderer M, Scheithauer W, Ferenci P. Treatment of pruritus in chronic liver disease with the 5-hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo-controlled, double-blind cross-over trial. Eur J Gastroenterol Hepatol 1998;10:865-870.","DOI":"10.1097\/00042737-199810000-00010"},{"key":"ref146","doi-asserted-by":"crossref","unstructured":"O’Donohue JW, Pereira SP, Ashdown AC, Haigh CG, Wilkinson JR, Williams R. A controlled trial of ondansetron in the pruritus of cholestasis. Aliment Pharmacol Ther 2005;21:1041-1045.","DOI":"10.1111\/j.1365-2036.2005.02430.x"},{"key":"ref147","doi-asserted-by":"crossref","unstructured":"Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ. Sertraline as a first-line treatment for cholestatic pruritus. 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Dig Dis Sci 2006;51:1103-1112.","DOI":"10.1007\/s10620-006-8015-x"},{"key":"ref151","unstructured":"Crippin JS, Jorgensen RA, Dickson ER, Lindor KD. Hepatic osteodystrophy in primary biliary cirrhosis: effects of medical treatment. Am J Gastroenterol 1994;89:47-50."},{"key":"ref152","doi-asserted-by":"crossref","unstructured":"Ormarsdottir S, Ljunggren O, Mallmin H, Olsson R, Prytz H, Loof L. Longitudinal bone loss in postmenopausal women with primary biliary cirrhosis and well-preserved liver function. J Intern Med 2002;252:537-541.","DOI":"10.1046\/j.1365-2796.2002.01066.x"},{"key":"ref153","doi-asserted-by":"crossref","unstructured":"Ormarsdottir S, Mallmin H, Naessen T, Petren-Mallmin M, Broome U, Hultcrantz R, Loof L. An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis. J Intern Med 2004;256:63-69.","DOI":"10.1111\/j.1365-2796.2004.01342.x"},{"key":"ref154","doi-asserted-by":"crossref","unstructured":"Pereira SP, O’Donohue J, Moniz C, Phillips MG, Abraha H, Buxton-Thomas M, Williams R. Transdermal hormone replacement therapy improves vertebral bone density in primary biliary cirrhosis: results of a 1-year controlled trial. Aliment Pharmacol Ther 2004;19:563-570.","DOI":"10.1111\/j.1365-2036.2004.01890.x"},{"key":"ref155","doi-asserted-by":"crossref","unstructured":"Guanabens N, Pares A, Monegal A, Peris P, Pons F, Alvarez L, de Osaba MJ, Roca M, Torra M, Rodes J. Etidronate versus fluoride for treatment of osteopenia in primary biliary cirrhosis: preliminary results after 2 years. Gastroenterology 1997;113:219-224.","DOI":"10.1016\/S0016-5085(97)70098-2"},{"key":"ref156","doi-asserted-by":"crossref","unstructured":"Wolfhagen FH, van Buuren HR, den Ouden JW, Hop WC, van Leeuwen JP, Schalm SW, Pols HA. 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Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial. Hepatology 2005;42:762-771.","DOI":"10.1002\/hep.20866"},{"key":"ref160","doi-asserted-by":"crossref","unstructured":"Floreani A, Chiaramonte M, Giannini S, Malvasi L, Lodetti MG, Castrignano R, Giacomini A, D’Angelo A, Naccarato R. Longitudinal study on osteodystrophy in primary biliary cirrhosis (PBC) and a pilot study on calcitonin treatment. J Hepatol 1991;12:217-223.","DOI":"10.1016\/0168-8278(91)90941-4"},{"key":"ref161","doi-asserted-by":"crossref","unstructured":"Lindor KD, Janes CH, Crippin JS, Jorgensen RA, Dickson ER. Bone disease in primary biliary cirrhosis: does ursodeoxycholic acid make a difference? Hepatology 1995;21:389-392.","DOI":"10.1002\/hep.1840210219"},{"key":"ref162","doi-asserted-by":"crossref","unstructured":"Longo M, Crosignani A, Podda M. Hyperlipidemia in Chronic Cholestatic Liver Disease. Curr Treat Options Gastroenterol 2001;4:111-114.","DOI":"10.1007\/s11938-001-0022-6"},{"key":"ref163","doi-asserted-by":"crossref","unstructured":"Del Puppo M, Galli Kienle M, Crosignani A, Petroni ML, Amati B, Zuin M, Podda M. Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. J Lipid Res 2001;42:437-441.","DOI":"10.1016\/S0022-2275(20)31668-0"},{"key":"ref164","doi-asserted-by":"crossref","unstructured":"Ritzel U, Leonhardt U, Nuther M, Schufer G, Armstrong VW, Ramadori G. Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers. J Hepatol 2002;36:454-458.","DOI":"10.1016\/S0168-8278(02)00006-5"},{"key":"ref165","doi-asserted-by":"crossref","unstructured":"Stojakovic T, Putz-Bankuti C, Fauler G, Scharnagl H, Wagner M, Stadlbauer V, Gurakuqi G, Stauber RE, Murz W, Trauner M. Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid. Hepatology 2007;46:776-784.","DOI":"10.1002\/hep.21741"},{"key":"ref166","doi-asserted-by":"crossref","unstructured":"Gong Y, Klingenberg SL, Gluud C. Systematic review and meta-analysis: D-Penicillamine vs. placebo\/no intervention in patients with primary biliary cirrhosis--Cochrane Hepato-Biliary Group. Aliment Pharmacol Ther 2006;24:1535-1544.","DOI":"10.1111\/j.1365-2036.2006.03164.x"},{"key":"ref167","doi-asserted-by":"crossref","unstructured":"Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997;113:884-890.","DOI":"10.1016\/S0016-5085(97)70183-5"},{"key":"ref168","doi-asserted-by":"crossref","unstructured":"Mitchison HC, Bassendine MF, Malcolm AJ, Watson AJ, Record CO, James OF. A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss. 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Hepatology 2005;42:1184-1193.","DOI":"10.1002\/hep.20897"},{"key":"ref179","doi-asserted-by":"crossref","unstructured":"Gonzalez-Koch A, Brahm J, Antezana C, Smok G, Cumsille MA. The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone. J Hepatol 1997;27:143-149.","DOI":"10.1016\/S0168-8278(97)80294-2"},{"key":"ref180","doi-asserted-by":"crossref","unstructured":"Hendrickse MT, Rigney E, Giaffer MH, Soomro I, Triger DR, Underwood JC, Gleeson D. Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial. Gastroenterology 1999;117:400-407.","DOI":"10.1053\/gast.1999.0029900400"},{"key":"ref181","doi-asserted-by":"crossref","unstructured":"Lombard M, Portmann B, Neuberger J, Williams R, Tygstrup N, Ranek L, Ring-Larsen H, Rodes J, Navasa M, Trepo C. Cyclosporin A treatment in primary biliary cirrhosis: results of a long-term placebo controlled trial. Gastroenterology 1993;104:519-526.","DOI":"10.1016\/0016-5085(93)90422-9"},{"key":"ref182","doi-asserted-by":"crossref","unstructured":"Bodenheimer H Jr, Schaffner F, Pezzullo J. Evaluation of colchicine therapy in primary biliary cirrhosis. Gastroenterology 1988;95:124-129.","DOI":"10.1016\/0016-5085(88)90300-9"},{"key":"ref183","doi-asserted-by":"crossref","unstructured":"Kaplan MM, Alling DW, Zimmerman HJ, Wolfe HJ, Sepersky RA, Hirsch GS, Elta GH, Glick KA, Eagen KA. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986;315:1448-1454.","DOI":"10.1056\/NEJM198612043152304"},{"key":"ref184","doi-asserted-by":"crossref","unstructured":"Warnes TW, Smith A, Lee FI, Haboubi NY, Johnson PJ, Hunt L. A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report. J Hepatol 1987;5:1-7.","DOI":"10.1016\/S0168-8278(87)80053-3"},{"key":"ref185","doi-asserted-by":"crossref","unstructured":"Zifroni A, Schaffner F. 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J Hepatol 2000;32:561-566."},{"key":"ref197","doi-asserted-by":"crossref","unstructured":"Papatheodoridis GV, Hadziyannis ES, Deutsch M, Hadziyannis SJ. Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year, prospective, randomized, controlled trial. Am J Gastroenterol 2002;97:2063-2070.","DOI":"10.1111\/j.1572-0241.2002.05923.x"},{"key":"ref198","doi-asserted-by":"crossref","unstructured":"Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. N Engl J Med 1994;330:1342-1347.","DOI":"10.1056\/NEJM199405123301903"},{"key":"ref199","doi-asserted-by":"crossref","unstructured":"Lindor KD, Therneau TM, Jorgensen RA, Malinchoc M, Dickson ER. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology 1996;110:1515-1518.","DOI":"10.1053\/gast.1996.v110.pm8613058"},{"key":"ref200","doi-asserted-by":"crossref","unstructured":"Gluud C, Christensen E. 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