Treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) with ursodeoxycholic acid (UDCA) has been in common use since 1985. In PBC, treatment with UDCA improves laboratory data, liver histology, enables a longer transplantation-free interval and prolongs disease survival. Because UDCA is unable to cure the disease newer drugs or combination therapies are still needed. Studies with UDCA and immunosuppressants such as prednisone, budesonide and azathioprine have shown that in selected patients combination therapy may be superior to UDCA monotherapy. PSC is treated successfully with UDCA and endoscropic dilatation of the bile duct strictures. Treatment of extrahepatic manifestations of cholestatic liver disease such as pruritus, fatigue, osteoporosis and steatorrhea can be problematic and time-consuming.

1.
Heathcote J: Update on primary biliary cirrhosis. Can J Gastroenterol 2000;14:43–48.
[PubMed]
2.
Fausa O, Schrumpf E, Elgjo K: Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis 1991;11:31–39.
[PubMed]
3.
Narayanan Menon KV, Wiesner RH: Etiology and natural history of primary sclerosing cholangitis. J Hepatobiliary Pancreat Surg 1999;6:343–351.
[PubMed]
4.
Agarwal K, Jones DE, Bassendine MF: Genetic susceptibility to primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:603–606.
[PubMed]
5.
Leuschner U, Leuschner M, Hübner K: Gallstone dissolution in patients with chronic active hepatitis (abstract). Gastroenterology 1981;80:1208.
6.
Leuschner U, Leuschner M, Sieratzki J, Kurtz W, Hübner K: Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up. A pilot study. Dig Dis Sci 1985;30:642–649.
[PubMed]
7.
David R, Kurtz W, Strohm WD, Leuschner U: Die Wirkung von Ursodesoxycholsäure bei chronischen Lebererkrankungen (abstract). Z Gastroenterol 1985;23:420.
8.
Beuers U, Boyer JL, Paumgartner G: Ursodeoxycholic acid in cholestasis: Potential mechanisms of action and therapeutic applications. Hepatology 1998;28:1449–1453.
[PubMed]
9.
Trauner M, Graziadei IW: Review article: Mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases. Aliment Pharmacol Ther 1999;13:979–996.
[PubMed]
10.
Hofmann AF: Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol Suppl 1994;204:1–15.
11.
Setchell KD, Rodrigues CM, Clerici C, Solinas A, Morelli A, Gartung C, Boyer J: Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology 1997;112:226–235.
[PubMed]
12.
van Nieuwerk CM, Groen AK, Ottenhoff R, van Wijland M, van den Bergh Weerman MA, Tytgat GN, Offerhaus JJ, Oude Elferink RP: The role of bile salt composition in liver pathology of mdr2 (–/–) mice: Differences between males and females. J Hepatol 1997;26:138–145.
[PubMed]
13.
Rodrigues CM, Fan G, Ma X, Kren BT, Steer CJ: A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 1998;101:2790–2799.
[PubMed]
14.
Kahn T: Value of CT and MRI in malignant hepatobiliary tumors. Zentralbl Chir 2000;125:610–615.
[PubMed]
15.
Güldütüna S, Zimmer G, Imhof M, Bhatti S, You T, Leuschner U: Molecular aspects of membrane stabilization by ursodeoxycholate. Gastroenterology 1993;104:1736–1744.
[PubMed]
16.
Güldütüna S, Deisinger B, Weiss A, Freisleben HJ, Zimmer G, Sipos P, Leuschner U: Ursodeoxycholate stabilizes phospholipid-rich membranes and mimics the effect of cholesterol: Investigations on large unilamellar vesicles. Biochim Biophys Acta 1997;1326:265–274.
[PubMed]
17.
Beuers U, Throckmorton DC, Anderson MS, Isales CM, Thasler W, Kullak-Ublick GA, Sauter G, Koebe HG, Paumgartner G, Boyer JL: Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology 1996;110:1553–1563.
[PubMed]
18.
Beuers U, Nathanson MH, Isales CM, Boyer JL: Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. J Clin Invest 1993;92:2984–2993.
[PubMed]
19.
Beuers U, Bilzer M, Chittattu A, Kullak-Ublick GA, Keppler D, Paumgartner G, Dombrowski F: Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver. Hepatology 2001;33:1206–1216.
[PubMed]
20.
Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, Lammert F, Stieger B, Meier PJ, Zatloukal K, Denk H, Trauner M: Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology 2001;121:170–183.
[PubMed]
21.
Kurz AK, Block C, Graf D, Dahl SV, Schliess F, Häussinger D: Phosphoinositide 3-kinase-dependent ras activation by tauroursodesoxycholate in rat liver. Biochem J 2000;350:207–213.
[PubMed]
22.
Wang X, Martindale JL, Liu Y, Holbrook NJ: The cellular response to oxidative stress: Influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem J 1998;333:291–300.
[PubMed]
23.
Yoshikawa M, Tsujii T, Matsumura K, Yamao J, Matsumura Y, Kubo R, Fukui H, Ishizaka S: Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology 1992;16:358–364.
[PubMed]
24.
Leuschner U, Fischer H, Kurtz W, Güldütüna S, Hübner K, Hellstern A, Gatzen M, Leuschner M: Ursodeoxycholic acid in primary biliary cirrhosis: Results of a controlled double-blind trial. Gastroenterology 1989;97:1268–1274.
[PubMed]
25.
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.
[PubMed]
26.
Lindor KD, Dickson ER, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA, Harrison JM, Wiesner RH, Anderson ML, Lange SM: Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology 1994;106:1284–1290.
[PubMed]
27.
Combes B, Carithers RL, Maddrey WC, Lin D, McDonald MF, Wheeler DE, Eigenbrodt EH, Munoz SJ, Rubin R, Garcia-Tsao G: A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995;22:759–766.
[PubMed]
28.
Heathcote EJ, Cauch-Dudek K, Walker V, Bailey RJ, Blendis LM, Ghent CN, Michieletti P, Minuk GY, Pappas SC, Scully LJ: The Canadian Multicenter Double-Blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1994;19:1149–1156.
[PubMed]
29.
Pasha T, Heathcote J, Gabriel S, Cauch-Dudek K, Jorgensen R, Therneau T, Dickson ER, Lindor KD: Cost-effectiveness of ursodeoxycholic acid therapy in primary biliary cirrhosis. Hepatology 1999;29:21–26.
[PubMed]
30.
Angulo P, Dickson ER, Therneau TM, Jorgensen RA, Smith C, DeSotel CK, Lange SM, Anderson ML, Mahoney DW, Lindor KD: Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: A randomized trial. J Hepatol 1999;30:830–835.
[PubMed]
31.
Verma A, Jazrawi RP, Ahmed HA, Davis T, Bland JM, Benson M, Orchard RT, Theodossi A, Maxwell JD, Northfield TC: Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:1069–1076.
[PubMed]
32.
van Hoogstraten HJ, De Smet MB, Renooij W, Breed JG, Engels LG, Den Ouden-Muller JW, Rijk MC, Smit AM, Zwertbroek R, Hop WC, van Berge Henegouwen GP, Schalm SW, van Buuren HR: A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg. Dutch Multicentre PBC Study Group. Aliment Pharmacol Ther 1998;12:965–971.
[PubMed]
33.
Heathcote EJ: Evidence-based therapy of primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:607–615.
[PubMed]
34.
Leuschner M, Dietrich CF, You T, Seidl C, Raedle J, Herrmann G, Ackermann H, Leuschner U: Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment. Gut 2000;46:121–126.
[PubMed]
35.
Floreani A, Zappala F, Mazzetto M, Naccarato R, Plebani M, Chiaramonte M: Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis according to severity of disease. Dig Dis Sci 1994;39:9–14.
[PubMed]
36.
Bolder U, Trang NV, Hagey LR, Schteingart CD, Ton-Nu HT, Cerre C, Elferink RP, Hofmann AF: Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats. Gastroenterology 1999;117:962–971.
[PubMed]
37.
Leuschner M, Schlichting J, Ackermann H, Leuschner U: Sulindac and ursodeoxycholic acid (UDCA) improve primary biliary cirrhosis (PBC) in patients not responding to UDCA. A prospective controlled pilot study (abstract). Hepatology 2000;32:309.
38.
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.
[PubMed]
39.
Leuschner U, Güldütüna S, Imhof M, Hübner K, Benjaminov A, Leuschner M: Effects of ursodeoxycholic acid after 4 to 12 years of therapy in early and late stages of primary biliary cirrhosis. J Hepatol 1994;21:624–633.
[PubMed]
40.
Poupon RE, Bonnand AM, Chretien Y, Poupon R: Ten-year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. The UDCA-PBC Study Group. Hepatology 1999;29:1668–1671.
[PubMed]
41.
Goulis J, Leandro G, Burroughs AK: Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: A meta-analysis. Lancet 1999;354:1053–1060.
[PubMed]
42.
Lindor KD, Poupon R, Heathcote EJ, Therneau T: Ursodeoxycholic acid for primary biliary cirrhosis. Lancet 2000;355:657–658.
43.
Batts KP, Jorgensen RA, Dickson ER, Lindor KD: Effects of ursodeoxycholic acid on hepatic inflammation and histological stage in patients with primary biliary cirrhosis. Am J Gastroenterol 1996;91:2314–2317.
[PubMed]
44.
Combes B, Markin RS, Wheeler DE, Rubin R, West AB, Mills AS, Eigenbrodt EH, Maddrey WC, Munoz SJ, Garcia-Tsao G, Bonner GF, Boyer JL, Luketic VA, Shiffman ML, Peters MG, White HM, Zetterman RK, Carithers RL: The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology 1999;30:602–605.
[PubMed]
45.
Degott C, Zafrani ES, Callard P, Balkau B, Poupon RE, Poupon R: Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression. Hepatology 1999;29:1007–1012.
[PubMed]
46.
Poupon RE, Balkau B, Eschwege E, Poupon R: A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med 1991;324:1548–1554.
[PubMed]
47.
Pares A, Caballeria L, Rodes J, Bruguera M, Rodrigo L, Garcia-Plaza A, Berenguer J, Rodriguez-Martinez D, Mercader J, Velicia R: Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: Results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol 2000;32:561–566.
[PubMed]
48.
Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R: The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology 2000;32:1196–1199.
[PubMed]
49.
Peterson TC, Slysz G, Isbrucker R: The inhibitory effect of ursodeoxycholic acid and pentoxifylline on platelet derived growth factor-stimulated proliferation is distinct from an effect by cyclic AMP. Immunopharmacology 1998;39:181–191.
[PubMed]
50.
Matsuzaki Y, Tanaka N, Osuga T, Aikawa T, Shoda J, Doi M, Nakano M: Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis. Am J Gastroenterol 1990;85:15–23.
[PubMed]
51.
Crippa G, Cagnoni C, Castelli A, Concesi C, Girometta S, Pancotti D, Sverzellati E, Tacchini G, Pierfranceschi MG, Carrara GC: Prolonged treatment with ursodeoxycholic acid for primary biliary cirrhosis. Clin Ter 1995;146:367–372.
[PubMed]
52.
Hwang SJ, Chan CY, Lee SD, Wu JC, Tsay SH, Lo KJ: Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: A short-term, randomized, double-blind controlled, cross-over study with long-term follow up. J Gastroenterol Hepatol 1993;8:217–223.
[PubMed]
53.
Almasio PL, Floreani A, Chiaramonte M, Provenzano G, Battezzati P, Crosignani A, Podda M, Todros L, Rosina F, Saccoccio G, Manenti F, Ballardini G, Bianchi FP, Scheuer PJ, Davies SE, Craxi A: Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis. Aliment Pharmacol Ther 2000;14:1645–1652.
[PubMed]
54.
Huët PM, Huët J, Deslauriers J: Portal hypertension in patients with primary biliary cirrhosis; in Lindor KD, Heathcote EJ, Poupon R (eds): Primary Biliary Cirrhosis: From Pathogenesis to Treatment. London, Kluwer Academic Publishers, 1998, pp 87–91.
55.
Lindor KD, Jorgensen RA, Therneau TM, Malinchoc M, Dickson ER: Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis. Mayo Clin Proc 1997;72:1137–1140.
[PubMed]
56.
Howat HT, Ralston AJ, Varley H, Wilson JA: The late results of long-term treatment of primary biliary cirrhosis by corticosteroids. Rev Int Hepatol 1966;16:227–238.
57.
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. Hepatology 1989;10:420–429.
[PubMed]
58.
Mitchison HC, Palmer JM, Bassendine MF, Watson AJ, Record CO, James OF: A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results. J Hepatol 1992;15:336–344.
[PubMed]
59.
Mazzella G, Fusaroli P, Pezzoli A, Azzaroli F, Mazzeo C, Zambonin L, Simoni P, Festi D, Roda E: Methylprednisolone administration in primary biliary cirrhosis increases cholic acid turnover, synthesis, and deoxycholate concentration in bile. Dig Dis Sci 1999;44:2478–2483.
[PubMed]
60.
Leuschner M, Güldütüna S, You T, Hübner K, Bhatti S, Leuschner U: Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis. J Hepatol 1996;25:49–57.
[PubMed]
61.
Wolfhagen FH, van Buuren HR, Schalm SW: Combined treatment with ursodeoxycholic acid and prednisone in primary biliary cirrhosis. Neth J Med 1994;44:84–90.
[PubMed]
62.
Möllmann HW, Barth J, Hochhaus G, Möllmann AC, Derendorf H, Tromm A: Principles of topical versus systemic corticoid treatment in inflammatory bowel disease; in Mollmann HW, May B (eds): Glucocorticoid Therapy in Chronic Inflammatory Bowel Disease. Boston, Kluwer, 1996, pp 42–60.
63.
Leuschner M, Maier KP, Schlichting J, Strahl S, Herrmann G, Dahm HH, Ackermann H, Happ J, Leuschner U: Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: Results of a prospective double-blind trial. Gastroenterology 1999;117:918–925.
[PubMed]
64.
Angulo P, Jorgensen RA, Keach JC, Dickson ER, Smith C, Lindor KD: Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 2000;31:318–323.
[PubMed]
65.
Crowe J, Christensen E, Smith M, Cochrane M, Ranek L, Watkinson G, Doniach D, Popper H, Tygstrup N, Williams R: Azathioprine in primary biliary cirrhosis: A preliminary report of an international trial. Gastroenterology 1980;78:1005–1010.
[PubMed]
66.
Christensen E, Neuberger J, Crowe J, Altman DG, Popper H, Portmann B, Doniach D, Ranek L, Tygstrup N, Williams R: Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial. Gastroenterology 1985;89:1084–1091.
[PubMed]
67.
Heathcote J, Ross A, Sherlock S: A prospective controlled trial of azathioprine in primary biliary cirrhosis. Gastroenterology 1976;70:656–660.
[PubMed]
68.
Wolfhagen FH, van Hoogstraten HJ, van Buuren HR, van Berge-Henegouwen GP, ten Kate FJ, Hop WC, van der Hoek EW, Kerbert MJ, van Lijf HH, den Ouden JW, Smit AM, de Vries RA, van Zanten RA, Schalm SW: Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: A 1-year randomized, placebo-controlled study. J Hepatol 1998;29:736–742.
[PubMed]
69.
Bach N, Thung SN, Schaffner F: The histologic effects of low-dose methotrexate therapy for primary biliary cirrhosis. Arch Pathol Lab Med 1998;122:342–345.
[PubMed]
70.
Sharma A, Provenzale D, McKusick A, Kaplan MM: Interstitial pneumonitis after low-dose methotrexate therapy in primary biliary cirrhosis. Gastroenterology 1994;107:266–270.
[PubMed]
71.
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.
[PubMed]
72.
Bonis PA, Kaplan MM: Low-dose methotrexate in primary biliary cirrhosis. Gastroenterology 1999;117:1510–1513.
[PubMed]
73.
Bergasa NV, Jones A, Kleiner DE, Rabin L, Park Y, Wells MC, Hoofnagle JH: Pilot study of low dose oral methotrexate treatment for primary biliary cirrhosis. Am J Gastroenterol 1996;91:295–299.
[PubMed]
74.
Kaplan MM, Knox TA: Treatment of primary biliary cirrhosis with low-dose weekly methotrexate. Gastroenterology 1991;101:1332–1338.
[PubMed]
75.
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.
[PubMed]
76.
van Steenbergen W, Sciot R, Van Eyken P, Desmet V, Fevery J: Combined treatment with methotrexate and ursodeoxycholic acid in non-cirrhotic primary biliary cirrhosis. Acta Clin Belg 1996;51:8–18.
[PubMed]
77.
Lindor KD, Dickson ER, Jorgensen RA, Anderson ML, Wiesner RH, Gores GJ, Lange SM, Rossi SS, Hofmann AF, Baldus WP: The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: The results of a pilot study. Hepatology 1995;22:1158–1162.
[PubMed]
78.
Buscher HP, Zietzschmann Y, Gerok W: Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. J Hepatol 1993;18:9–14.
[PubMed]
79.
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.
[PubMed]
80.
Wiesner RH, Ludwig J, Lindor KD, Jorgensen RA, Baldus WP, Homburger HA, Dickson ER: A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. N Engl J Med 1990;322:1419–1424.
[PubMed]
81.
Bodenheimer H, Schaffner F, Pezzullo J: Evaluation of colchicine therapy in primary biliary cirrhosis. Gastroenterology 1988;95:124–129.
[PubMed]
82.
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.
[PubMed]
83.
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.
[PubMed]
84.
Zifroni A, Schaffner F: Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy. Hepatology 1991;14:990–993.
[PubMed]
85.
Poupon RE, Hüet PM, Poupon R, Bonnand AM, Nhieu JT, Zafrani ES: A randomized trial comparing colchicine and ursodeoxycholic acid combination to ursodeoxycholic acid in primary biliary cirrhosis. UDCA-PBC Study Group. Hepatology 1996;24:1098–2003.
[PubMed]
86.
Ikeda T, Tozuka S, Noguchi O, Kobayashi F, Sakamoto S, Marumo F, Sato C: Effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: A prospective randomized study. J Hepatol 1996;24:88–94.
87.
Raedsch R, Stiehl A, Walker S, Scherrmann JM, Kommerell B: Combined ursodeoxycholic acid plus colchicine-treatment of primary biliary cirrhosis: Results of a placebo-controlled double-blind study. Z Gastroenterol 1992;30(suppl 1):55–57.
88.
Shibata J, Fujiyama S, Honda Y, Sato T: Combination therapy with ursodeoxycholic acid and colchicine for primary biliary cirrhosis. J Gastroenterol Hepatol 1992;7:277–282.
[PubMed]
89.
Bonis PA, Kaplan M: Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol. Gastroenterology 1999;117:395–399.
[PubMed]
90.
Kaplan MM, Schmid C, Provenzale D, Sharma A, Dickstein G, McKusick A: A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis. Gastroenterology 1999;117:1173–1180.
[PubMed]
91.
Nakai S, Masaki T, Kurokohchi K, Deguchi A, Nishioka M: Combination therapy of bezafibrate and ursodeoxycholic acid in primary biliary cirrhosis: A preliminary study. Am J Gastroenterol 2000;95:326–327.
[PubMed]
92.
Kurihara T, Niimi A, Maeda A, Shigemoto M, Yamashita K: Bezafibrate in the treatment of primary biliary cirrhosis: Comparison with ursodeoxycholic acid. Am J Gastroenterol 2000;95:2990–2992.
[PubMed]
93.
Bodenheimer HC, Charland C, Thayer WR, Schaffner F, Staples PJ: Effects of penicillamine on serum immunoglobulins and immune complex-reactive material in primary biliary cirrhosis. Gastroenterology 1985;88:412–417.
[PubMed]
94.
Dickson ER, Fleming TR, Wiesner RH, Baldus WP, Fleming CR, Ludwig J, McCall JT: Trial of penicillamine in advanced primary biliary cirrhosis. N Engl J Med 1985;312:1011–1015.
[PubMed]
95.
Hoofnagle JH, Davis GL, Schafer DF, Peters M, Avigan MI, Pappas SC, Hanson RG, Minuk GY, Dusheiko GM, Campbell G: Randomized trial of chlorambucil for primary biliary cirrhosis. Gastroenterology 1986;91:1327–1334.
[PubMed]
96.
Lee YM, Kaplan MM: Treatment of primary biliary cirrhosis and primary sclerosing cholangitis: Use of ursodeoxycholic acid. Curr Gastroenterol Rep 1999;1:38–41.
[PubMed]
97.
Stiehl A, Walker S, Stiehl L, Rudolph G, Hofmann WJ, Theilmann L: Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. J Hepatol 1994;20:57–64.
[PubMed]
98.
Lindor KD: Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med 1997;336:691–695.
[PubMed]
99.
Beuers U, Spengler U, Kruis W, Aydemir U, Wiebecke B, Heldwein W, Weinzierl M, Pape GR, Sauerbruch T, Paumgartner G: Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: A placebo-controlled trial. Hepatology 1992;16:707–714.
[PubMed]
100.
van Hoogstraten HJ, Wolfhagen FH, van de Meeberg PC, et al: Ursodeoxycholic acid therapy for primary sclerosing cholangitis: Results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses. J Hepatol 1998;29:417–423.
[PubMed]
101.
Mitchell SA, Bansi D, Hunt N, Christie J, Fleming K, Chapman R: High dose ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis (PSC): Results after two years of a randomized, double-blind, placebo- controlled trial (abstract). Gastroenterology 1997;112:757.
102.
De Maria N, Colantoni A, Rosenbloom E, Van Thiel DH: Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period. Hepatogastroenterology 1996;43:1472–1479.
[PubMed]
103.
Angulo P, Larson DR, Therneau TM, LaRusso NF, Batts KP, Lindor KD: Time course of histological progression in primary sclerosing cholangitis. Am J Gastroenterol 1999;94:3310–3313.
[PubMed]
104.
Broomé U, Bergquist A: Management for primary sclerosing cholangitis in adults (abstract). J Hepatol 2000;32:21–22.
105.
Angulo P, Batts KP, Jorgensen RA, LaRusso NA, Lindor KD: Oral budesonide in the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2000;95:2333–2337.
[PubMed]
106.
van Hoogstraten HJ, Vleggaar FP, Boland GJ, van Steenbergen W, Griffioen P, Hop WC, van Hattum J, van Berge Henegouwen GP, Schalm SW, van Buuren HR: Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: A randomized double-blind pilot study. Belgian-Dutch PSC Study Group. Am J Gastroenterol 2000;95:2015–2022.
[PubMed]
107.
Schramm C, Schirmacher P, Helmreich-Becker I, Gerken G, zum Buschenfelde KH, Lohse AW: Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series. Ann Intern Med 1999;131:943–946.
[PubMed]
108.
Wagner A: Azathioprine treatment in primary sclerosing cholangitis. Lancet 1971;2:663–664.
109.
Kyokane K, Ichihara T, Horisawa M, Suzuki N, Ichihara S, Suga S, Nakao A, Morise K: Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid. Hepatogastroenterology 1994;41:449–452.
[PubMed]
110.
Knox TA, Kaplan MM: A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis. Gastroenterology 1994;106:494–499.
[PubMed]
111.
Knox TA, Kaplan MM: Treatment of primary sclerosing cholangitis with oral methotrexate. Am J Gastroenterol 1991;86:546–552.
[PubMed]
112.
Van Thiel DH, Carroll P, Abu-Elmagd K, Rodriguez-Rilo H, Irish W, McMichael J, Starzl TE: Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: Results of an open-label preliminary trial. Am J Gastroenterol 1995;90:455–459.
[PubMed]
113.
Olsson R, Broomé U, Danielsson A, Hagerstrand I, Jarnerot G, Loof L, Prytz H, Ryden BO, Wallerstedt S: Colchicine treatment of primary sclerosing cholangitis. Gastroenterology 1995;108:1199–1203.
[PubMed]
114.
Lindor KD, Wiesner RH, Colwell LJ, Steiner B, Beaver S, LaRusso NF: The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Am J Gastroenterol 1991;86:57–61.
[PubMed]
115.
Bharucha AE, Jorgensen R, Lichtman SN, LaRusso NF, Lindor KD: A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2000;95:2338–2342.
[PubMed]
116.
Duchini A, Younossi ZM, Saven A, Bordin GM, Knowles HJ, Pockros PJ: An open-label pilot trial of cladibrine (2-cholordeoxyadenosine) in patients with primary sclerosing cholangitis. J Clin Gastroenterol 2000;31:292–296.
[PubMed]
117.
Stiehl A, Rudolph G, Sauer P, Benz C, Stremmel W, Walker S, Theilmann L: Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8-year prospective study. J Hepatol 1997;26:560–566.
[PubMed]
118.
Stiehl A, Benz C, Sauer P: Primary sclerosing cholangitis. Can J Gastroenterol 2000;14:311–315.
[PubMed]
119.
Ahrendt SA, Pitt HA: Surgical treatment for primary sclerosing cholangitis. J Hepatobiliary Pancreat Surg 1999;6:366–372.
[PubMed]
120.
Harnois DM, Lindor KD: Primary sclerosing cholangitis: Evolving concepts in diagnosis and treatment. Dig Dis 1997;15:23–41.
[PubMed]
121.
Broomé U, Olsson R, Loof L, Bodemar G, Hultcrantz R, Danielsson A, Prytz H, Sandberg-Gertzen H, Wallerstedt S, Lindberg G: Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996;38:610–615.
[PubMed]
122.
Strasser S, Sheil AG, Gallagher ND, Waugh R, McCaughan GW: Liver transplantation for primary sclerosing cholangitis versus primary biliary cirrhosis: A comparison of complications and outcome. J Gastroenterol Hepatol 1993;8:238–243.
[PubMed]
123.
Chalasani N, Baluyut A, Ismail A, Zaman A, Sood G, Ghalib R, McCashland TM, Reddy KR, Zervos X, Anbari MA, Hoen H: Cholangiocarcinoma in patients with primary sclerosing cholangitis: A multicenter case-control study. Hepatology 2000;31:7–11.
[PubMed]
124.
Ahrendt SA, Pitt HA, Nakeeb A, Klein AS, Lillemoe KD, Kalloo AN, Cameron JL: Diagnosis and management of cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Surg 1999;3:357–367.
[PubMed]
125.
Patel T: Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001;33:1353–1357.
[PubMed]
126.
Rumalla A, Petersen BT: Diagnosis and therapy of biliary tract malignancy. Semin Gastrointest Dis 2000;11:168–173.
[PubMed]
127.
Bjornsson E, Kilander A, Olsson R: CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis. Liver 1999;19:501–508.
[PubMed]
128.
Gores GJ: Early detection and treatment of cholangiocarcinoma. Liver Transpl 2000;6:S30–S34.
[PubMed]
129.
Harrison PM: Prevention of bile duct cancer in primary sclerosing cholangitis. Ann Oncol 1999;10(suppl 4):208–211.
130.
Boberg KM, Schrumpf E, Bergquist A, Broomé U, Pares A, Remotti H, Schjolberg A, Spurkland A, Clausen OP: Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development. J Hepatol 2000;32:374–380.
[PubMed]
131.
Batheja N, Suriawinata A, Saxena R, Ionescu G, Schwartz M, Thung SN: Expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis. Mod Pathol 2000;13:1265–1268.
[PubMed]
132.
Kockerling F, Schug-Pass C, Weskott HP, Tatchen R: Malignant hepatobiliary tumors. Surgical requirements concerning preoperative diagnosis. Zentralbl Chir 2000;125:616–623.
[PubMed]
133.
Yeh TS, Jan YY, Tseng JH, Chiu CT, Chen TC, Hwang TL, Chen MF: Malignant perihilar biliary obstruction: Magnetic resonance cholangiopancreatographic findings. Am J Gastroenterol 2000;95:432–440.
[PubMed]
134.
Furukawa H, Sano K, Kosuge T, Shimada K, Yamamoto J, Iwata R, Moriyama N: Hilar cholangiocarcinoma evaluated by three-dimensional CT cholangiography and rotating cine cholangiography. Hepatogastroenterology 2000;47:615–620.
[PubMed]
135.
Kluge R, Schmidt F, Caca K, Barthel H, Hesse S, Georgi P, Seese A, Huster D, Berr F: Positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose for diagnosis and staging of bile duct cancer. Hepatology 2001;33:1029–1035.
[PubMed]
136.
Gores GJ: Early detection and treatment of cholangiocarcinoma. Liver Transpl 2000;6(suppl 2):S30–S34.
137.
Shimada M, Takenaka K, Kawahara N, Yamamoto K, Shirabe K, Maehara Y, Sugimachi K: Chemosensitivity in primary liver cancers: Evaluation of the correlation between chemosensitivity and clinicopathological factors. Hepatogastroenterology 1996;43:1159–1164.
[PubMed]
138.
Gow PJ, Chapman RW: Liver transplantation for primary sclerosing cholangitis. Liver 2000;20:97–103.
[PubMed]
139.
Meyer CG, Penn I, James L: Liver transplantation for cholangiocarcinoma: Results in 207 patients. Transplantation 2000;69:1633–1637.
[PubMed]
140.
De Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG, Burgart L, Gores GJ: Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl 2000;6:309–316.
[PubMed]
141.
Papatheodoridis GV, Hamilton M, Mistry PK, Davidson B, Rolles K, Burroughs AK: Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis. Gut 1998;43:639–644.
[PubMed]
142.
LaRusso NF: The Fifth Carlos E. Rubio Memorial Lecture. Sclerosing cholangitis: Pathogenesis, pathology, and practice. PR Health Sci J 1999;18:11–17.
143.
Aitola P, Mattila J, Matikainen M: Liver involvement in patients operated for ulcerative colitis, with special reference to the association of cholangitis with colorectal dysplasia and carcinoma. Int J Colorectal Dis 2000;15:167–171.
[PubMed]
144.
Loftus EV, Aguilar HI, Sandborn WJ, Tremaine WJ, Krom RA, Zinsmeister AR, Graziadei IW, Wiesner RH: Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation. Hepatology 1998;27:685–690.
[PubMed]
145.
Tung BY, Emond MJ, Haggitt RC, Bronner MP, Kimmey MB, Kowdley KV, Brentnall TA: Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann Intern Med 2001;134:89–95.
[PubMed]
146.
Jones EA, Bergasa NV: The pathogenesis and treatment of pruritus and fatigue in patients with PBC. Eur J Gastroenterol Hepatol 1999;11:623–631.
[PubMed]
147.
Franco J: Pruritus. Curr Treat Options Gastroenterol 1999;2:451–456.
[PubMed]
148.
Podesta A, Lopez P, Terg R, Villamil F, Flores D, Mastai R, Udaondo CB, Companc JP: Treatment of pruritus of primary biliary cirrhosis with rifampicin. Dig Dis Sci 1991;36:216–220.
[PubMed]
149.
Bachs L, Pares A, Elena M, Piera C, Rodes J: Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet 1989;i:574–576.
150.
Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C: Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology 1990;99:211–215.
[PubMed]
151.
Berg CL, Gollan JL: Primary biliary cirrhosis: New therapeutic directions. Scand J Gastroenterol Suppl 1992;192:43–49.
[PubMed]
152.
Leuschner U: Cholestatic hepatopathy: Primary biliary cirrhosis. Schweiz Rundsch Med Prax 2000;89:1043–1048.
[PubMed]
153.
Bergasa NV, Alling DW, Talbot TL, Wells MC, Jones EA: Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: A controlled study. J Am Acad Dermatol 1999;41:431–434.
[PubMed]
154.
Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, van Buuren HR: Oral naltrexone treatment for cholestatic pruritus: A double-blind, placebo-controlled study. Gastroenterology 1997;113:1264–1269.
[PubMed]
155.
Bergasa NV, Alling DW, Talbot TL, Swain MG, Yurdaydin C, Turner ML, Schmitt JM, Walker EC, Jones EA: Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial. Ann Intern Med 1995;123:161–167.
[PubMed]
156.
Schworer H, Ramadori G: Treatment of pruritus: A new indication for serotonin type 3 receptor antagonists. Clin Investig 1993;71:659–662.
[PubMed]
157.
Heathcote J: The clinical expression of primary biliary cirrhosis. Semin Liver Dis 1997;17:23–33.
[PubMed]
158.
Swain MG, Maric M: Improvement in cholestasis-associated fatigue with a serotonin receptor agonist using a novel rat model of fatigue assessment. Hepatology 1997;25:291–294.
[PubMed]
159.
Jones EA: Fatigue associated with chronic liver disease: A riddle wrapped in a mystery inside an enigma. Hepatology 1995;22:1606–1608.
[PubMed]
160.
Watson JP, Jones DE, James OF, Cann PA, Bramble MG: Case report: Oral antioxidant therapy for the treatment of primary biliary cirrhosis: A pilot study. J Gastroenterol Hepatol 1999;14:1034–1040.
[PubMed]
161.
Crosbie OM, Freaney R, McKenna MJ, Hegarty JE: Bone density, vitamin D status, and disordered bone remodeling in end-stage chronic liver disease. Calcif Tissue Int 1999;64:295–300.
[PubMed]
162.
Angulo P, Therneau TM, Jorgensen A, DeSotel CK, Egan KS, Dickson ER, Hay JE, Lindor KD: Bone disease in patients with primary sclerosing cholangitis: Prevalence, severity and prediction of progression. J Hepatol 1998;29:729–735.
[PubMed]
163.
Isaia G, Di Stefano M, Roggia C, Ardissone P, Rosina F: Bone disorders in cholestatic liver diseases. Forum (Genova) 1998;8:28–38.
[PubMed]
164.
Fogelman I, Blake GM: Different approaches to bone densitometry. J Nucl Med 2000;41:2015–2025.
[PubMed]
165.
Pereira SP, Bray GP, Pitt PI, Li F, Moniz C, Williams R: Non-invasive assessment of bone density in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:323–328.
[PubMed]
166.
Hay JE: Vitamin D receptor polymorphism and posttransplantation bone loss. Liver Transpl 2001;7:68–69.
[PubMed]
167.
Vleggaar FP, van Buuren HR, Wolfhagen FH, Schalm SW, Pols HA: Prevention and treatment of osteoporosis in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:617–621.
[PubMed]
168.
Shiomi S, Masaki K, Habu D, Takeda T, Nishiguchi S, Kuroki T, Tanaka T, Ochi H: Calcitriol for bone disease in patients with cirrhosis of the liver. J Gastroenterol Hepatol 1999;14:547–552.
[PubMed]
169.
Camisasca M, Crosignani A, Battezzati PM, Albisetti W, Grandinetti G, Pietrogrande L, Biffi A, Zuin M, Podda M: Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis. Hepatology 1994;20:633–637.
[PubMed]
170.
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.
[PubMed]
171.
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.
[PubMed]
172.
Sambrook PN, Eisman JA: Osteoporosis prevention and treatment. Med J Aust 2000;172:226–229.
[PubMed]
173.
Olsson R, Mattsson LA, Obrant K, Mellstrom D: Estrogen-progestogen therapy for low bone mineral density in primary biliary cirrhosis. Liver 1999;19:188–192.
[PubMed]
174.
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.
[PubMed]
175.
Lindor KD, Jorgensen RA, Tiegs RD, Khosla S, Dickson ER: Etidronate for osteoporosis in primary biliary cirrhosis: A randomized trial. J Hepatol 2000;33:878–882.
[PubMed]
176.
Wolfhagen FH, van Buuren HR, den Ouden JW, Hop WC, van Leeuwen JP, Schalm SW, Pols HA: Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis. A prospective, controlled pilot study. J Hepatol 1997;26:325–330.
[PubMed]
177.
Kingham JG, Parker DR: The association between primary biliary cirrhosis and coeliac disease: A study of relative prevalences. Gut 1998;42:120–122.
[PubMed]
178.
Sorensen HT, Thulstrup AM, Blomqvist P, Norgaard B, Fonager K, Ekbom A: Risk of primary biliary liver cirrhosis in patients with coeliac disease: Danish and Swedish cohort data. Gut 1999;44:736–738.
[PubMed]
179.
Billaud EM: Clinical pharmacology of immunosuppressive drugs: Year 2000 – Time for alternatives. Therapie 2000;55:177–183.
[PubMed]
180.
Finn WF: FK506 nephrotoxicity. Ren Fail 1999;21:319–329.
[PubMed]
181.
Dumont FJ: FK506, an immunosuppressant targeting calcineurin function. Curr Med Chem 2000;7:731–748.
[PubMed]
182.
Ingle GR, Sievers TM, Holt CD: Sirolimus: Continuing the evolution of transplant immunosuppression. Ann Pharmacother 2000;34:1044–1055.
[PubMed]
183.
Keown PA: New immunosuppressive strategies. Curr Opin Nephrol Hypertens 1998;7:659–663.
[PubMed]
184.
Gonin JM: Maintenance immunosuppression: New agents and persistent dilemmas. Adv Ren Replace Ther 2000;7:95–116.
[PubMed]
185.
Gummert JF, Ikonen T, Morris RE: Newer immunosuppressive drugs: A review. J Am Soc Nephrol 1999;10:1366–1380.
[PubMed]
186.
Jones EA, ten Kate FJ, ter Borg F, Houben M, Reesink HW, Chamuleau RA: Combination therapy with mycophenolate mofetil and ursodeoxycholic acid for primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:1165–1169.
[PubMed]
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