Semin Liver Dis 2006; 26(1): 052-061
DOI: 10.1055/s-2006-933563
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Medical Management of Primary Sclerosing Cholangitis

Susan N. Cullen1 , Roger W. Chapman2
  • 1Wycombe General Hospital, High Wycombe, United Kingdom
  • 2John Radcliffe Hospital, Oxford, United Kingdom
Further Information

Publication History

Publication Date:
23 February 2006 (online)

ABSTRACT

Primary sclerosing cholangitis raises several challenges for the physician. These include the identification of a drug regimen that slows or reverses the progression of the disease, the effective management of the symptoms of cholestasis, and the prevention of complications of the disease, including the development of colorectal cancer. The most studied drug in PSC is ursodeoxycholic acid, which, despite a range of potentially valuable actions on the cholestatic liver, has not yet been proven to make a substantial change in the course of the disease. However, it may yet prove to be sufficiently effective in the prevention of colorectal neoplasia to be prescribable for this reason alone. Better progress has been made in identifying agents that can alleviate pruritus and prevent the progression of osteopenia.

REFERENCES

  • 1 Poupon R E, Lindor K D, Cauch-Dudek K, Dickson E R, Poupon R, Heathcote E J. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis.  Gastroenterology. 1997;  113 884-890
  • 2 Palma J, Reyes H, Ribalta J et al.. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.  J Hepatol. 1997;  27 1022-1028
  • 3 Mazzella G, Rizzo N, Azzaroli F et al.. Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers.  Hepatology. 2001;  33 504-508
  • 4 Colombo C, Battezzati P M, Podda M, Bettinardi N, Giunta A. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis.  Hepatology. 1996;  23 1484-1490
  • 5 Jacquemin E, Hermans D, Myara A et al.. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis.  Hepatology. 1997;  25 519-523
  • 6 Essell J H, Schroeder M T, Harman G S et al.. Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial.  Ann Intern Med. 1998;  128 975-981
  • 7 Lazaridis K N, Gores G J, Lindor K D. Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders’.  J Hepatol. 2001;  35 134-146
  • 8 Crosignani A, Setchell K D, Invernizzi P, Larghi A, Rodrigues C M, Podda M. Clinical pharmacokinetics of therapeutic bile acids.  Clin Pharmacokinet. 1996;  30 333-358
  • 9 Hempfling W, Dilger K, Beuers U. Systematic review: ursodeoxycholic acid-adverse effects and drug interactions.  Aliment Pharmacol Ther. 2003;  18 963-972
  • 10 Hofmann A F. Pharmacology of ursodeoxycholic acid, an enterohepatic drug.  Scand J Gastroenterol Suppl. 1994;  204 1-15
  • 11 Beuers U, Fischer S, Spengler U, Paumgartner G. Formation of iso-ursodeoxycholic acid during administration of ursodeoxycholic acid in man.  J Hepatol. 1991;  13 97-103
  • 12 Rost D, Rudolph G, Kloeters-Plachky P, Stiehl A. Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis.  Hepatology. 2004;  40 693-698
  • 13 van de Meeberg P C, Wolfhagen F H, Van Berge-Henegouwen G P et al.. Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response.  J Hepatol. 1996;  25 887-894
  • 14 Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited.  Hepatology. 2002;  36 525-531
  • 15 Guicciardi M E, Gores G J. Ursodeoxycholic acid cytoprotection: dancing with death receptors and survival pathways.  Hepatology. 2002;  35 971-973
  • 16 Patel T, Gores G J. Apoptosis and hepatobiliary disease.  Hepatology. 1995;  21 1725-1741
  • 17 Qiao L, Yacoub A, Studer E et al.. Inhibition of the MAPK and PI3K pathways enhances UDCA-induced apoptosis in primary rodent hepatocytes.  Hepatology. 2002;  35 779-789
  • 18 Rodrigues C M, Steer C J. Mitochondrial membrane perturbations in cholestasis.  J Hepatol. 2000;  32 135-141
  • 19 Rodrigues C M, Fan G, Ma X, Kren B T, Steer C J. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.  J Clin Invest. 1998;  101 2790-2799
  • 20 Smit J J, Schinkel A H, Oude Elferink R P et al.. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease.  Cell. 1993;  75 451-462
  • 21 Van Nieuwkerk C M, Elferink R P, Groen A K et al.. Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene.  Gastroenterology. 1996;  111 165-171
  • 22 Alpini G, Baiocchi L, Glaser S et al.. Ursodeoxycholate and tauroursodeoxycholate inhibit cholangiocyte growth and secretion of BDL rats through activation of PKC alpha.  Hepatology. 2002;  35 1041-1052
  • 23 Kitani K, Ohta M, Kanai S. Tauroursodeoxycholate prevents biliary protein excretion induced by other bile salts in the rat.  Am J Physiol. 1985;  248 G407-G417
  • 24 Beuers U, Nathanson M H, Isales C M, Boyer J L. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.  J Clin Invest. 1993;  92 2984-2993
  • 25 Heuman D M, Mills A S, McCall J, Hylemon P B, Pandak W M, Vlahcevic Z R. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat.  Gastroenterology. 1991;  100 203-211
  • 26 Kitani K, Kanai S, Sato Y, Ohta M. Tauro alpha-muricholate is as effective as tauro beta-muricholate and tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage in the rat.  Hepatology. 1994;  19 1007-1012
  • 27 Jazrawi R P, de Caestecker J S, Goggin P M et al.. Kinetics of hepatic bile acid handling in cholestatic liver disease: effect of ursodeoxycholic acid.  Gastroenterology. 1994;  106 134-142
  • 28 Stiehl A, Rudolph G, Sauer P, Theilmann L. Biliary secretion of bile acids and lipids in primary sclerosing cholangitis. Influence of cholestasis and effect of ursodeoxycholic acid treatment.  J Hepatol. 1995;  23 283-289
  • 29 Beuers U, Bilzer M, Chittattu A et al.. 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
  • 30 Fickert P, Zollner G, Fuchsbichler A et al.. Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.  Gastroenterology. 2001;  121 170-183
  • 31 Kurz A K, Graf D, Schmitt M, Vom Dahl S, Haussinger D. Tauroursodeoxycholate-induced choleresis involves p38(MAPK) activation and translocation of the bile salt export pump in rats.  Gastroenterology. 2001;  121 407-419
  • 32 Borum M, Fromm H. Expression of HLA molecules on hepatocytes: does ursodeoxycholic acid prevent immunologic injury?.  Gastroenterology. 1990;  99 561-562
  • 33 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. 1991;  86 1194-1199
  • 34 Bergamini A, Dini L, Baiocchi L et al.. Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells.  Hepatology. 1997;  25 927-933
  • 35 O'Brien C B, Senior J R, Arora-Mirchandani R, Batta A K, Salen G. Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30-month pilot study.  Hepatology. 1991;  14 838-847
  • 36 Beuers U, Spengler U, Kruis W et al.. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial.  Hepatology. 1992;  16 707-714
  • 37 Lo S K, Hermann R, Chapman R W et al.. Ursodeoxycholic acid in primary sclerosing cholangitis: a double blind placebo controlled trial [abstract].  Hepatology. 1992;  16 92A
  • 38 Stiehl A, Walker S, Stiehl L, Rudolph G, Hofmann W J, 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
  • 39 De Maria N, Colantoni A, Rosenbloom E, Van Thiel D H. Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period.  Hepatogastroenterology. 1996;  43 1472-1479
  • 40 Lindor K D. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group.  N Engl J Med. 1997;  336 691-695
  • 41 Olsson R G, Boberg K M, Schaffalitzky de Muckadel O et al.. Five year treatment with high dose UDCA in PSC.  J Hepatol. 2004;  40 161 (Abst)
  • 42 Hill M J, Melville D M, Lennard-Jones J E, Neale K, Ritchie J K. Faecal bile acids, dysplasia, and carcinoma in ulcerative colitis.  Lancet. 1987;  2 185-186
  • 43 Bayerdorffer E, Mannes G A, Richter W O et al.. Increased serum deoxycholic acid levels in men with colorectal adenomas.  Gastroenterology. 1993;  104 145-151
  • 44 Stadler J, Yeung K S, Furrer R, Marcon N, Himal H S, Bruce W R. Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer.  Cancer Lett. 1988;  38 315-320
  • 45 Reddy B S, Watanabe K, Weisburger J H, Wynder E L. Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F344 rats.  Cancer Res. 1977;  37 3238-3242
  • 46 Ochsenkuhn T, Bayerdorffer E, Meining A et al.. Colonic mucosal proliferation is related to serum deoxycholic acid levels.  Cancer. 1999;  85 1664-1669
  • 47 Rodrigues C M, Fan G, Wong P Y, Kren B T, Steer C J. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production.  Mol Med. 1998;  4 165-178
  • 48 Martinez J D, Stratagoules E D, LaRue J M et al.. Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation.  Nutr Cancer. 1998;  31 111-118
  • 49 Tung B Y, Emond M J, Haggitt R C et al.. 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
  • 50 Wolf J M, Rybicki L, BA L. Ursodeoxycholic acid is not chemoprotective for colorectal cancer in ulcerative colitis patients with primary sclerosing cholangitis [abstract].  Gastroenterology. 2001;  121 2276
  • 51 Pardi D S, Loftus Jr E V, Kremers W K, Keach J, Lindor K D. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis.  Gastroenterology. 2003;  124 889-893
  • 52 van Hoogstraten H J, Wolfhagen F H, van de Meeberg P C 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
  • 53 Mitchell S A, Bansi D S, Hunt N, Von Bergmann K, Fleming K A, Chapman R W. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis.  Gastroenterology. 2001;  121 900-907
  • 54 Harnois D M, Angulo P, Jorgensen R A, Larusso N F, Lindor K D. High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis.  Am J Gastroenterol. 2001;  96 1558-1562
  • 55 Okolicsanyi L, Groppo M, Floreani A et al.. Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.  Dig Liver Dis. 2003;  35 325-331
  • 56 Burgert S L, Brown B P, Kirkpatrick R B, LaBrecgue D R. Positive corticosteroid response in early primary sclerosing cholangitis [abstract].  Gastroenterology. 1984;  86 1037
  • 57 Sivak Jr M V, Farmer R G, Lalli A F. Sclerosing cholangitis: its increasing frequency of recognition and association with inflammatory bowel disease.  J Clin Gastroenterol. 1981;  3 261-266
  • 58 Lindor K D, Wiesner R H, Colwell L J, Steiner B, Beaver S, LaRusso N F. The combination of prednisone and colchicine in patients with primary sclerosing cholangitis.  Am J Gastroenterol. 1991;  86 57-61
  • 59 Angulo P, Batts K P, Jorgensen R A, LaRusso N A, Lindor K D. Oral budesonide in the treatment of primary sclerosing cholangitis.  Am J Gastroenterol. 2000;  95 2333-2337
  • 60 Grijm R, Huibregtse K, Bartelsman J, Mathus-Vliegen E M, Dekker W, Tytgat G N. Therapeutic investigations in primary sclerosing cholangitis.  Dig Dis Sci. 1986;  31 792-798
  • 61 Jeffrey G P, Reed W D, Laurence B H, Shilkin K B. Primary sclerosing cholangitis: clinical and immunopathological review of 21 cases.  J Gastroenterol Hepatol. 1990;  5 135-140
  • 62 Craig P I, Willaims S J, Hatfield A RW, Ng M, PB C. Endoscopic management of primary sclerosing cholangitis [abstract].  Gut. 1990;  31 1182
  • 63 Allison M C, Burroughs A K, Noone P, Summerfield J A. Biliary lavage with corticosteroids in primary sclerosing cholangitis. A clinical, cholangiographic and bacteriological study.  J Hepatol. 1986;  3 118-122
  • 64 Boberg K M, Egeland T, Schrumpf E. Long-term effect of corticosteroid treatment in primary sclerosing cholangitis patients.  Scand J Gastroenterol. 2003;  38 991-995
  • 65 Nakazawa T, Ohara H, Sano H et al.. Clinical differences between primary sclerosing cholangitis and sclerosing cholangitis with autoimmune pancreatitis.  Pancreas. 2005;  30 20-25
  • 66 Tjandra K, Le T, Swain M G. Glucocorticoid receptors are downregulated in hepatic T lymphocytes in rats with experimental cholangitis.  Gut. 2003;  52 1363-1370
  • 67 Knox T A, Kaplan M M. Treatment of primary sclerosing cholangitis with oral methotrexate.  Am J Gastroenterol. 1991;  86 546-552
  • 68 Knox T A, Kaplan M M. A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis.  Gastroenterology. 1994;  106 494-499
  • 69 Lindor K D, Jorgensen R A, Anderson M L, Gores G J, Hofmann A F, LaRusso N F. Ursodeoxycholic acid and methotrexate for primary sclerosing cholangitis: a pilot study.  Am J Gastroenterol. 1996;  91 511-515
  • 70 Sandborn W J, Wiesner R H, Tremaine W J, Larusso N F. Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin.  Gut. 1993;  34 242-246
  • 71 Kyokane K, Ichihara T, Horisawa M et al.. Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid.  Hepatogastroenterology. 1994;  41 449-452
  • 72 Van Thiel D H, Carroll P, Abu-Elmagd K et al.. Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial.  Am J Gastroenterol. 1995;  90 455-459
  • 73 Sterling R K, Salvatori J J, Luketic V A et al.. A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis.  Aliment Pharmacol Ther. 2004;  20 943-949
  • 74 Wagner A. Azathioprine treatment in primary sclerosing cholangitis.  Lancet. 1971;  2 663-664
  • 75 Javett S L. Azathioprine in primary sclerosing cholangitis.  Lancet. 1971;  1 810
  • 76 Duchini A, Younossi Z M, Saven A, Bordin G M, Knowles H J, Pockros P J. An open-label pilot trial of cladibrine (2-cholordeoxyadenosine) in patients with primary sclerosing cholangitis.  J Clin Gastroenterol. 2000;  31 292-296
  • 77 Bharucha A E, Jorgensen R, Lichtman S N, LaRusso N F, Lindor K D. A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis.  Am J Gastroenterol. 2000;  95 2338-2342
  • 78 Epstein M P, Kaplan M M. A pilot study of etanercept in the treatment of primary sclerosing cholangitis.  Dig Dis Sci. 2004;  49 1-4
  • 79 Schramm C, Schirmacher P, Helmreich-Becker I, Gerken G, zum Buschenfelde K H, Lohse A W. Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series.  Ann Intern Med. 1999;  131 943-946
  • 80 Vierling J. Aetiopathogenesis of primary sclerosing cholangitis. In: Manns P, Stieihl A, Wiesner R Primary Sclerosing Cholangitis. London; Kluwer Academic Publishers 1998: 9
  • 81 Farkkila M, Karvonen A L, Nurmi H et al.. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial.  Hepatology. 2004;  40 1379-1386
  • 82 Angulo P, MacCarty R L, Sylvestre P B et al.. Pirfenidone in the treatment of primary sclerosing cholangitis.  Dig Dis Sci. 2002;  47 157-161
  • 83 Olsson R, Broome U, Danielsson A et al.. Colchicine treatment of primary sclerosing cholangitis.  Gastroenterology. 1995;  108 1199-1203
  • 84 Ball K R, Kowdley K V. A review of Silybum marianum (milk thistle) as a treatment for alcoholic liver disease.  J Clin Gastroenterol. 2005;  39 520-528
  • 85 Angulo P, Bharucha A E, Jorgensen R A et al.. Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study.  Dig Dis Sci. 1999;  44 602-607
  • 86 Vleggaar F P, van Buuren H R, van Berge Henegouwen G P, Hop W C, van Erpecum K J. No beneficial effects of transdermal nicotine in patients with primary sclerosing cholangitis: results of a randomized double-blind placebo-controlled cross-over study.  Eur J Gastroenterol Hepatol. 2001;  13 171-175
  • 87 LaRusso N F, Wiesner R H, Ludwig J, MacCarty R L, Beaver S J, Zinsmeister A R. Prospective trial of penicillamine in primary sclerosing cholangitis.  Gastroenterology. 1988;  95 1036-1042
  • 88 Gross C R, Malinchoc M, Kim W R et al.. Quality of life before and after liver transplantation for cholestatic liver disease.  Hepatology. 1999;  29 356-364
  • 89 ter Borg P C, van Os E, van den Broek W W, Hansen B E, van Buuren H R. Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing cholangitis: a randomised controlled trial.  , [ISRCTN88246634] BMC Gastroenterol. 2004;  4 13
  • 90 Bjornsson E, Simren M, Olsson R, Chapman R W. Fatigue in patients with primary sclerosing cholangitis.  Scand J Gastroenterol. 2004;  39 961-968
  • 91 Mela M, Mancuso A, Burroughs A K. Review article: pruritus in cholestatic and other liver diseases.  Aliment Pharmacol Ther. 2003;  17 857-870
  • 92 Bergasa N V, Jones E A. The pruritus of cholestasis: potential pathogenic and therapeutic implications of opioids.  Gastroenterology. 1995;  108 1582-1588
  • 93 Richardson B P. Serotonin and nociception.  Ann NY Acad Sci. 1990;  600 511-520
  • 94 Thornton J R, Losowsky M S. Opioid peptides and primary biliary cirrhosis.  BMJ. 1988;  297 1501-1504
  • 95 Bergasa N V, Talbot T L, Alling D W et al.. A controlled trial of naloxone infusions for the pruritus of chronic cholestasis.  Gastroenterology. 1992;  102 544-549
  • 96 Bergasa N V, Schmitt J M, Talbot T L et al.. Open-label trial of oral nalmefene therapy for the pruritus of cholestasis.  Hepatology. 1998;  27 679-684
  • 97 Wolfhagen F H, Sternieri E, Hop W C, Vitale G, Bertolotti M, Van Buuren H R. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study.  Gastroenterology. 1997;  113 1264-1269
  • 98 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
  • 99 Muller C, Pongratz S, Pidlich J et al.. 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
  • 100 Ghent C N, Carruthers S G. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial.  Gastroenterology. 1988;  94 488-493
  • 101 Podesta A, Lopez P, Terg R et al.. Treatment of pruritus of primary biliary cirrhosis with rifampin.  Dig Dis Sci. 1991;  36 216-220
  • 102 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
  • 103 Woolf G M, Reynolds T B. Failure of rifampin to relieve pruritus in chronic liver disease.  J Clin Gastroenterol. 1990;  12 174-177
  • 104 Miguet J P, Mavier P, Soussy C J, Dhumeaux D. Induction of hepatic microsomal enzymes after brief administration of rifampicin in man.  Gastroenterology. 1977;  72 924-926
  • 105 Berg C L, Gollan J L. Primary biliary cirrhosis: new therapeutic directions.  Scand J Gastroenterol Suppl. 1992;  192 43-49
  • 106 Angulo P, Therneau T M, Jorgensen A et al.. Bone disease in patients with primary sclerosing cholangitis: prevalence, severity and prediction of progression.  J Hepatol. 1998;  29 729-735
  • 107 Campbell M S, Lichtenstein G R, Rhim A D, Pazianas M, Faust T. Severity of liver disease does not predict osteopenia or low bone mineral density in primary sclerosing cholangitis.  Liver Int. 2005;  25 311-316
  • 108 Jorgensen R A, Lindor K D, Sartin J S, LaRusso N F, Wiesner R H. Serum lipid and fat-soluble vitamin levels in primary sclerosing cholangitis.  J Clin Gastroenterol. 1995;  20 215-219

Roger W ChapmanM.D. 

John Radcliffe Hospital, Head ley Way, Heading ham, Oxford OX3 9DU, United Kingdom

Email: roger.chapman@clinical-medicine.oxford.ac.uk