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.
KEYWORDS
Ursodeoxycholic acid - cholestasis - apoptosis - pruritus - osteoporosis
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