Primary Sclerosing Cholangitis Treatment & Management
- Author: Vikas Khurana, MD, FACP, FACG; Chief Editor: Julian Katz, MD more...
No approved or proven therapy exists for primary sclerosing cholangitis (PSC). Pharmacotherapy is aimed at treating symptoms and managing complications. Immunosuppressants, chelators, and steroids are used in an attempt to control the disease process but have not shown significant benefit.
Further care is dictated by the stage and degree of progression of the disease. It involves care by a gastroenterologist, who must monitor the patient's condition with frequent laboratory tests and maintain vigilance for the many complications of PSC.
Liver transplantation is the only therapy that can alter the eventual outcome, with reported posttransplant survival rates of 85% at 5 years and 70% at 10 years. Suitability for liver transplantation should be determined expeditiously and, if appropriate, offered to the patient.
Endoscopic dilation of dominant strictures, with or without stenting, has been shown to alleviate cholestasis and to improve laboratory test results; however, it is not currently believed to affect disease progression. Ruling out malignancy in these strictures is difficult.
Ursodeoxycholic acid studies
Ursodeoxycholic acid has been shown to improve the liver function profile in some patients and, in conjunction with endoscopic dilation, has shown a survival benefit in some studies.
In a study by Lindor et al of adult patients with PSC who were given 28-30 mg/kg/day of ursodeoxycholic acid, versus placebo, the patients treated with ursodeoxycholic acid had a greater decrease in serum liver test results, but a higher risk of serious adverse events (ie, varices, cholangiocarcinoma, liver transplantation, and death). The risk of a primary endpoint was 2.3-fold greater for the ursodeoxycholic acid-treated group than those in the placebo group and 2.1-fold greater for death, transplantation, or minimal listing criteria.
Shi et al performed a meta-analysis of randomized, controlled trials comparing ursodeoxycholic acid with placebo or no treatment and found that ursodeoxycholic acid improved liver biochemistry study results and that there were trends in histologic and cholangiographic improvement. However, the study also showed no improvement for pruritus and fatigue, liver transplantation, or incidence of death.
Indications for liver transplantation in patients with primary sclerosing cholangitis (PSC) include variceal bleeding or portal gastropathy, intractable ascites, recurrent cholangitis, progressive muscle wasting, and hepatic encephalopathy. Survival rates have been shown to be 93.7% at 1 year, 92.2% at 2 years, 86.4% at 5 years, and 69.8% at 10 years. However, PSC has been shown to recur in 15-20% of patients after transplantation.[24, 25, 26]
In addition to liver transplantation, procedures include proctocolectomy for patients with ulcerative colitis and biliary reconstructive procedures. Note that proctocolectomy in patients with both PSC and ulcerative colitis has no effect on the course of PSC.
Posttransplantation complications include recurrence of PSC, worsening of inflammatory bowel disease (IBD) activity, and de novo IBD occurrence.
Diet and Activity
Patients with steatorrhea are encouraged to include medium-chain triglycerides in their diet. Fat-soluble vitamin deficiency correction should be attempted by supplementation. Oral supplementation is necessary if associated pancreatic enzyme deficiency is present. Calcium supplementation for bone disease may also be needed.
Physical activity should not be restricted; however, in patients with osteoporosis, the possibility of fractures should temper the type of activity allowed.
A gastroenterologist must be consulted. When needed, surgical consultation should be initiated by the gastroenterologist and when liver transplantation is offered. An endocrinologist may be consulted for management of bone disease.
Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015 May. 110 (5):646-59; quiz 660. [Medline].
Rossi RE, Conte D, Massironi S. Primary sclerosing cholangitis associated with inflammatory bowel disease: an update. Eur J Gastroenterol Hepatol. 2016 Feb. 28 (2):123-31. [Medline].
Sarkar S, Bowlus CL. Primary sclerosing cholangitis: multiple phenotypes, multiple approaches. Clin Liver Dis. 2016 Feb. 20 (1):67-77. [Medline].
Chaparro M, Trapero-Marugán M, Guijarro M, López C, Moreno-Otero R, Gisbert JP. Dysplasia and colorectal cancer in a patient with ulcerative colitis and primary sclerosing cholangitis: A case report and a short review of the literature. J Crohns Colitis. 2012 Apr 30. [Medline].
Gotthardt D, Chahoud F, Sauer P. Primary sclerosing cholangitis: diagnostic and therapeutic problems. Dig Dis. 2011. 29 Suppl 1:41-5. [Medline].
Shneider BL. Diagnostic and therapeutic challenges in pediatric primary sclerosing cholangitis. Liver Transpl. 2011 Dec 5. [Medline].
Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, et al. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat Genet. 2013 Jun. 45(6):670-5. [Medline]. [Full Text].
Trottier J, Bialek A, Caron P, Straka RJ, Heathcote J, Milkiewicz P, et al. Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study. Dig Liver Dis. 2011 Dec 8. [Medline].
Næss S, Shiryaev A, Hov JR, Franke A, Karlsen TH. Genetics in primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol. 2012 May 1. [Medline].
Okada H, Mizuno M, Yamamoto K, Tsuji T. Primary sclerosing cholangitis in Japanese patients: association with inflammatory bowel disease. Acta Med Okayama. 1996 Oct. 50(5):227-35. [Medline].
Kim WR, Therneau TM, Wiesner RH, et al. A revised natural history model for primary sclerosing cholangitis. Mayo Clin Proc. 2000 Jul. 75(7):688-94. [Medline].
Mayo Foundation for Medical Education and Research. The Revised Natural History Model for Primary Sclerosing Cholangitis. Available at http://www.mayoclinic.org/gi-rst/mayomodel3.html. Accessed: October 18, 2014.
Shetty K, Rybicki L, Carey WD. The Child-Pugh classification as a prognostic indicator for survival in primary sclerosing cholangitis. Hepatology. 1997 May. 25(5):1049-53. [Medline].
Rupp C, Rössler A, Halibasic E, et al. Reduction in alkaline phosphatase is associated with longer survival in primary sclerosing cholangitis, independent of dominant stenosis. Aliment Pharmacol Ther. 2014 Oct 14. [Medline].
Ananthakrishnan AN, Beaulieu DB, Ulitsky A, Zadvornova Y, Skaros S, Johnson K, et al. Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?. Inflamm Bowel Dis. 2009 Jul 27. [Medline].
Abbas G, Lindor KD. Cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Cancer. 2009 Aug 25. epub ahead of print. [Medline].
Jesudian AB, Jacobson IM. Screening and diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis. Rev Gastroenterol Disord. 2009 Spring. 9(2):E41-7. [Medline].
Ludwig J, Barham SS, LaRusso NF, et al. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981 Nov-Dec. 1(6):632-40. [Medline].
Kato T, Komori A, Bae SK, Migita K, Ito M, Motoyoshi Y, et al. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis. World J Gastroenterol. 2012 Jan 14. 18(2):192-6. [Medline]. [Full Text].
Eaton JE, Dzyubak B, Venkatesh SK, et al. Performance of magnetic resonance elastography in primary sclerosing cholangitis. J Gastroenterol Hepatol. 2015 Dec 21. [Medline].
Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009 May 20. [Medline]. [Full Text].
Shi J, Li Z, Zeng X, Lin Y, Xie WF. Ursodeoxycholic acid in primary sclerosing cholangitis: meta-analysis of randomized controlled trials. Hepatol Res. 2009 May 7. [Medline].
Eckhauser FE, Colleti LM, Knol JA. The changing role of surgery for sclerosing cholangitis. Dig Dis. 1996 May-Jun. 14(3):180-91. [Medline].
Graziadei IW, Wiesner RH, Batts KP, et al. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. 1999 Apr. 29(4):1050-6. [Medline].
Graziadei IW, Wiesner RH, Marotta PJ, et al. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology. 1999 Nov. 30(5):1121-7. [Medline].
Lian L, Menon KV, Shen B, Remzi F, Kiran RP. Inflammatory bowel disease complicated by primary sclerosing cholangitis and cirrhosis: is restorative proctocolectomy safe?. Dis Colon Rectum. 2012 Jan. 55(1):79-84. [Medline].
Yimam KK, Bowlus CL. Diagnosis and classification of primary sclerosing cholangitis. Autoimmun Rev. 2014 Apr-May. 13 (4-5):445-50. [Medline].