Liver transplantation for primary sclerosing cholangitis

Czech version

Authors: P. Drastich ¹; L. Bajer ¹; P. Wohl ¹; D. Kamenář ¹; J. Špičák ¹; E. Honsová ²; P. Trunečka ³
Authors‘ workplace: Klinika hepatogastroenterologie, IKEM, Praha ¹; Pracoviště klinické a transplantační patologie, IKEM, Praha ²; Transplantcentrum, IKEM, Praha ³
Published in: Gastroent Hepatol 2013; 67(5): 413-420
Category: Hepatology: Original Article

Overview

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease of unknown origin. PSC is closely associated with inflammatory bowel disease, mainly ulcerative colitis (UC). PSC presents a significantly increased risk of hepatobiliary and colorectal neoplastic changes. PSC gradually leads to cirrhosis with a significant portal hypertension. No effective medical therapy is available and treatment with a high dosage of ursodeoxycholic acid could even lead to a number of adverse effects. Liver transplantation (OLTx) is the only curative option currently available to improve survival. In this study, a retrospective analysis was performed for all patients who underwent OLTx for PSC over a 20-year period in the Institute for Clinical and Experimental Medicine (IKEM), Prague.

Results:
A total of 102 patients underwent OLTx for PSC with a mean age of 37 years (14–68). Inflammatory bowel disease (IBD) was confirmed in 64 patients (62.8%) pre-LT. Except for three cases with Crohn’s disease, all patients suffered from UC. Cumulated 1-, 5-, 10- and 15-year patient survival rates were 94.1%, 93.0%, 93.0% and 82.3% respectively. Recurrent PSC was determined in 28 patients (33.7%) with three who needed retransplantation. In six patients, cholangiocarcinoma was incidentally detected in explanted livers and three died due to advanced carcinoma. The course of ulcerative colitis (UC) was mild or in remission in 34/61 (55.7%) patients followed in our centre after OLTx without relevant clinical symptoms. The remaining 27 patients (44.3%) suffered from clinically active disease. Colectomy was performed in four patients due to refractory disease. On the other hand, UC newly developed in 13 patients after OLTx with a mild course of disease.

Conclusion:
The outcome for patients with PSC who have undergone transplantation is excellent. PSC frequently recurs in the hepatic allograft but retransplantation is seldom necessary. The course of UC after OLTx for PSC is frequently active despite immunosuppressive treatment. Detection of dysplastic changes and CRC confirm the usefulness of regular colonoscopic evaluations. New onset of UC can develop after OLTx. Incidentally found cholangiocarcinoma remains a difficult treatment problem with a low survival rate.

Key words:
liver transplantation – primary sclerosing cholangitis – ulcerative colitis – cholangiocarcinoma – colorectal cancer

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
21. 8. 2013

Accepted:
16. 9. 2013

Sources

1. Bergquist A, Montgomery SM, Bahmanyar S et al. Increased risk of primary sclerosing cholangitis and ulcerative colitis in firts-degree relatives of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2008; 6(8): 939–943.

2. Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med 1995; 332(14): 924–933.

3. Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol 2012; 18(1): 1–15.

4. Lindkvist B, Benito de Valle M, Gullberg B et al. Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden. Hepatology 2010; 52(2): 571–577.

5. Boonstra K, Weersma RK, van Erpecum KJ et al. Population-based epidemiology, malignancy risk and outcome of primary sclerosing cholangitis. Hepatology 2013. [In press].

6. Pallavicino F, Pellicano R, Reggiani S et al. Inflammatory bowel diseases and primary sclerosing cholangitis: hepatic and pancreatic side effects due to azathioprine. Eur Rev Med Pharmacol Sci 2013; 17(1): 84–87.

7. Mendes FD, Jorgensen R, Keach J et al. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol 2006; 101(9): 2070–2075.

8. Drastich P, Kamenar D, Spicak J. Ulcerative colitis in patients with primary sclerosing cholangitis (PSC-UC) – a specific subgroup of inflammatory bowel disease. Gastroenterology 2006; 130 (Suppl 2): A214.

9. Boonstra K, van Erpecum KJ, van Nieuwkerk KM et al. Primary sclerosing cholangitis is associated with distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(12): 2270–2276.

10. Wohl P, Hucl T, Drastich P. Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis. World J Gastroenterol 2013; 19(14): 2234–2241.

11. Navaneethan U, Venkatesh PG, Mukewar S et al. Progressive primary sclerosing cholangitis requiring liver transplantation is associated with reduced need for colectomy in patients with ulcerative colitis. Clin Gastroenterol Hepatol 2012; 10(5): 540–546.

12. Treeprasertsuk S, Björnsson E, Sinakos E et al. Outcome of patients with primary sclerosing cholangitis and ulcerative colitis undergoing colectomy. World J Gastrointest Pharmacol Ther 2013; 4(3): 61–68.

13. Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology 2011; 54(5): 1842–1852.

14. Karlsen TH, Schrumpf E, Boberg KM. Update on primary sclerosing cholangitis. Dig Liver Dis 2010; 42(6): 390–400.

15. Stanich PP, Björnsson E, Gossard AA et al. Alkaline phosphatase normalization is associated with better prognosis in primary sclerosing cholangitis. Dig Liver Dis 2011; 43(4): 309–313.

16. Lindor KD, Kowdley KV, Luketic VA et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50(3): 808–814.

17. Imam MH, Sinakos E, Gossard AA et al. High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis. Aliment Pharmacol Ther 2011; 34(10): 1185–1192.

18. Pardi DS, Loftus EV Jr, Kremers WK et al. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003; 124(4): 889–893.

19. Lindström L, Boberg KM, Wikman O et al. High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia. Aliment Pharmacol Ther 2012; 35(4): 451–457.

20. Singh S, Khanna S, Pardi DS et al. Effect of ursodeoxycholic acid use on the risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a systemic review and meta-analysis. Inflamm Bowel Dis 2013; 19(8): 1631–1638.

21. Patkowski W, Skalski M, Zieniewicz K et al. Orthotopic liver transplantation for cholestatic diseases. Hepatogastroenterology 2010; 57(99–100): 605–610.

22. Adam R, Hoti E. Liver transplantation: the current situation. Semin Liver Dis 2009; 29(1): 3–18.

23. Alabraba E, Nightingale P, Gunson B et al. A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl 2009; 15(3): 330–340.

24. Marelli L, Xirouchakis E, Kalambokis G et al. Does the severity of primary sclerosing cholangitis influence the clinical course of associated ulcerative colitis? Gut 2011; 60(9): 1224–1228.

25. Drastich P, Bajer L, Wohl P et al. Ulcerative colitis after orthotopic liver transplantation for primary sclerosing cholangitis- a single center experience. Gastroenterology 2013; 144 (Suppl 1): S628.

26. Papatheodoridis GV, Hamilton M, Mistry PK et al. Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis. Gut 1998; 43(5): 639–644.

27. Haagsma EB, Van den Berg AP, Kleibeuker JH et al. Inflammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens. Aliment Pharmacol Ther 2003; 18(1): 33–44.

28. Mohabbat AB, Sandborn WJ, Loftus EV Jr et al. Anti-tumour necrosis factor treatment of inflammatory bowel disease in liver transplant recipients. Aliment Pharmacol Ther 2012; 36(6): 569–574.

29. Singh S, Loftus EV Jr, Talwalkar JA. Inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Am J Gastroentrol 2013; 108(9): 1417–1425.

30. Clavien PA, Sharara AI, Camargo CA Jr et al. Evidence that ursodeoxycholic acid prevents steroid-resistant rejection in adult liver transplantation. Clin Transplant 1996; 10(6 Pt 2): 658–662.

31. Joshi D, Bjarnason I, Belgaumkar A et al. The impact of inflammatory bowel disease post-liver transplantation for primary sclerosing cholangitis. Liver Int 2011; 33(1): 53–61.

32. Bhanji RA, Mason AL, Girgis S et al. Liver transplantation for overlap syndromes of autoimmune liver diseases. Liver Int 2013; 33(2): 210–219.