Reply to “IBD is associated with an increase in carcinoma in PSC irrespective of the presence of dominant bile duct stenosis”
Authors: Daniel N. Gotthardt, Adolf Stiehl
Journal: Journal of Hepatology (2012)

IBD is associated with an increase in carcinoma in PSC irrespective of the presence of dominant bile duct stenosisJournal of HepatologyVol. 57Issue 2PreviewWe have read with great interest the paper by Rudolph et al. [1]. The authors have prospectively studied a large cohort of Primary Sclerosing Cholangitis (PSC) patients for up to two decades and identified that only patients with a dominant biliary stenosis with additional IBD had an increased rate in both biliary and colorectal carcinomas (CRC) compared to patients with no dominant stenosis or patients with a dominant stenosis without concomitant IBD. Their findings suggest that the occurrence of additional IBD in PSC patients has a carcinogenic potential and also results in reduced survival free of liver transplantation. Full-Text PDF Open AccessIn PSC with dominant bile duct stenosis, IBD is associated with an increase of carcinomas and reduced survivalJournal of HepatologyVol. 53Issue 2PreviewIn patients with primary sclerosing cholangitis (PSC) treated with ursodeoxycholic acid (UDCA), dominant stenoses are associated with reduced survival free of liver transplantation and the role of inflammatory bowel disease (IBD) in such patients is unclear. In the present study the influence of IBD on the outcome in patients with and without dominant stenosis has been evaluated. Full-Text PDF In a retrospective cohort, Janse et al. [[1]Janse M. Lamberts L. Verdonk R. Weersma R. IBD is associated with an increase in carcinoma in PSC irrespective of the presence of dominant bile duct stenosis.J Hepatol. 2012; 57: 473-474Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar] analyzed the association of malignancies with the presence of inflammatory bowel disease (IBD) and dominant stenosis (DS) in patients with primary sclerosing cholangitis (PSC). We have analyzed and published on these associations in our prospective cohort, previously [[2]Rudolph G. Gotthardt D. Kloeters-Plachky P. Rost D. Kulaksiz H. Stiehl A. In PSC with dominant bile duct stenosis, IBD is associated with an increase of carcinomas and reduced survival.J Hepatol. 2010; 53: 313-317Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. The present study of Janse et al. essentially confirms our data in a retrospective evaluation. Both studies acquired data on the number of carcinomas (cholangiocarcinoma, gallbladder carcinoma, and colorectal carcinoma) and analyzed a potential association with the concomitant presence of DS and/or IBD in these patients. We found the highest frequency of carcinomas in the group of patients having both DS and IBD of 20.9% (14/67); in the retrospective cohort of Janse et al., this group also had the highest number of carcinomas with a rate of 23.6% (13/55). The second highest frequency of carcinomas was found in both studies in the group of patients having DS irrespective of the presence of IBD (our study: 14.4% (14/97); Janse study: 18.2% (14/77)), and the third highest frequency in both studies was that of IBD patients irrespective of the presence of DS (our study: 12.5% (15/120); Janse study 13.8% (22/160)). The overall number of carcinomas appears somewhat higher in the cohort reported by Janse et al. [[1]Janse M. Lamberts L. Verdonk R. Weersma R. IBD is associated with an increase in carcinoma in PSC irrespective of the presence of dominant bile duct stenosis.J Hepatol. 2012; 57: 473-474Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar], which at least in part might be attributed to the referral bias of a large tertiary care center focused on liver transplantation. From their data, Janse et al. draw the conclusions that their results are different from ours and that there is no difference in IBD-patients whether they have DS or not. Although the p value is not explicitly mentioned in the text, in both studies the difference between patients with and without DS is significant (our study: 14/53 vs. 1/51 p= 0.002; Janse study: 13/55 vs. 9/105 p= 0.009). Thus, the data of Janse et al. confirm our data and our conclusion that DS is associated with more carcinomas. According to Janse et al., the number of carcinomas in the patients without dominant stenosis was higher than in our study but it seems to us difficult to evaluate such data retrospectively and therefore we do not believe that the two studies are comparable. In both studies, the frequency of carcinomas was higher in the DS group than in the IBD group and was even higher in the group having the combination of IBD and DS (see frequencies above). This of course does not exclude that IBD plays a substantial role. Janse et al. argue that in their study definitions of dominant stenosis might have some problems. Information on this topic appears essential (screening for DS by ERC?), since it will markedly affect the results. Definitions of DS are now implemented in the allocation system of Eurotransplant and are accepted both by the AASLD and EASL guidelines [3Chapman R. Fevery J. Kalloo A. Nagorney D.M. Boberg K.M. Shneider B. et al.Diagnosis and management of primary sclerosing cholangitis.Hepatology. 2010; 51: 660-678Crossref PubMed Scopus (957) Google Scholar, 4EASL Clinical Practice Guidelines Management of cholestatic liver diseases.J Hepatol. 2009; 51: 237-267Abstract Full Text Full Text PDF PubMed Scopus (1389) Google Scholar, 5Gotthardt D.N. Rudolph G. Kloters-Plachky P. Kulaksiz H. Stiehl A. Endoscopic dilation of dominant stenoses in primary sclerosing cholangitis: outcome after long-term treatment.Gastrointest Endosc. 2010; 71: 527-534Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar]. Lastly, we would like to mention a potential role of UDCA treatment which was performed in all of our patients. Although the anti-neoplastic potential of UDCA has been under debate, especially in very high doses, such an effect may influence the incidence of malignancies [6Rudolph G. Gotthardt D.N. Kloeters-Plachky P. Kulaksiz H. Schirmacher P. Stiehl A. In PSC with colitis treated with UDCA, most colonic carcinomas develop in the first years after the start of treatment.Dig Dis Sci. 2011; 56: 3624-3630Crossref PubMed Scopus (17) Google Scholar, 7Eaton J.E. Silveira M.G. Pardi D.S. Sinakos E. Kowdley K.V. Luketic V.A. et al.High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.Am J Gastroenterol. 2011; 106: 1638-1645Crossref PubMed Scopus (205) Google Scholar, 8Tung B.Y. Emond M.J. Haggitt R.C. Bronner M.P. Kimmey M.B. Kowdley K.V. 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: 89-95Crossref PubMed Scopus (428) Google Scholar, 9Pardi 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: 889-893Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar]. We agree with Janse et al. that surveillance in patients with PSC should be performed according to current guidelines. Our study and that of Janse et al. indicate that patients with dominant stenoses are at an increased risk of malignancy. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.