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      Systematic review with meta‐analysis: risk factors for recurrent primary sclerosing cholangitis after liver transplantation

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          Summary

          Background

          After liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC).

          Aim

          To define risk factors for rPSC.

          Methods

          We searched Pubmed, Embase, Web of Science, and Cochrane library for articles published until March 2018. Studies addressing risk factors for developing rPSC were eligible for inclusion. A random effects meta‐analysis was conducted using hazard ratios (HR) as effect measure. Study quality was evaluated with the Newcastle Ottawa scale. Statistical analysis was performed using Cochrane Review Manager.

          Results

          The electronic database search yielded 449 results. Twenty‐one retrospective cohort studies met the inclusion criteria for the review; 14 were included in the meta‐analysis. The final cohort included 2159 patients (age range 31‐49 years, 68.8% male), of whom 17.7% developed rPSC. Colectomy before liver transplantation, HR 0.65 (95% CI: 0.42‐0.99), cholangiocarcinoma before liver transplantation, HR 2.42 (95% CI: 1.20‐4.86), inflammatory bowel disease, HR 1.73 (95% CI: 1.17‐2.54), donor age, HR 1.24 (95% CI 1.0‐1.45) per ten years, MELD score, HR 1.05 (95% CI: 1.02‐1.08) per point and acute cellular rejection, HR of 1.94 (95% CI: 1.32‐2.83) were associated with the risk of rPSC.

          Conclusions

          Multiple risk factors for rPSC were identified. Colectomy before liver transplantation reduced the risk of rPSC.

          Related collections

          Most cited references36

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          Primary sclerosing cholangitis – a comprehensive review

          Primary sclerosing cholangitis (PSC) is a rare disorder characterised by multi-focal bile duct strictures and progressive liver disease. Inflammatory bowel disease is usually present and there is a high risk of cholangiocarcinoma and colorectal cancer. Most patients ultimately require liver transplantation, after which disease recurrence may occur. With limited therapeutic options and a lack of proven surveillance strategies, patients currently have significant unmet needs. In the present seminar, we provide a comprehensive review of the status of the field. We emphasise developments related to patient stratification and disease behaviour, and provide an overview of management options from a practical, patient-centered perspective. We survey advances made in the understanding of PSC pathogenesis and summarise the ongoing efforts to develop an effective therapy based on these insights.
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            Combining risk estimates from observational studies with different exposure cutpoints: a meta-analysis on body mass index and diabetes type 2.

            Studies on a dose-response relation often report separate relative risks for several risk classes compared with a referent class. When performing a meta-analysis of such studies, one has to convert these relative risks into an overall relative risk for a continuous effect. Apart from taking the dependence between separate relative risks into account, this implies assigning an exposure level to each risk factor class and allowing for the nonlinearity of the dose-response relation. The authors describe a relatively simple method solving these problems. As an illustration, they applied this method in a meta-analysis of the association between body mass index and diabetes type 2, restricted to results of follow-up studies (n=31). Results were compared with a more ad hoc method of assigning exposure levels and with a method in which the nonlinearity of the dose-response method was not taken into account. Differences with the ad hoc method were larger in studies with fewer categories. Not incorporating the nonlinearity of the dose response leads to an overestimation of the pooled relative risk, but this bias is relatively small.
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              A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts.

              Previously, we have found that the absence of the colon after liver transplantation (LT) protects the patient from recurrent primary sclerosing cholangitis (rPSC). As our previous observation has not been confirmed in other series, we have reviewed our cohort of patients grafted for primary sclerosing cholangitis (PSC) with greater numbers and longer follow-up to reassess the rate, consequences, and risk factors for rPSC. We collected data on patients who underwent LT for PSC between January 1986 and April 2006. Data were collected for cytomegalovirus status, inflammatory bowel disease status, time of colectomy, type of colectomy, donor-recipient gender mismatch, recipient sex, extended donor criteria (EDC), and donor risk index. Accepted criteria were used to diagnose rPSC. Of a total of 230 consecutive adult patients, 61 (27%) underwent colectomy pre-/peri-LT, and 54 (23.5%) developed rPSC at a median of 4.6 (range, 0.5-12.9) years post-LT. A total of 263 deceased donor grafts were used, and 73 were EDC grafts. A diagnosis of rPSC was made in 61 of the 263 grafts (23%). The recurrence-free patient survival was significantly better (P < 0.05) in patients who underwent pre-/peri-LT colectomy and in those with non-EDC grafts. In conclusion, in this larger cohort of 230 patients and with longer follow-up of 82.5 (range, 0.0-238.6) months [in comparison with the previous report of 152 recipients with a follow-up of 52.8 (range, 1-146) months], we have shown that colectomy remains a significant risk factor for rPSC and that colectomy before and during initial LT for PSC confers a protective effect against rPSC in subsequent graft(s). Moreover, we have shown that EDC grafts are also a significant risk factor for rPSC.

                Author and article information

                Contributors
                p.w.j.maljaars@lumc.nl
                Journal
                Aliment Pharmacol Ther
                Aliment. Pharmacol. Ther
                10.1111/(ISSN)1365-2036
                APT
                Alimentary Pharmacology & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                0269-2813
                1365-2036
                10 February 2019
                March 2019
                : 49
                : 6 ( doiID: 10.1111/apt.2019.49.issue-6 )
                : 636-643
                Affiliations
                [ 1 ] Department of Gastroenterology and Hepatology Leiden University Medical Centre Leiden The Netherlands
                [ 2 ] National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre Birmingham UK
                [ 3 ] University Hospitals Birmingham Birmingham UK
                [ 4 ] Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK
                [ 5 ] Institute of Applied Health Research University of Birmingham UK
                [ 6 ] Department of Biomedical Data Sciences Leiden University Medical Centre Leiden The Netherlands
                Author notes
                [*] [* ] Correspondence

                P. W. Jeroen Maljaars, Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.

                Email: p.w.j.maljaars@ 123456lumc.nl

                Author information
                https://orcid.org/0000-0001-6527-764X
                https://orcid.org/0000-0003-0477-9499
                Article
                APT15148
                10.1111/apt.15148
                6593422
                30740723
                d317e02a-9931-4ceb-893e-8d80a8a2d06a
                © 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 10 August 2018
                : 20 August 2019
                : 29 December 2018
                Page count
                Figures: 2, Tables: 1, Pages: 8, Words: 11876
                Categories
                Systematic Review with Meta‐analysis
                Systematic Reviews with Meta‐analysis
                Custom metadata
                2.0
                apt15148
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.5 mode:remove_FC converted:26.06.2019

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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