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

Published on Mar 1, 2019in Alimentary Pharmacology & Therapeutics7.515
· DOI :10.1111/APT.15148
Iris C. Steenstraten1
Estimated H-index: 1
(LEI: Leiden University),
Palak J. Trivedi25
Estimated H-index: 25
+ 4 AuthorsP. W. Jeroen Maljaars7
Estimated H-index: 7
(LEI: Leiden University)
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.
📖 Papers frequently viewed together
58 Citations
67 Citations
13 Authors (Ivo W. Graziadei, ..., Ruud A.F. Krom)
267 Citations
#1Palak J. TrivediH-Index: 25
#2J. Reece (University Hospitals Birmingham NHS Foundation Trust)H-Index: 2
Last. J. Ferguson (University of Birmingham)H-Index: 4
view all 14 authors...
BACKGROUND: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation. METHODS: Graft survival was evaluated across a prospectively accrued tran...
16 CitationsSource
#1Nicolas Goldaracena (UHN: University Health Network)H-Index: 22
#2Andre Gorgen (UHN: University Health Network)H-Index: 9
Last. Gonzalo Sapisochin (UHN: University Health Network)H-Index: 23
view all 3 authors...
: Cholangiocarcinoma (CCA) is the second most common liver cancer, and it is associated with a poor prognosis. CCA can be divided into intrahepatic, hilar, and distal. Despite the subtype, the median survival is 12-24 months without treatment. Liver transplantation (LT) is recognized worldwide as a curative option for hepatocellular carcinoma. On the other hand, the initial results for LT for CCA were very poor mainly due to a lack of adequate patient selection. In the last 2 decades, improvemen...
45 CitationsSource
#1Lina Lindström (Karolinska University Hospital)H-Index: 6
#2Kristin Kaasen Jørgensen (Oslo University Hospital)H-Index: 9
Last. Annika Bergquist (Karolinska University Hospital)H-Index: 51
view all 9 authors...
AbstractObjectives: The risk for recurrent primary sclerosing cholangitis (rPSC) after liver transplantation is associated with inflammatory bowel disease (IBD). We assessed the frequency of rPSC and studied risk factors for recurrent disease with special focus on IBD. We also evaluated the importance of rPSC for prognosis.Materials and methods: All liver transplanted PSC patients in the Nordic countries between 1984 and 2007 (n = 440), identified by the Nordic Liver Transplant Registry, were st...
34 CitationsSource
#1Caroline Nordenvall (KI: Karolinska Institutet)H-Index: 16
#2Ola Olén (KI: Karolinska Institutet)H-Index: 24
Last. Annika Bergquist (Karolinska University Hospital)H-Index: 51
view all 8 authors...
SummaryBackground Despite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains controversial. Aim To explore whether colectomy prior to PSC-diagnosis is associated with transplant-free survival. Methods A nationwide cohort study in Sweden including all patients aged 18 to 69 years in whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each patient was foll...
25 CitationsSource
#1Tom H. Karlsen (University of Oslo)H-Index: 67
#2Trine Folseraas (Oslo University Hospital)H-Index: 12
Last. Mette Vesterhus (Oslo University Hospital)H-Index: 22
view all 4 authors...
Summary 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 presen...
259 CitationsSource
#1Yoshihide Ueda (Kyoto University)H-Index: 30
#2Toshimi Kaido (Kyoto University)H-Index: 33
Last. Shinji UemotoH-Index: 88
view all 15 authors...
Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease, with liver transplantation being the sole life-saving treatment for end-stage PSC-related liver disease. However, recurrence of PSC after liver transplantation is a common complication, with the risk factors for recurrence being controversial. We conducted a retrospective chart review of 45 patients who had undergone liver transplantation for PSC at our institute. The risk factors for PSC recurrence and graft failur...
21 CitationsSource
#1Palak J. Trivedi (NIHR: National Institute for Health Research)H-Index: 25
#2Irene Scalera (University Hospitals Birmingham NHS Foundation Trust)H-Index: 9
Last. Paolo Muiesan (NIHR: National Institute for Health Research)H-Index: 61
view all 9 authors...
Background & Aim Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory cholangiopathy for which liver transplantation is the only life-extending intervention. These patients may benefit from accepting liver donation after circulatory death (DCD), however their subsequent outcome is unknown. The aim of this study was to determine the clinical impact of using DCD liver grafts in patients specifically undergoing transplantation for PSC. Methods Clinical outcomes were prospectivel...
22 CitationsSource
#1Aldo J. Montano-Loza (University of Alberta Hospital)H-Index: 35
#2Rahima A. Bhanji (University of Alberta Hospital)H-Index: 14
Last. Andrew L. Mason (University of Alberta Hospital)H-Index: 54
view all 4 authors...
SummaryBackground Autoimmune liver diseases (AILD) constitute the third most common indication for liver transplantation (LT) worldwide. Outcomes post LT are generally good but recurrent disease is frequently observed. Aims To describe the frequency and risk factors associated with recurrent AILD post-LT and provide recommendations to reduce the incidence of recurrence based on levels of evidence. Methods A systematic review was performed for full-text papers published in English-language journa...
59 CitationsSource
#1Aloysious Aravinthan (TGH: Toronto General Hospital)H-Index: 15
#2Adam Doyle (TGH: Toronto General Hospital)H-Index: 10
Last. Eberhard L. Renner (TGH: Toronto General Hospital)H-Index: 13
view all 14 authors...
Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for ...
15 CitationsSource
#1Fredric D. Gordon (Lahey Hospital & Medical Center)H-Index: 30
#2David S. Goldberg (UPenn: University of Pennsylvania)H-Index: 37
Last. Robert M. Merion (UM: University of Michigan)H-Index: 92
view all 8 authors...
Primary sclerosing cholangitis (PSC) recurs in 15%-25% of patients transplanted for PSC. In the United States, PSC transplant patients are more likely to receive an organ from a living donor (LD) than patients without PSC. Our aims were to (1) compare risk of PSC recurrence in LD versus deceased donor recipients and (2) identify risk factors for PSC recurrence. There were 241 living donor liver transplantations (LDLTs) and 65 deceased donor liver transplantation (DDLT) patients transplanted betw...
28 CitationsSource
Cited By21
The field of liver transplantation directly or indirectly embodies all liver diseases, in addition to specific ones related to organ rejection (cellular and humoral). The recommended non-invasive methods for determining the indication for liver transplantation are the Model for End-stage Liver Disease score, and the alpha-foetoprotein score in case of hepatocellular carcinoma. Radiological methods are the cornerstones for the diagnosis of vascular and biliary complications after liver transplant...
#1Palak J. TrivediH-Index: 25
#2Gideon M. Hirschfield (U of T: University of Toronto)H-Index: 69
Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be...
1 CitationsSource
#1Kristel Leung (U of T: University of Toronto)H-Index: 4
#2Maya Deeb (U of T: University of Toronto)H-Index: 4
Last. Aliya Gulamhusein (UHN: University Health Network)H-Index: 13
view all 4 authors...
Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets...
#1Burcin Özdirik (Charité)H-Index: 3
#2Tobias Müller (Charité)H-Index: 27
Last. Michael Sigal (Charité)H-Index: 8
view all 5 authors...
Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option...
#1Thijmen Visseren (EUR: Erasmus University Rotterdam)H-Index: 2
#2Nicole S. Erler (EUR: Erasmus University Rotterdam)H-Index: 16
Last. Sarwa Darwish Murad (EUR: Erasmus University Rotterdam)H-Index: 32
view all 17 authors...
BACKGROUND Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. METHODS Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out...
1 CitationsSource
Last. Alan BonderH-Index: 13
view all 5 authors...
Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifyin...
#1Fernanda de Quadros Onófrio (UHN: University Health Network)H-Index: 5
#2Nazia Selzner (UHN: University Health Network)H-Index: 32
Last. Gideon M. Hirschfield (UHN: University Health Network)H-Index: 69
view all 3 authors...
#1Nobuhisa Akamatsu (UTokyo: University of Tokyo)H-Index: 27
#2Kiyoshi Hasegawa (UTokyo: University of Tokyo)H-Index: 68
Last. Hajime Takikawa (Teikyo University)H-Index: 33
view all 9 authors...
The present study investigated the possible risk factors, including relationship/HLA matching between donor and recipient, and immunosuppressive therapies on the recurrence of PSC after liver transplantation (LT). Subjects were 197 recipients of LT for PSC, among whom 180 surviving more than 1 year after LT were further analyzed for risk factors of recurrence. The 5- and 10-year patient- and graft-survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was...
#1Matthew PeverelleH-Index: 3
#2Sarang PaleriH-Index: 1
Last. Paul J Gow (University of Melbourne)H-Index: 28
view all 5 authors...
BACKGROUND: The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS: One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patie...
6 CitationsSource
#1Thijmen Visseren (EUR: Erasmus University Rotterdam)H-Index: 2
#2Gwenny M. Fuhler (EUR: Erasmus University Rotterdam)H-Index: 24
Last. Maikel P. Peppelenbosch (EUR: Erasmus University Rotterdam)H-Index: 86
view all 8 authors...
Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we inv...