Liver transplantation for primary sclerosing cholangitis—morbidities including disease recurrence
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC10839727 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: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. 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 of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival.
| S-EPMC8456806 | biostudies-literature
Project description: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 failure after liver transplantation were analyzed.The graft survival rates were 55.4% at 5 years and 32.8% at 10 years after liver transplantation for PSC. PSC recurrence was diagnosed in 16 (40%) of 40 patients, at a median 30 months (range, 9-70 months) after liver transplantation. The cumulative incidence rate of PSC recurrence was 24.5% at 3 years, 39.3% at 5 years, and 45.8% at 6 years. Among the 16 patients diagnosed with PSC recurrence, the graft survival rate was 56.3% at 5 years, and 21.9% at 10 years after the recurrence. Active inflammatory bowel disease after liver transplantation was identified as an independent risk factor for PSC recurrence. Age younger than 30 years at the time of PSC diagnosis and bacteremia were factors significantly associated with graft failure after liver transplantation on multivariate analysis.PSC frequently recurred and progressed to graft failure after liver transplantation for PSC. Maintaining an inactive status of inflammatory bowel disease might offer protection against PSC recurrence.
| S-EPMC5828688 | biostudies-other
Project description: Not available
| S-EPMC10839713 | biostudies-literature
Project description:BackgroundThe course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD.MethodsIn a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis.ResultsThree hundred seventy-three patients were identified (mean age, 47.5 ± 11.7 years; 64.9% male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56/151 (37.1%) required escalation of therapy, whereas 87 had a stable course (57.6%) and 8 patients (5.3%) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0%, 18.5%, and 25.5%, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2%) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5%, 20.0%, and 25.4%, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective.ConclusionsThe 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5%, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4%. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093/ibd/izx096_video1izx096.video15746673864001.
| S-EPMC6085995 | biostudies-literature
Project description: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 investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn's disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.
| S-EPMC7689804 | biostudies-literature
Project description:Deciding who should receive a liver transplant (LT) depends on both urgency and utility. Most survival scores are validated through discriminative tests, which compare predicted outcomes between patients. Assessing post-transplant survival utility is not discriminate, but should be "calibrated" to be effective. There are currently no such calibrated models. We developed and validated a novel calibrated model to predict individual survival after LT for Primary Sclerosing Cholangitis (PSC). We applied a software tool, PSSP, to adult patients in the Scientific Registry of Transplant Recipients (n = 2769) who received a LT for PSC between 2002 and 2013; this produced a model for predicting individual survival distributions for novel patients. We also developed an appropriate evaluation measure, D-calibration, to validate this model. The learned PSSP model showed an excellent D-calibration (p = 1.0), and passed the single-time calibration test (Hosmer-Lemeshow p-value of over 0.05) at 0.25, 1, 5 and 10 years. In contrast, the model based on traditional Cox regression showed worse calibration on long-term survival and failed at 10 years (Hosmer-Lemeshow p value = 0.027). The calculator and visualizer are available at: http://pssp.srv.ualberta.ca/calculator/liver_transplant_2002. In conclusion we present a new tool that accurately estimates individual post liver transplantation survival.
| S-EPMC5854273 | biostudies-literature
Project description:BackgroundAfter liver transplantation primary sclerosing cholangitis (PSC), the condition returns in the transplanted liver in a subset of patients (recurrent primary sclerosing cholangitis, rPSC).AimTo define risk factors for rPSC.MethodsWe 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.ResultsThe 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.ConclusionsMultiple risk factors for rPSC were identified. Colectomy before liver transplantation reduced the risk of rPSC.
| S-EPMC6593422 | biostudies-literature
Project description: Not available
| S-EPMC5553912 | biostudies-literature
Project description:Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
| S-EPMC7829069 | biostudies-literature
Project description:BACKGROUND: The course of inflammatory bowel disease after liver transplantation has been reported as variable with usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity. AIMS: To evaluate the course of inflammatory bowel disease in primary sclerosing cholangitis transplant patients who were treated without long term steroids. METHODS: Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survived more than 12 months. Ulcerative colitis was diagnosed in 18 (60%) patients before transplantation; two had previous colectomy. All patients underwent colonoscopy before and after transplantation and were followed for 38 (12-92) months. All received cyclosporin or tacrolimus with or without azathioprine as maintenance immunosuppression. RESULTS: Ulcerative colitis course after transplantation compared with that up to five years before transplantation was the same in eight (50%) and worse in eight (50%) patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course, whereas it worsened in all four patients with pretransplant active course (p=0.08). New onset ulcerative colitis developed in three (25%) of the 12 patients without inflammatory bowel disease before transplantation. No colorectal cancer has been diagnosed to date. CONCLUSIONS: Preexisting ulcerative colitis often has an aggressive course, while de novo ulcerative colitis may develop in patients transplanted for primary sclerosing cholangitis and treated without long term steroids.
| S-EPMC1727300 | biostudies-other