Recurrence Of Primary Sclerosing Cholangitis Research Articles

DOP14 Proctocolectomy is associated with improved transplant-free survival in patients with primary sclerosing cholangitis: results from a pooled collaborative international study

Abstract Background It is hypothesized that the gut-liver axis plays a pivotal role in the aetiology of primary sclerosing cholangitis (PSC). Colectomy before liver transplantation is associated with decreased rates of recurrent PSC.1 We previously observed that proctocolectomy with permanent ileostomy is associated with better transplant-free survival in a population-based Dutch cohort.2 The aim of the present study is to confirm the effect of colectomy on PSC disease course in an international context. Methods We conducted a retrospective analysis on the International PSC Registry (IPSCR), comprising patients from Finland, Norway, Sweden, and the Netherlands. Endpoints were defined as liver transplantation (LT) and PSC-related death (excluding colorectal carcinoma) and were censored in the first year after colectomy to allow for a delayed protective effect. Cox proportional hazards regression was performed, with correction for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, and inflammatory bowel disease (IBD) status (i.e. ulcerative colitis, Crohn’s disease or IBD unspecified). IBD status and colectomy status were included as time-dependent exposure variables, the latter stratified for extent and indication for colectomy. Results A total of 2595 patients were included, of which 1341 from the Netherlands, 560 from Finland, 528 from Norway, and 166 from Sweden. Of all patients 1900(73%) were diagnosed with IBD and 346(15%) had undergone a colectomy; 34(9%) hemi-, 91(26%) subtotal, and 172(50%) proctocolectomy with pouch and 65(19%) with ileostomy. During a total follow-up of 28,282 patient years, 848(33%) patients reached the endpoint LT or PSC-related death. Hazard ratio (HR) of reaching LT or PSC-related death was significantly decreased in patients with proctocolectomy (0.70(0.52-0.93)) compared to patients without colectomy with variation per country (Netherlands 0.82(0.56-1.19), Finland 0.52(0.24-1.13), Norway 0.59(0.31-1.03), Sweden 0.28(0.06-1.24)). This effect was less pronounced in case of a hemi- or subtotal colectomy (HR 0.84(059-1.20)). The effect was most pronounced in the proctocolectomy with permanent ileostomy group (HR 0.55(0.30-0.99)). Of the known risk factors only a concurrent IBD diagnosis had no significant effect on transplant-free survival. Conclusion Our extended data confirm that colectomy is associated with a decreased risk of liver transplantation and PSC-related death. An incremental effect was seen with the extent of the colectomy, with the most pronounced effect in the proctocolectomy group with permanent ileostomy. Our data support the putative role of the gut-liver axis in the disease course of PSC.

Outcomes of patients with primary sclerosing cholangitis after liver transplantation in a predominantly living donor liver transplant center

Background and aimThe number of studies reporting in detail the complications that occur after liver transplantation in patients with primary sclerosing cholangitis (PSC), especially after living donor liver transplantation (LDLT), is limited. In this study we present the complications and outcomes of PSC patients after liver transplantation in a predominantly LDLT center. Materials and methodsAdult and pediatric patients who underwent liver transplantation for PSC between February 2008 and October 2020 were included in the study. The demographic characteristics, presence of co-existing diseases, indications for transplantation, type of transplantation, and immunosuppressive treatments used were recorded. Patient survival, survival times, cause of death, recurrences, rejection, and biliary complications were recorded. ResultsThirty patients who underwent liver transplantation for PSC were included in the study. Twenty-seven patients (90 %) were living donor transplants. The 1-, 3-, and 5-year survival rates after transplantation were 75.9 %, 74.9 %, and 74.9 %, respectively. Biliary complications occurred in 15 patients (50 %). All patients with biliary complications were successfully treated with endoscopic and percutaneous interventional treatments. Chronic rejection occurred in three patients (10 %) and acute rejection occurred in five patients (13.3 %). PSC recurrence developed in five patients (18.5 %). ConclusionBiliary complications are the most common complication after liver transplantation in patients with PSC in our center, where LDLT is used extensively and PSC patients are followed closely with respect to biliary complications after transplantation.

Liver transplant in primary sclerosing cholangitis: Current trends and future directions.

Primary sclerosing cholangitis (PSC) is a chronic and progressive immune-mediated cholangiopathy causing biliary tree inflammation and scarring, leading to liver cirrhosis and end-stage liver disease. Diagnosis of PSC is challenging due to its nonspecific symptoms and overlap with other liver diseases. Despite the rising incidence of PSC, there is no proven medical therapy that can alter the natural history of the disease. While liver transplantation (LT) is the most effective approach for managing advanced liver disease caused by PSC, post-transplantation recurrence of PSC remains a challenge. Therefore, ongoing research aims to develop better therapies for PSC, and continued efforts are necessary to improve outcomes for patients with PSC. This article provides an overview of PSC's pathogenesis, clinical presentation, and management options, including LT trends and future aspects. It also highlights the need for improved therapeutic options and ethical considerations in providing equitable access to LT for patients with PSC. Additionally, the impact of liver transplant on the quality of life and psychological outcomes of patients with PSC is discussed. Ongoing research into PSC's pathogenesis and post-transplant recurrence is crucial for improved understanding of the disease and more effective treatment options.

THU-527 - Primary sclerosing cholangitis recurrence after liver transplantation: a nationwide survey in Italy

THU-527 - Primary sclerosing cholangitis recurrence after liver transplantation: a nationwide survey in Italy

Intestinal Bacteremia After Liver Transplantation is a Risk Factor for Recurrence of Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic progressive pathological process, related to inflammatory bowel disease and subsequent bacterial translocation. Liver transplantation (LT) is the only curative therapy, but outcomes are compromised by recurrence of PSC (rPSC). The aim of the study was to investigate a potential link between intestinal bacteremia, fucosyltransferase-2 (FUT2), and rPSC after LT. LT recipients with PSC (n = 81) or without PSC (n = 271) were analyzed for clinical outcomes and positive bacterial blood cultures. A link between bacteremia and the genetic variant of the FUT2 gene was investigated. The incidence of inflammatory bowel disease was significantly higher in PSC recipients but not associated with rPSC. Bacteremia occurred in 31% of PSC recipients. The incidence of rPSC was 37% and was significantly more common in patients with intestinal bacteremia versus no bacteremia (82% versus 30%; P = 0.003). The nonsecretor polymorphism of the FUT2 gene was identified as a genetic risk factor for both intestinal bacteremia and rPSC. Combined FUT2 genotype and intestinal bacteremia in recipients resulted in the highest risk for rPSC (hazard ratio, 15.3; P < 0.001). Thus, in this article, we showed that bacterial translocation is associated with rPSC after LT and related to the FUT2 nonsecretor status.

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.

Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT. We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3-V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC-LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; Q FDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella , were associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia . Consistent mucosal microbiota features associated with PSC, PSC-IBD, and disease severity, irrespective of LT status, highlight the usefulness of investigating PSC and rPSC in parallel, and suggest that the impact of gut microbiota on posttransplant liver health should be investigated further.

Natural history and prognosis of pediatric PSC with updates on management.

Natural history and prognosis of pediatric PSC with updates on management.

OP10 Proctocolectomy with permanent ileostomy is associated with better transplant-free survival in patients with primary sclerosing cholangitis: a retrospective cohort study

Abstract Background Inflammatory bowel disease (IBD) is the strongest known risk factor for primary sclerosing cholangitis (PSC) and seems associated with a worse prognosis. After liver transplantation, colectomy is associated with decreased rates of recurrent PSC and better graft survival.1 At the same time, the effect of colectomy on the disease course of PSC remains unclear.2 Available evidence depends either on small patient numbers, may be confounded by unobserved risk factors or colectomy was not considered as time-depending covariate. The aim of our study is to estimate the effect of colectomy on the disease course of PSC by taking time dependency and known risk factors into account. Methods We conducted a retrospective cohort study between January 1st 2008 and December 31st 2021 based on the Dutch population-based EpiPSC2 cohort. Transplant-free survival was defined as liver transplantation or PSC-related death (excluding colorectal carcinoma). The effect of colectomy was determined as time depending variable via Cox proportional hazards regression and was corrected for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, time depending IBD status (i.e. no IBD, ulcerative colitis (UC), Crohn’s disease (CD) or IBD Unspecified (IBD-U)), and tertiary centre inclusion. Effect of colectomy was stratified for extent (i.e. hemi-, subtotal, or proctocolectomy with pouch or ileostomy). Indication of colectomy (i.e. active disease, dysplasia and colorectal carcinoma or other) was also considered as predictor variable. Events in the first year after colectomy were censored due to a presumed delayed effect of colectomy on disease course. Results Of the 1341 patients included, 912(68%) were diagnosed with IBD and 187(14%) had undergone a colectomy. During a total follow-up of 14,393 patient years, 370(28%) patients underwent liver transplantation and 318(24%) patients died due to a PSC-related cause. Median transplant-free survival time was 20 years. Hazard ratio (HR) was significantly decreased in patients who had undergone proctocolectomy with ileostomy (HR 0.47(0.24-0.93)) compared to patients without colectomy. This effect was absent in the group with any other type of colectomy (HR 0.90(0.67-1.19)). Indication of colectomy had no apparent effect. Presence of UC, CD or IBD-U was not associated with a worse prognosis compared to absence of IBD (HR 0.99(0.81-1.21), HR 0.85(0.64-1.13), HR 0.75(0.43-1.29)). Conclusion Our data suggest that proctocolectomy with ileostomy confers protection for liver transplantation and PSC-related death. This points towards the putative pathophysiologic role of the colonic microbiota in PSC and may open avenues to a better understanding of the aetiology of PSC.

LIVER TRANSPLANTATION IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A MULTICENTRIC STUDY.

The prevalence of primary sclerosing cholangitis (PSC) in the general population has not yet been clearly established. The management of PSC should focus on delaying the progression of the disease and restraining its complications. The only curative therapy for the disease remains liver transplantation (LT). PSC is currently the fifth most common indication for LT and corresponds to 5% of all LT indications in adults. Our objective is to evaluate the indications and outcomes of PSC patients undergoing LT in three liver transplantation centers in southern Brazil - Hospital Santa Isabel in Blumenau, Santa Catarina state, and Hospital das Clínicas and Hospital Nossa Senhora das Graças, in Curitiba, Parana state). This is a longitudinal observational study of patients with PSC who underwent LT in three major Brazilian medical centers. Electronic medical records and study protocols of all patients subjected to LT from January 2011 to December 2021 were retrospectively reviewed. Of the 1,362 transplants performed in the three medical centers, 37 were due to PSC. Recurrence of PSC occurred in three patients (8.1%) in 3.0±2.4 years (range, 1-4 years). The 1-year and 5-year survival rates after the first LT were 83.8 and 80.6%, respectively. The 1-year and 5-year graft survival rates were, respectively, 83.8 and 74.8%. Our experience with LT in patients with PSC demonstrated good patient and graft survival results. Most deaths were due to common factors in patients undergoing LT.

Primary sclerosing cholangitis-A long night's journey into day.

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Inflammatory conditions play a role in recurrence of PSC after liver transplantation: An international multicentre study

Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries. In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n= 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29-10.11) years post-LT. In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5-5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08-2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC. An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se. Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC. Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC.

S2763 Post-Transplant Lymphoproliferative Disorder Presenting as an Isolated Pre-Pouch Ileal Ulcer in a Liver Transplant Patient With Crohn’s Disease

Introduction: Post-transplant lymphoproliferative disorder (PTLD) can occur in solid organ and hematopoietic cell transplant recipients in the setting of chronic immunosuppression. It often results from Epstein-Barr virus (EBV) affected B-cell propagation. We present a case of PTLD in a liver transplant (LT) patient with Crohn’s disease (CD) on biologic therapy. Case Description/Methods: A 67-year-old male with primary sclerosing cholangitis (PSC) cirrhosis status post living donor LT in 2001 on tacrolimus, multiple skin cancers, recurrent PSC after transplant and pan-ulcerative colitis on sulfasalazine underwent total proctocolectomy with ileo-anal anastomosis in 2013 to 2014 for colonic dysplasia. In 2019, he was diagnosed with moderate-to-severe CD of the J-pouch and pre-pouch ileum, up to 50cm from the entry site. Vedolizumab (VDZ), an α4β7 integrin monoclonal antibody, was initiated with steroid-free clinical response on every four week dosing. Repeat pouchoscopy on VDZ showed pre-pouch ileitis up to 30cm and a large, isolated ulcer in the pre-pouch ileum, 10cm proximal to the ileitis (Figure). Biopsies revealed B-cell lymphoma, consistent with PTLD. Negative EBV-encoded RNA (EBER) in-situ hybridization suggested that this diagnosis was unrelated to EBV exposure. Positron emission tomography (PET) scan did not identify distant disease activity, and bone marrow biopsy was unremarkable. VDZ was stopped due to loss of response, budesonide resumed and R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was subsequently initiated. Follow-up pouchoscopy showed lymphoma regression but persistent CD activity. Discussion: PTLD typically presents as extra-nodal masses involving the central nervous system, lungs, gastrointestinal tract, liver, skin or allograft within one year of transplant. Immunosuppression reduction is the cornerstone of management; however, more aggressive cases, as in our patient, require systemic therapy. This case highlights a unique presentation of PTLD as an isolated ileal ulcer in a CD patient 19 years post-LT. Interestingly, the ulcer did not appear endoscopically distinct from CD-related ulceration. Furthermore, while malignancy is a potential risk of certain treatments for inflammatory bowel disease (IBD), our patient had never received thiopurines or anti-tumor necrosis factor (TNF) agents, and VDZ has not been associated with an increased risk of B-cell lymphoma. He is currently stable on low dose tacrolimus and budesonide.Figure 1.: Isolated pre-pouch ileal ulcer.

S3212 Very Late Hepatic Artery Thrombosis After Orthotopic Liver Transplantation

Introduction: Hepatic artery thrombosis (HAT) is a serious complication after orthotopic liver transplantation (OLT) and is the most common vascular complication. It is often categorized into early HAT which is defined as occurring < 30 days after liver transplantation & late HAT defined as occurring > 30 days post transplantation. The etiology of HAT is often related to surgical factors, such as vessel kinking, anastomotic stenosis, and intimal dissection, but can factors such as hypercoagulability, elderly donors, and rejection episodes can contribute. Symptoms can often be vague with common complaints being abdominal pain, fever, nausea, & emesis. Case Description/Methods: A 68-year-old male with OLT (20 years prior to presentation) for primary sclerosing cholangitis (PSC), ulcerative colitis presented with 1 month history of nausea, emesis, and weakness. He was afebrile & hemodynamically stable. On physical exam, abdomen was soft, nontender, nondistended, and patient was jaundice. Laboratory data was notable for a two-month elevation of alkaline phosphatase, ALT, AST, direct bilirubin. An ultrasound of the liver with doppler evaluation was obtained that demonstrated an absence of flow in the left and right hepatic arteries within the liver. A computed tomography angiography (CTA) of the abdomen was obtained that confirmed these findings (Figure 1). Due to the history of PSC, a magnetic resonance cholangiopancreatography was obtained that showed no biliary dilation or evidence of recurrent PSC. A liver biopsy demonstrated paucicellular ductopenia with cholestasis consistent with chronic arterial insufficiency and no significant fibrosis. Transplant surgery and interventional radiology were consulted for potential recanalization. However, due to prolonged elevations in liver enzymes >4 weeks, both teams determined that recanalization would likely provide no benefit yet held greater risk. Discussion: This case highlights an uncommon, very late presentation of HAT. In the literature, late HAT has been described in the order of months, not years as it was in this case. It is usually associated with a less fulminant presentation and a milder course, in comparison to cases of HAT that present earlier in the post-transplant course. This case highlights the importance of considering HAT as a diagnosis in a patient with history of OLT who presents with abdominal pain, nausea, and emesis.Figure 1.: Focal filling defect in the hepatic artery seen in this venous phase CTA.

Allograft liver failure awaiting liver transplantation in Japan.

Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan. Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test. The median period from the previous LT to listing for re-LT was 1548days (range, 4-8449days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure. Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.

Good Outcome of Living Donor Liver Transplant in Primary Sclerosing Cholangitis- An Experience From North India

Primary sclerosing cholangitis (PSC) is a cholestatic disorder wherein liver transplant is the definitive treatment for advance stages. However, recurrence of PSC after liver transplant is of concern which can leads to graft failure and may require retransplant. There is limited data on outcomes of living donor liver transplant (LDLT) in PSC. Also, in LDLT as donors are related there is possibility of disease recurrence. So, we conducted this retrospective study to analyse the outcomes of LDLT in PSC at a tertiary liver transplant centre in north India. Methods: We conducted a retrospective analysis of 3213 transplant recipients who underwent LDLT from January 2006 to May 2021. Of these 26 (0.80%) patients has PSC as indication for liver transplantation (PSC=24, PSC/AIH overlaP=2). Data analysis was done to look for baseline demographics, clinical details, transplant outcomes, PSC recurrence and survival. Results: Mean age of study group was 42(±13.8) years and 19 (73.1%) were males. All patients had decompensated cirrhosis at time of transplant. Mean CTP score and MELD score were 9.5(±1.8) and 18.9(±7.1) respectively. 16 patients received modified right lobe graft, 7 extended right lobe graft and 5 patients received left lateral graft. Average graft weight and GRWR were 633.5(IQR 473.5-633.5) grams and 1.23(SD±0.42) respectively. Most common biliary anastomosis was hepaticojejunostomy, done in 19(73.1%) while duct to duct anastomosis was performed in 7(26.9%) patients. Median follow- up was 96(36-123) months. One patient had ulcerative colitis and none had cholangiocarcinoma. Two (7.7%) patients had bile leak during early post-transplant period. Three (11.1%) patients developed graft rejection and managed successfully with steroid pulses. Three patients died during early post-transplant period while 7 deaths occurred during long term follow-up including one death due to COVID-19. Five (19.2%) patients had recurrence of PSC of which 2 patients lost their grafts including one after retransplantation. The overall 1 year and 5-year survival rates were 88.5% and 75% respectively. Conclusion: LDLT can be performed in PSC with good long-term outcomes with a risk of PSC recurrence in about 1/5th patients.

Posttransplant immune-mediated cholangiopathies.

Liver transplantation (LT) is the treatment of end-stage chronic liver diseases, mainly decompensated cirrhosis and hepatocellular carcinoma. Biliary complications can be schematically classified into macroscopic versus microscopic lesions. Immune-related cholangiopathies include rejection, graft-versus-host disease (GVHD) and recurrence of pre-LT auto-immune biliary diseases, i.e. primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Here, we review the various types of posttransplant immune-related cholangiopathies, and discuss their clinical implications, especially diagnostic issues. Recurrence of PBC and PSC after LT is increasingly well described in large cohorts and long-term follow-up. In this setting, the preventive effect of ursodeoxycholic acid on PBC recurrence, as well as the deleterious role of tacrolimus are now well documented. In addition, the significant negative impact of recurrent PBC on survival after LT has recently been demonstrated. With respect to rejection-associated biliary injury, a growing body of evidence is emerging on the role of anti-HLA antibody-mediated rejection. Immune-mediated cholangiopathies occurring after LT can be divided in two main nosologic groups: biliary lesions due to recurrence of PBC or PSC, or in the context of rejection, either acute or chronic, T-cell- or antibody-mediated. GVHD is very rare. Final diagnosis is strongly based on clinical context (indication for LT, delay since transplantation, biological abnormalities, imaging) but also and to an even greater extent on biopsy of liver graft. Clinico-pathological discussions are recommended, hearing in mind that diseases can be intertwined.

CAUGHT BY CONFUSA: A RARE CASE OF WEISELLA CONFUSA IN A LIVER TRANSPLANT PATIENT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Weisella confusa is a gram-positive bacteria typically found in gut flora. It is a rare cause of bacteremia in immunocompromised patients, especially those with malignancy. When grown in blood culture isolates, it serves as a harbinger of polymicrobial infection. It is inherently vancomycin resistant and treatment is based on susceptibility panel. In this case, we demonstrate W. confusa bacteremia in the setting of broad-spectrum antibiotic prophylaxis but no immunosuppressive therapy. CASE PRESENTATION: A 57-year-old woman with ulcerative colitis and autoimmune hepatitis and primary sclerosing cholangitis (PSC) overlap requiring liver transplant complicated by recurrent PSC was admitted for odynophagia due to a tongue lesion. She developed progressive synthetic liver dysfunction resulting in altered mental status, oliguric renal failure, and Klebsiella bacteremia with concurrent C. difficile colitis. Triple immunosuppressive therapy was halted and linezolid, aztreonam and oral vancomycin were initiated. Though she completed an antibiotic course with rapid clearance of bacteremia, prophylactic meropenem, micafungin, and oral vancomycin were administered and weekly surveillance cultures were drawn in anticipation of repeat transplant.One month later, four of four blood cultures grew W. confusa, followed by Lactobacillus rhamnosus, Enterococcus faecalis, and Candida krusei soon thereafter. Antimicrobials were escalated to amphotericin B, daptomycin, aztreonam, linezolid, and metronidazole, though she developed shock requiring multiple vasopressors. Computed tomography was obtained for source identification and demonstrated a right upper lobe pulmonary abscess and multiple hepatic abscesses. Upon discussions with the patient's family, care was withdrawn and she died soon after. DISCUSSION: W. confusa is a rare isolate from blood cultures and is generally associated with polymicrobial infections. Previous studies have shown that the majority of cases occur in the setting of malignancy, though there has been one other documented case in a liver transplant patient. In addition, a study conducted in pediatric liver transplant patients demonstrated Weisella isolates in stool samples, reflecting increased gut colonization with this organism. It is a naturally vancomycin resistant organism and misidentification as Lactobacillus by traditional speciation methods often results in inappropriate therapy. Here we demonstrate a case of Weisella bacteremia likely secondary to gut translocation. Given its natural vancomycin resistance, it is likely that prophylactic oral vancomycin for C. difficile resulted in W. confusa overgrowth and facilitated her decompensation via pre-existing defects to the gut mucosal barrier from ulcerative colitis. CONCLUSIONS: W. confusa should be considered an opportunistic bacteria warranting infectious disease specialist consultation to assist in management. REFERENCE #1: 1. Kamboj, K., Vasquez, A., & Balada-Llasat, J. M. (2015). Identification and significance of Weissella species infections. Frontiers in microbiology, 6, 1204. https://doi.org/10.3389/fmicb.2015.012042. Kumar, A., Augustine, D., Sudhindran, S., et. al. (2011). Weisella confusa: a rare cause of vancomycin-resistant Gram-positive bacteremia. Journal of Medical Microbiology, 60(10), 1538-41.3. Spiegelhauer, M. R., Yusibova, M., Rasmussen, I., Fuglsang, K. A., Thomsen, K., & Andersen, L. P. (2020). A case report of polymicrobial bacteremia with Weissella confusa and comparison of previous treatment for successful recovery with a review of the literature. Access microbiology, 2(5), acmi000119. https://doi.org/10.1099/acmi.0.0001194. Green, M., Barbadora, K., & Michaels, M. (1991). Recovery of vancomycin-resistant gram-positive cocci from pediatric liver transplant recipients. Journal of clinical microbiology, 29(11), 2503–2506. https://doi.org/10.1128/JCM.29.11.2503-2506.19915. Salimnia, H., Alangaden, G. J., Bharadwaj, R., Painter, T. M., Chandrasekar, P. H., & Fairfax, M. R. (2011). Weissella confusa: an unexpected cause of vancomycin-resistant gram-positive bacteremia in immunocompromised hosts. Transplant infectious disease : an official journal of the Transplantation Society, 13(3), 294–298. https://doi.org/10.1111/j.1399-3062.2010.00586.x6. Fairfax, M. R., Lephart, P. R., & Salimnia, H. (2014). Weissella confusa: problems with identification of an opportunistic pathogen that has been found in fermented foods and proposed as a probiotic. Frontiers in microbiology, 5, 254. https://doi.org/10.3389/fmicb.2014.00254 DISCLOSURES: No relevant relationships by Samuel Chung, source=Web Response No relevant relationships by Ashwin Kelkar, source=Web Response No relevant relationships by Joseph Mailman, source=Web Response

Recurrence of primary sclerosing cholangitis after liver transplantation – analysing the European Liver Transplant Registry and beyond

SummaryLiver 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.

Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions.

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 of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.

Autologous Hematopoietic Stem Cell Transplantation for Liver Transplant Recipients With Recurrent Primary Sclerosing Cholangitis: A Pilot Study.

Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance. Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection, and cryopreserved. Immunoablation using busulfan, cyclophosphamide, and rabbit antithymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic, and clinical evidence of rejection while off immunosuppression at 2 y post-aHSCT. Two of the 5 patients achieved operational tolerance with no clinical or histologic evidence of PSC progression or allorejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now >3 y after aHSCT. A fourth patient was weaned off immunosuppression but died 212 d after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T-cell clones, loss of autoantibodies, and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors. Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed render this specific protocol unsuitable for clinical adoption.