Inflammatory Bowel Disease In Primary Sclerosing Cholangitis Research Articles

Vancomycin may be an effective attempt in primary sclerosing cholangitis: antibiotic or immunomodulator

Primary Sclerosing Cholangitis(PSC) is a rare, chronic liver disease characterized by bile duct inflammation and concentric fibrogenesis. To date, there has been no evidence that any drug therapy can alter the natural course of this disease. PSC is often concomitant with inflammatory bowel disease(IBD), but the pathogenesis remains unclear. Oral antibiotics have been shown to improve PSC and concomitant IBD, and vancomycin is the most widely used. Therefore, this paper reviews literatures on the application of vancomycin in PSC, aiming to explore therapeutic approaches for PSC that target other pathophysiological pathways.

Long-term Outcomes Following Colectomy and Liver Transplantation for Inflammatory Bowel Disease with Primary Sclerosing Cholangitis.

To investigate the long-term outcomes of patients with combined primary sclerosing cholangitis/inflammatory bowel disease (PSC-IBD) undergoing both liver transplantation (LT) and total abdominal colectomy (TAC). The fraction of patients with PSC-IBD that require both LT and TAC is small, thereby limiting significant conclusions regarding long-term outcomes. Adult and pediatric patients from nine centers from the US IBD Surgery Collaborative who underwent staged LT and TAC for PSC-IBD were included. Long-term outcomes, including survival, were assessed. Among 127 patients, 66 underwent TAC-before-LT, with a median time from TAC to LT of 7.9 yrs, while 61 underwent LT-before-TAC, with a median time from LT to TAC of 4.4 years. Median patient survival post TAC was significantly worse in those undergoing LT-before-TAC (16.0 yrs vs. 42.6 yrs, P=0.007), while post LT survival was not impacted by the order of TAC and LT (21.6 yrs vs. 22.0 yrs, P=0.81). Patients undergoing TAC for medically refractory disease had a higher incidence of recurrent PSC (rPSC) (P=0.02) and biliary complications (0.09) compared to those undergoing TAC for oncologic indications. Definitive TAC reconstruction with either end ileostomy or ileal-pouch anal anastomosis (IPAA) did not impact post-LT or post-TAC outcomes. Long term survival in PSC-IBD was contingent upon progression to LT and was not impacted by the need for TAC. PSC-IBD patients undergoing TAC for medically refractory disease had a higher incidence of rPSC and biliary complications. The use of IPAA in PSC-IBD was a viable alternative to end ileostomy.

Efficacy of Biologics in the Treatment of Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

This is the first systematic review and meta-analysis that aims to address the scarcity of research on the use of biological therapy in primary sclerosing cholangitis-inflammatory bowel disease (PSC-IBD) and the historical inadequacy of therapeutic options. Its purpose is to investigate this matter comprehensively and furnish guidance for clinical practice. Utilizing Embase, PubMed, Medline, and clinicaltrials.gov studies investigating the roles of biologics and antibiotics in PSC-IBD were identified. The systematic literature review encompassed articles published from inception through September 2023. Two independent reviewers assessed the articles, and methodological quality was gauged using Review Manager 5.4.2. Nine studies were included in the systematic review and meta-analysis. However, only four met the criteria for inclusion in the meta-analysis due to variability and availability of data; the remaining studies underwent descriptive analysis. Notably, infliximab, adalimumab, vedolizumab, and tofacitinib showed ineffectiveness in reducing cholestatic markers. This review underscores the limited impact of biological and small-molecule therapies on disease progression in PSC-IBD patients, signifying the need for further exploration and development of treatment modalities in this domain.

Ileal Pouch-anal Anastomosis in Primary Sclerosing Cholangitis-inflammatory Bowel Disease (PSC-IBD): Long-term Pouch and Liver Transplant Outcomes.

To compare the effect of liver transplantation (LT) on ileal pouch-anal anastomosis (IPAA) outcomes in patients with primary sclerosing cholangitis and inflammatory bowel disease (PSC-IBD). Patients with PSC-IBD may require both IPAA for colitis and LT for PSC. Patients with PSC-IBD from out institutional pouch registry (1985-2022) were divided according to LT status and timing of LT (before and after IPAA) and their outcomes analyzed. A total of 160 patients were included: 112 (70%) nontransplanted at last follow-up; 48 (30%) transplanted, of which 23 (14%) before IPAA and 25 (16%) after. Nontransplanted patients at IPAA had more laparoscopic procedures [37 (46%) vs 8 (18%), P =0.002] and less blood loss (median 250 vs 400mL, P =0.006). Morbidity and mortality at 90 days were similar. Chronic pouchitis was higher in transplanted compared with nontransplanted patients [32 (67%) vs 51 (45.5%), P =0.03], but nontransplanted patients had a higher rate of chronic antibiotic refractory pouchitis. Overall survival was similar, but nontransplanted patients had more PSC-related deaths (12.5% vs 2%, P =0.002). Pouch survival at 10 years was 90% for nontransplanted patients and 100% for transplanted patients (log-rank P =0.052). Timing of LT had no impact on chronic pouchitis, pouch failure, or overall survival. PSC recurrence was 6% at 10 years. For transplanted patients, graft survival was similar regardless of IPAA timing. In patients with PSC-IBD and IPAA, LT is linked to an increased pouchitis rate but does not affect overall and pouch survival. Timing of LT does not influence short-term and long-term pouch outcomes.

Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta-analysis.

Previous studies have established an association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The disease burden of IBD in PSC patients was not well estimated. The study aimed to quantify the pooled prevalence of IBD in PSC and to investigate whether subtypes of PSC and sex influence the prevalence of IBD. PubMed, Embase, and Web of Science were searched through November 2021 for studies reporting data on IBD among PSC patients. The outcomes were the prevalence of IBD in patients with PSC, as well as the association (odds ratio [OR]) of IBD in PSC according to subtype and sex. Based on the analysis of 25 studies, the prevalence of IBD in patients with PSC was 71.1% (95% CI 68.2-75.1%), most commonly in UC (55.9%, 95% CI 52.5-59.3%). The pooled prevalence of IBD was 76.9% in Australia (95% CI 71.2-82.6%, 1 study), 75.9% (95% CI 69.5-82.3%, 4 studies) in North America, 70.9% (95% CI 65.8-76.0%, 17 studies) in Europe and 67.0% (95% CI 57.9-76.0%, 2 studies) in Asia. Male PSC patients had a higher prevalence of IBD (OR 1.67, 95% CI 1.52-1.83) and UC (OR 2.02, 95% CI 1.56-2.63) and a lower prevalence of CD (OR 0.77, 95% CI 0.67-0.88) than female patients. Large duct PSC patients had a higher prevalence of IBD (OR 2.57, 95% CI 2.03-3.25) and UC (OR 4.51, 95% CI 1.22-16.71) than small duct PSC patients. The study provided the first pooled estimates of the burden of IBD in patients with PSC and could be used as the basis for risk stratification of PSC patients.

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways.

BackgroundAlthough a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data.MethodsColonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration.ResultsThe colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD.ConclusionsColonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.

Clinical profile and outcome of primary sclerosing cholangitis: A single-centre experience from western India.

Primary sclerosing cholangitis (PSC), a chronic progressive cholestatic liver disease of unknown cause, is uncommon in India. The aim of this study was to define the profile and outcomes of patients with PSC in a tertiary centre from western India. A retrospective study of the prospectively maintained liver clinic database was searched for cases of PSC between January 2008 and December 2017 with minimum 6months follow up. All cases were reviewed for clinical profile, inflammatory bowel disease (IBD) co-morbidity and major endpoints like death, cholangiocarcinoma and liver transplantation (LT). We identified 28 (18 men) patients with PSC (19, 67% large-duct and 9, 33% small-duct) with a median age of 31.5years (range 7-63years) with median duration of follow up of 24months (6-125months). Six (21.4%) hadautoimmune hepatitis (AIH-PSC) overlap. Inflammatory bowel disease was seen in 12 (43%) cases, all were ulcerative colitis (UC). During follow up, seven patients (25%) developed dominant stricture or recurrent cholangitis, 11 (39%) had portal hypertension, 2 (7%) developed cholangiocarcinoma and 5 (17.8%) progressed to hepatic decompensation on follow up. Ten (35%) patients died, 5 from liver-related complications, 2 from cholangiocarcinoma, 1 each from brain hemorrhage and systemic sepsis and 1 due to unknown cause; 3 underwent liver transplantation. Revised Mayo score of patients who survived was lower than those who died (1.03 vs. 1.86, p value 0.03). PSC commonly presents in young ageand rapidly progresses to decompensation. Prevalence of IBD in PSC is lower and theproportion of small-duct PSC is higher than that observed in western populations.

Gut and Liver B Cells of Common Clonal Origin in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease.

B cells express an antigen‐specific B‐cell receptor (BCR) and may contribute to liver inflammation by recognizing shared antigens in the gut and liver. Herein, we used high‐throughput BCR sequencing of the immunoglobulin heavy chain, specifically the complementarity‐determining region 3 (CDR3), to characterize the B‐cell repertoire of freshly‐frozen paired gut and liver tissue samples from patients with primary sclerosing cholangitis (PSC) and concurrent inflammatory bowel disease (IBD) (PSC‐IBD, n = 10) and paired formalin‐fixed paraffin‐embedded (FFPE) tumor‐adjacent normal colon and liver tissue from patients with colorectal liver metastases (controls, n = 10). We observed significantly greater numbers of B cells (P < 0.01) and unique B‐cell clonotypes (P < 0.05) in gut samples compared to liver samples of patients with PSC‐IBD, whereas BCR sequences in FFPE normal gut and liver samples were nearly absent (14 ± 5 clonotypes; mean ± SD; n = 20). In PSC‐IBD, an average of 8.3% (range, 1.6%‐18.0%) of B‐cell clonotypes were found to overlap paired gut and liver samples following the exclusion of memory clonotypes reported in the blood of healthy controls. Overlapping gut and liver clonotypes showed stronger evidence of antigen‐driven activation compared to non‐overlapping clonotypes, including shorter CDR3 lengths and higher counts of somatic hypermutation (P < 0.0001). Conclusion: A proportion of gut and liver B cells originate from a common clonal origin (i.e., likely to recognize the same antigen) in patients with PSC which suggests B‐cell antigens are shared across the gut–liver axis. (Hepatology Communications 2018; 00:000‐000)

Cholestatic liver disease

Common cholestatic liver diseases are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both diseases are considered autoimmune disorders; however, the precise pathogenesis remains elusive. Patients usually show no symptoms or present with pruritus and fatigue. High alkaline phosphatase and the presence of antimitochondrial antibodies are sufficient to diagnose PBC. Ursodeoxycholic acid is approved and recommended for the treatment of PBC. The diagnosis of PSC is established by elevated alkaline phosphatase-levels and typical cholangiographic findings. Liver biopsy is not generally necessary for the diagnosis. The prevalence of inflammatory bowel disease in PSC is up to 80 %. There is no established pharmacological therapy, although Ursodeoxycholic acid is often prescribed. Endoscopic management of biliary obstructions offers clinical benefit. Liver transplantation is the definitive treatment for patients with advanced or decompensated cirrhosis.

Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease (IBD). Medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been proven to be effective in IBD. This study aimed to analyze (i) the natural history of patients with PSC with or without IBD and (ii) the long-term efficacy of biologics in patients with PSC and concomitant IBD or rheumatological disorders. This study included 92 consecutive PSC patients, 50 (54.3%) men and 42 (45.7%) women, with a mean age of 32.0±14.3 years at diagnosis and a mean follow-up duration of 103.8±86 months. Forty-nine (53.3%) patients had associated IBD (38 ulcerative colitis, 10 Crohn's disease, one indeterminate colitis). No significant differences were found between PSC patients with and without associated IBD in terms of liver transplantation, cancer, and death rates. Cholangiocarcinoma was only identified among patients with PSC alone, whereas other cancers (hepatocellular carcinoma, colorectal, and gallbladder cancer) were found only in the group with associated IBD. Five PSC patients were treated with biologic agents: three with adalimumab and one with infliximab for IBD or for rheumatoid arthritis, and one patient with rituximab for rheumatoid arthritis. Adalimumab decreased alkaline phosphatase in two of three patients after 6 and 12 months, infliximab reduced γ-glutamyltransferase after 6 and 12 months, but liver function tests tended to deteriorate thereafter. Cholangiography changes remained stable in all patients. Biologic agents may improve liver function tests in PSC patients, but may be associated with adverse events including deterioration of liver function.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disease characterized by inflammation and fibrosis that may involve the entire biliary tree. The fibrosis causes diffuse narrowing of the intrahepatic and extrahepatic bile ducts, and the resulting biliary stasis leads to secondary biliary cirrhosis and associated complications. This review addresses PSC through its epidemiology, etiopathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Figures show pouchoscopy, liver biopsy, and endoscopic retrograde cholangiopancreatography; direct peroral cholangioscopy visualization of cholangiocarcinoma; and algorithms depicting diagnosis of cholangiocarcinoma and screening for inflammatory bowel disease (IBD) in patients with PSC. Tables list characteristics of IBD in PSC, prevalence of antibodies in PSC, differential diagnosis of PSC, diagnostic approach in PSC, and risk of cancers in PSC. This review contains 6 highly rendered figures, 5 tables, and 91 references.

Mo1711 Interleukin 35 and 37 Intestinal Expression and Peripheral Synthesis by Subsets of Regulatory Cells in Patients With Inflammatory Bowel Disease

Background: Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree characterised by inflammation, fibrosis and stenoses. Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC IBD) is considered to be a distinct phenotype of IBD with a multi factorial origin where microbiota most likely have a substantial role. In our pilot study, our aim was to compare the microbiota composition in PSC and/or IBD groups with ulcerative colitis (UC) and healthy controls. Methods: Total number of 15 individuals was used in presented study: 4 control healthy samples, 4 UC patients, 4 PSC-IBD patients and 3 PSC (without IBD). Fecal microbiota composition was assesed by sequencing of variable V4 and V5 region of 16S rRNA gene on Personal Genome Machine platform (Fisher Scientific). Library preparation, template preparation and template sequencing was performed according to manufacturer's protocols. Obtained data were filtered by quality and length and processed for alpha and beta diversity analyses using QIIME software package. Results: Following significant changes in bacterial numbers were observed among tested groups: PSC versus PSC-IBD: Higher Bifidobacterium sp. (18 vs 2.71 %), Lachnospira (4.58 vs 0,68 %) and Dorea sp (5.7 vs 1.55 %) and lower Enterococcus sp. (0 vs 9.14 %), Faecallibacterium sp. (1.31 vs 4.12 %) and Prevotella/ Paraprevotella sp. (0 vs 9.71 %) numbers. PSC-IBD versus UC: Higher Bacteroides sp. (17.13 vs. 4.86 %), Enterococcus sp. (9.14 vs 0 %) and Prevotella/Paraprevotella sp. (9.71 vs 2.13 %) and lower Bifidobacterium sp (2.71 vs 12.95 %) and Faecallibacterium sp. (4.12 vs 16.4 %) numbers. The clustering of samples according to the type is stronger with the unweighted UniFrac metric than with the weighted metric, suggesting that differences in community membership (rather than community structure) discriminate better among groups. Conclusions: Members of genus Faecallibacterium and Prevotella showed highest variations with regards to PSC /PSC-IBD/UC groups comparison. Control samples showed higher species richness than patients samples. Our data suggest that microbiota composition differs among patients with PSC (without IBD), PSC IBD and UC. Presented data should be considered as preliminary, as more samples are needed for statistical analyses to support detected observations.

Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis.

To review the current literature for the specific clinical characteristics of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC). A systematical review for clinical characteristics of IBD in PSC was performed by conducting a broad search for "primary sclerosing cholangitis" in Pubmed. "Clinical characteristics" were specified into five predefined subthemes: epidemiology of IBD in PSC, characteristics of IBD in PSC (i.e., location, disease behavior), risk of colorectal cancer development, IBD recurrence and de novo disease after liver transplantation for PSC, and safety and complications after proctocolectomy with ileal pouch-anal anastomosis. Papers were selected for inclusion based on their relevance to the subthemes, and were reviewed by two independent reviewers. Only full papers relevant to PSC-IBD were included. Additionally the references of recent reviews for PSC (< 5 years old) were scrutinized for relevant articles. Initial literature search for PSC yielded 4704 results. After careful review 65 papers, comprising a total of 11406 PSC-IBD patients, were selected and divided according to subtheme. Four manuscripts overlapped and were included in two subthemes. Prevalence of IBD in PSC shows a large variance, ranging from 46.5% to 98.7% with ulcerative colitis (UC) being the most common type (> 75%). The highest IBD rates in PSC are found in papers reviewing both endoscopic and histological data for IBD diagnosis. Although IBD in PSC is found to be a quiescent disease, pancolitis occurs often, with rates varying from 35% to 95%. Both backwash ileitis and rectal sparing are observed infrequently. The development of dysplasia or colorectal carcinoma is increased in PSC-IBD; the cumulative 10 years risk varying between 0% and 11%. Exacerbation of IBD is common after liver transplantation for PSC and de novo disease is seen in 1.3% to 31.3% of PSC-IBD patients. The risk for development of pouchitis in PSC-IBD is found to be significant, affecting 13.8% to 90% of the patients after proctocolectomy with ileo anal-pouch anastomosis. IBD in primary sclerosing cholangitis represents a distinct phenotype that differs from UC and Crohn's disease and therefore requires specialized management.

Prognosis of primary sclerosing cholangitis in israel is independent of coexisting inflammatory bowel Disease.

Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8 ± 15.4 years and duration of follow-up was 7.93 ± 6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC–IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3 ± 1.4 years and mean transplant-free survival was 23.5 ± 1.6 years. Cox proportional hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 (p = 0.004) and 2.58 (p = 0.046), respectively]. Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD.

PWE-152 Primary Sclerosing Cholangitis-inflammatory Bowel Disease Is Associated With An Increased Frequency Of Post-transplant Colonic Lymphoma

IntroductionPost-transplant lymphoproliferative disease (PTLD) is a recognised complication of liver transplantation (LT). Although small intestinal involvement is common, factors predisposing to colonic disease are not well characterised.MethodsA case-note review of...

Inflammatory Bowel Disease in Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) has a well-established association with inflammatory bowel disease (IBD) and may represent a distinctive phenotype. It is unknown whether changes in the clinical and endoscopic presentation of newly diagnosed IBD among patients with PSC might have occurred over time. Initial clinical and endoscopic presentations of IBD in PSC were studied for 2 different time periods: 1993 to 1997 (early cohort) compared with 2003 to 2007 (recent cohort). The baseline characteristics were similar in the 57 early cohort and 72 recent cohort patients. Compared with the recent cohort, alkaline phosphatase concentrations were higher in the early cohort (7.1 versus 2.6 × upper limit of normal, P = 0.0001). PSC was diagnosed before IBD in the recent cohort compared with the early cohort (50% versus 35%, P = 0.0009). The initial clinical and endoscopic presentations of IBD were similar in the 2 cohorts. The majority of patients had mild pancolitis, whereas rectal sparing and backwash ileitis were detected in one third and one fourth of patients, respectively. In addition, no differences in IBD outcomes or PSC characteristics were revealed. Immunomodulators and biological treatments were more commonly used in the recent cohort when compared with the early cohort (90% versus 56%, P = 0.03, and 13% versus 4%, P = 0.08, respectively). IBD in PSC has unique characteristics, and the clinical features of this unique presentation have remained stable over time. A shift in the timing of diagnosis of the 2 diseases has occurred in recent years, with PSC being more often diagnosed first.

Inflammatory bowel disease in patients with primary sclerosing cholangitis: Clinical characterization in liver transplanted and nontransplanted patients

Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) seems to differ from IBD without PSC, but a systematic, prospective study of IBD in PSC has until now not been reported. We aimed to describe the clinical, endoscopic, and histopathologic features of PSC-IBD in liver-transplanted and nontransplanted patients. PSC patients (n = 184) were included and underwent ileocolonoscopy with assessment of segmental histopathology. A total of 155 (84%) patients had IBD, of whom 39 (25%) had undergone colectomy. The patients with an intact colon and complete tissue samples (n = 110) were further investigated. Forty-two (38%) patients had undergone liver transplantation. The median IBD duration was 11 (range, 0-50) years. The majority (65%) had no or sparse IBD symptoms. Inflammatory findings were more frequent by histology than by endoscopy (89% versus 47%, P < 0.001). Histopathological signs of inflammation involved the right colon in 86% of patients and were purely right-sided in 23%. The findings of inflammation were higher in the right compared to the left colon (P < 0.001), but the general inflammatory activity was low. Backwash ileitis was demonstrated in 20% (17/87) of patients and rectal sparing in 65% (70/107). The liver-transplanted patients had lower clinical (P = 0.035) and histological (P = 0.013) IBD activity than the nontransplanted group. PSC-IBD may represent a distinct entity of colitis in which low endoscopic activity may mask an active histologic inflammation that possibly contributes to an increased risk of malignancy. Circumstances related to liver transplantation seem to act favorably on colonic inflammation in PSC.