Presence Of Primary Sclerosing Cholangitis Research Articles

The impact of primary sclerosing cholangitis or inflammatory bowel disease on cholangiocarcinoma phenotype, therapy, and survival.

Background and AimPrimary sclerosing cholangitis (PSC), with or without inflammatory bowel disease (IBD), confers the risk of cholangiocarcinoma. Isolated IBD may be an independent risk factor for cholangiocarcinoma. We sought to compare cholangiocarcinoma phenotype and outcomes between patients with PSC, IBD, and neither.MethodsPatients with malignancy were separated into cohorts by the presence of PSC and IBD. Data regarding demographics, clinical presentation, therapeutic regimens, and survival were collected. Statistical analysis was carried out using GraphPad and R‐Studio.ResultsOf 946 patients, 22 had PSC, and 18 had isolated IBD. PSC and IBD patients were younger than controls (P < 0.001, P = 0.01). Cholangiocarcinoma prevalence was estimated at 0.01% for IBD patients, 0.6% for PSC patients, and 0.002% for all other patients. All cohorts most often presented at stage 4. PSC patients presented more often at stage 3 (P = 0.04) and with perihilar disease (P = 0.001). Patients with PSC or IBD received less chemotherapy (P = 0.004, 0.01). Median overall survivals were 15 months (PSC), 11 months (IBD), and 10 months (controls) (P = 0.79). Patients with intrahepatic tumors had longer survival (P < 0.001). Curative intent resection improved survival in all cohorts (P < 0.001). Multivariate regression identified resection as a predictor of improved survival. Extrahepatic, perihilar, gallbladder, and unspecified biliary tumors were predictors of death.ConclusionsCholangiocarcinoma presents at a late stage and portends dismal survival regardless of PSC or IBD status. Survival was dependent on tumor location and surgical resection. These data suggest that efforts should focus on developing protocols that are able to detect and treat cholangiocarcinoma in high‐risk populations (PSC) at an early stage.

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies.

Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal neoplasia than patients with IBD, but not PSC. Stratification by IBD type show that the presence of PSC is associated with an increased risk for the development of colorectal neoplasia in patients with UC; however, there is a nonsignificant association in CD patients. When the risk of colorectal cancer alone is analysed, the conclusion does not change.

The presence of primary sclerosing cholangitis in patients with ileal pouch anal- anastomosis is associated with an additional risk for vitamin D deficiency.

Objective: Vitamin D deficiency is common in patients with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Whether vitamin D levels are further lowered in patients with concomitant IPAA and primary sclerosing cholangitis (PSC) is not known. The aim of this study was to evaluate the presence of PSC as a risk factor for vitamin D deficiency in patients with UC and IPAA.Methods: In this case control study, 74 patients with concurrent IPAA and PSC were included in the study group, and 79 patients with IPAA, but without PSC, served as controls. Forty-four variables were analyzed. Univariate analysis and multivariate analysis with stepwise logistic regression were performed.Results: A total 153 eligible patients were included, with 74 (48.4%) in the study group and 79 (51.6%) in the control group. Vitamin D level in the study group was 18.9 ± 1.4 ng/dL compared with 30.3 ± 1.7 ng/d in the control group (P = 0.011). Vitamin D deficiency (≤ 20 ng/dL) was present in 65 (42.5%) patients. PSC occurred in 49 (75.4%) of the 65 patients with vitamin D deficiency. In the multivariate analysis, only the presence of PSC (odds ratio [OR]: 7.56; 95% confidence interval [CI]: 2.39–24.08; P = 0.001) and vitamin D supplementation (OR: 2.58; 95% CI: 1.57–9.19; P = 0.018) remained associated with vitamin D deficiency.Conclusion: The presence of PSC was found to be an independent risk factor for vitamin D deficiency in UC patients with IPAA. These patients should be routinely screened and closely monitored for vitamin D deficiency.

Primary sclerosing cholangitis and the risk of colon neoplasia in patients with Crohn's colitis.

Background and aim: Crohn’s colitis (CC) is associated with primary sclerosing cholangitis (PSC). However the risk of colon cancer or dysplasia in CC and PSC is unclear. Our aim was to study the risk of colon neoplasia in CC in patients with and without PSC.Methods: This is a nested, case-control cohort study of all patients diagnosed with concurrent CC and PSC, seen at the Cleveland Clinic between 1985 and 2012. Forty-three patients with both CC and PSC were compared with a random sample of 159 CC controls without PSC during the same period.Results: Seven (16.3%) of 43 CC patients with PSC developed colon cancer or dysplasia, compared with 22 (13.8%) of 159 controls (P = 0.98). Of seven colon neoplasia cases in the PSC group, 100% occurred proximal to the splenic flexure, compared with 50% (11/22) cases of colon neoplasia in controls occurring in the proximal colon (P = 0.001). Based on Cox regression analysis, male gender independently increased the risk of neoplasia [hazard ratio (HR) = 2.68; 95% confidence interval (CI) 1.30–5.54; P = 0.008], as did age at CC diagnosis (HR = 1.29; 95% CI 1.14–1.47; P < 0.001), while the use of azathioprine/6-mercaptopurine was protective (HR = 0.30; 95% CI 0.13–0.70; P = 0.005). The presence of PSC did not increase the risk for colon neoplasia (HR = 0.45; 95% CI 0.18–1.13; P = 0.09).Conclusions: CC patients with PSC appear not to be at increased risk of developing colon neoplasia. Among patients in our cohort with colon neoplasia and concurrent PSC, the neoplasia occurred in the proximal colon in all cases.

Hepatobiliary manifestations of ulcerative colitis: an example of gut-liver crosstalk.

The interaction between inflammatory bowel disease (IBD) and hepatobiliary manifestations represents a classic example of liver–gut crosstalk. The importance of liver–gut crosstalk in IBD is demonstrated in the pathogenesis and outcome of primary sclerosing cholangitis (PSC) in IBD patients. Immunoglobulin G4-associated cholangitis (IAC), which has recently been described in UC patients, may also illustrate the significance of gut–liver interaction in these patients. Presence of these hepatobiliary manifestations influences the outcome of associated IBD, in particular ulcerative colitis (UC), and vice versa. The pathogenesis of PSC is postulated to be related to gut inflammation in IBD that results in inflammation in the portal tracts (the ‘leaky gut’). Enterohepatic circulation of lymphocytes from the gut to the liver is also of potential relevance to PSC pathogenesis and outcomes. The presence of PSC and gut inflammation in IBD influences the course and outcomes of both diseases. Further research is required, to understand the mutual effect of liver–gut crosstalk in the outcomes of UC patients, and highlights the importance of an interdisciplinary approach—involving gastroenterologists, hepatologists, advanced endoscopists and liver transplant surgeons—in the management of these patients.

Mortality in inflammatory bowel disease patients under 65 years of age

Objective. To assess mortality in inflammatory bowel disease (IBD) patients under 65 years of age and to identify the factors related to death in this age group. Methods. We studied 2570 IBD patients who were diagnosed as having disease before 65 years of age and attended a single tertiary referral center area between 1983 and 2012. Follow-up was censored at 65 years. The causes of death were determined from death certificates obtained from the Irish registry office of births, marriages and deaths. Observed all-cause survival was compared with expected survival of persons of the same age and sex in the general population. Expected survival was obtained from national life tables produced by the central statistics office. Survival estimates were calculated for disease type, disease site, gender, the presence of primary sclerosing cholangitis (PSC), immunomodulator use, biologic therapy use, presence of fistulating disease and prior surgery. Results. Fifty-two deaths were reported in the population younger than 65 years, of which 41 were IBD related. We found little difference in survival in the first 25 years of follow-up, but relative survival decreased in both the Crohn's disease (CD) and ulcerative colitis (UC) cohort thereafter, so that 30-year mortality was excessive in both groups. An adjusted multivariate regression analysis of patients with CD identified PSC as the only predictor of premature mortality (p = 0.003). PSC was also identified as the only independent predictor of mortality in UC patients (p = 0.03). Conclusions. The presence of PSC poses the greatest risk for mortality in both UC and CD.

The Presence of Primary Sclerosing Cholangitis Is Protective for Ileal Pouch from Crohnʼs Disease

Primary sclerosing cholangitis (PSC) has been shown to increase the risk for chronic pouchitis. However, the association between PSC and Crohn's disease (CD) of the pouch has not been studied. Consecutive inflammatory bowel disease patients undergoing proctocolectomy with ileal pouch-anal anastomosis in our Pouchitis Registry from 2002 to 2012 were studied. Cases consisted of patients with CD of the pouch. Both univariable and multivariable analyses were performed. A total of 1425 patients met the inclusion criteria, including 265 (18.6%) with CD of the pouch and 78 (5.5%) with PSC. In the whole cohort, 799 patients (56.1%) were male and the mean ages at the time of diagnosis of inflammatory bowel disease and at pouch surgery were 25.5 ± 12.3 years and 35.4 ± 13.9 years, respectively. Patients with PSC had a longer duration from inflammatory bowel disease diagnosis to pouch construction (P < 0.001). Fewer patients with PSC had toxic megacolon at the time of colectomy (P = 0.009), but more patients with PSC had neoplasia as the indication for colectomy (P < 0.001), concurrent autoimmune disorders (P < 0.001), and liver transplantation (P = 0.001). In the multivariate analysis, the presence of PSC was shown to be inversely associated with the risk for the development of CD of the pouch, with a hazard ratio of 0.39 (95% confidence interval: 0.16 to 0.95, P = 0.038). However, no significant difference in terms of the distribution of phenotypes of CD of the pouch between patients with and without PSC was identified (P = 0.59). The presence of PSC is inversely associated with the development of CD of the pouch.

Su1184 Impact of Ulcerative Colitis on Patient Quality of Life in a Real-World Clinical Setting

a single tertiary referral centre between 1983 and 2012. Follow up was censored at 65 years and the overall follow-up included 22,965 patient years. Causes of death were determined from death certificates obtained from the Irish registry office of births, marriages and deaths. Observed all-cause survival was compared with expected survival of persons of the same age and sex in the general population (for each year of follow-up). Expected survival (annual survival probability by single year of age) was obtained from national life tables produced by the central statistics office. Survival estimates were calculated for disease type, disease site, gender, the presence of primary sclerosing cholangitis (PSC), immunomodulator use, biologic therapy use, presence of fistulating disease and prior surgery. Results: There were 52 deaths in the under 65 year old population, of which 40 were directly or indirectly related to inflammatory bowel disease. The 20 and 40 year relative survival rate for Crohn’s disease patients was 97.7% and 77.4% respectively and for ulcerative colitis patients was 98.6% and 86.9%. An adjusted multivariate regression analysis of patients with Crohn’s disease that included age, gender, disease site, surgery, presence of PSC and medication use identified PSC as the only predictor of premature mortality (p = 0.003). PSC was also identified as the only independent predictor of mortality in ulcerative colitis patients (p = 0.03). Conclusions: 20 year survival for both Crohn’s disease and ulcerative colitis patients is similar to that of the general population, but 40 year mortality is excessive in both groups. The presence of PSC poses the greatest risk for mortality in both ulcerative colitis and Crohn’s disease.

Mo1370 Incidence and Predictors of Early Readmission in Patients With Severe Ulcerative Colitis: Results From a Tertiary Care Center

Introduction: A number of studies have assessed survival in inflammatory bowel disease patients when compared with the general population, however, none has focussed on mortality on younger patients. Aim: To assess mortality in IBD patients under 65 years relative to the normal population and identify factors related to death in this age group. Methods: We studied 2,570 IBD patients diagnosed before 65 years (mean age 32 years at diagnosis; 1265 male) attending a single tertiary referral centre between 1983 and 2012. Follow up was censored at 65 years and the overall follow-up included 22,965 patient years. Causes of death were determined from death certificates obtained from the Irish registry office of births, marriages and deaths. Observed all-cause survival was compared with expected survival of persons of the same age and sex in the general population (for each year of follow-up). Expected survival (annual survival probability by single year of age) was obtained from national life tables produced by the central statistics office. Survival estimates were calculated for disease type, disease site, gender, the presence of primary sclerosing cholangitis (PSC), immunomodulator use, biologic therapy use, presence of fistulating disease and prior surgery. Results: There were 52 deaths in the under 65 year old population, of which 40 were directly or indirectly related to inflammatory bowel disease. The 20 and 40 year relative survival rate for Crohn's disease patients was 97.7% and 77.4% respectively and for ulcerative colitis patients was 98.6% and 86.9%. An adjusted multivariate regression analysis of patients with Crohn's disease that included age, gender, disease site, surgery, presence of PSC and medication use identified PSC as the only predictor of premature mortality (p=0.003). PSC was also identified as the only independent predictor of mortality in ulcerative colitis patients (p=0.03). Conclusions: 20 year survival for both Crohn's disease and ulcerative colitis patients is similar to that of the general population, but 40 year mortality is excessive in both groups. The presence of PSC poses the greatest risk for mortality in both ulcerative colitis and Crohn's disease.

Backwash Ileitis and the Risk of Colon Neoplasia in Ulcerative Colitis Patients Undergoing Restorative Proctocolectomy

The significance of backwash ileitis (BWI) relating to the risk of colon neoplasia in ulcerative colitis (UC) patients is controversial. We investigated the association between BWI and the presence of colon neoplasia in the colectomy specimen. From 4,198 UC patients in a prospectively maintained pouch database from 1983 to 2011, patients with extensive colitis and BWI (n = 178) in proctocolectomy were compared with 537 controls [extensive colitis (n = 385) and left-sided colitis (n = 152)] without ileal inflammation. Colon neoplasia (colon dysplasia and/or colon cancer) was seen in 32 (18 %) patients with BWI in contrast to 45 (11.7 %) with extensive colitis and 13 (8.6 %) with left-sided colitis alone (p = 0.03). Of those with BWI, colon cancer was seen in 10 patients (5.6 %), while low grade and high grade dysplasia were seen in 7 (3.9 %) and 15 (8.4 %) patients respectively. On multivariate analysis, the presence of BWI with extensive colitis [odds ratio (OR) = 3.53; 95 % confidence interval (CI) 1.01-12.30, p = 0.04], presence of primary sclerosing cholangitis (PSC) (OR = 5.79, 95 % CI 1.92-17.40, p = 0.002) and moderate to severe disease activity at UC diagnosis (OR 4.29, 95 % CI 2.06-9.01, p < 0.001) were associated with an increased risk for identifying any colon neoplasia. For colon cancer, the presence of PSC (OR = 11.30, 95 % CI 1.54-80.9, p = 0.01) was the only factor independently associated with an increased risk. The presence of BWI with extensive colitis was associated with the risk of identifying colon neoplasia but not cancer alone in the proctocolectomy specimen.

The Presence of Primary Sclerosing Cholangitis is Associated with a Lower Risk for Crohnʼs Disease of the Ileal Pouch

Purpose: Concomitant primary sclerosing cholangitis (PSC) was shown to increase the risk for chronic pouchitis. However, the association between concomitant PSC and Crohn's disease (CD) of the ileal pouch has NOT been studied. Clinically, we seldom encountered patients who had both CD of the pouch and PSC. The aim of this study was to investigate the association between PSC and occurrence of CD of the pouch. Methods: Consecutive inflammatory bowel disease (IBD) patients undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) seen in our subspecialty Pouchitis Clinic from 2002-2011 were studied. Cases consisted of patients with CD of the ileal pouch. The association between the presence of concomitant PSC and CD of the ileal pouch was evaluated. Results: A total of 1,289 patients met the inclusion criteria, including 246 (19.1%) with CD of the ileal pouch, diagnosed based on a combined assessment of clinical presentation, endoscopy, histology, radiography and examination under anesthesia. Seven-hundred eleven patients (55.2%) were male. The mean age at the time of diagnosis of IBD and at pouch surgery was 25.4±12.3 years and 35.4±13.9 years, respectively. Preoperative diagnosis of IBD was ulcerative colitis in 1190 (92.5%) patients, indeterminate colitis in 76 (5.9%) and Crohn's disease in 20 (1.6%). There were 67 PSC patients (5.2%). Concomitant PSC was significantly less common in patients with CD of the ileal pouch (N=62, 5.9%) than those without (N=5, 2.0%) (P=0.013). In the multivariate analysis, the presence of concomitant PSC was shown be negatively associated with the risk for the development of CD of the ileal pouch, with an odds ratio (OR) of 0.375 (95% confidence interval [CI]: 0.128-0.872, P=0.020). However, no significant difference in terms of the distribution of phenotypes of CD of the ileal pouch between patients with and without concomitant PSC was identified (P=0.369). Conclusion: The presence of PSC is inversely associated with the development of CD of the ileal pouch, in contrast to the consistent finding in the literature that PSC is associated with an increased risk for chronic pouchitis. The opposite impact of the liver disease on the two chronic inflammatory conditions of the pouch suggests that CD of the pouch and chronic pouchitis may have different etiopathogenetic pathways.Table 1: Risk factors associated with CD of the ileal pouch: multivariate logistic regression analysisTable 2: PSC and phenotypes of CD of the ileal pouch

Risk for Colorectal Neoplasia in Patients With Colonic Crohn's Disease and Concomitant Primary Sclerosing Cholangitis

Patients with ulcerative colitis and concomitant primary sclerosing cholangitis (PSC) have a greater risk of developing colorectal dysplasia or invasive cancer than patients with only ulcerative colitis. Therefore, annual surveillance colonoscopies are recommended. We investigated whether primary sclerosing cholangitis is also a risk factor for colorectal dysplasia or cancer in patients with Crohn's disease of the colon. We performed a retrospective review of data from a tertiary care hospital on 166 patients with PSC and inflammatory bowel disease; 120 had concomitant ulcerative colitis, 35 had Crohn's disease, and 11 had indeterminate colitis. The controls comprised 114 patients with colonic involvement of Crohn's disease and 102 patients with ulcerative colitis. The main outcome parameter was the development of colorectal cancer or intraepithelial neoplasia. Only 1 patient with colonic Crohn's disease and concomitant PSC developed dysplasia in an adenomatous polyp during a median follow-up of 10 years (range, 7-16 years). In contrast, 2 cancers and 8 cases of colorectal dysplasia were diagnosed in patients with ulcerative colitis and PSC during a median follow up of 11 years (range, 8-16 years); the crude annual incidence of dysplasia or colorectal cancer was 1 in 150 patients with ulcerative colitis. Among patients with colonic Crohn's disease without PSC, 2 developed colorectal cancer during follow-up. The presence of PSC did not increase the risk of developing colorectal dysplasia in patients with Crohn's disease (P = 1.00). PSC does not seem to increase the risk for dysplasia of the colon in patients with colonic Crohn's disease.

Risk Factors for Abnormal Liver Function Tests in Patients With Ileal Pouch–Anal Anastomosis for Underlying Inflammatory Bowel Disease

Liver involvement is common in patients with inflammatory bowel disease (IBD). However, the frequency and the significance of liver function test (LFT) abnormalities in patients with ileal pouch-anal anastomosis (IPAA) for underlying IBD have not been studied. The aim of this study was to evaluate the prevalence and to identify risk factors for abnormal LFTs in patients with IPAA and underlying IBD. All patients were identified from our prospectively maintained Pouchitis Database between 2002 and 2008. Abnormal LFTs were classified as the following: (i) any abnormal elevation of transaminases, and/or alkaline phosphatase (ALP), and/or bilirubin; (ii) hepatitis, if there was more than twice the elevation of transaminases; and (iii) cholestatic, if there was more than 1.5 times elevation of ALP. Clinical, endoscopic, and histological variables were assessed using Cox proportional hazard models for evaluating risk for abnormal LFTs. A total of 545 IPAA patients with underlying IBD were identified from the database, of which 373 patients who had LFTs done after their pouch surgery were included. This included 346 patients with ulcerative colitis, 25 with indeterminate colitis, and 2 with Crohn's colitis before surgery. Their mean age was 45.9+/-13.8 years. A total of 65 patients (17.4%) (40 men, 25 women, median age: 47 years) had abnormal LFTs. Of the patients, 52 (13.9%) had abnormal transaminases, whereas 15 (4%) were classified as having hepatitis. Thirty-five (9.4%) patients had an abnormal ALP level, with 18 (4.8%) classified as cholestatic. The most common cause of an abnormal LFT was transient elevation in 32 (49.2%) patients, followed by fatty liver (fatty change on imaging with body mass index (BMI) > or =25 kg/m(2) in the absence of other causes, including alcohol abuse and drug-induced hepatitis) in 10 (15.4%), drug-induced abnormal LFTs in 7 (10.7%), and chronic hepatitis B or C in 6 (9.2%). Primary sclerosing cholangitis (PSC) was responsible for abnormal LFTs in 10 patients (15.4%). Cox proportional hazard model analysis showed that BMI (hazard ratio (HR)=1.07, 95% confidence interval (95% CI): 1.02, 1.12; P=0.003), the presence of PSC (HR=4.49, 95% CI: 1.45, 13.89; P=0.009), autoimmune disorder (HR=2.54, 95% CI: 1.09, 5.93; P=0.031), a family history of IBD (HR=2.32, 95% CI: 1.29, 4.17; P=0.005), and extensive colitis before colectomy (HR=4.59, 95% CI: 2.04, 10.33; P<0.001) predicted any abnormal LFTs. Abnormal LFTs were common in patients with IPAA in this cohort. The presence of co-existing autoimmune disorder, a family history of IBD, extensive colitis before colectomy, the presence of PSC, and a high BMI appear to be a significant risk factors for abnormal LFTs. Whether abnormal LFTs affect health-related quality of life, pouch survival, and selection of pouch-related medical therapy requires further investigation.

Primary sclerosing cholangitis in two brothers: report of a family with special emphasis on molecular HLA and MICA genotyping

Immune mechanisms play a role in the pathogenesis of primary sclerosing cholangitis (PSC), as suggested by its association with certain HLA haplotypes. Genetic predisposition is supported by its occurrence in families, but data are scarce. Our aim is to report on two brothers with PSC, and to investigate HLA and MICA alleles in this family. The clinical, biochemical, radiological, and pathological findings in two brothers with PSC as well as in their sister and parents were reviewed. Molecular genotyping of HLA class II and MICA alleles was performed in all five family members. In two brothers, p-ANCA positive PSC was found. The youngest also had ulcerative colitis, and had evolved into cirrhosis at the age of 17 years. Their mother had positive p-ANCA and mild cholestatic changes. Their father and sister were unaffected. Both brothers were homozygous for the MICA*00801 allele, and were positive for the susceptibility HLA haplotypes DR3-DQ2 and DR6-DQ6. Their unaffected father and sister both carried the protective DR4 allele. The presence of PSC in two brothers, and the distribution of HLA haplotypes and MICA alleles, adds supportive evidence for an immunogenetic origin of PSC.

Imaging and estimation of the prognostic features of primary sclerosing cholangitis by ultrasonography and MR cholangiography.

To evaluate the ability of US and MR cholangiography (MRC) to detect bile duct changes and prognostic signs of primary sclerosing cholangitis (PSC) seen at endoscopic retrograde cholangiography (ERC). In a prospective study, 9 patients with PSC underwent US, MRC, MR imaging and ERC of the bile ducts and the liver. Eight age- and sex-matched control patients were examined with MRC, MR imaging and ERC. A segmental comparison was performed to assess the ability of MRC-MR and US to reveal the accurate ductal involvement in different segments of the biliary tree and the specific criteria of poor prognostic outcome in PSC. The ability of MRC-MR to detect the presence of PSC in different patients was analysed blindly. MRC-MR depicted changes of PSC correctly in 9 patients (radiologist 1) and in 8 patients with 1 false-positive finding (radiologist 2) in the blinded analysis. In the segmental comparison, MRC missed especially bile duct dilatations. MRC was too pessimistic in the evaluation of the outcome. US detected features suggestive of PSC in 8 patients (radiologist 3). US was unable to show the predictors of poor outcome. MRC and US seem to be useful in the detection of PSC. US is unable and MRC is too pessimistic to estimate the outcome of PSC.

Prevalence of primary sclerosing cholangitis and other liver diseases in Japanese patients with chronic ulcerative colitis.

An association between primary sclerosing cholangitis (PSC) and chronic ulcerative colitis (CUC) is well known in Western countries, but there have been no reports on this association in Japan. We reviewed 163 consecutive CUC patients (91 males and 72 females) diagnosed from 1984 to 1990 at Tokyo Women's Medical College. Abnormal liver function tests were found in 42 patients with CUC (25.8%), but chronic liver disease was only diagnosed in seven patients (4.3%). Among these seven patients, there were four with PSC, one with small-duct PSC, one with transfusion-associated chronic hepatitis and one with Type B liver cirrhosis. No relationship was found between the documented colonic manifestations of CUC and the presence of PSC. The four PSC patients did not have a longer history of CUC at the time of diagnosis of PSC than CUC patients without PSC. At the time of PSC diagnosis, two patients were asymptomatic, one presented with right upper quadrant pain, and the other had fatigue. Three patients were diagnosed as having CUC before the onset of PSC (range 2-13 years), and the other patient had both diseases simultaneously. All four had a good prognosis. Thus PSC was the most common chronic liver disease associated with CUC in our series, and it was present in all our CUC patients with alkaline phosphatase levels exceeding twice the upper limit of normal and mild transaminase elevation.

Primary sclerosing cholangitis in ulcerative colitis—A risk factor for the development of dysplasia and DNA aneuploidy?

In a 15-year surveillance program for long-standing, total ulcerative colitis (UC), 72 patients were followed up with colonoscopic biopsies. Seventeen patients developed definite dysplasia, carcinoma, and/or DNA aneuploidy. Alkaline phosphatase and transaminases were examined in all patients. In the group with dysplasia, carcinoma, and/or DNA aneuploidy, 5 patients (28%) were found to have primary sclerosing cholangitis (PSC) based on histological and/or cholangiographic criteria. In the group without definite dysplasia or DNA aneuploidy, no patient with PSC appeared, although two patients with other forms of chronic liver disorders were found. The difference in distribution of PSC between the two groups was statistically significant (P = 0.0004). Using logistic regression, the presence of PSC and the duration of UC were identified as independent risk factors associated with dysplasia and/or DNA aneuploidy. Thus, UC patients with PSC seem to run an increased risk of developing colonic dysplasia and/or DNA aneuploidy. Although the reason for the increased risk is still unclear, these results warrant increased surveillance among patients with both PSC and longstanding, total UC.