Incidence Of Primary Sclerosing Cholangitis Research Articles

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.

Colectomy in patients with ulcerative colitis is not associated to future diagnosis of primary sclerosing cholangitis.

Primary Sclerosing Cholangitis (PSC) is a hepatobiliary disease closely related to ulcerative colitis (UC). In PSC patients, colectomy has been linked to improved prognosis, especially following liver transplantation. This suggests an involvement of the gut-liver axis in PSC etiology. We aimed to investigate the association between colectomy and the risk of future PSC in an epidemiological setting. Through nationwide registers, we identified all adults diagnosed with UC in Sweden 1990-2018 and retrieved information on PSC diagnosis and colectomy. Within the UC cohort (n=61,993 patients), we matched 5577 patients with colectomy to 15,078 without colectomy. Matching criteria were sex, age at UC onset (±5years), year of UC onset (±3years), and proctitis at the time of colectomy. Incidence rates of PSC per 1000-person year were calculated, and the Cox proportional hazard regression model estimated hazard ratios (HRs) for PSC until 31 December 2019. During the follow-up, 190 (3.4%) colectomized UC patients and 450 (3.0%) UC comparators developed PSC, yielding incidence rates of 2.6 and 2.4 per 1000 person-years (HR 1.07 [95% CI 0.90-1.28]). The cumulative incidence of colectomy decreased remarkably over calendar periods, but the cumulative incidence of PSC remained unchanged. The risk of developing PSC in colectomized versus comparators changed over time (HR 0.68 [95% CI; 0.48-0.96] in 1990-97 and HR 2.10 [95% CI; 1.37-3.24] in 2011-18). In UC patients, colectomy was not associated with a decreased risk of subsequent PSC. The observed differences in the risk of PSC development over calendar periods are likely due to changes in PSC-diagnosis and UC-treatment.

INCIDENCE AND PREVALENCE OF PRIMARY SCLEROSING CHOLANGITIS: A META-ANALYSIS OF POPULATION-BASED STUDIES

Primary sclerosing cholangitis (PSC) is a chronic liver disease associated with significant morbidity, mortality and healthcare utilization—with nearly 80% of PSC patients having inflammatory bowel disease (IBD). Understanding the incidence of PSC is important in defining the burden of disease and planning for allocation of healthcare resources.

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.

The Epidemiology of UK Autoimmune Liver Disease Varies With Geographic Latitude

Background & AimsThe epidemiology of autoimmune liver disease (AILD) is challenging to study because of the diseases’ rarity and because of cohort selection bias. Increased incidence farther from the Equator has been reported for multiple sclerosis, another autoimmune disease. We assessed the incidence of primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) in relation to latitude.MethodsWe performed a retrospective cohort study using anonymized UK primary care records from January 1, 2002, to May 10, 2016. All adults without a baseline diagnosis of AILD were included and followed up until the first occurrence of an AILD diagnosis, death, or they left the database. Latitude was measured as registered general practice rounded down to whole degrees.ResultsThe cohort included 8,590,421 records with 53.3 × 107 years of follow-up evaluation from 694 practices. There were 1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences were as follows: PBC, 2.47 (95% CI, 2.34–2.60); PSC, 0.74 (95% CI, 0.67–0.82); and AIH, 1.94 (95% CI, 1.83–2.06) per 100,000 per year. PBC incidence correlated with female sex, smoking, and deprivation; PSC incidence correlated with male sex and non-smoking; AIH incidence correlated with female sex and deprivation. A more northerly latitude was associated strongly with incidence of PBC: 2.16 (95% CI, 1.79–2.60) to 4.86 (95% CI, 3.93–6.00) from 50°N to 57°N (P = .002) and incidence of AIH: 2.00 (95% CI, 1.65–2.43) to 3.28 (95% CI, 2.53–4.24) (P = .003), but not incidence of PSC: 0.82 (95% CI, 0.60–1.11) to 1.02 (95% CI, 0.64–1.61) (P = .473). Incidence after adjustment for age, sex, smoking, and deprivation status showed similar positive correlations for PBC and AIH with latitude, but not PSC. Incident AIH cases were younger at more northerly latitude.ConclusionsWe describe an association in the United Kingdom between more northerly latitude and the incidence of PBC and AIH that requires both confirmation and explanation.

S3394 A Case Report of Atypical Ulcerative Colitis

INTRODUCTION: Ulcerative colitis(UC) and Crohns disease usually have specific presentation on colonoscopy with some overlap seen in select cases. UC predominantly involves colon, with almost always involving the rectum and rarely involving the ileum. However, in about 5% of the cases, IBD can present in atypical way labelled as “indeterminate” or “unclassified”. In these cases, UC can present with skip lesions with rectal sparing which can pose a diagnostic challenge if only visual diagnosis is focused upon. CASE DESCRIPTION/METHODS: 27 year old female presented to GI clinic with rectal pain and diarrhea for several months. On the rectal exam, there was pinhole like opening and ulceration. Outpatient colonoscopy was performed and revealed few skip lesions of erythematous, friable and ulcerated mucosa in the transverse colon and terminal ileum. The pathology showed mild acute, focal inflammation and crypt abscess in terminal ileum, transverse, descending and sigmoid colon. Rectal biopsy showed normal findings. The stool studies were sent and C diff test came positive. After the 2week course of oral vancomycin, symptoms were significantly improved. Subsequently, she was placed on Mesalamine. 8 months later, repeat colonoscopy revealed inflamed, erythematous, congested skip lesions at terminal ileum and transverse colon. UC was confirmed again with the presence of mild inflammation and cryptitis. DISCUSSION: Patients who have RST(rectal sparing of UC) represent resistance to treatment, prolong duration of active disease and increased rate of recurrence. It might be a prediction for future colectomy given the severity of the disease. Severity of the disease was significantly worse in patients with RST compared to the control group and 24/46 pts with RST required urgent surgery compared with 107/436 non RST group. These patients have also seen to have a lack of response to conventional pharmacotherapy. Frequency of PSC (primary sclerosing cholangitis) with and without rectal sparing is also studied. The reported incidence showed a mean(30.9% vs 9.9%) in PSC with rectal sparing, compared with the group without rectal sparing. Overall, incidence of PSC was 3 times higher in rectal sparing group. In conclusion, the presence of relative or absolute RST in patients with UC is an atypical presentation. This group of patients should be selectively reclassified due to worse prognosis with higher incidence rate of emergent surgery, primary sclerosing cholangitis and refractoriness of pharmacologist therapies.Figure 1.: Congested, erythematous, friable and inflamed terminal ileum.Figure 2.: Rectum with normal appearing mucosa.

An update on primary sclerosing cholangitis epidemiology, outcomes and quantification of alkaline phosphatase variability in a population-based cohort.

Contemporary primary sclerosing cholangitis (PSC) population-based cohorts describing the epidemiology, natural history, and long-term fluctuations in serum alkaline phosphatase (SAP) and their prognostic relevance are lacking. Therefore, we investigated the incidence and natural history of PSC and quantified SAP fluctuations among those with PSC in Olmsted County, Minnesota over the last 41years. The Rochester Epidemiology Project was used to identify 56 subjects diagnosed with PSC between 1976 and 2017 in Olmsted County. The primary endpoint (n = 19) included liver transplantation, hepatic decompensation, and cholangiocarcinoma. The age- and sex-adjusted incidence of PSC (per 100,000 person years) nearly doubled from 2001 to 2017 compared to 1976-2000 (1.47; 95% CI 0.99-1.96 versus 0.79; 95% CI 0.42-1.16, p = 0.02). This increase paralleled a rise in patients with markers of a milder phenotype at the time of diagnosis: normal SAP (26.32% versus 0%, p < 0.01) and lower Mayo PSC risk score [0.36 (-0.57 to 1.55) versus -0.50 (-1.25 to 0.35), p = 0.03]. Intra-individual SAP fluctuates with a median coefficient of variation of 36.20%. SAP normalization and dropping below 1.5 × upper limit of normal (ULN) occurs at a rate of 5% and 10% per year, respectively. SAP less than 1.5 × ULN was associated with a lower risk of PSC-related complications (hazard ratio 0.11; 95% CI 0.03-0.42). The patients with PSC are increasingly being diagnosed with a milder phenotype. While a lower SAP is associated with improved outcomes, the high intra-individual variation of SAP levels calls into question the practice of using a single SAP value as a surrogate endpoint in clinical trials.

Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population-based study in Finland

Background: There are only a few and mostly small population-based epidemiological studies of primary sclerosing cholangitis (PSC).Objective: We aimed to estimate prevalence and incidence rates of PSC, and survival and malignancy risk for PSC patients in a large population-based study.Methods: We retrieved 632 PSC patients from 1990 to 2015 in the Hospital District of Helsinki and Uusimaa (HUS), comprising 29% of the Finnish population. Mortality information of the PSC patients was obtained from the national Population Registry, malignancy information from the Finnish Cancer Registry and the causes of death from the Statistics Finland. Standardized incidence ratio and standardized mortality ratio (SMR) were calculated for predefined malignancy types.Results: The crude incidence of PSC in the HUS area was 1.58/100,000 person-years, and the point prevalence in 2015 was 31.7/100,000 inhabitants. The mean time from diagnosis to death was 21.9 years. The risk for any malignancy was three-fold and the risk for colorectal carcinoma was five-fold when comparing with the general population. During the first year after diagnosis of PSC, the risk for cholangiocarcinoma is 900-fold compared to the general population and after that 150-fold. SMR for all malignant neoplasms was 5.9 (95% CI 4.2–8.1).Conclusion: We found that the incidence of PSC in the HUS area in Finland is similar or higher than previously reported from other countries. The prevalence is markedly higher than reported elsewhere, probably due to the active search of the disease, suggesting that the disease is underdiagnosed.

Frumkomin trefjunargallgangabólga á Íslandi 1992-2012

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease affecting the intra- and/or extrahepatic biliary tree with inflammation and progressive stricture formation that can lead to cirrhosis, end stage liver failure and liver transplantation. Known risk factors include inflammatory bowel diseases (IBD), mainly ulcerative colitis (UC). Highest reported incidence in an adult population is 1.2-1.3/100.000 in Norway and Sweden, where 60-76% have IBD. The aim of this study was to investigate epidemiology of PSC in Iceland in the years 1992 to 2012 and the patients outcomes. A search for the diagnosis "cholangitis" (ICD-10, K83.0) was performed in the database for hospital records in Landspítali (The National University Hospital of Iceland, LSH) and Akureyri Hospital from 1992 to 2012. We also looked through all ERCP and MRCP imaging done in LSH in the same period along with a text search in both the hospital records and the pathology database for liver biopsies. Data on these patients was collected until the end of 2016. A total of 42 patient got the diagnosis PSC within the period. Median age at diagnosis was 34 years, 67% were male and 90% adults (≥18 years old). Mean incidence per year was 0.69/100.000. Overall 88% of patients had IBD, thereof 89% UC. Seven patients have been diagnosed with cancer, four with cancer in the bile ducts and one in the gallbladder. Within the study period a total of five patients died (12%), 51 months (median) from diagnosis and three from cholangiocarcinoma, 51 months (median) from diagnosis. Three patients (7%) underwent liver transplantation, one required a transplant two times. The incidence of PSC in Iceland turned out to be lower than in our neighbouring countries in Scandinavia. It is unclear if this is due to underdiagnosis or, more likely, that PSC is simply more uncommon in Iceland. Overall 7% underwent liver transplantation and 12% died within the study period, main cause of mortality being cholangiocarcinoma.

Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom.

Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts. We assessed PSC epidemiology and natural history within the UK Clinical Practice Research Datalink (CPRD).Incidence and natural history of PSC were evaluated in a retrospective cohort study using linkage of CPRD, Hospital Episode Statistics, and Office for National Statistics data. Data from age, sex, and general practice-matched population controls provided a context for the incident PSC patients. Liver disease other than PSC was defined as autoimmune hepatitis, hepatitis, hepatomegaly, liver failure, cirrhosis, portal hypertension, cholangiocarcinoma, or hepatobiliary cancer.The age-standardized incidence of PSC was 0.68 (95% confidence interval [CI] 0.45–0.99) per 100,000 person-years and the age-standardized prevalence was 5.58 (95% CI 4.82–7.35) per 100,000 during 1998 to 2014. In all, 250 incident PSC patients met the inclusion criteria and each was matched with 5 controls (mean age 54 ± 18 years, men 63.2%). A higher percentage of PSC patients had a history of inflammatory bowel disease (54% vs 2%) and liver disease other than PSC (22% vs 1%) than controls (standardized differenceweighted >0.1). During a median follow-up of 5 years, PSC patients were more likely to develop adverse health outcomes. The mortality rate per 1000 person-years was 3-fold higher in PSC than population controls (49.5 vs 16.1; incidence rate ratio 3.1, 95% CI 2.2–4.2).The incidence and prevalence of PSC observed in the UK CPRD were either comparable with or higher than previous studies. Compared with the general population, PSC patients had worse health outcomes including PSC disease progression, complications, and higher mortality.

The evolution of natural history of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare, idiopathic biliary disease often with an insidious onset, variable disease course, and premature death related to benign and malignant PSC-related sequelae. This review aims to discuss the epidemiology, clinical variants, and natural history of PSC, incorporating data from recent population-based studies. PSC naturally leads to cirrhosis, cholangiocarcinoma, other hepatobiliary malignancies, dominant strictures, hepatic osteodystrophy, and bacterial cholangitis. The incidence of PSC appears to be increasing, the reasons for which are unclear. The time from diagnosis to liver transplant appears to be longer in more recent studies compared with earlier studies, suggesting a better overall prognosis than previously believed. In addition, with an increasing number of patients undergoing liver transplantation for PSC, the frequency of death because of liver failure has decreased, whereas cancer-related deaths have increased among patients with PSC. PSC is a heterogeneous disease with a variety of clinical outcomes, both fatal and nonfatal. The progression of liver fibrosis in an individual patient is difficult to predict and may vary from a relatively benign, nonprogressive form to a rapidly progressive form with the need for liver transplantation.

Primary Sclerosing Cholangitis with Inflammatory Bowel Disease in Korean Children.

PurposePrimary sclerosing cholangitis (PSC) is a rare condition that can be associated with inflammatory bowel disease (IBD). The aim of this study was to evaluate PSC and its association with IBD in children.MethodsWe retrospectively enrolled 13 pediatric patients (<18 years) with PSC treated at Asan Medical Center between June 1989 and December 2013. Clinical findings and long-term outcomes were investigated. During the same period, the incidence of PSC among IBD patients was evaluated among 600 Crohn disease (CD) and 210 ulcerative colitis (UC) patients.ResultsAll 13 study patients diagnosed with PSC also presented with IBD. Eleven boys and two girls with a median age of 15.0 years old (9.0-17.8 years) were included. The cumulative incidence of PSC for UC was 5.7% (12 of 210) and 0.2% for CD (1 of 600), respectively. PSC occurred during follow-up for IBD for five patients (38.5%) whereas, IBD developed during follow-up for PSC for two patients (15.4%), and was diagnosed during the initial work-up for PSC for 6 patients (46.2%). For the 77.3 month median follow-up period, 9/13 patients (69.2%), neither the clinical symptoms nor blood test results worsened. Two cases (15.4%) developed liver cirrhosis and underwent liver transplantation. Among 13 PSC patients with IBD, two (15.4%) developed colorectal cancer, and no one developed cholangiocarcinoma.ConclusionAll patients with PSC in this study had associated IBD. The incidence of PSC was not rare compared to reports in adults. PSC should be considered during the management of IBD and vice versa in children.

Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis

To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation. Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests. PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score. Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.

Inflammatory Bowel Disease Is Associated With Poor Outcomes of Patients With Primary Sclerosing Cholangitis

Little is known about the exact etiology of primary sclerosing cholangitis (PSC); epidemiologic data are scarce. We performed a population-based epidemiologic study of PSC in Canterbury, New Zealand. By using multiple case-finding methods, we searched public and private adult and pediatric outpatient clinics, hospital discharge summaries, and radiology and pathology reports to identify all cases of PSC in the region. Cases were included if PSC was identified by endoscopic retrograde cholangiography, magnetic resonance cholangiography, or liver biopsy analysis (n = 79). The incidence of PSC in 2008 was 1.6 per 100,000 persons (95% confidence interval [CI], 0.5-2.7). The point prevalence on December 31, 2008, was 11.7 per 100,000 persons (95% CI, 8.7-14.8). The mean and median ages at diagnosis were 50 years (95% CI, 46-53 years) and 49 years (range, 17-80 years), respectively. Patients who had inflammatory bowel disease (IBD) presented with PSC earlier than those without IBD (P = .003), were more likely to develop serious malignant complications (P = .017), and were more likely to require liver transplantation or die (P = .03). In a population-based epidemiology study of PSC in Canterbury, New Zealand, we observed large differences between PSC patients with or without concurrent IBD in age at diagnosis, development of cancer, mortality, and requirement for liver transplantation. IBD therefore affects outcomes of patients with PSC, an important observation that requires further study.

Will we ever model PSC? – “It's hard to be a PSC model!”

Cholangiopathies such as primary sclerosing cholangitis (PSC) represent an important group of liver diseases of the intra- and extrahepatic bile ducts frequently causing end-stage liver disease with significant morbidity and mortality due to limited treatment options. The relatively low incidence of PSC and the difficult accessibility of the human bile duct system for longitudinal studies may represent some of the critical reasons for the lack of profound knowledge in regard to PSC pathophysiology. Therefore, there is an urgent need for reliable, well-defined and easily reproducible animal models to learn more about the pathophysiology of PSC and to test novel treatment modalities. In an ideal world, immunogenetically predisposed animals would develop fibrous-obliterative cholangitis of the intra- and extrahepatic bile ducts in association with inflammation of the gut (especially colitis) in a highly reproducible manner allowing to test new drugs. To date, however, no such animal model is available. We aimed to provide a systematic overview of current available rodent models for sclerosing cholangitis and biliary fibrosis and therefore critically analyzed the characteristics of models for chemically-induced cholangitis, knock-out mouse models with cholangitis, cholangitis induced by infectious agents, models of experimental biliary obstruction, models involving enteric bacterial cell-wall components or colitis, and models of primary biliary epithelial and endothelial cell injury.

Incidence of primary sclerosing cholangitis: A systematic review and meta-analysis

Incidence studies of primary sclerosing cholangitis (PSC) are important for describing the disease's burden and for shedding light on the disease's etiology. The purposes of this study were to conduct a systematic review of the incidence studies of PSC with a meta-analysis and to investigate possible geographic variations and temporal trends in the incidence of the disease. A systematic literature search of MEDLINE (1950-2010) and Embase (1980-2010) was conducted to identify studies investigating the incidence of PSC. The incidence of PSC was summarized with an incidence rate (IR) and 95% confidence intervals. The test of heterogeneity was performed with the Q statistic. Secondary variables extracted from the articles included the following: the method of case ascertainment, the country, the time period, the age, the male/female incidence rate ratio (IRR), and the incidence of PSC subtypes (small-duct or large-duct PSC and inflammatory bowel disease). Stratified and sensitivity analyses were performed to explore heterogeneity between studies and to assess effects of study quality. Time trends were used to explore differences in the incidence across time. The search retrieved 1669 potentially eligible citations; 8 studies met the inclusion criteria. According to a random-effects model, the pooled IR was 0.77 (0.45-1.09) per 100,000 person-years. However, significant heterogeneity was observed between studies (P < 0.001). Sensitivity analyses excluding non-population-based studies increased the overall IR to 1.00 (0.82-1.17) and eliminated the heterogeneity between studies (P = 0.08). The IRR for males versus females was 1.70 (1.34-2.07), and the median age was 41 years (35-47 years). All studies investigating time trends reported an overall increase in the incidence of PSC. The incidence of PSC is similar in North American and European countries and continues to increase over time. Incidence data from developing countries are lacking, and this limits our understanding of the global incidence of PSC.

Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in sweden†

Population-based studies on the epidemiology of primary sclerosing cholangitis (PSC) are sparse. The aim of the present study was to investigate prevalence and temporal trends in the incidence of PSC 1992-2005 in an adult population in Västra Götaland, a region in southern Sweden with a defined population of about 1.5 million. Patients with PSC aged 18 years or above were identified through a computerized search for diagnostic codes. A total number of 199 incident cases fulfilling Mayo criteria for PSC were identified through retrospective validation of clinical records. Temporal trends in the incidence of PSC were investigated by Poisson regression and expressed as average annual percent change (AAPC) with a 95% confidence interval (CI). The point prevalence of PSC on December 31, 2005, was 16.2/100,000 in the total adult population (men, 23.7/100,000; women, 8.9/100,000). The annual incidence was 1.22/100,000 in the total adult population (men, 1.78/100,000; women, 0.69/100,000). The overall incidence rate of PSC increased significantly over the investigation period (AAPC 3.06, 95% CI 0.01-6.20). Stratified analysis revealed significantly increasing trends for inflammatory bowel disease (IBD)-associated PSC (AAPC 7.01, 95% CI 0.24-14.24) and large duct PSC (AAPC 6.32, 95% CI 0.03-13.02) in women and for PSC without IBD (AAPC 9.69, 95% CI 0.82-19.33) and small duct PSC (AAPC 17.88, 95% CI 0.95-40.25) in men. This is the first study to report a significantly increasing trend in the incidence of PSC. The prevalence of PSC at the end of the study period is the highest reported to date. This implies that the medical burden of PSC may be higher than estimated previously.

Early Onset of Ulcerative Colitis: Long‐term Follow‐up With Special Reference to Colorectal Cancer and Primary Sclerosing Cholangitis

Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). The onset of UC at a young age has been considered a specific risk factor for CRC. This study reports the outcome with respect to DNA aneuploidy, dysplasia, CRC, and PSC in a cohort of patients with early-onset UC from a defined catchment area who were followed up for 45 years. The study period was from 1961 through 2005. In all, 46 children and adolescents, ages 18 or younger from our catchment area, were affected with UC during this time. Data were collected from our colonoscopic surveillance program and other medical records in the same hospital. The incidence rate of UC was 1.6 children or adolescents per 100,000 inhabitants per year. The onset of disease was at age 14 years (mean and median), and the observed duration of disease was 0 to 44 years. Five patients died, 3 of them of intercurrent disease. CRC developed in 1 patient, and no death caused by this disease was observed. PSC was diagnosed in 4 patients, in all of whom the onset of UC occurred before age 15. The earlier reports of increased risk of CRC in patients with early-onset UC was not seen in this study. This could be due to a high frequency of surgery together with a well-functioning surveillance program with excellent compliance. The recommendation of surgery in cases of high-grade dysplasia or repeated findings of low-grade dysplasia seems to be effective in the attempt to minimize the risk for CRC. We observed a rather high incidence of PSC, which may indicate that more attention should be paid to a search for this diagnosis in patients with early-onset UC.

Incidence and mortality of primary sclerosing cholangitis in the UK: A population-based cohort study

Little is known about the occurrence of Primary Sclerosing Cholangitis (PSC) in the population of the United Kingdom or its associated risks of mortality and malignancy. We aimed to fill these gaps in knowledge. We identified 223 people with PSC and 2217 control subjects from the General Practice Research Database in the UK. We calculated incidence rates (1991-2001) and mortality rates and used Poisson and Cox regression to make comparisons between populations. There were 149 incident cases giving a rate of 0.41 per 100,000 person years (95% CI 0.34-0.48) and a prevalence in 2001 of 3.85 per 100,000 (95% CI 3.04 to 4.80). The incidence of PSC increased about 50% over the period studied and was higher in men compared with women. There was a three-fold mortality rate increase (Hazard ratio 2.92 (95% CI 2.16-3.94) in people with PSC compared to the general population, a two-fold increase in risk of any malignancy and a 40-fold increase in the risk of primary liver cancer (HR 2.23 and 37.44, respectively). We believe this paper provides the most reliable estimates of the occurrence of PSC and of its risk in terms of death and malignancy in the UK available to date.

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect.