No abstract

Extensive population-based studies are much needed to accurately establish epidemiology and disease course in patients with primary sclerosing cholangitis (PSC). We aimed to obtain population-based prevalence and incidence figures, insight in disease course with regard to survival, liver transplantation (LT), and occurrence of malignancies, as well as risk factors thereof. Four independent hospital databases were searched in 44 hospitals in a large geographically defined area of the Netherlands, comprising 50% of the population. In addition, all PSC patients in the three Dutch liver transplant centers and all inflammatory bowel disease (IBD) patients in the adherence area of a large district hospital were identified. All medical records were reviewed on-site, verifying diagnosis. Five hundred and ninety PSC patients were identified, resulting in an incidence of 0.5 and a point prevalence of 6.0 per 100,000. Median follow up was 92 months. Estimated median survival from diagnosis until LT or PSC-related death in the entire cohort was 21.3 years, as opposed to 13.2 years in the combined transplant centers cohort (n 5 422; P < 0.0001). Colorectal carcinoma (CRC) risk was 10-fold increased, as compared to ulcerative colitis controls, and developed at a much younger age (39 years; range, 26-64), compared to IBD controls (59 years; range, 34-73; P 5 0.019). Colonoscopic surveillance was associated with significantly better outcome. Conclusion: This study exemplifies that, for relatively rare diseases, it is paramount to collect observational data from large, population-based cohorts, because incidence and prevalence rates of PSC are markedly lower and survival much longer than previously reported. The selection of a bias-free, population-based cohort showed a significantly longer survival, compared to the tertiary referral cohort. CRC can develop at an early age, warranting surveillance from time of PSC diagnosis. (HEPATOLOGY 2013;58:2045-2055 P rimary sclerosing cholangitis (PSC) is an enigmatic cholestatic liver disease affecting the intraand extrahepatic bile ducts. PSC is more common in men than in women (2:1) and can occur at any age, with a peak incidence around 40.1 Common symptoms associated with PSC are jaundice, pruritus, and upper abdominal discomfort, although approximately 40% of patients are asymptomatic at

FXR activation prevents chemically induced intestinal inflammation, with improvement of colitis symptoms, inhibition of epithelial permeability, and reduced goblet cell loss. Furthermore, FXR activation inhibits proinflammatory cytokine production in vivo in the mouse colonic mucosa, and ex vivo in different immune cell populations. The findings provide a rationale to explore FXR agonists as a novel therapeutic strategy for IBD.

Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin ('pigment') stones. Black pigment stones can be caused by chronic haemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and overnutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for ∼25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general.