Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; PPeer reviewe

Gallbladder and pancreatic disease in patients with primary sclerosing cholangitis

The aims of this study were to assess the occurrence of gallbladder abnormalities and dysfunction, to evaluate clinically useful biomarkers for premalignancy and malignancy in gallbladder epithelium and to assess presence of pancreatic duct changes and early pancreatic abnormalities in patients with primary sclerosing cholangitis (PSC). In paper I and III we investigated presence of gallbladder abnormalities in 286 patients with PSC treated at Karolinska University Hospital, Huddinge, between 1970 and 2005. Gallbladder abnormalities were found in 41% of the patients, gallstones in 25% and cholecystitis in 25%. Six % (18/286) of the patients had a gallbladder mass lesion with a mean size of 21(±9) mm(SD) of whom 56% (10/18) constituted adenocarcinoma. All available gallbladder specimens (n=53) were re-reviewed and immunohistochemical staining was compared on all available paraffin blocks of gallbladdercarcinoma/dysplasia (n=13) and benign tissue (n =6). A significant association was found between presence of moderate-severe lymphoplasmacytic chronic inflammation and fibrosis and dysplasia/adenocarcinoma. Immunoreactivity for the cell-cycle-regulating proteins p53, Ki67, Cyclin D1 and pCEA were detected in significantly more cases of dysplasia and carcinoma of the gallbladder compared to non-cancerous epithelium, and the thioredoxin family proteins TrxR1-v,2,3,5 was significantly overexpressed in the dysplastic and tumors tissue whereas Grx1 was downregulated. In paper II we studied gallbladder volumes in patients with PSC (n=20) and healthy controls (n=10) with magnetic resonance imaging (MRI). Median fasting and postprandial gallbladder volumes in patients with PSC were significantly larger than in healthy controls. There was no difference in ejection fraction or gallbladder emptying volume between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than in controls. No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls. Paper IV evaluated the presence of pancreatic parenchymal and duct changes using MRI and magnetic resonance cholangio pancreatography (MRCP) in 103 patients with PSC. Pancreatic duct changes were found in 24%. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but neither associated with early radiological signs of chronic pancreatitis such as pancreas-spleen signal intensity ratio (SIR), arterial and early venous phase ratio (A/PV) nor to pancreas size, previous post endoscopic retrograde cholangiopancreatography or previous episodes of acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Conclusions: Gallbladder and pancreatic abnormalities are common in patients with PSC and gallbladder mass lesions regardless of their size are frequently malignant in PSC. Our data support an inflammation-fibrosis-dysplasia-carcinoma sequence of the gallbladder epithelium. The overexpression of TrxR1-v2,3,5 and downregulation of Grx1 in dysplastic gallbladder epithelium may be of help for the early diagnosis of biliary malignancy in PSC but needs to be further evaluated. Pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as chronic pancreatitis. Severe pancreatic duct changes may contribute to abdominal pain in PSC, however, gallbladder size or emptying does not seem to be involved in the development of pain in PSC

Gallbladder emptying in patients with primary sclerosing cholangitis

AIM: To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis (PSC). METHODS: Twenty patients with PSC and ten healthy subjects were investigated. Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging. Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed. RESULTS: Median fasting gallbladder volume in patients with PSC [67 (19-348) mL] was twice that in healthy controls [32 (16-55) mL] (P < 0.05). The median postprandial gallbladder volume in patients with PSC was significantly larger than that in healthy controls (P < 0.05). There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls; (69% ± 32%) and (42% ± 21%) (P < 0.05). No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls. CONCLUSION: Patients with PSC have increased fasting gallbladder volume. Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder

The Role of Immunoglobulin G4 in Outcomes of Primary Sclerosing Cholangitis

Introduction: Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease that is characterized by an inflammatory and fibrotic process affecting bile ducts which eventually develops into liver cirrhosis and liver failure. The aim of this study was to investigate serum IgG subclass distribution in patients with PSC and its possible association with PSC outcomes. Patients and methods: We performed a retrospective analysis of 181 patients who had been diagnosed with PSC between January 1970 and December 2015 and followed at our outpatient clinic. Their demographic, immunological, and clinical characteristics were recorded and analyzed. Results: This study included 181 patients with PSC (120 males, 61 females). There was no association between IgGs and the development of autoimmune hepatitis, cirrhosis, cholangiocarcinoma, liver transplantation, inflammatory bowel disease, and colectomy. Patients with elevated IgG4 had statistically significant higher rates of cholangitis (p = 0.02) and endoscopic retrograde cholangiopancreatography (ERCP) (p = 0.009). High IgG4 values were observed in nine patients who underwent ERCP. In these nine patients, on average, IgG4 was evaluated 5 years after ERCP (min 3 days, max 11 years). Subanalysis considering only IgG4 values evaluated before ERCP showed no significant difference but remains significant if we consider IgG4 values after ERCP. Conclusion: Elevated IgG4 in our study showed a possible association with higher rates of cholangitis and ERCP among patients with primary sclerosing cholangitis. It seems that IgGs may be a useful tool for the prediction of outcomes in patients with PSC. A prospective study is necessary, especially to study the trends of IgGs values during disease as well as the role of possible seroconversion

Prevalence of Viremic hepatitis C, hepatitis B, and HIV infection, and vaccination status among prisoners in Stockholm County

Abstract Background Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination. Methods A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class. Results The median age was 35 (IQR 26–44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects. Conclusions The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons. </jats:sec

Prevalence of Viremic hepatitis C, hepatitis B, and HIV infection, and vaccination status among prisoners in Stockholm County

Background: Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination. Methods: A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class. Results: The median age was 35 (IQR 26-44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects. Conclusions: The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons