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

Management of Clinically Significant Itch in Cholestatic Liver Disease

Cholestatic liver diseases include primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and progressive familial intrahepatic cholestasis (PFIC). In all of these conditions, cholestatic itch is a major symptom that can severely and chronically impact a person’s quality of life (QoL). At a satellite symposium presented at the 2022 meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C., USA, leading experts discussed the importance of assessing itch in all patients with one of these cholestatic liver diseases. The experts presented patient cases to illustrate the challenges of managing itch in these cholestatic liver diseases. Studies show that many of these patients are not being adequately treated for this important symptom. However, while there are several treatments for itch, although not all are specifically approved medications, finding the right one for each patient may be a process of trial and error. In some cases, for people with severe, chronic, non-treatment-responsive cholestatic itch, a liver transplant may be the only treatment option

Epidemiology, natural history and outcomes of primary sclerosing cholangitis: A systematic review of population-based studies.

BACKGROUND The aim of this study was to quantify the global epidemiology of primary sclerosing cholangitis (PSC), alongside the incidence of liver transplantation, cancer and death, through robust systematic review of population-based data. METHODS We searched MEDLINE and EMBASE up to and including June 30 2020 to identify population-based studies reporting the incidence and/or prevalence of PSC. Studies that did not report original data, or of exclusively pediatric-onset disease (diagnosis age <16 years) or exclusively PSC-associated with inflammatory bowel disease were excluded. RESULTS Of 4922 published studies, 17 fulfilled inclusion criteria; 16 documenting incidence and 14 prevalence. The highest reported incidence of PSC was reported in Northern Europe (Finland: 1.58 and Norway 1.3 per-100,000 population, respectively) and North America (Minnesota USA, 1.47); with the lowest being observed across the Mediterranean Basin (Italy, 0.1). Prevalence ranged from 31.7 in Finland and 23.99 in Minnesota, to 1.33 in Singapore and 0.0 in Alaska. Of studies reporting temporal occurrence, an increase in disease incidence was observed across North America and Northern Europe (four studies), alongside an increase in prevalence over time (four studies). The incidence and risks for clinical outcomes were presented by nine of the included studies. Median transplant-free survival ranged from 9.7 (USA) to 20.6 years (Netherlands), with standardized mortality ratios of 2.5 and 4.2 compared to the control population. The standardized incidence of cholangiocarcinoma ranged from 235 (Finland) to 398 (Netherlands). CONCLUSIONS Estimates of PSC incidence and prevalence vary, with most studies conducted in North America and Western Europe; the latter showing a steady increase in disease occurrence over time. Further research is needed to understand changes in disease epidemiology, including etiological drivers, the implications of rising case burden on healthcare policy, and better appreciation of PSC in the developing world

HIV drug resistance early warning indicators in Ethiopia: variability at regional and health facility levels and trend over time

Objective: The aim of this study was to assess status of early warning indicators (EWIs) for HIV drug resistance in Ethiopia. Methods: A retrospective cohort study was conducted among 90 health facilities (HFs) in 2015. Data were abstracted for ‘on time pill pickup’ (EWI-I), ‘Retention in care’ (EWI-II), ‘drug supply continuity’(EWI-III) and ‘dispensing practices’ (EWI-IV). Data analysis was conducted using WHO Excel tool and SPSS V20. Results: EWI-IV was excellent across all of the six rounds of EWI surveys conducted between 2008 and 2015. There were improvements in EWI-II over time from 55.6% to 81%. However, EWI-I and EWI-III declined from 86.7% to 31% and 100% to 41%, respectively. During 2015, half of the HFs in Gambella, Amhara and Southern Nation, Nationalities and people regional (SNNPR) states achieved excellent performance for EWI-I. Similarly, all HFs in Afar, Amhara, Dire Dawa, Harari and Tigray regions achieved excellent performance for EWI-II. There were also differences by level of HFs for EWI-III; 62% of hospitals and 28% of health centers were out of stock of one or more ARV drugs by 2015. Conclusion: Excellent performance of EWI-IV and improvement of EWI-II over time shall be maintained. The program shall further work to ensure medication adherence and supply continuity

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C-C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC. This was a single-arm, open-label, exploratory study of CVC in adults with a clinical diagnosis of PSC, serum alkaline phosphatase (ALP) ≥1.5 times the upper limit of normal (ULN), with or without inflammatory bowel disease, across eight sites in the United States and Canada. The primary endpoint was percent change in ALP over 24 weeks; key secondary efficacy endpoints were proportion of participants who achieved ALP normalization and overall response (decrease to &lt;1.5 times the ULN or 50% decrease). Of the 24 participants, 20 completed the study. The mean age was 43 years, 50% were female, and the mean body mass index was 25 kg/m2. From a median ALP baseline of 369 U/L (range: 173, 1,377 U/L), a median absolute reduction of 49.5 U/L (range: -460, 416 U/L) was achieved at week 24, corresponding to a median reduction of 18.0% (range: -46%, 89%). No participant achieved ALP normalization or a 50% decrease; 2 participants (10%) achieved a reduction in ALP to &lt; 1.5 times the ULN, and 4 had ≥25% increase. Twenty participants (83.3%) reported at least one adverse event; most were mild to moderate in severity. The most frequent events were rash, fatigue, and dizziness. Conclusion: After 24 weeks of CVC treatment, adults with PSC achieved a modest reduction (median 18%) in the surrogate endpoint of ALP. CVC was well tolerated, and no new safety signals were observed. ClinicalTrials.gov identifier: NCT02653625