Metabolic Profile Reflects Stages of Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with fibrosis stage being the main predictor for clinical outcomes. Here, we present the metabolic profile of NAFLD patients with regards to fibrosis progression. We included all consecutive new referrals for NAFLD services between 2011 and 2019. Demographic, anthropometric and clinical features and noninvasive markers of fibrosis were recorded at baseline and at follow-up. Significant and advanced fibrosis were defined using liver stiffness measurement (LSM) as LSM ≥ 8.1 kPa and LSM ≥ 12.1 kPa, respectively. Cirrhosis was diagnosed either histologically or clinically. Fast progressors of fibrosis were defined as those with delta stiffness ≥ 1.03 kPa/year (25% upper quartile of delta stiffness distribution). Targeted and untargeted metabolic profiles were analysed on fasting serum samples using Proton nuclear magnetic resonance (1H NMR). A total of 189 patients were included in the study; 111 (58.7%) underwent liver biopsy. Overall, 11.1% patients were diagnosed with cirrhosis, while 23.8% were classified as fast progressors. A combination of metabolites and lipoproteins could identify the fast fibrosis progressors (AUROC 0.788, 95% CI: 0.703-0.874, p < 0.001) and performed better than noninvasive markers. Specific metabolic profiles predict fibrosis progression in patients with nonalcoholic fatty liver disease. Algorithms combining metabolites and lipids could be integrated in the risk-stratification of these patients.

Disease-modifying therapies and symptomatic management for primary biliary cholangitis.

Primary biliary cholangitis is a chronic condition characterised by autoimmune destruction of intralobular bile ducts. Publications have shown widespread gaps in the care of patients with primary biliary cholangitis. This article reviews the literature regarding currently licensed first- and second-line therapies and evaluates therapeutic options for symptomatic management of primary biliary cholangitis. Ursodeoxycholic acid is recommended for all patients with primary biliary cholangitis, with obeticholic acid available as second-line therapy, both having demonstrated safety and efficacy. Potential disease-modifying therapies, such as fibrates and budesonide, require further investigation before licensing. Cholestyramine is first-line therapy for pruritus, albeit with limited evidence and common side-effects. There is no licensed therapy for primary biliary cholangitis-related fatigue; treating underlying causes where applicable is recommended. Disease-modifying and symptomatic therapies must be considered in tandem when managing patients with primary biliary cholangitis. Emerging therapies show initial promise but further randomised trials with long-term follow up are required to evaluate their efficacy as single or combination therapies.

Medical students' pattern of self-directed learning prior to and during the coronavirus disease 2019 pandemic period and its implications for Free Open Access Meducation within the United Kingdom

PURPOSE: Self-directed learning (SDL) has been increasingly emphasized within medical education. However, little is known about the SDL resources medical students use. This study aimed to identify patterns in medical students' SDL behaviors, their SDL resource choices, factors motivating these choices, and the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on these variables. Methods: An online cross-sectional survey comprising multiple-choice, ranked, and free-text response questions were disseminated to medical students across all 41 UK medical schools between April and July 2020. Independent study hours and sources of study materials prior to and during the COVID-19 pandemic were compared. Motivational factors guiding resource choices and awareness of Free Open Access Meducation were also investigated. Results: The target sample was 75 students per medical school across a total of 41 medical schools within the United Kingdom (3,075 total students), and 1,564 responses were analyzed. University-provided information comprised the most commonly used component of independent study time, but a minority of total independent study time. Independent study time increased as a result of the COVID-19 pandemic (P<0.001). All sub-cohorts except males reported a significant increase in the use of resources such as free websites and question banks (P<0.05) and paid websites (P<0.05) as a result of the pandemic. Accessibility was the most influential factor guiding resource choice (Friedman's µrank=3.97, P<0.001). Conclusion: The use of learning resources independent of university provision is increasing. Educators must ensure equitable access to such materials while supporting students in making informed choices regarding their independent study behaviors.