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Background and aimsNon-alcoholic fatty liver disease (NAFLD) is associated with a high risk of cardiovascular disease. Whether risk scores developed in the general population accurately assess cardiovascular risk in the NAFLD population is unknown. This study aimed to evaluate the performance of the Pooled Cohort Equations (PCE) in NAFLD.MethodsIndividuals in the Multi-Ethnic Study of Atherosclerosis with baseline non-contrast cardiac computed tomography scans with sufficient data to determine the presence of hepatic steatosis were identified and assessed for the development of incident 10-year atherosclerotic cardiovascular disease. The discrimination and calibration of the PCE were evaluated, and the observed and expected events by risk category (

Background and aimsPrimary sclerosing cholangitis (PSC) is a heterogeneous cholangiopathy characterized by progressive biliary fibrosis. RNA sequencing of liver tissue from patients with PSC (n = 74) enrolled in a 96-week clinical trial was performed to identify associations between biological pathways that were independent of fibrosis and clinical events.Approach and resultsThe effect of fibrosis was subtracted from gene expression using a computational approach. The fibrosis-adjusted gene expression patterns were associated with time to first PSC-related clinical event (e.g., cholangitis, hepatic decompensation), and differential expression based on risk groups and Ingenuity Pathway Analysis were performed. Baseline demographic data were representative of PSC: median age 48 years, 71% male, 49% with inflammatory bowel disease, and 44% with bridging fibrosis or cirrhosis. The first principle component (PC1) of RNA-sequencing data accounted for 18% of variance and correlated with fibrosis stage (ρ = -0.80; P  0.05). The top pathways identified by Ingenuity Pathway Analysis were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling. Genes involved in the unfolded protein response, activating transcription factor 6 (ATF6) and eIF2, were differentially expressed between the PSC clusters (down-regulated in the high-risk group by log-fold changes of -0.18 [P = 0.02] and -0.16 [P = 0.02], respectively). Clinical events were enriched in the high-risk versus low-risk group (38% [12/32] vs. 2.4% [1/42], P

Background & Aims:A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC). Methods:Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). Age acceleration was calculated as the difference between DNAm age and chronological age. Comparisons between patients with high and low age acceleration (≥ vs. < the median) were made and Cox regression evaluated the association between age acceleration and PSC-related clinical events (e.g. decompensation, cholangitis, transplantation). Results:Age acceleration was significantly higher in patients with PSC compared to a healthy reference cohort (median, 11.1 years, p

Background: There is a lack of randomized controlled trials of behavioral interventions and process‐level research related to alcohol reduction among patients with chronic liver disease (e.g., hepatitis C viral (HCV) infection). We conducted a process‐level, secondary analysis of the Hepatitis C‐Alcohol Reduction Treatment (HepART) trial to investigate the association between change in psychological processes posited by the Integrated Behavioral Model (IBM) and change in World Health Organization (WHO) drinking risk levels. Methods: Patients with HCV who consume alcohol were recruited from hepatology clinics and received provider‐delivered SBIRT (Screening, Brief Intervention, Referral to Treatment) or SBIRT+ 6 months of co‐located alcohol counseling. Treatment arms were combined for this analysis because no between‐group differences were found. At baseline and 6 months, the timeline followback method was used to determine alcohol risk levels according to the 2000 WHO risk categories (based on average grams of alcohol per day). Changes in alcohol consumption and WHO risk levels were quantified and regressed on change in individual psychological processes (e.g., readiness, self‐efficacy, motives, attitudes, and strategies) from baseline to 6 months. Results: At the baseline assessment, 162 participants were classified as abstinent (5%), low (47%), moderate (16%), high (19%), or very high (13%) WHO risk levels. At 6 months, 38% remained at the same risk level and 48% decreased by at least one level. In univariate analyses, changes in 7 of 12 psychological processes were associated with change in risk levels. Adjusted multivariate analyses demonstrated that change in four processes were significantly associated with change in risk levels, including SOCRATES Taking Steps, Ambivalence, and Recognition scores and alcohol reduction strategies. Conclusions: These findings demonstrate significant reductions in quantitative indices of alcohol consumption following opportunistic alcohol interventions in patients with HCV. However, results provided mixed support for associations between change in IBM psychological processes and alcohol consumption. [ABSTRACT FROM AUTHOR]