Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins.

Background: Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain the mainstay of drug therapy. However, ~40% of patients do not respond to this treatment, and the mechanisms underlying the altered response to corticosteroids are not understood.

Identification of integrated proteomics and transcriptomics signature of alcohol-associated liver disease using machine learning.

Distinguishing between alcohol-associated hepatitis (AH) and alcohol-associated cirrhosis (AC) remains a diagnostic challenge. In this study, we used machine learning with transcriptomics and proteomics data from liver tissue and peripheral mononuclear blood cells (PBMCs) to classify patients with alcohol-associated liver disease. The conditions in the study were AH, AC, and healthy controls.

Clinical trial facilitators: A novel approach to support the execution of clinical research at the study site level.

In the summer of 2020, multiple efforts were undertaken to establish safe and effective vaccines to combat the spread of the coronavirus disease (COVID-19). In the United States (U.S.

A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis.

Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States.

Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.

Integrated Transcriptomic and Proteomic Analysis Identifies Plasma Biomarkers of Hepatocellular Failure in Alcohol-Associated Hepatitis.

Alcohol-associated hepatitis (AH) is a form of liver failure with high short-term mortality. Recent studies have shown that defective function of hepatocyte nuclear factor 4 alpha (HNF4a) and systemic inflammation are major disease drivers of AH. Plasma biomarkers of hepatocyte function could be useful for diagnostic and prognostic purposes.

Differentiating between liver diseases by applying multiclass machine learning approaches to transcriptomics of liver tissue or blood-based samples.

Background & Aims: Liver disease carries significant healthcare burden and frequently requires a combination of blood tests, imaging, and invasive liver biopsy to diagnose. Distinguishing between inflammatory liver diseases, which may have similar clinical presentations, is particularly challenging. In this study, we implemented a machine learning pipeline for the identification of diagnostic gene expression biomarkers across several alcohol-associated and non-alcohol-associated liver diseases, using either liver tissue or blood-based samples.

Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis.

Alcohol-associated liver disease is a global health care burden, with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) being two clinical manifestations with poor prognosis. The limited efficacy of standard of care for AC and AH highlights a need for therapeutic targets and strategies. The current study aimed to address this need through the identification of hepatic proteome and phosphoproteome signatures of AC and AH.

Development and implementation of standardized study performance metrics for a VA healthcare system clinical research consortium.

The cost of conducting clinical trials is continuously increasing and is driven in large part by the time and resources required to activate trials and reach accrual targets. The impact of low enrollment in a clinical trial can negatively affect the validity of study results and delay its generalizability to the broader population. Quality is a multidimensional concept which could relate to the design, conduct, and analysis of a trial, its clinical relevance, protection/safety of study participants, or quality of reporting.

Increasing access to clinical research using an innovative mobile recruitment approach: The (MoRe) concept.

Background: Access to healthcare delivery programs and systems is a primary correlate to the overall health and well-being of Veterans and the general population. Participation in clinical research is a gateway to novel therapies that are intended to address current global health issues. Meeting or exceeding recruitment goals in clinical research is one of the key determinants of the timely and successful completion of a study.

Research site mentoring: A novel approach to improving study recruitment.

Background/aims: The VA Cooperative Studies Program's (CSP) Network of Dedicated Enrollment Sites (NODES) is a consortium of nine VA medical centers (VAMCs) with teams (nodes) dedicated to enhance performance, compliance, and management of CSP multi-site clinical trials. The West Haven CSP Coordinating Center (WH-CSPCC), study coordinating center for CSP #577, looscopy Versus ecal mmunochemical Test (FIT) in educing ortality from Colorectal Cancer (CONFIRM) trial, and NODES piloted a "site mentoring" (hub-and-spoke) model. In this model, a node site would work one-on-one with a low enrolling CONFIRM site to identify and overcome barriers to recruitment.

A cross-cutting approach to enhancing clinical trial site success: The Department of Veterans Affairs' Network of Dedicated Enrollment Sites (NODES) model.

Background: Recruitment into clinical trials remains a key determinant to study completion and success. While various strategies have been proposed, it is unclear how they apply across different populations, diseases, and/or study goals. The ability to effectively overcome challenges may require different approaches that more broadly focus on addressing obstacles among sites that cannot be overcome by individual studies.

Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study.

Objective: This study evaluated the distinctive clinical and biological manifestations of depressive symptom subtypes (i.e., cognitive-affective and somatic) in Veterans with hepatitis C viral infection (HCV) before and during interferon-alpha (IFN) based antiviral therapy.