Development, validation, and prognostic evaluation of LiverPRO for the prediction of significant liver fibrosis in primary care: a prospective cohort study.

Background: Clinically significant liver fibrosis is associated with future adverse events in patients with steatotic liver disease. We designed a software tool for detection of clinically significant liver fibrosis in primary care.

Methods: In this prospective cohort study, we developed and validated LiverPRO using six independent cohorts from Denmark, Germany, and England that included patients from primary and secondary care with steatotic liver disease related to alcohol or metabolic dysfunction.

Corrigendum: The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study.

[This corrects the article DOI: 10.3389/fimmu.2024.

Interpreting elevated liver blood test results through a genetic lens: A genome-wide association study.

Background And Aims: Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs).

Methods: A genome-wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.

Neem leaf glycoprotein binding to Dectin-1 receptors on dendritic cell induces type-1 immunity through CARD9 mediated intracellular signal to NFκB.

Background: A water-soluble ingredient of mature leaves of the tropical mahogany 'Neem' (Azadirachta indica), was identified as glycoprotein, thus being named as 'Neem Leaf Glycoprotein' (NLGP). This non-toxic leaf-component regressed cancerous murine tumors (melanoma, carcinoma, sarcoma) recurrently in different experimental circumstances by boosting prime antitumor immune attributes. Such antitumor immunomodulation, aid cytotoxic T cell (T)-based annihilation of tumor cells.

The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study.

Introduction: Murine tumor growth restriction by neem leaf glycoprotein (NLGP) was established in various transplanted models of murine sarcoma, melanoma and carcinoma. However, the role of NLGP in the sequential carcinogenic steps has not been explored. Thus, tongue carcinogenesis in Swiss mice was induced by 4-nitroquinoline-1-oxide (4NQO), which has close resemblance to human carcinogenesis process.

Deep learning-based harmonization of trabecular bone microstructures between high- and low-resolution CT imaging.

Background: Osteoporosis is a bone disease related to increased bone loss and fracture-risk. The variability in bone strength is partially explained by bone mineral density (BMD), and the remainder is contributed by bone microstructure. Recently, clinical CT has emerged as a viable option for in vivo bone microstructural imaging.

CRL4b Inhibition Ameliorates Experimental Autoimmune Encephalomyelitis Progression.

Multiple sclerosis, and its murine model experimental autoimmune encephalomyelitis (EAE), is a neurodegenerative autoimmune disease of the CNS characterized by T cell influx and demyelination. Similar to other autoimmune diseases, therapies can alleviate symptoms but often come with side effects, necessitating the exploration of new treatments. We recently demonstrated that the Cullin-RING E3 ubiquitin ligase 4b (CRL4b) aided in maintaining genome stability in proliferating T cells.

Implementation of a liver health check in people with type 2 diabetes.

As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes.

c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8 T cell immunity.

During infection, virus-specific CD8 T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8 T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b).

An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the commonest cause of chronic liver disease worldwide and represents an unmet precision medicine challenge. We established a retrospective national cohort of 940 histologically defined patients (55.4% men, 44.

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas.

PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease.

Background & Aims: Fibroblast activity is a key feature of fibrosis progression and organ function loss, leading to liver-related complications and mortality. The fibrogenesis marker, PRO-C3, has been shown to have prognostic significance in relation to fibrosis progression and as a treatment efficacy marker. We investigated whether PRO-C3 was prognostic for clinical outcome and mortality in two distinct cohorts of compensated cirrhosis.

Continuum finite element analysis generalizestrabecular bone microstructural strength measures between two CT scanners with different image resolution.

Fragility of trabecular bone (Tb) microstructure is increased in osteoporosis, which is associated with rapid bone loss and enhanced fracture-risk. Accurate assessment of Tb strength usingimaging available in clinical settings will be significant for management of osteoporosis and understanding its pathogenesis. Emerging CT technology, featured with high image resolution, fast scan-speed, and wide clinical access, is a promising alternative forTb imaging.

Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK.

Background: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK.

Methods: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource.

Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction.

Objective: Magnetic resonance spectroscopy (MRS) provides a powerful method of measuring fat fraction. However, previous studies have shown that MRS results give lower values compared with visual estimates from biopsies in fibrotic livers. This study investigated these discrepancies and considered whether a tissue water content correction, as assessed by MRI relaxometry, could provide better agreement.

Time to focus on chronic liver diseases in the community: A review of primary care hepatology tools, pathways of care and reimbursement mechanisms.

Addressing primary care's low confidence in detecting and managing chronic liver disease is becoming increasingly important owing to the escalating prevalence of its common lifestyle-related metabolic risk factors - obesity, physical inactivity, smoking and alcohol consumption. Whilst liver blood testing is frequently carried out in the management of long-term conditions, its interpretation is not typically focused on specific liver disease risk. Educational steps for primary care should outline how liver fibrosis is the flag of pathological concern, encourage use of pragmatic algorithms such as fibrosis-4 index to differentiate between those requiring referral for further fibrosis risk assessment and those who can be managed in the community, and emphasise that isolated minor liver function test abnormalities are unreliable for estimating the risk of fibrosis progression.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression.

Background: We annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies.

Methods: Patients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group.

Tumor activated platelets induce vascular mimicry in mesenchymal stem cells and aid metastasis.

Extent of metastasis influences activation of platelets in tumor-microenvironment. Activated platelets potentiate mesenchymal-stem-cells (MSCs) to migrate in secondary metastatic sites without participation in process of invasion. Presence of higher percentage of MSCs along with activated-platelets induces formation of vascular-mimicry (VM).

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

Background: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease.

Genetic variation in modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence.

Computed Tomography-Based Stiffness Measures of Trabecular Bone Microstructure: Cadaveric Validation and In Vivo Application.

Osteoporosis causes bone fragility and elevates fracture risk. Applications of finite element (FE) analysis (FEA) for assessment of trabecular bone (Tb) microstructural strength at whole-body computed tomography (CT) imaging are limited due to challenges with Tb microstructural segmentation. We present a nonlinear FEA method for distal tibia CT scans evading binary segmentation of Tb microstructure, while accounting for bone microstructural distribution.