MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

Background: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner.

Sexual dimorphism of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD.

Predictors of controlled attenuation parameter in metabolic dysfunction.

Background & Aims: Hepatic fat content can be non-invasively estimated by controlled attenuation parameter (CAP) during transient elastography. The aim of this study was to examine the determinants and predictors of CAP values in individuals with metabolic dysfunction.

Methods: We enrolled 1230 consecutive apparently healthy individuals (Liver-Bible-2022 cohort) with ≥3 metabolic dysfunction features.

Liver Involvement in Patients with Rare Variants and Intellectual Disability: A Case Report and Literature Review.

The membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) protein is an acyltransferase catalyzing arachidonic acid incorporation into lysophosphatidylinositol. Patients with rare, biallelic loss-of-function variants of the gene display intellectual disability with neurodevelopmental defects. The rs641738 inherited variant associated with reduced hepatic MBOAT7 expression has been linked to steatotic liver disease susceptibility.

Validation of a targeted gene panel sequencing for the diagnosis of hereditary chronic liver diseases.

The cause of chronic liver diseases (CLD) remains undiagnosed in up to 30% of adult patients. Whole-Exome Sequencing (WES) can improve the diagnostic rate of genetic conditions, but it is not yet widely available, due to the costs and the difficulties in results interpretation. Targeted panel sequencing (TS) represents an alternative more focused diagnostic approach.

Impact of PNPLA3 rs738409 Polymorphism on the Development of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is a complex disease, resulting from the interplay between environmental determinants and genetic variations. Single nucleotide polymorphism rs738409 C>G in the PNPLA3 gene is associated with hepatic fibrosis and with higher risk of developing hepatocellular carcinoma. Here, we analyzed a longitudinal cohort of biopsy-proven NAFLD subjects with the aim to identify individuals in whom genetics may have a stronger impact on disease progression.

Metabolic dysfunction outperforms ultrasonographic steatosis to stratify hepatocellular carcinoma risk in patients with advanced hepatitis C cured with direct-acting antivirals.

Background And Aims: Metabolic dysfunction (MD)-associated fatty liver disease has been proposed to identify individuals at risk of liver events irrespectively of the contemporary presence of other liver diseases. The aim of this study was to examine the impact of MD in patients cured of chronic hepatis C (CHC).

Patients And Methods: We analysed data from a real-life cohort of 2611 Italian patients cured of CHC with direct antiviral agents and advanced liver fibrosis, without HBV/HIV, transplantation and negative for hepatocellular carcinoma (HCC) history (age 61.

Adverse effect of PNPLA3 p.I148M genetic variant on kidney function in middle-aged individuals with metabolic dysfunction.

Background: The PNPLA3 p.I148M variant is the main genetic determinant of nonalcoholic fatty liver disease, and PNPLA3 silencing is being evaluated to treat this liver condition. Data suggest that the p.

Clinical and genetic determinants of the fatty liver-coagulation balance interplay in individuals with metabolic dysfunction.

Background & Aims: The aim of this study was to examine the determinants of the interplay between liver damage and the coagulation balance in individuals at risk of non-alcoholic fatty liver disease (NAFLD).

Methods: We considered 581 healthy participants with ≥3 metabolic alterations undergoing clinical and genomic evaluation, measurement of liver stiffness (LSM) and controlled attenuation parameter (CAP) by Fibroscan, Pro-C3, coagulation balance (von Willebrand factor [vWF], factor VIII/protein C ratio [F8/PC] as the main outcome, D-dimer as marker of coagulation/fibrinolysis activation).

Results: Liver fibrosis indices (both Fibrosis-4 [FIB-4] and liver stiffness measurement [LSM]), but not liver fat (CAP), were independently associated with higher F8/PC ratio ( <0.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.

Rare ATG7 genetic variants predispose patients to severe fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.

Methods: We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs.

Clinical exome sequencing for diagnosing severe cryptogenic liver disease in adults: A case series.

Liver diseases remain unexplained in up to 30% of adult patients; genetic analysis could help establish the correct diagnosis. In six adult patients with cryptogenic liver disease, we performed whole-exome sequencing (WES) and evaluated the individual predisposition to progressive fatty liver disease by polygenic risk scores (PRS). In one patient, WES was allowed to diagnose the Hermansky-Pudlak syndrome.

Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease.

Context: Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity.

Objective: To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD.

Design: Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3).

Dysmetabolism, Diabetes and Clinical Outcomes in Patients Cured of Chronic Hepatitis C: A Real-Life Cohort Study.

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.

Ceruloplasmin gene variants are associated with hyperferritinemia and increased liver iron in patients with NAFLD.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder resulting from genetic and environmental factors. Hyperferritinemia has been associated with increased hepatic iron stores and worse outcomes in patients with NAFLD. The aim of this study was to evaluate the prevalence of variants of iron-related genes and their association with hyperferritinemia, hepatic iron stores and liver disease severity in patients with NAFLD.

SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 outbreak in Milan.

Background: The Milan metropolitan area in Northern Italy was among the most severely hit by the SARS-CoV-2 outbreak. The aim of this study was to examine the seroprevalence trends of SARS-CoV-2 in healthy asymptomatic adults, and the risk factors and laboratory correlates of positive tests.

Materials And Methods: We conducted a cross-sectional study in a random sample of blood donors, who were asymptomatic at the time of evaluation, at the beginning of the first phase (February 24 to April 8 2020; n=789).