Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD)

Abstract

Background: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. Results: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. Conclusions: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

Impact of MAFLD on HBV-Related Stage 0/A Hepatocellular Carcinoma after Curative Resection

“…T2DM was defined based on the World Health Organization (WHO) National diabetic group criteria [23]. Lean-MAFLD was subclassified as a BMI < 23 kg/m 2 in Asians [24].…”

Is Drinking Alcohol Really Linked to Cardiovascular Health? Evidence from the Kardiovize 2030 Project

“…Thus, we investigated the association between alcohol consumption and CVH, with the aim of understanding whether alcohol quantity, drinking patterns, and types of alcoholic beverage might exert different effects on their relationship. For doing that, we conducted a cross-sectional analysis on data from the Kardiovize study, a population-based prospective study assessing both traditional and novel risk factors for CVD, in a randomly selected~1% of the urban population of Brno (Czech Republic) [14][15][16][17][18][19][20][21][22][23]. We have chosen this cohort since previous findings from the Kardiovize study were consistent with the WHO report in showing that approximately 80% Czech adult drank alcohol in the form of beer, spirits, or wine [1,24].…”

Circulating cell-free nucleosomes as biomarker for kidney transplant rejection: a pilot study

“…Currently, we are collecting samples in a larger cohort of kidney transplant recipients where the effect of IRI on CCFN during rejection should be explored by comparing rejections occurring shortly after transplantation with rejections occurring later on after transplantation. It would also be of interest to investigate CCFN using ImageStream(X)-based imaging technology, a newly identified promising methodological approach to measure CCFN [ 26 ].…”