Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease.

Alcohol use and metabolic syndrome are highly prevalent in the population and frequently co-exist. Both are implicated in a large range of health problems, including chronic liver disease, hepatocellular carcinoma, and liver-related outcomes (i.e.

Geographical similarity and differences in the burden and genetic predisposition of NAFLD.

NAFLD has become a major public health problem for more than 2 decades with a growing prevalence in parallel with the epidemic of obesity and type 2 diabetes (T2D). The disease burden of NAFLD differs across geographical regions and ethnicities. Variations in prevalence of metabolic diseases, extent of urban-rural divide, dietary habits, lifestyles, and the prevalence of NAFLD risk and protective alleles can contribute to such differences.

PNPLA3 rs738409 and risk of fibrosis in NAFLD: Exploring mediation pathways through intermediate histological features.

Background And Aims: It is unclear whether rs738409 (p.I148M) missense variant in patatin-like phospholipase domain-containing 3 rs738409 promotes fibrosis development by triggering specific fibrogenic pathways or by creating an unfavorable microenvironment by promoting steatosis, inflammation, and ultimately fibrosis. We tested the hypothesis that intermediate histologic traits, including steatosis, lobular and portal inflammation, and ballooning may determine the effect of rs738409 on liver fibrosis among individuals with biopsy-proven NAFLD.

MicroRNAs as messengers of liver diseases: has the message finally been decrypted?

MicroRNAs (miRNAs), which are regarded as crucial regulators of gene expression and diverse aspects of cell biology, can be present in various body fluids as highly stable molecules. It is also known that miRNAs exert tissue-specific regulation of gene transcription. Large amount of clinical and experimental evidence provided the rationale for raising the intriguing question of whether miRNAs can mediate cell-cell communication.

Computational Pipeline for Next-Generation Sequencing (NGS) Studies in Genetics of NASH.

High-throughput sequencing (HTS) technologies have contributed to expand current knowledge of the biology of complex diseases, including nonalcoholic fatty liver disease (NAFLD). Genome-wide association studies, whole exome sequencing, and sequencing of entire genes are used to identify variants and/or mutations that predispose to the disease pathogenesis. Here, we present a tutorial that may guide readers to manage high volume of genetics data in the context of Next-Generation Sequencing (NGS) studies.

The influence of host genetics on liver microbiome composition in patients with NAFLD.

Background: Human body microbiotas are influenced by several factors, including the interaction of the host with the environment and dietary preferences. The role of host genetics in modulating the liver microbiota in the context of NAFLD remains unknown. To address this gap, we examined the interplay between the liver metataxonomic profile and host genetics.

Metabolic dysfunction-associated fatty liver disease: advances in genetic and epigenetic implications.

Purpose Of Review: Fatty liver associated with metabolic dysfunction, also known under the acronym NAFLD (nonalcoholic fatty liver disease) is the leading global cause of chronic liver disease. In this review, we address the state of research on genetics and epigenetics of NAFLD with focus on key discoveries and conceptual advances over the past 2 years.

Recent Findings: The analysis of NAFLD-associated genetic variant effects on the whole-transcriptome, including quantitative trait loci (QTL) associated with gene expression (eQTL) or splicing (sQTL) may explain pleiotropic effects.

The Protection Conferred by HSD17B13 rs72613567 Polymorphism on Risk of Steatohepatitis and Fibrosis May Be Limited to Selected Subgroups of Patients With NAFLD.

Introduction: Our study aimed to explore how PNPLA3 rs738409 or phenotypic risk factors may moderate the relationship between HSD17B13 rs72613567 and risk of steatohepatitis and fibrosis.

Methods: This analysis consisted of 1,153 non-Hispanic whites with biopsy-proven nonalcoholic fatty liver disease enrolled in the nonalcoholic steatohepatitis Clinical Research Network studies. Nonalcoholic fatty liver disease severity was determined by liver histology scored centrally according to the nonalcoholic steatohepatitis Clinical Research Network criteria.

Liver tissue microbiota in nonalcoholic liver disease: a change in the paradigm of host-bacterial interactions.

Nonalcoholic fatty liver disease (NAFLD) pathogenesis is explained by the complex relationship among diet and lifestyle-predisposing factors, the genetic variance of the nuclear and mitochondrial genome, associated phenotypic traits, and the yet not fully explored interactions with epigenetic and other environmental factors, including the microbiome. Despite the wealth of knowledge gained from molecular and genome-wide investigations in patients with NAFLD, the precise mechanisms that explain the variability of the histological phenotypes are not fully understood. Earlier studies of the gut microbiota in patients with NAFLD and nonalcoholic steatohepatitis (NASH) provided clues on the role of the fecal microbiome in the disease pathogenesis.

Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD.

Introduction: This study explored the relationship between patatin-like phospholipase domain-containing 3 gene (PNPLA3 rs738409), nutrient intake, and liver histology severity in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: PNPLA3-rs738409 variant was genotyped in 452 non-Hispanic whites with histologically confirmed NAFLD who completed Food Frequency Questionnaire within 6 months of their liver biopsy. The fibrosis severity on liver histology was the outcome of interest.

Precision medicine in nonalcoholic fatty liver disease: New therapeutic insights from genetics and systems biology.

Despite more than two decades of extensive research focusing on nonalcoholic fatty liver disease (NAFLD), no approved therapy for steatohepatitis-the severe histological form of the disease-presently exists. More importantly, new drugs and small molecules with diverse molecular targets on the pathways of hepatocyte injury, inflammation, and fibrosis cannot achieve the primary efficacy endpoints. Precision medicine can potentially overcome this issue, as it is founded on extensive knowledge of the druggable genome/proteome.

Liver mitochondrial DNA damage and genetic variability of Cytochrome b - a key component of the respirasome - drive the severity of fatty liver disease.

Background And Aims: The progression of nonalcoholic fatty liver disease (NAFLD) into severe histological forms (steatohepatitis - NASH) is paralleled by the occurrence of complex molecular processes. Mitochondrial dysfunction is a hallmark feature of advanced disease. Mitochondrially encoded cytochrome B (cytochrome b, MT-CYB), a member of the oxidative phosphorylation system, is a key component of the respirasome supercomplex.

Epigenetics factors in nonalcoholic fatty liver disease.

: Fatty liver disease, defined by the presence of liver fat infiltration, is part of a cluster of disorders that occur in the context of metabolic syndrome. Epigenetic factors - defined as stable and heritable changes in gene expression without changes in the DNA sequence - may not only play an important role in the disease development in adulthood, but they may start exerting their influence in the prenatal stage.: By using systems biology approaches, we review the main epigenetic modifications and highlight their likely roles in the pathogenesis of nonalcoholic fatty liver disease.

Estimation of Renin-Angiotensin-Aldosterone-System (RAAS)-Inhibitor effect on COVID-19 outcome: A Meta-analysis.

Background And Rationale: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis.

Aim And Methods: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis.

ADH1B∗2 Is Associated With Reduced Severity of Nonalcoholic Fatty Liver Disease in Adults, Independent of Alcohol Consumption.

Background & Aims: Alcohol dehydrogenase 1B (ADH1B) is involved in alcohol metabolism. The allele A (ADH1B∗2) of the rs1229984: A>G variant in ADH1B is associated with a higher alcohol metabolizing activity compared to the ancestral allele G (ADH1B∗1). Moderate alcohol consumption is associated with reduced severity of nonalcoholic fatty liver disease (NAFLD), based on histologic analysis, compared with no alcohol consumption.

Genetic Pathways in Nonalcoholic Fatty Liver Disease: Insights From Systems Biology.

Nonalcoholic fatty liver disease (NAFLD) represents a burgeoning worldwide epidemic whose etiology reflects multiple interactions between environmental and genetic factors. Here, we review the major pathways and dominant genetic modifiers known to be relevant players in human NAFLD and which may determine key components of the heritability of distinctive disease traits including steatosis and fibrosis. In addition, we have employed general assumptions which are based on known genetic factors in NAFLD to build a systems biology prediction model that includes functional enrichment.

Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease.

Objective: We aimed to characterise the liver tissue bacterial metataxonomic signature in two independent cohorts of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosis, as differences in the host phenotypic features-from moderate to severe obesity-may be associated with significant changes in the microbial DNA profile.

Design And Methods: Liver tissue samples from 116 individuals, comprising of 47 NAFLD overweight or moderately obese patients, 50 NAFLD morbidly obese patients elected for bariatric surgery and 19 controls, were analysed using high-throughput 16S rRNA gene sequencing.

Results: Liver bacterial DNA profile significantly differs between morbidly obese and non-morbidly obese patients with NAFLD.