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

Åberg, Fredrik; Byrne, Christopher D.; Pirola, Carlos José; Männistö, Ville; Sookoian, Silvia

doi:10.1016/j.jhep.2022.08.030

Cited by 67 publications

(22 citation statements)

References 159 publications

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“…Furthermore, the role of environmental modifiers, such as alcohol consumption 37 and liver tissue microbiota 48 . For example, we found a trend towards a relatively increased abundance of Tyzzerella in the liver of subjects with arterial hypertension compared to non‐hypertensive individuals 49 .…”

Section: Discussionmentioning

confidence: 77%

Non‐alcoholic fatty liver disease mediates the effect of obesity on arterial hypertension

Pirola

Sookoian

2023

Liver International

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BackgroundIt has been consistently shown that obesity contributes directly to arterial hypertension and cardiovascular disease (CVD), independently of other risk factors. Likewise, non‐alcoholic fatty liver disease (NAFLD) is acknowledged as a contributor and a risk enhancer for CVD.ObjectivesWe tested the hypothesis of a causal role of NAFLD in the effect of obesity on arterial hypertension.MethodsUsing causal mediation analysis, we quantified the magnitude of the body mass index (BMI) effect on arterial hypertension and CV‐traits mediated by NAFLD. First, we analysed data from 1348 young adults in the Bogalusa Heart Study (BHS), a cohort aimed at assessing the natural history of CVD. Then, we used data from 3359 participants of the National Health and Nutrition Examination Survey (2017–2018 cycle, NHANES) to replicate the findings.ResultsWe found that roughly 92% of the effects of BMI on arterial hypertension in the BHS and 51% in the NHANES population are mediated by NAFLD. In addition, indirect effects of BMI on systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) through NAFLD explained up to 91%, 93%, and 100% of the total effect, respectively, in the BHS. In the NHANES survey, indirect effects of BMI through NAFLD on CV traits explain a significant proportion of the total effects (SBP = 60.4%, HR = 100%, and pulse pressure = 88%).ConclusionNAFLD mediates a substantial proportion of the effect of obesity on the presence of hypertension and CV‐parameters independently of relevant covariates. This conclusion has implications for clinical management.

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Section: Discussionmentioning

confidence: 77%

Non‐alcoholic fatty liver disease mediates the effect of obesity on arterial hypertension

Pirola

Sookoian

2023

Liver International

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“…Liver diseases are closely associated with metabolic syndromes [ 29 ]. In this study, GO and KEGG functional enrichment analysis showed that DE mRNAs were majorly implicated in the metabolic process, including Amino acid metabolism, Carbon metabolism, Fatty acid metabolism, and Tryptophan metabolism, all of which might be responsible for LPS-induced metabolic syndrome observed during septic liver injury.…”

Section: Discussionmentioning

confidence: 99%

RNA-Sequencing Characterization of lncRNA and mRNA Functions in Septic Pig Liver Injury

Zhang

Xue

Zhao

et al. 2023

Genes

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We assessed differentially expressed (DE) mRNAs and lncRNAs in the liver of septic pigs to explore the key factors regulating lipopolysaccharide (LPS)-induced liver injury. We identified 543 DE lncRNAs and 3642 DE mRNAs responsive to LPS. Functional enrichment analysis revealed the DE mRNAs were involved in liver metabolism and other pathways related to inflammation and apoptosis. We also found significantly upregulated endoplasmic reticulum stress (ERS)-associated genes, including the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), the eukaryotic translation initiation factor 2α (EIF2S1), the transcription factor C/EBP homologous protein (CHOP), and activating transcription factor 4 (ATF4). In addition, we predicted 247 differentially expressed target genes (DETG) of DE lncRNAs. The analysis of protein-protein interactions (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway detected key DETGs that are involved in metabolic pathways, such as N-Acetylgalactosaminyltransferase 2 (GALNT2), argininosuccinate synthetase 1 (ASS1), and fructose 1,6-bisphosphatase 1 (FBP1). LNC_003307 was the most abundant DE lncRNA in the pig liver, with a marked upregulation of >10-fold after LPS stimulation. We identified three transcripts for this gene using the rapid amplification of the cDNA ends (RACE) technique and obtained the shortest transcript sequence. This gene likely derives from the nicotinamide N-methyltransferase (NNMT) gene in pigs. According to the identified DETGs of LNC_003307, we hypothesize that this gene regulates inflammation and endoplasmic reticulum stress in LPS-induced liver damage in pigs. This study provides a transcriptomic reference for further understanding of the regulatory mechanisms underlying septic hepatic injury.

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“…27 The CLivD score combines the effects of several risk factors and also considers low levels of alcohol intake and adiposity, providing a more sensitive estimate of overall risk compared to an impressive increase in a single risk factor. 28 The ELF test has been widely validated 29 and shown to outperform FIB-4 and APRI for detection of advanced fibrosis or cirrhosis in both NAFLD and alcohol-related liver disease patients. 7,8 In addition, in alcohol-related liver disease and mixed-aetiology liver diseases, the ELF test predicts liver-related outcomes as least as well as liver histology.…”

Section: Discussionmentioning

confidence: 99%

“…We recently showed that the CLivD score performed better at selecting individuals for liver fibrosis testing than traditional risk factors, such as harmful alcohol use, diabetes, or obesity considered in isolation 27 . The CLivD score combines the effects of several risk factors and also considers low levels of alcohol intake and adiposity, providing a more sensitive estimate of overall risk compared to an impressive increase in a single risk factor 28 …”

Section: Discussionmentioning

confidence: 99%

Combined use of the ELF test and CLivD score improves prediction of liver‐related outcomes in the general population

Åberg

Saarinen

Jula

et al. 2023

Liver International

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Background and AimsEffective and feasible population screening strategies are needed for the early detection of individuals at high risk of future severe liver‐related outcomes. We evaluated the predictive performance of the combination of liver fibrosis assessment, phenotype profile, and genetic risk.MethodsData from 5795 adults attending the Finnish Health 2000 Survey were linked with healthcare registers for liver‐related outcomes (hospitalization, hepatocellular cancer, and death). Fibrosis was assessed using the enhanced liver fibrosis (ELF) test, phenotype profile by the chronic liver disease (CLivD) risk score, and genetic risk by a validated Polygenic Risk Score (PRS‐5). Predictive performance was assessed by competing‐risk analyses.ResultsDuring a median 13‐year follow‐up, 64 liver‐related outcome events were recorded. ELF, CLivD score, and PRS‐5 were independently associated with liver‐related outcomes. The absolute 10‐year risk of liver‐related outcomes at an ELF value of 11.3 ranged from 0.3% to 33% depending on the CLivD score. The CLivD score added 51% of new predictive information to the ELF test and improved areas under the curve (AUCs) from 0.91, 0.81, and 0.71 for ELF alone to 0.95, 0.85, and 0.80, respectively, for ELF combined with the CLivD score at 1, 5, and 10 years. The greatest improvement was for 10‐year predictions (delta‐AUC 0.097, p < .0001). Adding PRS‐5 did not significantly increase predictive performance. Findings were consistent in individuals with obesity, diabetes, or alcohol risk use, and regardless of whether gamma‐glutamyltransferase was used in the CLivD score.ConclusionA combination of ELF and CLivD score predicts liver‐related outcomes significantly better than the ELF test alone.

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

Cited by 67 publications

References 159 publications

Non‐alcoholic fatty liver disease mediates the effect of obesity on arterial hypertension

Non‐alcoholic fatty liver disease mediates the effect of obesity on arterial hypertension

RNA-Sequencing Characterization of lncRNA and mRNA Functions in Septic Pig Liver Injury

Combined use of the ELF test and CLivD score improves prediction of liver‐related outcomes in the general population

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