Alcohol Intake Thresholds Among Individuals With Steatotic Liver Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Yeo YH
PROVIDER: S-EPMC10722338 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Alcohol Intake Thresholds Among Individuals With Steatotic Liver Disease.
Yeo Yee Hui YH Zhu Yixuan Y Arab Juan Pablo JP Ni Wenjing W Xu Xiaoming X Shi Junping J Li Jie J
JAMA network open 20231201 12
Similar Datasets
Project description:Background & aimsQuantifying alcohol intake is crucial for subclassifying participants with steatotic liver disease (SLD) and interpreting clinical trials of alcohol-related liver disease (ALD) and metabolic and alcohol-related liver disease (MetALD). However, the accuracy of self-reported alcohol intake is considered imprecise. We compared the diagnostic and prognostic utility of self-reported alcohol intake with blood-based biomarkers of alcohol intake: phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT).MethodsWe studied 192 participants from two randomized controlled trials on MetALD and ALD, all with current or former excessive alcohol intake (≥24/36 [♀/♂] grams daily for at least 1 year) and biopsy-proven liver disease. We assessed self-reported alcohol intake, PEth, and CDT at four time points. We collected follow-up data on hepatic decompensation and death manually through electronic medical records.ResultsMost participants were male (n = 161, 84%) with a mean age of 59 (SD 9) years and 73 participants reported 1-week abstinence before inclusion; the remaining reported a median alcohol intake of 43 g/day. Median PEth was 0.5 μmol/L (IQR: 0.0-1.3) and %CDT = 1.9 (IQR: 1.6-2.3). Of 32 patients reporting at least 6 months of abstinence; 27 (84%) was confirmed by PEth <0.05 μmol/L. Self-reported alcohol intake correlated well with PEth (r = 0.617) and moderately with CDT (r = 0.316). Self-reported alcohol intake, PEth, and CDT all predicted hepatic decompensation and death. However, PEth showed the highest prediction, surpassing self-reported alcohol intake (Harrel's C, PEth = 0.80 vs. self-reported = 0.68, p = 0.026).ConclusionsSelf-reported abstinence can be considered reliable in clinical trials. However, PEth is superior in predicting hepatic decompensation and death in patients with MetALD and ALD.Impact and implicationsAn accurate quantification of alcohol intake is crucial in the clinical phenotyping of patients with steatotic liver disease and when designing clinical trials. This study found self-reported abstinence to be reliable but phosphatidylethanol was a more accurate prognostic biomarker of hepatic decompensation and death in a clinical trial setting. Findings may inform the design of future trials in patients with steatotic liver disease.
| S-EPMC11652777 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), both of them accounting for fatty liver disease (FLD), are among the most common chronic liver diseases globally, contributing to substantial public health burden. Both NAFLD and ALD share a similar picture of clinical presentation yet may have differences in prognosis and treatment, which renders early and accurate diagnosis difficult but necessary. While NAFLD is the fastest increasing chronic liver disease, the prevalence of ALD has seemingly remained stable in recent years. Lately, the term steatotic liver disease (SLD) has been introduced, replacing FLD to reduce stigma. SLD represents an overarching term to primarily comprise metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as alcohol-related liver disease (ALD), and MetALD, defined as a continuum across which the contribution of MASLD and ALD varies. The present review discusses current knowledge on common denominators of NAFLD/MASLD and ALD in order to highlight clinical and research needs to improve our understanding of SLD.
| S-EPMC10452742 | biostudies-literature
Project description:IntroductionThis study aimed to investigate the liver-related outcomes of newly suggested metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD), as well as alcohol-associated liver disease (ALD).MethodsFrom a National Health Insurance Service Health Screening Cohort, we included 369,094 participants who underwent health checkups between 2009 and 2010 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥60. The risk of primary liver cancer (PLCa), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), incident cirrhosis, and decompensated cirrhosis was compared with no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model regarding competing risks.ResultsA total of 3,232 participants (0.9%) developed PLCa during the median follow-up of 3,227,176 person-years: 0.5% with no SLD, 1.1% with MASLD, 1.3% with MetALD, and 1.9% with ALD. Competing risk analysis revealed that compared with no SLD, MASLD (SHR: 1.65; 95% CI: 1.44-1.88), MetALD (SHR: 1.87; 95% CI: 1.52-2.29), and ALD (SHR: 1.86; 95% CI: 1.39-2.49) were associated with an increased risk of PLCa. MASLD (SHR: 1.96; 95% CI: 1.67-2.31), MetALD (SHR: 2.23; 95% CI: 1.75-2.84), and ALD (SHR: 2.34; 95% CI: 1.67-3.29) were associated with a higher risk of HCC. No significant difference was observed in the risk of iCCA. The risk of incident cirrhosis and decompensated cirrhosis increased in the order of no SLD, MASLD, MetALD, and ALD.ConclusionMASLD, MetALD, and ALD have an increased risk of PLCa, HCC, incident cirrhosis, and decompensated cirrhosis but not iCCA. These findings may serve as a robust ground for the prognostic value of the newly suggested MASLD and MetALD.
| S-EPMC11305668 | biostudies-literature
Project description:BackgroundSteatotic liver disease (SLD) is a potentially reversible condition but often goes unnoticed with the risk for end-stage liver disease.PurposeTo opportunistically estimate SLD on lung screening chest computed tomography (CT) and investigate its prognostic value in heavy smokers participating in the National Lung Screening Trial (NLST).Material and methodsWe used a deep learning model to segment the liver on non-contrast-enhanced chest CT scans of 19,774 NLST participants (age 61.4 ± 5.0 years; 41.2% female) at baseline and on the 1-year follow-up scan if no cancer was detected. SLD was defined as hepatic fat fraction (HFF) ≥5% derived from Hounsfield unit measures of the segmented liver. Participants with SLD were categorized as lean (body mass index [BMI] < 25 kg/m2) and overweight (BMI ≥ 25 kg/m2). The primary outcome was all-cause mortality. Cox proportional hazard regression assessed the association between (1) SLD and mortality at baseline and (2) the association between a change in HFF and mortality within 1 year.ResultsThere were 5.1% (1000/19,760) all-cause deaths over a median follow-up of 6 (range, 0.8-6) years. At baseline, SLD was associated with increased mortality in lean but not in overweight/obese participants as compared to participants without SLD (hazard ratio [HR] adjusted for risk factors: 1.93 [95% confidence interval 1.52-2.45]; p = 0.001). Individuals with an increase in HFF within 1 year had a significantly worse outcome than participants with stable HFF (HR adjusted for risk factors: 1.29 [1.01-1.65]; p = 0.04).ConclusionSLD is an independent predictor for long-term mortality in heavy smokers beyond known clinical risk factors.
| S-EPMC11846076 | biostudies-literature
Project description:Metabolic-associated steatotic liver disease (MASLD) represents the most common chronic hepatopathy worldwide and an independent risk factor for cardiovascular disease and mortality, particularly when liver fibrosis occurs. Epigenetic alterations, such as DNA methylation, may influence MASLD susceptibility and progression; yet mechanisms underlying this process are limited. This study aimed to investigate whether active DNA demethylation in peripheral blood mononuclear cells (PBMCs) from individuals with MASLD, alongside the methylation and mRNA levels of inflammation- and fibrosis-related candidate genes, is associated with liver fibrosis. For this study, global demethylation intermediates (5-hydroxymethylcytosine [5hmC], 5-formylcytosine [5fC]) were quantified in PBMCs from 89 individuals with/without MASLD using ELISA. Site-specific DNA methylation of SOCS3, SREBF1, and TXNIP was analyzed by mass spectrometry-based bisulfite sequencing; mRNA expression was assessed via RT-PCR. Individuals with MASLD and moderate-to-high fibrosis risk (estimated by the fibrosis non-alcoholic steatohepatitis (NASH) index, FNI) progressively exhibited greater global 5hmC and 5fC levels. Higher FNI was associated with reduced methylation of the SOCS3 gene and increased mRNA expression of the SOCS3, TXNIP, IL-6, and MCP-1 genes. In conclusion, elevated fibrosis risk in MASLD is associated with active global DNA demethylation, as well as differential methylation and expression patterns of genes, which are key regulators of inflammation and fibrosis. These epigenetic alterations in PBMCs may mirror DNA methylation changes in the liver, which may potentially contribute to liver fibrogenesis and represent novel biomarkers for MASLD progression toward fibrosis.
| S-EPMC11818491 | biostudies-literature
Project description:BackgroundExcessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study, we investigate the effect of alcohol consumption and folate intake on HCC incidence and liver disease mortality in the NIH-American Association of Retired Persons Diet and Health Study.MethodsThe study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n = 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n = 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics.ResultsConsumption of more than three drinks per day was positively associated with both HCC incidence (HR: 1.92; 95%CI: 1.42-2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81-7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction = 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction = 0.54).ConclusionsThese results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC.ImpactFolate intake may be beneficial in the prevention of alcohol-associated HCC.
| S-EPMC3596467 | biostudies-literature
Project description:Steatotic liver disease (SLD) is a common chronic liver disease without effective therapeutic options. Some studies suggest potential health benefits of dietary live microbes. This study aims to investigate the association between dietary live microbes intake and metabolic dysfunction-associated steatotic liver disease (MASLD) / metabolic alcohol-related liver disease (MetALD) / alcoholic liver disease (ALD) in adults. Data from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. MASLD was defined according to the latest Delphi Consensus standard. Participants were grouped based on estimated dietary live microbe intake: low (< 104 CFU/g), moderate (104-107 CFU/g), and high (> 107 CFU/g). Multivariable logistic regression analysis was employed to assess the impact of dietary live microbes on MASLD/MetALD/ALD, along with further investigations into non-dietary probiotic/prebiotic relationships. Participants had a weighted mean age of 47.05 years (SE, 0.24) and 50.59% were female. MASLD proportions differ among low (21.76%), moderate (22.24%), and high (18.96%) microbe groups. Similarly, for MetALD, proportions are 7.75%, 6.95%, and 6.44%, and for ALD, 5.42%, 3.59%, and 2.97% in respective groups. The high dietary live microbe intake group was associated with a 16% lower risk of MASLD compared to those in the low intake group (trend test, P = 0.02), while the risk of ALD was reduced by 25% in the moderate intake group. A lack of association was identified between non-dietary prebiotic/probiotic and MASLD/MetALD/ALD. Our study suggests that a relatively high intake of live microbes diets in adults is associated with a lower risk of SLD.
| S-EPMC11829948 | biostudies-literature
Project description:Background & aimsChronic alcohol consumption is a leading risk factor for the development of hepatocellular carcinoma (HCC), which is associated with a marked increase in hepatic expression of pro-inflammatory IL-17A and its receptor IL-17RA.MethodsGenetic deletion and pharmacological blocking were used to characterize the role of IL-17A/IL-17RA signaling in the pathogenesis of HCC in mouse models and human specimens.ResultsWe demonstrate that the global deletion of the Il-17ra gene suppressed HCC in alcohol-fed diethylnitrosamine-challenged Il-17ra-/- and major urinary protein-urokinase-type plasminogen activator/Il-17ra-/- mice compared with wild-type mice. When the cell-specific role of IL-17RA signaling was examined, the development of HCC was decreased in both alcohol-fed Il-17raΔMΦ and Il-17raΔHep mice devoid of IL-17RA in myeloid cells and hepatocytes, but not in Il-17raΔHSC mice (deficient in IL-17RA in hepatic stellate cells). Deletion of Il-17ra in myeloid cells ameliorated tumorigenesis via suppression of pro-tumorigenic/inflammatory and pro-fibrogenic responses in alcohol-fed Il-17raΔMΦ mice. Remarkably, despite a normal inflammatory response, alcohol-fed Il-17raΔHep mice developed the fewest tumors (compared with Il-17raΔMΦ mice), with reduced steatosis and fibrosis. Steatotic IL-17RA-deficient hepatocytes downregulated the expression of Cxcl1 and other chemokines, exhibited a striking defect in tumor necrosis factor (TNF)/TNF receptor 1-dependent caspase-2-SREBP1/2-DHCR7-mediated cholesterol synthesis, and upregulated the production of antioxidant vitamin D3. The pharmacological blocking of IL-17A/Th-17 cells using anti-IL-12/IL-23 antibodies suppressed the progression of HCC (by 70%) in alcohol-fed mice, indicating that targeting IL-17 signaling might provide novel strategies for the treatment of alcohol-induced HCC.ConclusionsOverall, IL-17A is a tumor-promoting cytokine, which critically regulates alcohol-induced hepatic steatosis, inflammation, fibrosis, and HCC.Lay summaryIL-17A is a tumor-promoting cytokine, which critically regulates inflammatory responses in macrophages (Kupffer cells and bone-marrow-derived monocytes) and cholesterol synthesis in steatotic hepatocytes in an experimental model of alcohol-induced HCC. Therefore, IL-17A may be a potential therapeutic target for patients with alcohol-induced HCC.
| S-EPMC7167339 | biostudies-literature
Project description:BackgroundDespite classical association between metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity, there is increasing evidence on the development of MASLD in lean individuals. The aim of the study was to assess the prevalence and risk factors of MASLD and significant liver fibrosis in lean participants with inflammatory bowel disease (IBD).MethodsThis was a cross-sectional, case-control study including 300 lean cases with IBD and 80 lean controls without IBD, matched by sex and age. All participants underwent a liver ultrasound, transient elastography, and laboratory tests.ResultsThe lean IBD group showed a significantly higher prevalence of MASLD compared with lean non-IBD group (21.3% vs 10%; P = .022), but no differences were observed in the prevalence of significant liver fibrosis (4.7% vs 0.0%; P = 1.000). No differences were found between the prevalence of MASLD in IBD and non-IBD participants who were overweight/obese (66.8% vs 70.8%; P = .442). In addition, the prevalence of MASLD was significantly higher in the overweight/obese IBD group compared with the lean IBD group (P < .001). IBD was an independent risk factor for MASLD in lean participants (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.05-7.01; P = .04), after adjusting for classic metabolic risk factors and prior history of systemic steroid use. Nevertheless, no association between IBD related factors and MASLD was identified in lean IBD participants. When the overweight/obese and lean IBD groups with MASLD were compared, the overweight/obese IBD group with MASLD showed higher levels of the homeostatic model assessment of insulin resistance (OR, 1.49; 95% CI, 1.11-1.98; P = .007) and history of smoking (OR, 4.66; 95% CI, 1.17-18.49; P = .029).ConclusionsMASLD prevalence was higher in the lean IBD group compared with lean non-IBD group, independent of classic metabolic risk factors.
| S-EPMC11291618 | biostudies-literature
Project description:Background and aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic and is the most rapidly rising cause of HCC. Clonal hematopoiesis of indeterminate potential (CHIP) contributes to neoplastic and cardiometabolic disorders and is considered a harbinger of tissue inflammation. CHIP was recently associated with increased risk of liver disease. The aim of this study was to examine whether CHIP is associated with HCC development in patients with SLD.Approach and resultsWe considered individuals with MASLD-HCC (n=208) and controls with (n =414) and without (n =259) advanced fibrosis who underwent whole exome sequencing. CHIP was diagnosed when ≥2 variant callers identified a known myeloid mutation with variant allele frequency ≥2%. CHIP was observed in 116 participants (13.1%), most frequently in DNMT3A, TET2, TP53 , and ASXL1 , and correlated with age ( p <0.0001) and advanced liver fibrosis (p=0.001). Higher aspartate aminotransferase levels predicted non- DNMT3A -CHIP, in particular with variant allele frequency ≥10% (OR: 1.14, 1.03 -1.28 and OR: 1.30, 1.12 -1.49, respectively, p <0.05). After adjustment for sex, diabetes, and a polygenic risk, a score of inherited MASLD predisposition CHIP was associated with cirrhosis (2.00, 1.30 -3.15, p =0.02), and with HCC even after further adjustment for cirrhosis (OR: 1.81, 1.11 -2.00, 1.30 -3.15, p =0.002). Despite the strong collinearity among aging and development of CHIP and HCC, non- DNTM3A -CHIP, and TET2 lesions remained associated with HCC after full correction for clinical/genetics covariates and age (OR: 2.45, 1.35 -4.53; OR: 4.8, 1.60 -17.0, p =0.02).ConclusionsWe observed an independent association between CHIP, particularly related to non- DNTM3A and TET2 genetic lesions and MASLD-HCC.
| S-EPMC11407776 | biostudies-literature