Alterations in Circulating Bile Acids in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis
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PROVIDER: S-EPMC10526305 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:Global hepatic DNA methylation change has been linked to human patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DNA demethylation is regulated by the TET family proteins, whose enzymatic activities require 2-oxoglutarate (2-OG) and iron that both are elevated in MASLD human patients. We aimed to investigate liver TET1 in MASLD progression. Depleting TET1 using two different strategies substantially alleviated MASLD progression. Knockout of TET1 slightly improved diet induced obesity and glucose homeostasis. Intriguingly, hepatic cholesterols, triglycerides, and CD36 were significantly decreased upon TET1 depletion. Consistently, liver specific TET1 KO led to improvement of MASLD progression. Mechanistically, TET1 promoted CD36 expression through transcriptional upregulation via DNA demethylation control. Overexpression of CD36 reversed the impacts of TET1 downregulation on fatty acid uptake in hepatocytes. More importantly, targeting TET1 with a small molecule inhibitor significantly suppressed MASLD progression. Liver TET1 plays a deleterious role in MASLD, suggesting the potential of targeting TET1 in hepatocytes to suppress MASLD.
| S-SCDT-10_1038-S44321-025-00224-4 | biostudies-other
Project description:Multiple observation studies and meta-analysis have linked growth hormone (GH) deficiency with metabolic-dysfunction-associated steatotic liver disease (MASLD). No meta-analysis has analysed the efficacy and safety of GH therapy on different aspects of MASLD. We undertook this meta-analysis to address this gap in knowledge. Electronic databases were searched for RCTs involving patients with MASLD receiving GH therapy. Primary outcome was to evaluate changes in radiologic measures of MASLD (magnetic resonance spectroscopy (MRS) and ultrasonography) and liver enzymes. Secondary outcomes were to evaluate alterations in body composition parameters [dual-energy X-ray absorptiometry (DXA)], lipids, glycaemia and side effects. From initially searched 1047 articles, data from three RCTs (120 patients) which fulfilled all criteria were analysed. After 6 months of GH therapy in MASLD, the per cent reduction in intrahepatic lipid (MRS) was significantly higher with GH as compared to placebo [MD -5.85% (95%CI:-11.41- -0.30); P = 0.04; I2 = 63%]. Visceral adipose tissue (VAT) area reduction (DXA) was significantly higher with GH [MD-9.94 cm2 (95%CI:-19.04- -0.84); P = 0.03; I2 = 0%]. Serum insulin-like growth factor-1 (IGF-1) was significantly raised in MASLD patients receiving GH as compared to placebo [MD +166.86 ng/ml (95%CI: 79.19-254.53); P < 0.0.001; I2 = 90%]. High-sensitivity C-reactive protein (hsCRP) was significantly lower in patients receiving GH [MD -0.89 mg/L (95%CI:-1.40--0.38); P = 0.0.0006; I2 = 0%]. Patients receiving GH had similar changes in triglycerides [MD-1.06 mg/L (95%CI:-20.45-18.34); P = 0.91; I2 = 15%] and fasting glucose [MD -0.56 mg/L (95%CI:-4.67-3.55); P = 0.79; I2 = 39%]. Gamma-glutamyl transpeptidase was significantly lower in patients receiving GH [MD -7.86 U/L (95%CI:-12.46--3.27); P = 0.0008; I2 = 0%]. No increase in new-onset hypothyroidism was noted [OR 5.49 (95%CI: 0.25-121.18); P = 0.28]. Short-term 6-month GH therapy in MASLD is associated with a significant reduction in intrahepatic lipid content, visceral adiposity, GGT and hsCRP without any increased occurrence of dysglycaemia or hypothyroidism.
| S-EPMC11451958 | 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:Epidemiological studies have reported an association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of urolithiasis. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between MASLD and urolithiasis. We systematically searched PubMed, Scopus, and Web of Science from database inception to March 31, 2024, using predefined keywords to identify relevant observational studies in which imaging methods or survey questionnaires diagnosed MASLD and urolithiasis. Meta-analysis was performed using random-effects modelling. We identified seven cross-sectional studies and one prospective cohort study with aggregate data on 248,936 adults from different countries. MASLD was significantly associated with an increased risk of prevalent urolithiasis (pooled random-effects odds ratio 1.87, 95% CI 1.34-2.60; I2 = 91%). This association remained significant in those studies whose results were adjusted for age, sex, ethnicity, obesity, diabetes, and other potential confounders. There was a positive graded association between the ultrasonographic severity of MASLD and urolithiasis. Meta-analysis of the single prospective cohort study showed that MAFLD was not associated with risk of developing incident urolithiasis (pooled random-effects hazard ratio 1.08, 95% CI 0.90-1.30), although a significant association was reported in men. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. This updated meta-analysis provides evidence for a significant association between MASLD and the presence of urolithiasis. Whether MASLD is associated with a higher risk of developing incident urolithiasis remains to be established.
| S-EPMC11405432 | biostudies-literature
Project description:The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) have been steadily increasing worldwide, with a huge societal and economic burden. Recently, NAFLD and non-alcoholic steatohepatitis have been renamed and redefined as metabolic dysfunction associated steatotic liver disease (MASLD) and steatohepatitis (Metabolic Dysfunction Associated Steatohepatitis (MASH)), which result from an imbalance between metabolic and inflammatory stress (mainly as a consequence of adipose tissue dysfunction and insulin resistance) and the defence and repair mechanisms of the steatotic liver. Once MASLD progresses to end-stage of liver disease, treatment efficacy becomes limited and may require liver transplantation. Early detection and intervention are crucial. Lifestyle modification is consequently the cornerstone of its management. Timely consideration of bariatric surgeries should be given to patients meeting specific criteria. A multidisciplinary approach is warranted, starting from the concept that MASLD/MASH is at the centre of the cardiovascular-liver-metabolic syndrome. In some cases, pharmacological treatment can complement lifestyle modification. Several drugs used to treat the cardiometabolic co-morbidities have some potential efficacy in slowing Down disease progression, and some have demonstrated efficacy on histological endpoints that are likely to translate into long-term clinical benefits. Optimising the use of these drugs within their licenced indications is thus paramount for patients with MASLD. Several MASH-specific drugs are on the horizon and are likely to enrich our therapeutic armamentarium in the near future, particularly in non-cirrhotic stages of the disease. Much work still needs to be done to understand the specific features of MASH cirrhosis and develop efficacious treatments for this disease stage.
| S-EPMC10954426 | biostudies-literature
Project description:ImportanceIn the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC.ObjectiveTo develop a prediction model for HCC incidence in a cohort of patients with MASLD.Design, setting, and participantsThis prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024.ExposureData were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD.Main outcome and measuresThe cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk.ResultsA total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241.Conclusions and relevanceThis prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.
| S-EPMC11240192 | biostudies-literature
Project description:BackgroundAlterations in the production of short-chain fatty acids (SCFAs) may reflect disturbances in the gut microbiota and have been linked to metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed plasma SCFAs in patients with MASLD and healthy controls.MethodsFasting venous blood samples were collected and eight SCFAs were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). Relative between-group differences in circulating SCFA concentrations were estimated by linear regression, and the relation between SCFA concentrations, MASLD, and fibrosis severity was investigated using logistic regression.ResultsThe study includes 100 patients with MASLD (51% with mild/no fibrosis and 49% with significant fibrosis) and 50 healthy controls. Compared with healthy controls, MASLD patients had higher plasma concentrations of propionate (21.8%, 95% CI 3.33 to 43.6, p = 0.02), formate (21.9%, 95% CI 6.99 to 38.9, p = 0.003), valerate (35.7%, 95% CI 4.53 to 76.2, p = 0.02), and α-methylbutyrate (16.2%, 95% CI 3.66 to 30.3, p = 0.01) but lower plasma acetate concentrations (- 30.0%, 95% CI - 40.4 to - 17.9, p < 0.001). Among patients with MASLD, significant fibrosis was positively associated with propionate (p = 0.02), butyrate (p = 0.03), valerate (p = 0.03), and α-methylbutyrate (p = 0.02). Six of eight SCFAs were significantly increased in F4 fibrosis.ConclusionsIn the present study, SCFAs were associated with MASLD and fibrosis severity, but further research is needed to elucidate the potential mechanisms underlying our observations and to assess the possible benefit of therapies modulating gut microbiota.
| S-EPMC10804800 | biostudies-literature
Project description:Background/Objectives: Psoriasis is a chronic immune-mediated skin disease associated with several metabolic comorbidities. Metabolic dysfunction-associated steatotic liver disease (MASLD) is also linked to psoriasis, but evidence regarding the severity of this association remains inconclusive. This meta-analysis aimed to investigate the relationship between MASLD and varying severities of psoriasis. Methods: We conducted an extensive search of four databases, MEDLINE, EMBASE, OSF, and ClinicalTrials.gov to identify relevant published articles assessing the risk of prevalent MASLD in patients with moderate-to-severe psoriasis up to April 2024. Effect estimates from each included study were combined together to calculate a pooled effect estimate for the meta-analysis using the generic inverse variance method of DerSimonian and Laird. Results: This meta-analysis included eight studies with a total of 109,806 participants. A 4.01-fold increased risk of prevalent MASLD was observed in patients with moderate-to-severe psoriasis compared to those without psoriasis (95% CI: 2.17, 7.77; I2 = 67%, p < 0.0001). The evidence supporting this outcome had low certainty. Conclusions: An incremental trend of MASLD was observed in patients with moderate-to-severe psoriasis. Routine screening for MASLD should be emphasized in this population.
| S-EPMC11855964 | biostudies-literature
Project description:ObjectiveGlobally, the occurrence of Metabolic dysfunction-associated steatotic liver disease (MASLD) is on a steady rise. Fish oil has anti-inflammatory effects and can improve lipid metabolism. The article aims to assess the impact of fish oil supplementation on MASLD.MethodsWe conducted a systematic search of Cochrane, Embase, PubMed, and Web of Science up to September 31, 2024, for randomized control trials (RCTs). The risk of bias of the included RCTs was evaluated using the Cochrane Collaboration's tool. Outcomes measured were aspects of liver injury, lipid profile, insulin resistance, anthropometric measurements, and more.ResultsSeven randomized controlled trials (RCTs) involving 439 participants were incorporated into the analysis. In general, the risk of bias in these RCTs was either low or not clearly defined. Pooled analysis showed that triglycerides [TG, pooled standard mean difference (SMD): -0.40 (95% CI: -0.58 to -0.21)], aspartate transaminase [AST, SMD: -0.29 (95% CI: -0.48 to -0.10)], HOMA-IR [SMD: -2.06 (95% CI: -3.36 to -0.49)] and waist circumference [Waist-C, SMD: -0.31 (95% CI: -0.54 to -0.08)] were significantly improved. But showed no significant benefits on alanine transaminase [ALT, SMD: -0.15 (95% CI: -0.45 to 0.15)], gamma-glutamyl transpeptidase [GGT, SMD: -0.07 (95% CI: -0.26 to 0.12)], body mass index [BMI, SMD: 0.16 (95% CI: -0.34 to 0.02)], high-density lipoprotein cholesterol [HDL, SMD: 0.02 (95% CI: -0.18 to 0.22)], low-density lipoprotein cholesterol [LDL, SMD: -0.01 (95% CI: -0.20 to 0.18)], Total Cholesterol [TC, SMD: -0.34 (95% CI: -0.70 to 0.01)] and so on.ConclusionThe current evidence supports the fish oil supplementation in improving MASLD. Fish oil supplementation may also regulate blood lipids and improve glucose metabolism disorders.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024513246.
| S-EPMC11804523 | biostudies-literature
Project description: Not available
| S-EPMC11016929 | biostudies-literature