PNPLA3, TM6SF2, and MBOAT7 Influence on Nutraceutical Therapy Response for Non-alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Introduction: PNPLA3, TM6SF2, and MBOAT7 genes play a crucial role in non-alcoholic fatty liver disease (NAFLD) development and worsening. However, few data are available on their treatment response influence. The aim of this trial is to explore the effect derived from silybin-phospholipids complex (303 mg of silybin-phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E twice a day for 6 months) oral administration in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926, or MBOAT7-rs641738 genetic variants.Materials and Methods: In all, 92 biopsy-proven NAFLD patients were grouped in 30 NAFLD wild type controls, 30 wild type treated patients, and 32 mutated treated ones. We assessed glycemia (FPG), insulinemia, HOMA-IR, aspartate and alanine aminotransferases (AST, ALT), C-reactive protein (CRP), thiobarbituric acid reactive substance (TBARS), stiffness, controlled attenuation parameter (CAP), dietary daily intake, and physical activity at baseline and end of treatment.Results: The wild-type treated group showed a significant improvement of FPG, insulinemia, HOMA-IR, ALT, CRP, and TBARS (p < 0.05), whereas no improvements were recorded in the other two study groups. NAFLD wild type treated patients showed higher possibilities of useful therapeutic outcome (p < 0.01), obtained from the prescribed therapeutic regimen, independently from age, sex, comorbidities, medications, CAP, and stiffness in comparison to the mutated group.Discussion: The assessed mutations are independently associated with no response to a silybin-based therapeutic regimen and could be considered as useful predictive markers in this context.Clinical Trial Registry Number:www.ClinicalTrials.gov, identifier: NCT04640324.

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Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.261.ely ◽

2017 ◽

Vol 26 (1) ◽

pp. 59-67 ◽

Cited By ~ 25

Author(s):

Ahmed Elgebaly ◽

Ibrahim A. I. Radwan ◽

Mohamed M. AboElnas ◽

Hamza H. Ibrahim ◽

Moutaz F. M. Eltoomy ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Randomized Clinical Trials ◽

Controlled Trial ◽

Antioxidant Properties ◽

Density Lipoprotein ◽

Current Evidence ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.

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Faculty Opinions recommendation of Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726337644.793518074 ◽

2016 ◽

Author(s):

Philip Rosenthal

Keyword(s):

Randomized Controlled Trial ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Controlled Trial ◽

Alcoholic Fatty Liver ◽

Randomized Controlled ◽

Alcoholic Fatty Liver Disease

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Nutrigenetics-based intervention approach for adults with non-alcoholic fatty liver disease (NAFLD): study protocol for a randomised controlled feasibility trial

BMJ Open ◽

10.1136/bmjopen-2020-045922 ◽

2021 ◽

Vol 11 (4) ◽

pp. e045922

Author(s):

Laura Haigh ◽

Stuart McPherson ◽

John C Mathers ◽

Quentin M Anstee

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Controlled Trial ◽

Phase 1 ◽

Feasibility Trial ◽

Alcoholic Fatty Liver ◽

Intervention Protocol ◽

Randomised Controlled ◽

Alcoholic Fatty Liver Disease

IntroductionLifestyle interventions targeting weight loss and improved dietary patterns are the recommended treatment for non-alcoholic fatty liver disease (NAFLD). However, the effectiveness of current established diet therapies is suboptimal. The patatin‐like phospholipase domain containing 3 (PNPLA3) gene modifies disease outcome and hepatic lipid handling, but the role of PNPLA3 variants in modulating responsiveness to different diet therapies is unknown.Methods and analysisThis project aims to assess the feasibility of conducting a genotype-driven randomised controlled trial (RCT) investigating the differential response to a Mediterranean diet (MD) intervention of NAFLD patients according to genotype for the rs738409 (I148M) variant of PNPLA3. A single-centre randomised controlled feasibility trial will be undertaken. We will recruit 60 adults with NAFLD from a tertiary hepatology centre in England. In a cross-over design, participants will undertake Diet 1 (MD) and Diet 2 (control) for 4 weeks, in random order (1:1 allocation), separated by a 4 weeks washout period. Participants will complete one-to-one diet and lifestyle consultations at baseline, end of diet phase 1, end of washout and end of diet phase 2. Participants will be advised to maintain baseline levels of physical activity and body weight. The primary outcome is the acceptability and feasibility of the intervention protocol. Secondary outcomes include exploratory assessment of liver fibrosis biomarkers and lipid biomarkers.Ethics and disseminationEthical approval was granted by East of Scotland Research Ethics Service REC 1 (19/ES/0112). Results will be disseminated through peer-reviewed journals and presented at local, national and international meetings and conferences. The findings of this trial will lay the foundation for a future definitive RCT by informing trial design and optimising the intervention diets, instruments and procedures.Trial registration numberISRCTN93410321.

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Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

Scientific Reports ◽

10.1038/srep39328 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 62

Author(s):

Robin Mesnage ◽

George Renney ◽

Gilles-Eric Séralini ◽

Malcolm Ward ◽

Michael N. Antoniou

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Low Dose ◽

Daily Intake ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Metabolome Analysis ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Abstract The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure.

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