Causal relationships between metabolic‐associated fatty liver disease and iron status: Two‐sample Mendelian randomization

He, He; Liao, Shenling; Zeng, Yuping; Liang, Libo; Chen, Jie; Tao, Chuanmin

doi:10.1111/liv.15455

Cited by 21 publications

(14 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By means of Mendelian randomization as a robust epidemiological approach to analyse the causal estimation of fatty liver disease associated with metabolic dysfunction (also known as metabolic dysfunctionassociated fatty liver disease (MAFLD)) as an outcome using genetic variants, a study published in 2022 that included European individuals showed that the genetically predicted increase in liver levels of iron was associated with an increased risk of fatty liver disease. Although they need confirmation, these data support a causal association between deposition levels of iron in the liver and metabolic dysfunction 38 .…”

Section: Acquiredmentioning

confidence: 75%

Consensus Statement on the definition and classification of metabolic hyperferritinaemia

et al. 2023

View full text Add to dashboard Cite

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes. Sections MethodologyGiven the high prevalence of hyperferritinaemia in clinical practice, combined with a growing understanding of the underlying pathophysiology and clinical implications, an updated definition and grading system is warranted. The overall goal of this Consensus Statement was therefore to provide a proposal for a more accurate diagnosis and classification of MHF, to be validated by prospective studies, to provide suggestions on the design of these studies and to highlight some of the main unmet research needs in the field. Owing to the current absence of robust evidence to support the recommendation to screen for and diagnose MHF and then to treat this condition with a specific approach (such as iron depletion), the current Consensus Statement is mainly directed at clinicians who work in tertiary referral centres and clinical and basic researchers. The updated MHF definition will enable larger collaborative studies on the clinical implications, pathophysiology and therapy of this condition, although it will still require prospective validation and further refinement. The long-term goal is the improvement of clinical management of patients with MHF. On the basis of current evidence, we also provide expert recommendations for clinicians on the diagnosis, management, follow-up and treatment of this condition (presented in the Supplementary material).Consensus was reached by a multidisciplinary global panel of expert researchers with an interest in MHF from five continents and 14 countries working in the fields of iron metabolism, clinical endocrinology, ...

show abstract

Section: Acquiredmentioning

confidence: 75%

Consensus Statement on the definition and classification of metabolic hyperferritinaemia

et al. 2023

View full text Add to dashboard Cite

show abstract

“…10 A recent Mendelian randomization study using data from the UK Biobank showed tentative evidence for a potential causal association of liver iron on fatty liver. 11 At the same time, oxidative stress induced by iron overload leads to increased insulin resistance, establishing a link between circulating markers of iron metabolism and T2D. 12 Sex-specific associations, with higher T2D risk conferred by elevated ferritin levels in women compared to men, have been reported.…”

Section: Backg Rou N Dmentioning

confidence: 99%

“…An association between markers of iron metabolism and liver disease has already been established 10 . A recent Mendelian randomization study using data from the UK Biobank showed tentative evidence for a potential causal association of liver iron on fatty liver 11 …”

Section: Introductionmentioning

confidence: 98%

Trajectories of glycaemic traits exhibit sex‐specific associations with hepatic iron and fat content: Results from the KORA‐MRI study

Niedermayer

Krüchten

et al. 2023

Liver International

View full text Add to dashboard Cite

BackgroundNon‐alcoholic fatty liver disease (NAFLD) represents a major disease burden in the population. While the bidirectional association between NAFLD and diabetes is established, little is known about the association of hepatic iron content and glycaemia. Moreover, analyses of sex‐specific effects and of dynamic changes in glycaemia are scarce.MethodsWe investigated 7‐year sex‐specific trajectories of glycaemia and related traits (HbA1c, fasting glucose, fasting insulin, HOMA‐IR, 2‐h glucose and cross‐sectional 2‐h insulin) in a sample from a population‐based cohort (N = 365; 41.1% female). Hepatic iron and fat content were assessed by 3T‐Magnetic Resonance Imaging (MRI). Two‐step multi‐level models adjusted for glucose‐lowering medication and confounders were applied.ResultsIn women and men, markers of glucose metabolism correlated with hepatic iron and fat content. Deterioration of glycaemia was associated with increased hepatic iron content in men (normoglycaemia to prediabetes: beta = 2.21 s−1, 95% CI [0.47, 3.95]). Additionally, deterioration of glycaemia (e.g. prediabetes to diabetes: 1.27 log(%), [0.84, 1.70]) and trajectories of glucose, insulin and HOMA‐IR were significantly associated with hepatic fat content in men. Similarly, deterioration of glycaemia as well as trajectories of glucose, insulin and HOMA‐IR was significantly associated with increased hepatic fat content in women (e.g. trajectory of fasting insulin: 0.63 log(%), [0.36, 0.90]).ConclusionsUnfavourable 7‐year trajectories of markers of glucose metabolism are associated with increased hepatic fat content, particularly in women, whereas the association with hepatic iron content was less clear. Monitoring changes of glycaemia in the sub‐diabetic range might enable early identification of hepatic iron overload and steatosis.

show abstract

“…Similar findings have been reported regarding the dietary intake of vitamin K ( 10 ). On the other hand, a mendelian randomization study showed an elevated risk of MAFLD associated with an increase in liver iron concentration ( 11 ). Multiple factors, such as oxidative stress-induced lipotoxicity and cellular senescence, contribute to the pathogenesis and progression of MAFLD ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Association of multiple serum minerals and vitamins with metabolic dysfunction-associated fatty liver disease in US adults: National Health and Nutrition Examination Survey 2017–2018

Guo,

2024

Front. Nutr.

View full text Add to dashboard Cite

BackgroundDespite the rapid increase in the global prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), there are no approved therapeutic drugs for MAFLD yet. Nutrient supplementation might mitigate the risk of MAFLD. It is more typical for individuals to consume multiple nutrients simultaneously. However, the studies exploring the combined effects of multiple nutrients on MAFLD are limited. This study aimed to investigate the relationship between both individual nutrients and their combined influence on the risk of MAFLD.MethodsData were obtained from National Health and Nutrition Examination Survey (NHANES), and 18 types of nutrients were considered in this study. Logistic regression analysis was performed to evaluate the correlation between single nutrients and the risk of MAFLD. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to pinpoint the most relevant nutrient associated with the risk of MAFLD. Subsequently, both Weighted Quantile Sum (WQS) regression and Quantile g-computation (Qgcomp) were used to assess the combined effects of multiple nutrients on the risk of MAFLD.ResultsA total of 3,069 participants were included in this study. LASSO regression analysis showed that Se, α-tocopherol, and γ-tocopherol exhibited a positive association with the risk of MAFLD. In contrast, the serum levels of Co, P, α-cryptoxanthin, LZ, and trans-β-carotene were inversely associated with the prevalence of MAFLD. When Se and two types of vitamin E were excluded, the WQS index showed a significant inverse relationship between the remaining 15 nutrients and the risk of MAFLD; α-cryptoxanthin showed the most substantial contribution. Similarly, Qgcomp suggested that the combined effects of these 15 nutrients were associated with a lower risk of MAFLD, with α-cryptoxanthin possessing the most significant negative weights.ConclusionThis study suggested that the complex nutrients with either a low proportion of Se, α-tocopherol, and γ-tocopherol or without them should be recommended for patients with MAFLD to reduce its risk.

show abstract

Causal relationships between metabolic‐associated fatty liver disease and iron status: Two‐sample Mendelian randomization

Cited by 21 publications

References 50 publications

Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Trajectories of glycaemic traits exhibit sex‐specific associations with hepatic iron and fat content: Results from the KORA‐MRI study

Association of multiple serum minerals and vitamins with metabolic dysfunction-associated fatty liver disease in US adults: National Health and Nutrition Examination Survey 2017–2018

Contact Info

Product

Resources

About