Mendelian Randomization Analysis Reveals No Causal Relationship Between Nonalcoholic Fatty Liver Disease and Severe COVID-19

Li, Jiuling; Tian, Aowen; Zhu, Haoxue; Chen, Lanlan; Wen, Jianping; W, Liu; Chen, Peng

doi:10.1016/j.cgh.2022.01.045

Cited by 47 publications

(40 citation statements)

References 40 publications

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“…Indeed, one study from the UK biobank even reported a possible protective immunomodulatory effect of the PNPLA3 rs738409 G allele [ 77 ], although this was not replicated following targeted PNPLA3 genotyping in 383 consecutive Sicilian patients with COVID-19 [ 78 ]. Separate independent analyses using two-step Mendelian randomization techniques have also failed to identify a causal relationship between NAFLD and COVID-19 susceptibility and severity [ 79 , 80 ]. This approach attempts to overcome confounding by using genetic variants as instrument variables to draw causal inferences between risk factors and health outcomes [ 79 ].…”

Section: Risk Stratification and Disease Course Of Sars-cov-2 Infecti...mentioning

confidence: 99%

Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper

Marjot

Eberhardt

Böettler

et al. 2022

Journal of Hepatology

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Section: Risk Stratification and Disease Course Of Sars-cov-2 Infecti...mentioning

confidence: 99%

Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper

Marjot

Eberhardt

Böettler

et al. 2022

Journal of Hepatology

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Section: Interplay Between Mafld and Covid-19mentioning

confidence: 99%

“…However, a recent study demonstrated that while MAFLD may be associated with severe COVID-19 at the population level, MAFLD is not a causal risk factor for severe COVID-19 based on two-sample Mendelian randomization (TSMR) analysis [111]. The authors mentioned that their results may be limited by the small sample size and other unknown clinical covariates [111]. In addition, TSMR studies consider the lifetime effects of genetic variation rather than short-term measurements of specific parameters, and in some cases Mendelian randomization and its biological plausibility may not hold.…”

Section: Interplay Between Mafld and Covid-19mentioning

confidence: 99%

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

Chen¹,

Chen²

2022

Int. J. Biol. Sci.

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COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.

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“…The strong effects exerted by liver fat in our cohort might reflect the transformation from a metabolically low-risk state to a metabolically high-risk state of obesity, as discussed previously [ 44 ], and matches the findings of other cohorts, in which nonalcoholic/metabolic associated fatty liver disease (N/MAFLD) is associated with a worse outcome for COVID-19 patients [ 45 ]. However, whether MAFLD displays an independent risk factor or is rather a byproduct of visceral obesity remains controversial [ 46 , 47 , 48 ]. To conclude, our study adds further information that overweight and obesity play a crucial role in COVID-19 and highlights that the widely accepted single use of BMI as a measure of excess adipose tissue is insufficient and might not display the effective risk.…”

Section: Discussionmentioning

confidence: 99%

Risk Stratification Based on a Pattern of Immunometabolic Host Factors Is Superior to Body Mass Index—Based Prediction of COVID-19-Associated Respiratory Failure

Santos

Gerisch²,

Hellmuth

et al. 2022

Nutrients

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Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.

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Mendelian Randomization Analysis Reveals No Causal Relationship Between Nonalcoholic Fatty Liver Disease and Severe COVID-19

Cited by 47 publications

References 40 publications

Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper

Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

Risk Stratification Based on a Pattern of Immunometabolic Host Factors Is Superior to Body Mass Index—Based Prediction of COVID-19-Associated Respiratory Failure

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