NAFLD and Cardiometabolic Risk Factors: The Liver Fibrosis Trajectory Through the Lens of Biological Interactions

Pirola, Carlos José; Sookoian, Silvia

doi:10.1002/hep.31672

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…These findings emphasize the future significance of identifying protective factors to understand the varying trajectories of fibrosis. [ 22 ] Detecting such factors could aid in identifying patients with a higher probability of achieving regression, which might subsequently enhance prognostic classification and improve existing approaches for clinical management.…”

Section: Resultsmentioning

confidence: 99%

Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study

Sariyar¹

2023

Hepatology Forum

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Background and Aim This study aimed to investigate the predictive value of various non-invasive scores for identifying the progression of hepatic fibrosis over time in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Materials and Methods We examined 69 patients with NAFLD who had undergone two liver biopsies at an average interval of 21.3±9.7 months. Progression and regression of fibrosis were defined as an increase or decrease of at least one stage in fibrosis between the initial and follow-up biopsies, respectively. The Fibrosis-4 Index (FIB-4), NAFLD Fibrosis Score (NFS), Agile 3+, Agile 4, and FibroScan-AST (FAST) scores were calculated at the initial biopsy. Results Comparison of paired biopsies revealed that 45% of participants (n=31) exhibited no change in fibrosis stages, 26% (n=18) experienced progression, and 29% (n=20) demonstrated regression. Multivariable logistic regression analysis identified the FAST score as the only independent predictor of progressive fibrosis, with the odds increasing by 19% (95% CI: 8–38%, p<0.05) for each unit increase in the FAST score at the initial biopsy. No independent predictors for fibrosis regression were identified. Conclusion Higher baseline FAST scores were associated with an increased likelihood of fibrosis progression, independent of other variables. Thus, the FAST score could serve as both a diagnostic and prognostic tool for fibrosis in patients with NAFLD.

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Section: Resultsmentioning

confidence: 99%

Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study

Sariyar¹

2023

Hepatology Forum

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“…Concurrently, massive cardiometabolic risk factors are considered in many syndromes, including cardiovascular diseases[ 64 , 65 ], hepatobiliary disorders[ 66 , 67 ], nervous system disruption[ 68 , 69 ], and reproductive disturbance[ 70 ]. For instance, metabolic traits[ 1 , 2 , 8 , 9 ], dietary behaviors[ 15 - 17 ], physical activity[ 18 , 19 ], and socioeconomic factors[ 21 ] have attracted ubiquitous attention, playing protective roles or serving as risk factors in the process of gallstones.…”

Section: Discussionmentioning

confidence: 99%

Association of education with cholelithiasis and mediating effects of cardiometabolic factors: A Mendelian randomization study

Li,

Liu,

Lan

et al. 2024

World J Clin Cases

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BACKGROUND Education, cognition, and intelligence are associated with cholelithiasis occurrence, yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated. AIM To explore the causal associations between education, cognition, and intelligence and cholelithiasis, and the cardiometabolic risk factors that mediate the associations. METHODS Applying genome-wide association study summary statistics of primarily European individuals, we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, and cognition on cholelithiasis and cholecystitis (FinnGen study, 37041 and 11632 patients, respectively; n = 486484 participants) and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis. RESULTS Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education, cognition, or intelligence were not independently associated with cholelithiasis and cholecystitis; when adjusted for cholelithiasis, higher education still presented an inverse effect on cholecystitis [odds ratio: 0.292 (95%CI: 0.171-0.501)], which could not be induced by cognition or intelligence. Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis, including body mass index (20.84%), body fat percentage (40.3%), waist circumference (44.4%), waist-to-hip ratio (32.9%), and time spent watching television (41.6%), while time spent watching television was also a mediator from cognition (20.4%) and intelligence to cholelithiasis (28.4%). All results were robust to sensitivity analyses. CONCLUSION Education, cognition, and intelligence all play crucial roles in the development of cholelithiasis, and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.

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“…One common molecular mechanism is the activation of hepatic stellate cells (HSCs) by various injury factors and their transformation into myofibroblasts (MFs). 1,2 Earlier research has confirmed that after removal of persistent injury factors, the degree of liver fibrosis can be significantly improved. Therefore, comprehensive investigation of the reversibility of HSCs activation is of significant clinical value.…”

Section: Introductionmentioning

confidence: 98%

“…Liver fibrosis is a key link in the progression of various chronic liver disorders, from viral hepatitis and fatty liver to end‐stage liver disease. One common molecular mechanism is the activation of hepatic stellate cells (HSCs) by various injury factors and their transformation into myofibroblasts (MFs) 1,2 . Earlier research has confirmed that after removal of persistent injury factors, the degree of liver fibrosis can be significantly improved.…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte‐derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis

Xu,

Mo,

Han

et al. 2024

J Cellular Molecular Medi

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Liver fibrosis is characterized by the activation and transformation of hepatic stellate cells (HSCs) induced by various injury factors. The degree of liver fibrosis can be significantly improved, but persistent injury factors present a significant therapeutic challenge. Hepatocytes are the most important parenchymal cell type in the liver. In this study, we explored the molecular mechanisms by which damaged liver cells activate HSCs through extracellular vesicles. We established a coculture model of LO2 and LX2 and validated its exosomal transmission activity. Subsequently, differentially expressed long noncoding RNAs (lncRNAs) were screened through RNA sequencing and their mechanisms of action as competing endogenous RNAs (ceRNAs) further confirmed using biological methods, such as FISH and luciferase assays. Damaged liver cells induced activation of LX2 and upregulation of liver fibrosis‐related markers. Exosomes extracted and identified from the supernatant fraction contained differentially expressed lncRNA cytoskeleton regulator RNA (CYTOR) that competed with microRNA‐125 (miR‐125) for binding to glial cell line‐derived neurotrophic factor (GDNF) in HSCs, in turn, promoting LX2 activation. MiR‐125 could target and regulate both CYTOR and GDNF and vice versa, as verified using the luciferase assay. In an in vivo model, damaged liver extracellular vesicles induced the formation of liver fibrosis. Notably, downregulation of CYTOR within extracellular vesicles effectively inhibited liver fibrosis. The lncRNA CYTOR in exosomes of damaged liver cells is upregulated and modulates the expression of downstream GDNF through activity as a ceRNA, providing an effective mechanism for activation of HSCs.

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NAFLD and Cardiometabolic Risk Factors: The Liver Fibrosis Trajectory Through the Lens of Biological Interactions

Cited by 5 publications

References 6 publications

Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study

Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study

Association of education with cholelithiasis and mediating effects of cardiometabolic factors: A Mendelian randomization study

Hepatocyte‐derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis

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