scholarly journals Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

2020 ◽  
Vol 21 (18) ◽  
pp. 6698
Author(s):  
Sneha S. Pillai ◽  
Hari Vishal Lakhani ◽  
Mishghan Zehra ◽  
Jiayan Wang ◽  
Anum Dilip ◽  
...  

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population.

Author(s):  
Bin Liu ◽  
Huan Zheng ◽  
Guanghui Liu ◽  
Zhiling Li

Background: Insulin resistance(IR) is confirmed as a key feature of nonalcoholic fatty liver disease (NAFLD) in children and adolescents. Numerous studies report that adiponectin (APN) levels are inversely associated with the status of IR in adults with NAFLD. This study aimed to investigate the relationship between serum total APNand homeostasis model assessment insulin resistance(HOMA-IR) in adolescents with NAFLD. Methods: 382 newly-diagnosed NAFLD adolescents, aged 9-16 years old, were enrolled and divided into 3 subgroups according to the APNtertile. Simple and multiple linear regression analyses were performed to assess the correlation between HOMA-IR and APN in boys and girls, respectively. Results: The HOMA-IR values tended to decrease in boys according to APN tertiles: 5.6(4.4-7.3) vs. 5.2(4.6-6.9) vs. 4.9(4.1-5.8) (P<0.01), and there was a significant difference in the HOMA-IR values among three APN tertile subgroups in girls(P<0.01).Univariate analysis showed thatbody mass index, waist circumference, weight-to-height ratio, fasting blood glucose, insulin, triglyceride, and APN were significantly associated with HOMA-IR in boys (P<0.05). In girls, body mass index, fasting blood glucose, insulin, total cholesterol, triglyceride, and APN were significantly associated with HOMA-IR (P<0.05).APN was found to be a significant determinant for HOMA-IR only in boys (β=-0.147, P<0.01). Conclusion: Our findings showed that APN was an independent and significant determinant for increased HOMA-IR in boys with NAFLD. Further studies are needed to explore the underlying mechanisms.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Şule Demir ◽  
Mustafa Ünübol ◽  
Serap Ünübol Aypak ◽  
Emrah İpek ◽  
Serdar Aktaş ◽  
...  

It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (p<0.001). The mean fasting blood glucose was 126.25 ± 23.4 mg/dL in hypothyroidism-induced group and 102.63 ± 15.51 mg/dL in the control group, with a statistically significant difference between the groups (p=0.032). The two groups did not differ statistically significantly with respect to visfatin levels (p>0.05). In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255822
Author(s):  
Jeong-An Gim ◽  
Soo Min Bang ◽  
Young-Sun Lee ◽  
Yoonseok Lee ◽  
Sun Young Yim ◽  
...  

Noninvasive techniques for evaluating the severity of nonalcoholic fatty liver disease (NAFLD) have shown limited diagnostic performance. MicroRNAs (miRNAs) are useful biomarkers for diagnosing and monitoring the progression and treatment response to several diseases. Here, we evaluated whether serum exosomal miRNAs could be used for the diagnosis and prognosis of NAFLD severity. Exosomal miRNAs were isolated from the sera of 41 patients with NAFLD (diagnosed using liver biopsy) for microarray profiling. The degree of NAFLD severity was determined using inflammation, steatosis, and ballooning scores and the NAFLD activity score (NAS). Correlations between miRNA expression, clinical and biochemical parameters, and mRNA expression were analyzed. Overall, 25, 11, 13, and 14 miRNAs correlated with the inflammation score, steatosis score, ballooning score, and NAS, respectively, with 33 significant correlations observed between 27 miRNAs and six clinical variables. Eight miRNAs (let-7b-5p, miR-378h, -1184, -3613-3p, -877-5p, -602, -133b, and 509-3p) showed anticorrelated patterns with the corresponding mRNA expression. In fibrosis, 52 and 30 interactions corresponding to high miRNA-low mRNA and low miRNA-high mRNA expression, respectively, were observed. The present results therefore suggest that serum exosomal miRNAs can be used to evaluate NAFLD severity and identify potential targets for NAFLD treatment.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Rajalingham Sakthiswary ◽  
Grace Yin Lai Chan ◽  
Ee Tzun Koh ◽  
Khai Pang Leong ◽  
Bernard Yu Hor Thong

Background. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore.Methods. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis.Results. Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g,P≤0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly,P=0.033), and fasting blood glucose (P=0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P=0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P<0.05, standardised beta coefficient 0.512).Conclusion. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.


2021 ◽  
Author(s):  
Jeong-An Gim ◽  
Soo Min Bang ◽  
Young-Sun Lee ◽  
Yoonseok Lee ◽  
Sun Young Yim ◽  
...  

Abstract Noninvasive modalities exhibit limited diagnostic performance for evaluating the severity of nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) serve as useful biomarkers for diagnosing and monitoring disease progression and treatment response. Here, we evaluated whether serum exosomal miRNAs can be used to clinically predict the severity of NAFLD. Exosomal miRNAs were isolated from the sera of 41 NAFLD patients (diagnosed using biopsy) for array profiling. To compare differentially expressed miRNAs, the degree of severity was determined using inflammation, steatosis, ballooning, and NAFLD activity score (NAS). The correlation of miRNAs with clinical and biochemical parameters was analyzed. The correlation between miRNA and mRNA expression was analyzed by comparing our miRNA expression data with publicly available mRNA expression data. Twenty-five, eleven, thirteen, and fourteen miRNAs correlated with inflammation score, steatosis score, ballooning score, and NAS, respectively. Thirty-three significant correlations were observed between twenty-seven miRNAs and six clinical variables (age, ALP, AST, ALT, GGT, and NAS). In fibrosis, 52 and 30 interactions corresponding to high miRNA-low mRNA and low miRNA-high mRNA expression, respectively, were observed. We demonstrated that serum exosomal miRNAs can be used to evaluate NAFLD severity and also delineate potential targets for NAFLD treatment.


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