scholarly journals Potential New Biomarkers Discovery of Early Nonalcoholic Fatty Liver Disease in Human by Liquid Chromatography–Mass Spectrometry

Author(s):  
Cheng Hu ◽  
Tao Wang ◽  
Jiaqi Zhang ◽  
Yuanye Jiang ◽  
Qin Cao

Abstract BackgroundNAFLD is a common metabolic disorders disease which influenced 20~30% people. NAFLD can progress to cirrhosis, liver fibrosis and even liver cancer. Liver puncture is the gold standard. However, due to its trauma and possible complications, its clinical use is currently limited. Therefore, it is of great clinical significance and value to find a noninvasive biochemical index that can diagnose NAFLD early.ObjectiveOur aim was to identify the potential biomarkers in NAFLD people in early stage via untargeted metabolomics study.MethodsIn our research, From January to October 2019, 224 patients aged 18-55 were selected from the outpatient department and ward of gastroenterology department of Putuo Hospital in Shanghai.According to the NAFLD diagnostic criteria of the guidelines for diagnosis and treatment of nonalcoholic fatty liver disease (2018) formulated by the National workship on Fatty liver and alcoholic liver disease and Chinese Society on Hepatology, they were divided into the healthy control group and the experimental group.Besides,on the same day, the height, weight, waist, BMI, blood pressure and heart rate of patients were measured, and fasting blood was taken to obtain blood glucose,ALT, AST, TB, DB, TP, ALB, Che, ALP, γ - GT, TG, TC, HDL-C, LDL-C and other serum data.Serum samples were analyzed using LC/MS and data was processed by SIEVE software and simca-P to validate the potential biomarkers. The altered metabolites were identified by variable importance in projection value (VIP > 1) and ANOVA (p<0.01). The pathway analysis was performed by using MetaboAnalyst 4.0. In addition, our project has passed the review of ethics committee of Putuo Hospital Affiliated to Shanghai University of traditional Chinese medicine, and its ethics approval number is ptec-a-2018-49-1.ResultsThe serum biochemical indicators of early NAFLD patients showed no significant difference with NC (p>0.05). While there was significant difference of blood lipids indicators between NAFLD and NC (p<0.001). Finally, 55 metabolites were identified and the AUC of ROC curve results showed that new identified biomarkers owned high predictability and reliability. ConclusionIt is found that 15 metabolites in serum were of great diagnostic value in early NAFLD patients. AUC of these biomarkers (>0.9) were much higher than clinical indicators (0.770). This may be worth further research in the clinic.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Hu ◽  
Tao Wang ◽  
Xiaoyu Zhuang ◽  
Qiaoli Sun ◽  
Xiaochun Wang ◽  
...  

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20–30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD. Objective The aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach. Methods One hundred and twelve patients with early-stage NAFLD aged 18–55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP > 1) and ANOVA (p < 0.01). Pathway analysis was performed using MetaboAnalyst 4.0. Results The liver function test of early NAFLD patients showed no statistical differences to control group (p > 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p < 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients. Conclusion In this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.


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.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1884-P
Author(s):  
YAN MA ◽  
YAN WANG ◽  
XIN WANG ◽  
LONGYAN YANG ◽  
JIANAN LANG ◽  
...  

Author(s):  
Gholamreza Rezamand ◽  
Touraj Mahmoudi ◽  
Seidamir Pasha Tabaeian ◽  
Hamid Farahani ◽  
Fatemeh Shahinmehr ◽  
...  

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease worldwide. Considering the powerful association between NAFLD, insulin resistance (IR) and obesity, as well as the key role of ghrelin in these metabolic disorders, we hypothesized that some single nucleotide polymorphisms (SNPs) of the ghrelin (GHRL) and ghrelin receptor (GHSR) genes might be associated with NAFLD. Methods We conducted a case-control retrospective study of 150 cases with biopsy-proven NAFLD and 155 controls. The diagnosis of NAFLD was established before the start of the genotyping process. All the 305 subjects were genotyped for GHRL SNP rs26802 or -501T>G and GHSR SNP rs572169 or Arg159Arg using the PCR-RFLP method. Results The GHRL rs26802 “GG” genotype compared with the “TT” genotype and “TT+TG” genotype appears to be a marker of decreased NAFLD susceptibility even after adjustment for confounding factors (P = 0.006; OR = 0.14, 95% CI = 0.03–0.56 and P = 0.003; OR = 0.16, 95% CI = 0.05–0.53, respectively). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for GHSR SNP rs572169. Conclusions These findings proposed, for the first time, that the GHRL rs26802 “GG” genotype has a protective effect against NAFLD. Nonetheless, this observation warrants further investigations in other populations.


Author(s):  
U. O. Mudra

Background. Gout is still one of the major health problems despite significant advances in treatment in recent years. It has been proved that pathogenetic mechanisms of development and progression of gout are associated with nonalcoholic fatty liver disease. Complex pathogenic treatment of patients aimed at different parts of the pathological process has recently been supplemented with the enterosorbents. Objective. The aim of the research is to study the clinical features of gout with concomitant nonalcoholic fatty liver disease (NAFLD) and to evaluate the effect of carbon enterosorbent on its course. Methods. 123 patients were involved in the study. They were divided into 2 groups: group 1 included patients with gout without liver damage, and group 2 included patients with concomitant NAFLD. Each of these groups was divided into subgroups, in which the patients received carbon enterosorbent carboline plus basic treatment. The control group consisted of 30 healthy persons. Anamnesis, physical examination, uric acid (UA), C-reactive protein (CRP) content, erythrocyte sedimentation rate (ESR) in serum were determined. Gout activity was evaluated using the Gout Activity Score (GAS). Results. Basic treatment in combination with carbon enterosorbent contributed to faster cure of intoxication, pain and joint syndromes, as well as decrease of the inflammatory process activity. Conclusions. The course of gout in the patients with concomitant NAFLD is more severe. Adding of carbon granular enterosorbent carboline in the complex treatment of patients with gout with or without concomitant NAFLD in the exacerbation phase contributes to a faster cureing dynamics of clinical and laboratory manifestations of the disease.


2021 ◽  
Vol 5 (2) ◽  
pp. 34-37
Author(s):  
Zhahid Hassan ◽  
Muzamil Latief ◽  
Mahroosa Ramzan ◽  
Farhat Abbas ◽  
Summyia Farooq

Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, obesity, and other features of metabolic syndrome. It is identified as the most common cause of liver enzyme derangement. Lately, NAFLD has generated interest in exploring treatment options, including weight loss and dietary interventions. An association of NAFLD with metabolic syndrome has been suggested in contemporary literature. In this study, we attempted to look into the association of NAFLD with metabolic syndrome. In this study, 80 adult NAFLD patients were recruited from a tertiary care hospital. Among these, 42 were males and 38 females with a mean age of 44.46±13.146 years (range 18–82 years). Grades of fatty liver and presence or absence of metabolic syndrome were studied in this patient population. Patients who did not qualify for the criteria of met-abolic syndrome were placed in Group 1 and those who fulfilled the stated criteria were considered in Group 2. There were 29 (36.25%) patients in Group 1 and 51 (63.75%) in Group 2. All the patients in Group 1 were having Grade I fatty liver whereas patients in Group 2 were found to having varying grades of fatty liver, with six patients having Grade III fatty liver. We found statistically significant difference in various parameters of study (liver enzymes, high-density lipoprotein (HDL), triglycerides, and blood pressure) between Group 1 and Group 2. Ultrasound evidence of a fatty liver should be considered as a predictor of metabolic syndrome, and these patients must be investigated for the different components of metabolic syndrome so as to have early diagnosis and intervention to alter development of long-term metabolic disorders and their inherent complications.


2020 ◽  
Vol 106 (1) ◽  
pp. e34-e44
Author(s):  
Aya Bardugo ◽  
Cole D Bendor ◽  
Inbar Zucker ◽  
Miri Lutski ◽  
Tali Cukierman-Yaffe ◽  
...  

Abstract Context The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. Objective To assess type 2 diabetes risk among adolescents with NAFLD. Design and Setting A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997–2011 and were followed until December 31, 2016. Participants A total of 1 025 796 normoglycemic adolescents were included. Interventions Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. Main Outcome Measures Type 2 diabetes incidence. Results During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47–4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). Conclusions Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Bin Huang ◽  
Shengju Yang ◽  
Shandong Ye

Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants’ records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p<0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r=0.221, p=0.010), and negative correlations were noted between TSH and BMR (r=−0.618, p<0.001) and between BMR and FT3 (r=−0.452, p<0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t=2.468, p=0.0167) and TSH (t=2.658, p=0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.


Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 600 ◽  
Author(s):  
Oral ◽  
Sahin ◽  
Turker ◽  
Kocak

Background and objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as hypertension, diabetes, dyslipidemia, obesity, and hyperuricemia. We aim to investigate the relationship between uric acid and NAFLD in a non-obese and young population. Materials and Methods: This study was performed in January 2010–2019 with a group of 367 (225 patients in the NAFLD group and 142 in the control group) patients with liver biopsy-proven NAFLD or no NAFLD. Patients with NAFLD were classified according to the percentage of steatosis as follows, group I had 1–20% and group II >20%. Demographic, clinical, and laboratory (biochemical parameters) features were collected retrospectively. Results: The mean body mass index (BMI) and age of the patients were 26.41 ± 3.42 and 32.27 ± 8.85, respectively. The BMI, homeostatic model of assessment (HOMA-IR), and uric acid (UA) values of the NAFLD group were found to be significantly higher than those of the controls. A positive correlation was found between the NAFLD stage and UA. The following factors were independently associated with NAFLD: BMI, HOMA-IR, and UA. In addition, the cut-off value of UA was 4.75 mg/dl with a sensitivity of 45.8% and a specificity of 80.3%. Conclusions: UA is a simple, non-invasive, cheap, and useful marker that may be used to predict steatosis in patients with NAFLD.


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