Role of Serum Biomarkers in Early Detection of Non-Alcoholic Steatohepatitis and Fibrosis in West Virginian Children

Sodhi, Komal; Bracero, Lucas; Feyh, Andrew; Nichols, Alexandra; Srikanthan, Krithika; Latif, Tariq; Preston, Deborah L.; Shapiro, Joseph I.; Elitsur, Yoram

doi:10.4172/2155-9899.1000393

Cited by 9 publications

(7 citation statements)

References 51 publications

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“… Higher circulating FGF-21 in women, but not in men, with LEAD compared to those without LEAD. Sodhi (2016) 60 Cross-sectional Obese children with IR (27) or without IR (16) vs lean controls without IR (28) Higher circulating FGF-21 in obese children with or without IR compared to lean controls. Waluga (2017) 64 Cross-sectional Women with severe obesity and biopsy-defined NAFLD or non-NAFLD during bariatric surgery (56) Similar circulating FGF-21 and hepatic FGF-21 mRNA in different degree of NAS.…”

Section: Clinical Studiesmentioning

confidence: 99%

“…However, a limitation of many of these studies was that NAFLD patients had higher body mass index (BMI) and/or waist circumference than controls, which may have distorted the association between FGF-21 and NAFLD, since FGF-21 is also upregulated in obesity. 52 , 54 , 58 , 60 On the other hand, limited data from patients with NAFLD and T2DM or IR showed that FGF-21 may not be largely affected by T2DM 53 or IR 60 specifically in NAFLD patients, which may imply that NAFLD itself is a more important drive than T2DM or IR for FGF-21 upregulation. Other authors also speculated that FGF-21 is more closely associated with lipid metabolism than glucose metabolism and IR.…”

Section: Clinical Studiesmentioning

confidence: 99%

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Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Raptis¹,

Mantzoros²,

Polyzos³

2023

TCRM

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Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease without any approved treatment to-date despite intensive research efforts by researchers and pharmaceutical industry. Fibroblast growth factor (FGF)-21 has been gaining increasing attention as a possible contributing factor and thus therapeutic target for obesity-related metabolic disorders, including NAFLD, mainly due to its effects on lipid and carbohydrate metabolism. Most animal and human observational studies have shown higher FGF-21 concentrations in NAFLD than non-NAFLD, implying that FGF-21 may be increased to counteract hepatic steatosis and inflammation. However, although Mendelian Randomization studies have revealed that variations of FGF-21 levels within the physiological range may have effects in hyperlipidemia and possibly nonalcoholic steatohepatitis, they also indicate that FGF-21, in physiological concentrations, may fail to reverse NAFLD and may not be able to control obesity and other diseases, indicating a state of FGF-21 resistance or insensitivity that could not respond to administration of FGF-21 in supraphysiological concentrations. Interventional studies with FGF-21 analogs (eg, pegbelfermin, efruxifermin, BOS-580) in humans have provided some favorable results in Phase 1 and Phase 2 studies. However, the definite effect of FGF-21 on NAFLD may be clarified after the completion of the ongoing clinical trials with paired liver biopsies and histological endpoints. The aim of this review is to critically summarize experimental and clinical data of FGF-21 in NAFLD, in an attempt to highlight existing knowledge and areas of uncertainty, and subsequently, to focus on the potential therapeutic effects of FGF-21 and its analogs in NAFLD.

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Section: Clinical Studiesmentioning

confidence: 99%

Section: Clinical Studiesmentioning

confidence: 99%

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Raptis¹,

Mantzoros²,

Polyzos³

2023

TCRM

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“…According to a Chinese prospective study, this protein is an independent predictor of NAFLD[ 31 ]. The possible use of FGF-21 as an NAFLD marker has also been described in an American study conducted in children[ 32 ]. However, the above study demonstrated significant relationships between the level of this marker and the prevalence of obesity, with or without insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

Sak¹,

Prystupa²,

Kiciński³

et al. 2021

WJH

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BACKGROUND The importance of early diagnosis of alcoholic liver disease underscores the need to seek better and especially non-invasive diagnostic procedures. Leukocyte cell-derived chemotaxin-2 (LECT2) has been widely studied to determine its usefulness in monitoring the course of non-alcoholic fatty liver disease but not for alcoholic liver cirrhosis (ALC). AIM To determine the concentration of LECT2 in the blood serum of patients in relation to progressive stages of ALC, its relation to fibroblast growth factor 1 (FGF-1) and FGF-21, and to examine the possible wider use of LECT2 in diagnosing ALC. METHODS A retrospective case-control study was conducted with 69 ALC cases and 17 controls with no ALC. Subjects were recruited from the region of Lublin (eastern Poland). Liver cirrhosis was diagnosed based on clinical features, history of heavy alcohol consumption, laboratory tests, and abdominal ultrasonography. The degree of ALC was evaluated according to Pugh-Child criteria (the Pugh-Child score). Blood was drawn and, after centrifugation, serum was collected for analysis. LECT2, FGF-1, and FGF-21 were determined using enzyme-linked immunosorbent assay kits. RESULTS The LECT2 Levels in the control group were 18.99 ± 5.36 ng/mL. In the study groups, they declined with the progression of cirrhosis to 11.06 ± 6.47 ng/mL in one group and to 8.06 ± 5.74 ng/mL in the other ( P < 0.0001). Multiple comparison tests confirmed the statistically significant differences in LECT2 Levels between the control group and both test groups ( P = 0.006 and P < 0.0001). FGF-21 Levels were 44.27 ± 64.19 pg/mL in the first test group, 45.4 ± 51.69 pg/mL in the second ( P = 0.008), and 13.52 ± 7.51 pg/mL in the control group. The difference between the control group and the second test group was statistically significant ( P = 0.007). CONCLUSION We suggest that LECT2 may be a non-invasive diagnostic factor for alcohol-induced liver cirrhosis. The usefulness of LECT2 for non-invasive monitoring of alcohol-induced liver cirrhosis was indirectly confirmed by the multiple regression model developed on the basis of our statistical analysis.

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“…With an increasing number of patients developing NASH-related end-stage liver disease, the development and validation of non-invasive biomarkers that accurately diagnose and predict clinically relevant outcomes to monitor both NAFLD and fibrosis are critically needed. The findings from our laboratory previously demonstrated the correlation between obesity, insulin resistance and biomarkers associated with NASH in pediatric patients from WV [55]. Owing to the increasing burden of obesity, metabolic disease and poor health care system, the risk of developing NAFLD in WV population is very high, especially in the female population.…”

Section: Introductionmentioning

confidence: 86%

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

Pillai

Lakhani

Zehra

et al. 2020

IJMS

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(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.

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Role of Serum Biomarkers in Early Detection of Non-Alcoholic Steatohepatitis and Fibrosis in West Virginian Children

Cited by 9 publications

References 51 publications

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

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

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