scholarly journals Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1248
Author(s):  
Reda Albadawy ◽  
Sara H. A. Agwa ◽  
Eman Khairy ◽  
Maha Saad ◽  
Naglaa El El Touchy ◽  
...  

Background: Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. Methods: Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients’ sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. Results: We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. Conclusion: This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.

2015 ◽  
Vol 24 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Ramesh P. Arasaradnam ◽  
Michael McFarlane ◽  
Emma Daulton ◽  
Erik Westenbrink ◽  
Nicola O’Connell ◽  
...  

Background & Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is the commonest cause of chronic liver disease in the western world. Current diagnostic methods including Fibroscan have limitations, thus there is a need for more robust non-invasive screening methods. The gut microbiome is altered in several gastrointestinal and hepatic disorders resulting in altered, unique gut fermentation patterns, detectable by analysis of volatile organic compounds (VOCs) in urine, breath and faeces. We performed a proof of principle pilot study to determine if progressive fatty liver disease produced an altered urinary VOC pattern; specifically NAFLD and Non-Alcoholic Steatohepatitis (NASH).Methods: 34 patients were recruited: 8 NASH cirrhotics (NASH-C); 7 non-cirrhotic NASH; 4 NAFLD and 15 controls. Urine was collected and stored frozen. For assay, the samples were defrosted and aliquoted into vials, which were heated to 40±0.1°C and the headspace analyzed by FAIMS (Field Asymmetric Ion Mobility Spectroscopy). A previously used data processing pipeline employing a Random Forrest classification algorithm and using a 10 fold cross validation method was applied.Results: Urinary VOC results demonstrated sensitivity of 0.58 (0.33 - 0.88), but specificity of 0.93 (0.68 - 1.00) and an Area Under Curve (AUC) 0.73 (0.55 -0.90) to distinguish between liver disease and controls. However, NASH/NASH-C was separated from the NAFLD/controls with a sensitivity of 0.73 (0.45 - 0.92), specificity of 0.79 (0.54 - 0.94) and AUC of 0.79 (0.64 - 0.95), respectively.Conclusions: This pilot study suggests that urinary VOCs detection may offer the potential for early non-invasive characterisation of liver disease using 'smell prints' to distinguish between NASH and NAFLD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlo De Matteis ◽  
Marica Cariello ◽  
Giusi Graziano ◽  
Stefano Battaglia ◽  
Patrizia Suppressa ◽  
...  

AbstractVisceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
K A Mohamed ◽  
E E Mohamed ◽  
D M Ahmed ◽  
M A Sayed ◽  
A R Hussien

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide, with a prevalence of 15%-30% in Western populations. Non-alcoholic fatty liver disease (NAFLD) has emerged as the most important cause of chronic liver disease related to the increase in incidence of obesity and diabetes mellitus type II in the population. Aim of the Work To predict nonalcholic steatohepatitis in patient with NAFLD through measurement of interleukin 6 to prevent progression of the disease into liver cirrhosis through early diagnosis. Patients and Methods This study was designed to be case control study; it was conducted on 70 patients selected from Internal Medicine and Hepatology outpatient clinics and inpatient wards at Ain Shams University Hospitals from (Jun/2017 to Jul 9/2018) and 20 healthy subjects as control group. Results NASH patients had more obesity (BMI 30) (83.3%) than both simple steatosis patients (57.5%) and control (55.0%). NASH patients had higher BMI as compared to simple steatosis patients and control (p value =0.01). The present study revealed that there is a statistically significant difference between groups according to IL6 (P > 0.001) as IL6 was positive in 70% of patients with NASH while in patients with simple steatosis and control was positive in 25%, 20% respectively. Conclusion NAFLD is a highly prevalent condition, shares many features of the metabolic syndrome (MetS), a highly atherogenic condition. Recommendations Large scale multi-centre studies are recommended to study the prevalence of NAFLD in Egypt. Further studies on the effect of presence of steatosis and increased risk of hepatocellular carcinoma.


2006 ◽  
Vol 111 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Piero Portincasa ◽  
Ignazio Grattagliano ◽  
Bernhard H. Lauterburg ◽  
Vincenzo O. Palmieri ◽  
Giuseppe Palasciano ◽  
...  

Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([13C]methacetin and [13C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=−0.701), serum hyaluronate (r=−0.644) and body size (r=−0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired 13CO2 for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.


2020 ◽  
Vol 1 (5) ◽  
Author(s):  
Valerio Rosato ◽  
Mario Masarone ◽  
Andrea Aglitti ◽  
Marcello Persico

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury. Until now, liver biopsy is still required to differentiate simple steatosis from NASH and evaluate the degree of liver fibrosis. Unfortunately, this technique has well-known limitations, including invasiveness and expensiveness. Moreover, it may be biased by sampling error and intra- or inter-observed variability. Furthermore, due to the increasing prevalence of NAFLD worldwide, to program a systematic screening with liver biopsy is not imaginable. In recent years, different techniques were developed and validated with the aim of non-invasively identifying NASH and assess liver fibrosis degrees. The non-invasive tests range from simple blood-tests analyses to composite scores and complex imaging techniques. Nevertheless, even if they could represent cost-effective strategies for diagnosing NASH, advanced fibrosis and cirrhosis, their accuracy and consequent usefulness are to be discussed. With this aim, in this review the authors summarize the current state of non-invasive assessment of NAFLD. In particular, in addition to the well-established tests, the authors describe the future perspectives in this field, reporting the latest tests based on OMICS, gut-miocrobioma and micro-RNAs. Finally, the authors provide an accurate assessment of how these non-invasive tools perform in clinical practice depending on the clinical context, with the aim of giving the clinicians a useful tool to try to resolve the diagnostic conundrum of NAFLD.


Author(s):  
Tasneem A. Gameel ◽  
Sherine Rady ◽  
Sanaa Kamal

Non-alcoholic Steatohepatitis Disease (NASH), a progression of Non-alcoholic Fatty Liver Disease (NAFLD), occurs in case of the increase of fat accumulation in the liver. The disease can next progress to fibrosis, cirrhosis or liver cancer. The most accurate way to diagnose NAFLD progression into NASH is through a liver biopsy. This is painful, expensive and difficult to repeat several times to monitor the fibrosis progression. Thus, finding a non-invasive solution through markers can reliably help tracking the disease progression. The objective of this study is to assess the diagnostic and prognostic performance of serum markers to monitor liver disease progression in comparison to findings by liver biopsy. An association rule mining system is proposed using a Frequent Pattern mining algorithm to reach this objective. An Egyptian cohort consisting of 2300 NAFLD and NASH patients is included in an experimental study, where the results showed that the blood tests and serum markers, PIIINP and ELF, can predict the progression of NAFLD into NASH, and can discriminate between the different stages of NASH with confidence value 0.9. The presented results indicate an advantageous promising non-invasive solution in medicine for predicting of the disease and its progression, while avoiding alternative biopsy exposition


2018 ◽  
Vol 3 (1) ◽  
pp. 179-183 ◽  
Author(s):  
Irena Ciećko-Michalska ◽  
Małgorzata Szczepanek ◽  
Iga Wierzbicka-Tutka ◽  
Janina Zahradnik-Bilska ◽  
Tomasz Mach

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 230
Author(s):  
Jung Gil Park ◽  
Gyeonghwa Kim ◽  
Se Young Jang ◽  
Yu Rim Lee ◽  
Eunhye Lee ◽  
...  

Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in humans is TCONS_00016452. Here, we aimed to evaluate the potential of lncRNA LeXis as a non-invasive diagnostic marker for NASH. We analyzed a total of 44 NAFLD patients whose diagnosis was confirmed by a pathologist through analysis of a percutaneous liver biopsy. The expression of LeXis in the plasma of NAFLD patients with and without NASH was compared using quantitative real-time polymerase chain reaction. The expression of plasma LeXis was significantly higher in patients with NASH than in those with NAFL (8.2 (5.0–14.9); 4.6 (4.0–6.6), p = 0.025). The area under the receiver operating characteristic curve was 0.743 (95% CI 0.590–0.895, p < 0.001), and a sensitivity of 54.3% and specificity of 100% could be achieved for NASH diagnosis. Low LeXis was independently associated with NASH diagnosis in patients with NAFLD (p = 0.0349, odds ratio = 22.19 (5% CI, 1.25–395.22)). Therefore, circulating lncRNA LeXis could be a potential non-invasive diagnostic biomarker for NASH.


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