Evaluation of MicroRNA-122 as A Non-invasive Diagnostic Biomarker For Non-Alcoholic Fatty Liver Disease and NASH related Cirrhosis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nevine Ibrahim Musa ◽  
Sara Hassan Agwa ◽  
Heba Ahmed Faheem ◽  
Ahmed Mohamed Gharib Alam El-din
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Invasive Technique ◽  
University Hospitals ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
Normal Controls

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. NAFLD is considered to represent the hepatic manifestation of metabolic syndrome. NAFLD was traditionally considered as a relatively benign liver disease. However, some patients with NAFLD progress to liver fibrosis, cirrhosis and hepatocellular carcinoma 8-13. Therefore, the precise diagnosis and staging of NAFLD patients is clinically important. Liver biopsy is the gold standard for the evaluation of NAFLD patients in terms of staging. However, liver biopsy is an invasive technique, and the identification of noninvasive biomarkers is required. Objective To assess the value of MicroRNA-122 as a non-invasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Patients and Methods In the present study, we assess the value of MicroRNA-122 as a noninvasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Gastroenterology and Hepatology outpatient clinic at: Ain Shams University Hospitals, Shebin El-Kom Teaching Hospital, Kafr Elsheikh University Hospitals. Clinical Pathology department at Faculty of Medicine, Ain Shams University. Results Patients with NASH had higher NAFLD score than patients with NAFLD than normal control. Patients with NASH had significantly higher frequency of upregulated miRNA-22. Patients with NASH had higher miRNA 122 expression than normal controls and patients with NAFLD. Likewise, patients with NAFLD had higher miRNA 122 expression than normal controls. The miRNA 122 was a significant discriminator of NAFLD and NASH with a sensitivity of 75% and specificity of 82% for NAFLD and a sensitivity of 91% and specificity of 86% for the NASH. Conclusion miRNA-122 is a sensitive and specific biomarker in the early detection of NAFLD and NASH as they are linked to the lipid metabolism reducing the need for liver biopsy. NAFLD fibrosis score had high sensitivity in differentiating the NAFLD groups from the control group and in differentiating the steatosis group from the NASH group. Serum levels of miRNA-122 were positively correlated with BMI, ALT and AST.

Evaluation of MicroRNA-122 as A Non-invasive Diagnostic Biomarker For Non-Alcoholic Fatty Liver Disease and NASH related Cirrhosis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nevine Ibrahim Musa ◽  
Sara Hassan Agwa ◽  
Heba Ahmed Faheem ◽  
Ahmed Mohamed Gharib Alam El-din
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Invasive Technique ◽  
University Hospitals ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
Normal Controls

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. NAFLD is considered to represent the hepatic manifestation of metabolic syndrome. NAFLD was traditionally considered as a relatively benign liver disease. However, some patients with NAFLD progress to liver fibrosis, cirrhosis and hepatocellular carcinoma 8-13. Therefore, the precise diagnosis and staging of NAFLD patients is clinically important. Liver biopsy is the gold standard for the evaluation of NAFLD patients in terms of staging. However, liver biopsy is an invasive technique, and the identification of noninvasive biomarkers is required. Objective To assess the value of MicroRNA-122 as a non-invasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Patients and Methods In the present study, we assess the value of MicroRNA-122 as a noninvasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Gastroenterology and Hepatology outpatient clinic at: Ain Shams University Hospitals, Shebin El-Kom Teaching Hospital, Kafr Elsheikh University Hospitals. Clinical Pathology department at Faculty of Medicine, Ain Shams University. Results Patients with NASH had higher NAFLD score than patients with NAFLD than normal control. Patients with NASH had significantly higher frequency of upregulated miRNA-22. Patients with NASH had higher miRNA 122 expression than normal controls and patients with NAFLD. Likewise, patients with NAFLD had higher miRNA 122 expression than normal controls. The miRNA 122 was a significant discriminator of NAFLD and NASH with a sensitivity of 75% and specificity of 82% for NAFLD and a sensitivity of 91% and specificity of 86% for the NASH. Conclusion miRNA-122 is a sensitive and specific biomarker in the early detection of NAFLD and NASH as they are linked to the lipid metabolism reducing the need for liver biopsy. NAFLD fibrosis score had high sensitivity in differentiating the NAFLD groups from the control group and in differentiating the steatosis group from the NASH group. Serum levels of miRNA-122 were positively correlated with BMI, ALT and AST.

scholarly journals Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods

2017 ◽  
Vol 10 (1) ◽  
pp. 19-26 ◽  
Author(s):  
AM Lăpădat ◽  
◽  
IR Jianu ◽  
BS Ungureanu ◽  
LM Florescu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Imaging Techniques ◽  
Current Status ◽  
Alcoholic Fatty Liver ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application.Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed.

scholarly journals Diagnosis of Fibrosis Using Blood Markers and Logistic Regression in Southeast Asian Patients With Non-alcoholic Fatty Liver Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Sang ◽  
Hongmei Yan ◽  
Wah Kheong Chan ◽  
Xiaopeng Zhu ◽  
Tao Sun ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Nafld Fibrosis Score ◽  
Glutamyl Transferase ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of fibrosis. Liver biopsy remains the gold standard for the confirmation of fibrosis in NAFLD patients. Effective and non-invasive diagnosis of advanced fibrosis is essential to disease surveillance and treatment decisions. Herein we used routine medical test markers and logistic regression to differentiate early and advanced fibrosis in NAFLD patients from China, Malaysia, and India (n1 = 540, n2 = 147, and n3 = 97) who were confirmed by liver biopsy. Nine parameters, including age, body mass index, fasting blood glucose, presence of diabetes or impaired fasting glycemia, alanine aminotransferase, γ-glutamyl transferase, triglyceride, and aspartate transaminase/platelet count ratio, were selected by stepwise logistic regression, receiver operating characteristic curve (ROC), and hypothesis testing and were used for model construction. The area under the ROC curve (auROC) of the model was 0.82 for differentiating early and advanced fibrosis (sensitivity = 0.69, when specificity = 0.80) in the discovery set. Its diagnostic ability remained good in the two independent validation sets (auROC = 0.89 and 0.71) and was consistently superior to existing panels such as the FIB-4 and NAFLD fibrosis score. A web-based tool, LiveFbr, was developed for fast access to our model. The new model may serve as an attractive tool for fibrosis classification in NAFLD patients.

scholarly journals Elastography—A Bona Fide Non-Invasive Method for Assessing Non-Alcoholic Fatty Liver Disease in Children

2021 ◽  
Vol 11 (7) ◽  
pp. 3240
Author(s):  
Cristina Oana Mărginean ◽  
Lorena Elena Meliț ◽  
Maria Oana Săsăran
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Stiffness ◽  
Major Public Health Problem ◽  
Systemic Complications ◽  
Alcoholic Fatty Liver ◽  
Non Invasive

Pediatric obesity has become a major public health problem worldwide, resulting in a wide spectrum of systemic complications. Liver disease associated with obesity, also known as nonalcoholic fatty liver disease (NAFLD), is currently the most common chronic liver condition in children. Therefore, its timely and proper diagnosis is essential for preventing further development of cirrhosis. Multiple studies focused on identifying the most accurate non-invasive diagnostic method for liver fibrosis or cirrhosis. Although liver biopsy remains the gold-standard in terms of this hepatopathy, elastography methods emerged as a relatively reliable alternative to liver biopsy. Thus, recent studies revealed the great importance of these non-invasive methods not only in diagnosing pediatric NAFLD, but also in its staging. MRE is commonly considered to have a greater accuracy than ultrasound-based elastography methods, but with lower availability and higher costs. Ultrasound-based elastography methods (transient elastography (TE), p-SWE, and 2-dimensional shear wave elastography (2D-SWE)) were proved to have similar accuracy in NAFLD staging. Nevertheless, multiple confounding factors account for potential challenges when using elastography for liver stiffness measurement, such as age, obesity itself (i.e., BMI), transaminase levels, or portal flow. A potential solution for facing these challenges might be represented by a complex approach based on the combination between elastography, clinical and laboratory findings. Although the studies that assessed the role of elastography in pediatric NAFLD staging are scarce, the current knowledge underlines a crucial role of these techniques taking into account their ability to distinguish between fibrosis degrees, their non-invasive patterns, lower costs and side effects when compared to liver biopsy. Therefore, elastography might become a cornerstone in staging pediatric NAFLD.

scholarly journals The diagnostic conundrum in non-alcoholic fatty liver disease

2020 ◽  
Vol 1 (5) ◽  
Author(s):  
Valerio Rosato ◽  
Mario Masarone ◽  
Andrea Aglitti ◽  
Marcello Persico
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Simple Steatosis ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

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.

Diagnosis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Concepts

2019 ◽  
Vol 24 (38) ◽  
pp. 4574-4586 ◽  
Author(s):  
Margarita Papatheodoridi ◽  
Evangelos Cholongitas
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Diagnostic Tools ◽  
Routine Practice ◽  
Advanced Fibrosis ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score

Nonalcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The majority of NAFLD patients do not progress to NASH and their morbidity risk is low. However, clinical and economic burden of the disease is considerable since the prevalence of the disease is estimated as high as 25% of the general population. Liver biopsy remains the current gold standard for diagnosis, despite limitations regarding sampling variability, invasive nature, and high cost. However, numerous non-invasive biomarkers, including mainly serum markers or imaging modalities, intend to detect the presence of steatosis, NASH or advanced fibrosis. To date, ultrasound is suggested as first-line screening tool for defining steatosis in a selected population, while diagnosis of NAFLD requires exclusion of other chronic liver disease etiology or other steatosis causes. A crucial step in the management of NAFLD patients is the identification of advanced fibrosis, which may be reliably excluded by using NAFLD-Fibrosis score or FIB-4 score or by performing transient elastography. The most robust modalities implement Magnetic Resonance technology and manage to accurately quantify steatosis or identify fibrosis stage, but are not yet applicable in routine practice. The most challenging endpoint has proved to be a non-invasive diagnosis of NASH since no reliable biomarkers have been found to detect or predict inflammation in NAFLD. Lately, research focuses on validating existing markers as robust diagnostic tools for clinical use and investigating novel experimental markers of disease. Current strategies concepts aim to safely diagnose NAFLD patients, aid drug development and finally, guide personalised treatment.

scholarly journals Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1884-1892 ◽  
Author(s):  
Cyrielle Caussy ◽  
Veeral H Ajmera ◽  
Puneet Puri ◽  
Cynthia Li-Shin Hsu ◽  
Shirin Bassirian ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Unmet Need ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Serum Metabolites ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
Alcoholic Fatty Liver Disease

ObjectiveNon-invasive and accurate diagnostic tests for the screening of disease severity in non-alcoholic fatty liver disease (NAFLD) remain a major unmet need. Therefore, we aimed to examine if a combination of serum metabolites can accurately predict the presence of advanced fibrosis.DesignThis is a cross-sectional analysis of a prospective derivation cohort including 156 well-characterised patients with biopsy-proven NAFLD and two validation cohorts, including (1) 142 patients assessed using MRI elastography (MRE) and(2) 59 patients with biopsy-proven NAFLD with untargeted serum metabolome profiling.ResultsIn the derivation cohort, 23 participants (15%) had advanced fibrosis and 32 of 652 analysed metabolites were significantly associated with advanced fibrosis after false-discovery rate adjustment. Among the top 10 metabolites, 8 lipids (5alpha-androstan-3beta monosulfate, pregnanediol-3-glucuronide, androsterone sulfate, epiandrosterone sulfate, palmitoleate, dehydroisoandrosterone sulfate, 5alpha-androstan-3beta disulfate, glycocholate), one amino acid (taurine) and one carbohydrate (fucose) were identified. The combined area under the receiver operating characteristic curve (AUROC) of the top 10 metabolite panel was higher than FIB--4 and NAFLD Fibrosis Score (NFS) for the detection of advanced fibrosis: 0.94 (95% CI 0.897 to 0.982) versus 0.78 (95% CI0.674 to 0.891), p=0.002 and versus 0.84 (95% CI 0.724 to 0.929), p=0.017, respectively. The AUROC of the top 10 metabolite panel remained excellent in the independent validation cohorts assessed by MRE or liver biopsy: c-statistic of 0.94 and 0.84, respectively.ConclusionA combination of 10 serum metabolites demonstrated excellent discriminatory ability for the detection of advanced fibrosis in an derivation and two independent validation cohorts with greater diagnostic accuracy than the FIB-4-index and NFS. This proof-of-concept study demonstrates that a non-invasive blood-based diagnostic test can provide excellent performance characteristics for the detection of advanced fibrosis.

scholarly journals Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Leen J. M. Heyens ◽  
Dana Busschots ◽  
Ger H. Koek ◽  
Geert Robaeys ◽  
Sven Francque
Keyword(s):  
At Risk ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Diagnostic Tools ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

An increasing percentage of people have or are at risk to develop non-alcoholic fatty liver disease (NAFLD) worldwide. NAFLD comprises different stadia going from isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is a chronic state of liver inflammation that leads to the transformation of hepatic stellate cells to myofibroblasts. These cells produce extra-cellular matrix that results in liver fibrosis. In a normal situation, fibrogenesis is a wound healing process that preserves tissue integrity. However, sustained and progressive fibrosis can become pathogenic. This process takes many years and is often asymptomatic. Therefore, patients usually present themselves with end-stage liver disease e.g., liver cirrhosis, decompensated liver disease or even hepatocellular carcinoma. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Currently, only a minority of patients with liver fibrosis are identified to be at risk and hence referred for treatment. This is not only because the disease is largely asymptomatic, but also due to the fact that currently liver biopsy is still the golden standard for accurate detection of liver fibrosis. However, performing a liver biopsy harbors some risks and requires resources and expertise, hence is not applicable in every clinical setting and is unsuitable for screening. Consequently, different non-invasive diagnostic tools, mainly based on analysis of blood or other specimens or based on imaging have been developed or are in development. In this review, we will first give an overview of the pathogenic mechanisms of the evolution from isolated steatosis to fibrosis. This serves as the basis for the subsequent discussion of the current and future diagnostic biomarkers and anti-fibrotic drugs.

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