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 Simple non-invasive biomarkers of advanced fibrosis in the evaluation of non-alcoholic fatty liver disease

2014 ◽  
Vol 2 (4) ◽  
pp. 276-280 ◽  
Author(s):  
E. B. Tapper ◽  
K. Krajewski ◽  
M. Lai ◽  
T. Challies ◽  
R. Kane ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

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 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.

scholarly journals Systematic Review with Meta-Analysis: Diagnostic Accuracy of Pro-C3 for Hepatic Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1920
Author(s):  
Anne Linde Mak ◽  
Jenny Lee ◽  
Anne-Marieke van Dijk ◽  
Yasaman Vali ◽  
Guruprasad P. Aithal ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Advanced Fibrosis ◽  
Inclusion Criteria ◽  
Alcoholic Fatty Liver ◽  
Significant Fibrosis ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

The prevalence and severity of non-alcoholic fatty liver disease (NAFLD) is increasing, yet adequately validated tests for care paths are limited and non-invasive markers of disease progression are urgently needed. The aim of this work was to summarize the performance of Pro-C3, a biomarker of active fibrogenesis, in detecting significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), cirrhosis (F4) and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. A sensitive search of five databases was performed in July 2021. Studies reporting Pro-C3 measurements and liver histology in adults with NAFLD without co-existing liver diseases were eligible. Meta-analysis was conducted by applying a bivariate random effects model to produce summary estimates of Pro-C3 accuracy. From 35 evaluated reports, eight studies met our inclusion criteria; 1568 patients were included in our meta-analysis of significant fibrosis and 2058 in that of advanced fibrosis. The area under the summary curve was 0.81 (95% CI 0.77–0.84) in detecting significant fibrosis and 0.79 (95% CI 0.73–0.82) for advanced fibrosis. Our results support Pro-C3 as an important candidate biomarker for non-invasive assessment of liver fibrosis in NAFLD. Further direct comparisons with currently recommended non-invasive tests will demonstrate whether Pro-C3 panels can outperform these tests, and improve care paths for patients with 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.

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