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.

scholarly journals FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (11) ◽  
pp. 2415
Author(s):  
Yasaman Vali ◽  
Jenny Lee ◽  
Jérôme Boursier ◽  
René Spijker ◽  
Joanne Verheij ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Multiple Thresholds ◽  
Meta Analyses ◽  
Alcoholic Fatty Liver Disease

(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.

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

Non-invasive Stratification of Non-Alcoholic Fatty Liver Disease by Whole-transcriptome Cell-free mRNA Characterization

2021 ◽  
Author(s):  
Naga Chalasani ◽  
Shusuke Toden ◽  
John J Sninsky ◽  
Richard P Rava ◽  
Jerome V Braun ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Healthy Subjects ◽  
Rna Seq ◽  
Alcoholic Fatty Liver ◽  
Significant Fibrosis ◽  
Non Invasive ◽  
Clinically Significant ◽  
Alcoholic Fatty Liver Disease

Hepatic fibrosis stage is the most important determinant of outcomes in patients with non-alcoholic fatty liver disease (NAFLD). There is an urgent need for non-invasive tests that can accurately stage fibrosis and determine efficacy of interventions. Here we describe a novel cf-mRNA-Sequencing approach that can accurately and reproducibly profile low levels of circulating mRNAs and evaluate the feasibility of developing a cf-mRNA-based NAFLD fibrosis classifier. Using separate discovery and validation cohorts with biopsy-confirmed NAFLD (n=176 and 59, respectively) and healthy subjects (n=23), we performed serum cf-mRNA RNA-Seq profiling. Differential expression analysis identified 2498 dysregulated genes between NAFLD and healthy subjects and 134 fibrosis-associated genes in NAFLD patients. Comparison between cf-mRNA and liver tissues transcripts revealed significant overlap of fibrosis associated genes and pathways indicating that the circulating cf-mRNA transcriptome reflects molecular changes in the livers of NAFLD patients. In particular, metabolic and immune pathways reflective of known underlying steatosis and inflammation were highly dysregulated in the cf-mRNA profile of patients with advanced fibrosis. Finally, we used an elastic net ordinal logistic model to develop a classifier that predicts clinically significant fibrosis (F2-4). In an independent cohort, the cf-mRNA classifier was able to identify 50% of patients with at least 90% probability of clinically significant fibrosis. We demonstrate a novel and robust cf-mRNA-based RNA-Seq platform for non-invasive identification of diverse hepatic molecular disruptions and for fibrosis staging with promising potential for clinical trials and clinical practice.

scholarly journals Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324243
Author(s):  
Ferenc Emil Mózes ◽  
Jenny A Lee ◽  
Emmanuel Anandraj Selvaraj ◽  
Arjun Narayan Ajmer Jayaswal ◽  
Michael Trauner ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Liver Biopsies ◽  
Alcoholic Fatty Liver Disease ◽  
Rule Out

ObjectiveLiver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.DesignIndividual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.ResultsData were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63–68) and 86% (84–87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37–39) and specificity of 90% (89–91) with 19% needing biopsy.ConclusionSequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

scholarly journals Systematic review and meta-analysis: non-invasive detection of non-alcoholic fatty liver disease related fibrosis in the obese

2017 ◽  
Vol 19 (2) ◽  
pp. 281-294 ◽  
Author(s):  
G. J. Ooi ◽  
S. Mgaieth ◽  
G. D. Eslick ◽  
P. R. Burton ◽  
W. W. Kemp ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease
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