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

(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.

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

Gut ◽

10.1136/gutjnl-2021-324243 ◽

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.

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Comparison of FIB-4 index, NAFLD fibrosis score and BARD score for prediction of advanced fibrosis in adult patients with non-alcoholic fatty liver disease: A meta-analysis study

Hepatology Research ◽

10.1111/hepr.12647 ◽

2016 ◽

Vol 46 (9) ◽

pp. 862-870 ◽

Cited By ~ 53

Author(s):

Wenjing Sun ◽

Hongli Cui ◽

Ning Li ◽

Yanling Wei ◽

Shujie Lai ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Meta Analysis ◽

Advanced Fibrosis ◽

Fibrosis Score ◽

Alcoholic Fatty Liver ◽

Analysis Study ◽

Nafld Fibrosis Score ◽

Alcoholic Fatty Liver Disease

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Systematic Review with Meta-Analyses: Diagnostic Accuracy of FibroMeter Tests in Patients with Non-Alcoholic Fatty Liver Disease

Journal of Clinical Medicine ◽

10.3390/jcm10132910 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2910

Author(s):

Anne-Marieke van Dijk ◽

Yasaman Vali ◽

Anne Linde Mak ◽

Jenny Lee ◽

Maarten E. Tushuizen ◽

...

Keyword(s):

Liver Disease ◽

Diagnostic Accuracy ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Cochrane Library ◽

Advanced Fibrosis ◽

Alcoholic Fatty Liver ◽

Meta Analyses ◽

The Cochrane Library ◽

Alcoholic Fatty Liver Disease

Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains.

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

Biomedicines ◽

10.3390/biomedicines9121920 ◽

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.

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The Effects of Modest Alcohol Consumption on Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.744713 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wasit Wongtrakul ◽

Sorachat Niltwat ◽

Phunchai Charatcharoenwitthaya

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Alcohol Consumption ◽

Alcohol Use ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Meta Analysis ◽

Advanced Fibrosis ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background and Objective: There is no consensus regarding modest alcohol consumption in patients with non-alcoholic fatty liver disease (NAFLD) due to conflicting results. The aim of this meta-analysis was to examine the effects of modest alcohol consumption on histological severity, histological course, hepatocellular carcinoma, and long-term clinical outcomes in NAFLD patients.Methods: We searched MEDLINE and EMBASE databases from inception to October 2020 for studies evaluating the effects of modest alcohol consumption among patients with NAFLD. A random-effects meta-analysis using pooled odds ratio (OR) and hazard ratio (HR) was calculated with 95% confidence interval (CI). Study quality was assessed with the Newcastle-Ottawa Scale.Results: Fourteen cross-sectional or cohort studies with aggregate data on 14,435 patients were included in the analysis. Modest alcohol consumption resulted in lower risks for steatohepatitis (OR 0.59; 95% CI 0.45–0.78; I2 = 12%) and advanced fibrosis (OR 0.59, 95% CI 0.36–0.95; I2 = 75%). Histological follow-up data showed that modest alcohol use was associated significantly with less steatohepatitis resolution but not with fibrosis progression. The HR for developing hepatocellular carcinoma was 3.77 (95% CI 1.75–8.15; I2 = 0%). NAFLD patients with modest alcohol intake had a lower mortality risk than lifelong abstainers (HR 0.85; 95% CI 0.75–0.95; I2 = 64%).Conclusion: This meta-analysis suggests that medical advice for modest alcohol drinking should be made cautiously in caring for an individual patient based on the clinical context. Practically, patients with steatohepatitis or advanced fibrosis should avoid alcohol use, whereas patients with low fibrosis risk may be allowed for modest and safe drinking.

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