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Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data.

Poynard T, Lassailly G, Diaz E, Clement K, Caïazzo R, Tordjman J, Munteanu M, Perazzo H, Demol B, Callafe R, Pattou F, Charlotte F, Bedossa P, Mathurin P, Ratziu V, FLIP consorti - PLoS ONE (2012)

Bottom Line: Weighted AUROC (wAUROC Obuchowski method) was used to prevent multiple testing and spectrum effect.Using the classical meta-analysis (random effect model) the mean AUROCs were: FibroTest = 0.72 (0.63-0.79; P<0.0001); SteatoTest = 0.71 (0.66-0.75; P<0.0001); and ActiTest = 0.74 (0.68-0.79; P<0.0001).Despite more metabolic risk factors in one cohort, results were similar according to gender, presence of diabetes and between the 3 cohorts.

View Article: PubMed Central - PubMed

Affiliation: APHP UPMC Liver Center, Paris, France. tpoynard@teaser.fr

ABSTRACT

Background: Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions in patients with severe obesity. The aim of this study was to perform an overview of 3 studies which assessed the performance of non-invasive markers of fibrosis (FibroTest), steatosis (SteatoTest) and steato-hepatitis (NashTest, ActiTest) in these patients.

Methods: 494 patients with interpretable biopsy and biomarkers using of three prospective cohorts of patients with severe obesity (BMI >35 kg/m2) were included. Histology (NAS score) and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity, specificity, positive and negative predictive values were assessed. Weighted AUROC (wAUROC Obuchowski method) was used to prevent multiple testing and spectrum effect. Two meta-analyses were performed; one used the individual patient, and the other a classical meta-analysis.

Results: Prevalence of advanced fibrosis (bridging) was 9.9%, advanced steatosis (>33%) 54.2%, and steato-hepatitis (NAS score >4) 17.2%. The mean wAUROCs were: FibroTest for advanced fibrosis (95%CI; significance)  =  0.85 (0.83-0.87; P<0.0001); SteatoTest for advanced steatosis = 0.80 (0.79-0.83); and ActiTest for steato-hepatitis = 0.84 (0.82-0.86; P<0.0001). Using the classical meta-analysis (random effect model) the mean AUROCs were: FibroTest = 0.72 (0.63-0.79; P<0.0001); SteatoTest = 0.71 (0.66-0.75; P<0.0001); and ActiTest = 0.74 (0.68-0.79; P<0.0001). Despite more metabolic risk factors in one cohort, results were similar according to gender, presence of diabetes and between the 3 cohorts.

Conclusion: In patients with severe obesity, a significant diagnostic performance of FibroTest, SteatoTest and ActiTest was observed for liver lesions.

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Related in: MedlinePlus

Included patients with morbid obesity.*In the Lille cohort a total of 296 patients have been excluded, 94 because histological staging was missing, 19 were duplicate, 229 for biomarkers non assessed (including 39 with more than one cause of exclusion) and 3 patients with not interpretable FT/ST (extreme value of triglycerides/glucose/ApoA1 detected by security algorithms). In the Paris cohort 6 patients have excluded, 2 with BMI lower than 35, 3 because histological staging was missing, and one for biomarkers not assessed. In the Bethune cohort 8 patients have excluded, 3 with BMI lower than 35, and 5 because histological staging was missing.
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pone-0030325-g001: Included patients with morbid obesity.*In the Lille cohort a total of 296 patients have been excluded, 94 because histological staging was missing, 19 were duplicate, 229 for biomarkers non assessed (including 39 with more than one cause of exclusion) and 3 patients with not interpretable FT/ST (extreme value of triglycerides/glucose/ApoA1 detected by security algorithms). In the Paris cohort 6 patients have excluded, 2 with BMI lower than 35, 3 because histological staging was missing, and one for biomarkers not assessed. In the Bethune cohort 8 patients have excluded, 3 with BMI lower than 35, and 5 because histological staging was missing.

Mentions: Among these 212 studies, three were included as specifically conducted in patients with severe obesity (Figure 1 and Figure S2): three [10], [24], [25] assessed FT, ST, AT and NT. One study is part of an ongoing cohort (Lille cohort) [10], [26]; for the other two (Paris and Bethune cohorts) [24], [25] the performances of biomarkers were not detailed in the publications but the authors shared the individual data; five other studies investigated these tests in patients with NAFLD but not specifically in severe obese patients and were not included: FT [9], [13], ST [11], [13], NT 12,13.


Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data.

Poynard T, Lassailly G, Diaz E, Clement K, Caïazzo R, Tordjman J, Munteanu M, Perazzo H, Demol B, Callafe R, Pattou F, Charlotte F, Bedossa P, Mathurin P, Ratziu V, FLIP consorti - PLoS ONE (2012)

Included patients with morbid obesity.*In the Lille cohort a total of 296 patients have been excluded, 94 because histological staging was missing, 19 were duplicate, 229 for biomarkers non assessed (including 39 with more than one cause of exclusion) and 3 patients with not interpretable FT/ST (extreme value of triglycerides/glucose/ApoA1 detected by security algorithms). In the Paris cohort 6 patients have excluded, 2 with BMI lower than 35, 3 because histological staging was missing, and one for biomarkers not assessed. In the Bethune cohort 8 patients have excluded, 3 with BMI lower than 35, and 5 because histological staging was missing.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303768&req=5

pone-0030325-g001: Included patients with morbid obesity.*In the Lille cohort a total of 296 patients have been excluded, 94 because histological staging was missing, 19 were duplicate, 229 for biomarkers non assessed (including 39 with more than one cause of exclusion) and 3 patients with not interpretable FT/ST (extreme value of triglycerides/glucose/ApoA1 detected by security algorithms). In the Paris cohort 6 patients have excluded, 2 with BMI lower than 35, 3 because histological staging was missing, and one for biomarkers not assessed. In the Bethune cohort 8 patients have excluded, 3 with BMI lower than 35, and 5 because histological staging was missing.
Mentions: Among these 212 studies, three were included as specifically conducted in patients with severe obesity (Figure 1 and Figure S2): three [10], [24], [25] assessed FT, ST, AT and NT. One study is part of an ongoing cohort (Lille cohort) [10], [26]; for the other two (Paris and Bethune cohorts) [24], [25] the performances of biomarkers were not detailed in the publications but the authors shared the individual data; five other studies investigated these tests in patients with NAFLD but not specifically in severe obese patients and were not included: FT [9], [13], ST [11], [13], NT 12,13.

Bottom Line: Weighted AUROC (wAUROC Obuchowski method) was used to prevent multiple testing and spectrum effect.Using the classical meta-analysis (random effect model) the mean AUROCs were: FibroTest = 0.72 (0.63-0.79; P<0.0001); SteatoTest = 0.71 (0.66-0.75; P<0.0001); and ActiTest = 0.74 (0.68-0.79; P<0.0001).Despite more metabolic risk factors in one cohort, results were similar according to gender, presence of diabetes and between the 3 cohorts.

View Article: PubMed Central - PubMed

Affiliation: APHP UPMC Liver Center, Paris, France. tpoynard@teaser.fr

ABSTRACT

Background: Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions in patients with severe obesity. The aim of this study was to perform an overview of 3 studies which assessed the performance of non-invasive markers of fibrosis (FibroTest), steatosis (SteatoTest) and steato-hepatitis (NashTest, ActiTest) in these patients.

Methods: 494 patients with interpretable biopsy and biomarkers using of three prospective cohorts of patients with severe obesity (BMI >35 kg/m2) were included. Histology (NAS score) and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity, specificity, positive and negative predictive values were assessed. Weighted AUROC (wAUROC Obuchowski method) was used to prevent multiple testing and spectrum effect. Two meta-analyses were performed; one used the individual patient, and the other a classical meta-analysis.

Results: Prevalence of advanced fibrosis (bridging) was 9.9%, advanced steatosis (>33%) 54.2%, and steato-hepatitis (NAS score >4) 17.2%. The mean wAUROCs were: FibroTest for advanced fibrosis (95%CI; significance)  =  0.85 (0.83-0.87; P<0.0001); SteatoTest for advanced steatosis = 0.80 (0.79-0.83); and ActiTest for steato-hepatitis = 0.84 (0.82-0.86; P<0.0001). Using the classical meta-analysis (random effect model) the mean AUROCs were: FibroTest = 0.72 (0.63-0.79; P<0.0001); SteatoTest = 0.71 (0.66-0.75; P<0.0001); and ActiTest = 0.74 (0.68-0.79; P<0.0001). Despite more metabolic risk factors in one cohort, results were similar according to gender, presence of diabetes and between the 3 cohorts.

Conclusion: In patients with severe obesity, a significant diagnostic performance of FibroTest, SteatoTest and ActiTest was observed for liver lesions.

Show MeSH
Related in: MedlinePlus