Methodological aspects of the interpretation of non-invasive biomarkers of liver fibrosis: a 2008 update

Poynard, Thierry; Muntenau, M.; Morra, Rachel; Ngo, Yen; Imbert‐Bismut, Françoise; Thabut, Dominique; Messous, Djamila; Massard, Julien; Lebray, Pascal; Moussalli, J.; Benhamou, Yves; Ratziu, Vlad

doi:10.1016/s0399-8320(08)73990-3

Cited by 40 publications

(52 citation statements)

References 55 publications

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“…We believe this is the reason why ''changing the definition of diseased liver from F4 to F2F3F4 is associated with a decrease in the AUROC for a biomarker" and not because the biomarker is ''not adequate" as stated in the accompanying editorial [3]. We have shown that an AUROC of 0.90 for F4, an AUR-OC of 0.80 for F2F3F4 and an AUROC of 0.65 for the distinction between F1 and F2 are all similarly ''adequate" [2]. Remarkably, this is true for any diagnostic test including liver biopsy.…”

Section: Letters To the Editormentioning

confidence: 71%

“…When compared to the real gold standard, which is the liver in its entirety, liver biopsy displays similarly reduced AUROCs for the distinction of adjacent fibrosis stages (e.g. F1 vs. F2) than for distant/ end of spectrum stages [2]. Biomarkers or biopsy do not perform any differently in that regard.…”

Section: Letters To the Editormentioning

confidence: 90%

“…In chronic hepatitis C core fragments of 40 mm have a 25% rate of misclassification of META-VIR stages [2]. Ironically, striving for the highest AUR-OC will only result in a test having the same high rate of misclassification vs. the presence of the disease.…”

Section: Letters To the Editormentioning

confidence: 99%

Section: Letters To the Editormentioning

confidence: 99%

“…Clinical discussion of discordance cases and exclusion of spectrum bias are examples of such new methods [2]. Spectrum bias is a significant confounder of AUROC and that differences in prevalence of stages defining advanced or non-advanced fibrosis (or defining non-cirrhosis versus cirrhosis) can explain variability of AUROCs for the same test when performed in different populations [2]. We believe this is the reason why ''changing the definition of diseased liver from F4 to F2F3F4 is associated with a decrease in the AUROC for a biomarker" and not because the biomarker is ''not adequate" as stated in the accompanying editorial [3].…”

Section: Letters To the Editormentioning

confidence: 99%

See 4 more Smart Citations

Liver biopsy: The best standard…when everything else fails

Poynard

Benhamou

Thabut

et al. 2009

Journal of Hepatology

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Section: Letters To the Editormentioning

confidence: 71%

Section: Letters To the Editormentioning

confidence: 90%

Section: Letters To the Editormentioning

confidence: 99%

Section: Letters To the Editormentioning

confidence: 99%

Section: Letters To the Editormentioning

confidence: 99%

See 3 more Smart Citations

Liver biopsy: The best standard…when everything else fails

Poynard

Benhamou

Thabut

et al. 2009

Journal of Hepatology

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Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014

et al. 2015

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There is an urgent need to develop antifibrotic therapies for chronic liver disease, and to clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. AASLD sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and to develop recommendations on clinical trial design for liver fibrosis. In this review we summarize the salient and novel elements of this conference and provide directions for future clinical trial design. The paper follows the structure of the conference and is organized into five areas: I) Antifibrotic trial design; II) Preclinical proof of concept studies; III) Pharmacologic targets: rationale and lessons to learn; IV) Rational drug design and development; V) Consensus and recommendations on design of clinical trials in liver fibrosis. Expert overviews and collaborative discussions helped to summarize the key unmet needs and directions for the future, including: 1) Greater clarification of at-risk populations and study groups; 2) Standardization of all elements of drug discovery and testing; 3) Standardization of clinical trial approaches; 4) Accelerated development of improved non-invasive markers; 5) Need for exploration of potential off-target toxicities of future antifibrotic drugs.

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Noninvasive assessment of hepatic fibrosis in patients with chronic hepatitis C using serum Fourier transform infrared spectroscopy

Scaglia

Sockalingum

Schmitt³

et al. 2011

Anal Bioanal Chem

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Assessment of liver fibrosis is of paramount importance to guide the therapeutic strategy in patients with chronic hepatitis C (CHC). In this pilot study, we investigated the potential of serum Fourier transform infrared (FTIR) spectroscopy for differentiating CHC patients with extensive hepatic fibrosis from those without fibrosis. Twenty-three serum samples from CHC patients were selected according to the degree of hepatic fibrosis as evaluated by the FibroTest: 12 from patients with no hepatic fibrosis (F0) and 11 from patients with extensive fibrosis (F3-F4). The FTIR spectra (ten per sample) were acquired in the transmission mode and data homogeneity was tested by cluster analysis to exclude outliers. After selection of the most discriminant wavelengths using an ANOVA-based algorithm, the support vector machine (SVM) method was used as a supervised classification model to classify the spectra into two classes of hepatic fibrosis, F0 and F3-F4. Given the small number of samples, a leave-one-out cross-validation algorithm was used. When SVM was applied to all spectra (n = 230), the sensitivity and specificity of the classifier were 90.1% and 100%, respectively. When SVM was applied to the subset of 219 spectra, i.e., excluding the outliers, the sensitivity and specificity of the classifier were 95.2% and 100%, respectively. This pilot study strongly suggests that the serum from CHC patients exhibits infrared spectral characteristics, allowing patients with extensive fibrosis to be differentiated from those with no hepatic fibrosis.

show abstract

Methodological aspects of the interpretation of non-invasive biomarkers of liver fibrosis: a 2008 update

Cited by 40 publications

References 55 publications

Liver biopsy: The best standard…when everything else fails

Liver biopsy: The best standard…when everything else fails

Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014

Noninvasive assessment of hepatic fibrosis in patients with chronic hepatitis C using serum Fourier transform infrared spectroscopy

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