Elsevier

Journal of Hepatology

Volume 53, Issue 6, December 2010, Pages 1013-1021
Journal of Hepatology

Research Article
Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study)

https://doi.org/10.1016/j.jhep.2010.05.035Get rights and content

Background & Aims

The diagnostic accuracy of non-invasive liver fibrosis tests that may replace liver biopsy in patients with chronic hepatitis remains controversial.

We assessed and compared the accuracy of FibroScan® and that of the main biomarkers used for predicting cirrhosis and significant fibrosis (METAVIR  F2) in patients with chronic viral hepatitis.

Methods

A multicenter prospective cross-sectional diagnostic accuracy study was conducted in the Hepatology departments of 23 French university hospitals. Index tests and reference standard (METAVIR fibrosis score on liver biopsy) were measured on the same day and interpreted blindly. Consecutive patients with chronic viral hepatitis (hepatitis B or C virus, including possible Human Immunodeficiency Virus co-infection) requiring liver biopsy were recruited in the study.

Results

The analysis was first conducted on the total population (1839 patients), and after excluding 532 protocol deviations, on 1307 patients (non-compliant FibroScan® examinations). The overall accuracy of FibroScan® was high (AUROC 0.89 and 0.90, respectively) and significantly higher than that of biomarkers in predicting cirrhosis (AUROC 0.77–0.86). All non-invasive methods had a moderate accuracy in predicting significant fibrosis (AUROC 0.72–0.78). Based on multilevel likelihood ratios, non-invasive tests provided a relevant gain in the likelihood of diagnosis in 0–60% of patients (cirrhosis) and 9–30% of patients (significant fibrosis).

Conclusions

The diagnostic accuracy of non-invasive tests was high for cirrhosis, but poor for significant fibrosis. A clinically relevant gain in the likelihood of diagnosis was achieved in a low proportion of patients. Although the diagnosis of cirrhosis may rely on non-invasive tests, liver biopsy is warranted to diagnose intermediate stages of fibrosis.

Introduction

Diagnosis and treatment of patients with chronic hepatitis mostly rely on the staging of liver fibrosis. Antiviral therapy is proposed if moderate to severe (METAVIR stages F2 and F3) [1] fibrosis is present. If cirrhosis is present, specific surveillance is initiated, in particular for the early detection of hepatocellular carcinoma. Despite its limitations, liver biopsy is the usual procedure for staging fibrosis and is recommended by the international guidelines [2], [3].

Non-invasive procedures such as transient elastography (FibroScan®, Echosens, Paris, France) and serum biomarkers (particularly Fibrometre®, Fibrotest®, Hepascore and APRI) have been developed in order to avoid biopsy. Transient elastography is a new imaging technique measuring liver stiffness, i.e. its elasticity. As highlighted by recent meta-analyses [4], its diagnostic accuracy is difficult to judge because of the small sample sizes of most published studies and because of the inter-study variability of accuracy estimates and elasticity thresholds, varying in the literature from 8.4 to18.2 kPa for the diagnosis of cirrhosis and from 5.0 to 11.8 for the diagnosis of significant fibrosis (METAVIR fibrosis score ⩾F2) [4], [5]. In addition, there are few direct comparisons of transient elastography and of serum biomarkers [6] and the reported accuracy parameters do not always allow clinicians to estimate the probability of a condition in a given patient [7].

We evaluated the diagnostic accuracy and clinical usefulness of FibroScan® in predicting two conditions – significant histological liver fibrosis (METAVIR ⩾F2) and cirrhosis (F4) – in patients with chronic viral hepatitis, in a multicenter prospective study funded by the French Ministry of Health (the FIBROSTIC study). The secondary objectives were: (i) to assess variations in the diagnostic accuracy of FibroScan® by cause of infection and by patient selection criteria for liver biopsy; (ii) to compare the diagnostic accuracy of the most common liver fibrosis serum biomarkers with that of transient elastography; (iii) to assess the gain in likelihood of target conditions provided by non-invasive tests.

Section snippets

Design overview, setting, and participants

This was a multicenter prospective cross-sectional diagnostic accuracy study. From June 15, 2006, to July 15, 2008, the hepatology departments of 23 French university hospitals included all consecutive patients with chronic viral hepatitis due to hepatitis C virus (HCV) or hepatitis B virus (HBV) (with or without Human Immunodeficiency Virus – HIV co-infection) in whom liver fibrosis assessment was indicated. Chronic hepatitis C was defined as the presence of anti-HCV antibodies for more than 6 

Flow diagram and patients’ characteristics

Among the 1839 potentially eligible patients, 532 (29%) were not eligible, mostly because their transient elastography examinations did not comply with the recommendations for high measurement reproducibility [16] (Fig. 1). The more frequent reason of exclusion was an interquartile range of elasticity >30% of the median (269 patients, 14%). We conducted the main analysis on the group of patients complying with the adequate technique, but results on the whole group were analyzed in a sensitivity

Discussion

The FIBROSTIC study has compared the performance of transient elastography (FibroScan®) with that of the main non-invasive biological methods of liver fibrosis assessment in a large representative sample of patients suffering from viral chronic hepatitis and consecutively selected for liver biopsy in routine clinical practice. The performance of FibroScan® in predicting cirrhosis was high and higher than that of biomarkers. However, the performance of all the non-invasive methods in predicting

Funding

French health authorities (National STIC grant).

Conflict of interests

The authors do not have a relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research.

Acknowledgements

We are indebted to Florence Tubach, Yolande Costa and Virginia Olympio (Unité de Recherche Clinique Paris Nord) for their outstanding contribution to the setting up and monitoring of this study. Calculations of Fibrometre and Fibrotest are a courtesy of Bioliverscale and Biopredictive and we thank them.

We thank Professor Bruno Falissard, President of the Scientific Committee of the study for helpful discussion. We also thank Tiiu Ojasoo for help in editing the manuscript.

References (33)

  • EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol...
  • M.G. Ghani et al.

    Diagnosis, management and treatment of hepatitis C: an update

    Hepatology

    (2009)
  • M. Friedrich-Rust et al.

    Performance of transient elastography for the staging of liver fibrosis: a meta-analysis

    Gastroenterology

    (2008)
  • R. Jaeschke et al.

    Users’ Guides to the Medical Literature: III. How to use an article about a diagnostic Test: B. What are the results and will they help me in caring for my patients?

    JAMA

    (1994)
  • D.C. Rockey et al.

    Liver biopsy

    Hepatology

    (2009)
  • J. Boursier et al.

    Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C

    Eur J Gastroenterol Hepatol

    (2009)
  • Cited by (0)

    see Appendix 1 for the participating centers.

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