Research ArticleDiagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study)
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.
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see Appendix 1 for the participating centers.