Diagnostic and Prognostic Markers and ToolsReviewNoninvasive Methods to Assess Liver Disease in Patients With Hepatitis B or C
Section snippets
Methodologies
The performance of a noninvasive diagnostic method is evaluated by calculation of the area under the receiver operator characteristic curve (AUROC), taking liver biopsy as the reference standard. However, biopsy analysis is an imperfect reference standard: taking into account a range of accuracies of the biopsy, even in the best possible scenario, an AUROC >0.90 cannot be achieved even for a perfect marker of liver disease.13
The AUROC can vary based on the prevalence of each stage of fibrosis,
Noninvasive Methods
Fibrosis can be measured noninvasively, based on a “biological” approach (quantifying biomarkers in serum samples) or based on a “physical” approach (measuring liver stiffness). Although these approaches are complementary, they are based on a different rationale. Liver stiffness corresponds to a genuine and intrinsic physical property of liver parenchyma, whereas serum biomarkers indicate several, not strictly liver-specific features of blood that have been associated with fibrosis stage, as
Quantifying Markers of Liver Fibrosis in Serum
The diagnostic performances of serum biomarkers of fibrosis for significant fibrosis and cirrhosis are summarized in Table 3. Overall, biomarkers are less accurate in detecting intermediate stages of fibrosis than cirrhosis. The most widely used and validated are the APRI (a free nonpatented index) and the FibroTest (a patented test that is not widely available). A meta-analysis by the developer58 that analyzed data from 6378 subjects (individual data from 3282 subjects) who received the
Assessing the Stage of Liver Disease
In clinical practice, the determination of fibrosis stage does not need to be as exact as the pathologic scoring system; the absolute stage is less important than determining whether patients have mild or advanced liver disease.
For identifying patients with significant fibrosis, sensitivities and specificities above 85% can be considered sufficient because there are no relevant clinical consequences of false positives or false negatives.80 Because performances of TE and serum biomarkers have
Future Directions
Significant progress has been made over the past decade in noninvasive assessment of liver disease in patients with hepatitis B or C, but there is no perfect method. On the one hand, there is increasing awareness that liver biopsy is an imperfect standard. On the other hand, an increasing number of noninvasive methods are available: TE, FibroTest, and APRI are the most widely used and validated worldwide. The introduction of these methods several years ago in France for the management of
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Conflicts of interest The author discloses the following: Dr Castera has served on the speaker's bureau or as an advisor for Bristol-Myers Squibb, Echosens, Ferrer, Gilead, and Merck.