Contribution of the ELFG test in algorithms of non-invasive markers towards the diagnosis of significant fibrosis in chronic hepatitis C.

BACKGROUND AND AIMS: We aimed to determine the best algorithms for the diagnosis of significant fibrosis in chronic hepatitis C (CHC) patients using all available parameters and tests. PATIENTS AND METHODS: We used the database from our study of 507 patients with histologically proven CHC in which fibrosis was evaluated by liver biopsy (Metavir) and tests: Fibrometer®, Fibrotest®, Hepascore®, Apri, ELFG, MP3, Forn's, hyaluronic acid, tissue inhibitor of metalloproteinase-1 (TIMP1), MMP1, collagen IV and when possible Fibroscan™. For the first test we used 90% negative predictive value to exclude patients with F≤1, next an induction algorithm was applied giving the best tests with at least 80% positive predictive value for the diagnosis of F≥2. The algorithms were computed using the R Software C4.5 program to select the best tests and cut-offs. The algorithm was automatically induced without premises on the part of the investigators. We also examined the inter-observer variations after independent review of liver biopsies by two pathologists. A medico-economic analysis compared the screening strategies with liver biopsy. RESULTS: In "intention to diagnose" the best algorithms for F≥2 were Fibrometer ®, Fibrotest®, or Hepascore® in first intention with the ELFG score in second intention for indeterminate cases. The percentage of avoided biopsies varied between 50% (Fibrotest® or Fibrometer®+ELFG) and 51% (Hepascore®+ELFG). In "per-analysis" Fibroscan™+ELFG avoided liver biopsy in 55% of cases. The diagnostic performance of these screening strategies was statistically superior to the usual combinations (Fibrometer® or Fibrotest®+Fibroscan™) and was cost effective. We note that the consensual review of liver biopsies between the two pathologists was mainly in favor of F1 (64-69%). CONCLUSION: The ELFG test could replace Fibroscan in most currently used algorithms for the diagnosis of significant fibrosis including for those patients for whom Fibroscan™ is unusable

Scores from the different tests and selected parameters for the 507 CHC patients having all the blood tests (intention to diagnose population) and the 396 CHC patients with all the blood tests and reliable Fibroscan^TM (per protocol population).

*<p>TIMP1: tissue inhibitor of metalloproteinase-1; **MM1: matrix metalloproteinase-1;</p>***<p>PIIINP: N-terminal peptide of type III procollagen.</p

Economic analysis.

<p>Average cost of screening per patient (in euros) of the various combinations of tests, taking 3 levels of liver biopsy cost based on published data and the cost in our hospital: 800 Euros, 1,000 Euros and 1,200 Euros. *Cost of Fibroscan, for use equivalent to 10 acts per month. * *Cost of Fibroscan, for use equivalent to 32 acts per month.</p

Study Flow Chart.

<p>N: number of chronic hepatitis C patients with test results; and the number of patients without the test or with missing test data are shown in parentheses.</p

Characteristics of liver biopsy for each algorithm, when liver biopsy is required, and in the overall population.

<p>Characteristics of liver biopsy for each algorithm, when liver biopsy is required, and in the overall population.</p

Proposed algorithm: automatically determined by the C4.5 program with the number of avoided liver biopsies.

<p>The bottom line gives the total number of liver biopsies avoided following one of the three most validated blood tests or Fibroscan followed by the ELFG test for those patients for whom the first test was not conclusive. N: number of patients; F: Metavir liver biopsy Fibrosis score; NPV: Negative Predictive Value with the cut-off in parentheses; PPV: Positive Predictive Value with the cut-off range in brackets. * = cut-off = >−0.32; ** = per protocol analysis.</p

Comparison between proposed algorithm, with ELFG, and published algorithms (that include Fibroscan^TM) in terms of number of patients with avoided liver biopsies.

<p>Comparison between proposed algorithm, with ELFG, and published algorithms (that include Fibroscan^TM) in terms of number of patients with avoided liver biopsies.</p

Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study.

International audienceBACKGROUND & AIMS: Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC). METHODS: This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method. RESULTS: Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis. CONCLUSIONS: Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis