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

Abstract

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.

Figure 1. Study Flow Chart.

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.

Figure 2. Proposed algorithm: automatically determined by the C4.5 program with the number of avoided liver biopsies.

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.

Figure 3. Economic analysis.

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.