Fibrosis assessment using FibroMeter combined to first generation tests in hepatitis C

To evaluate the performance of FibroMeter^Virus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC).

First generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeter^Virus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeter^Virus3G and Forns plus FibroMeter^Virus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeter^Virus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C.

Seven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeter^Virus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeter^Virus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeter^Virus3G in derivation population presented similar performance compared to FibroMeter^Virus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeter^Virus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeter^Virus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeter^Virus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3).

The stepwise combination of APRI or Forns with FibroMeter^Virus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.