Published online Feb 28, 2017. doi: 10.4254/wjh.v9.i6.310
Peer-review started: September 27, 2016
First decision: November 22, 2016
Revised: December 15, 2016
Accepted: February 8, 2017
Article in press: February 13, 2017
Published online: February 28, 2017
To evaluate the performance of FibroMeterVirus3G 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. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G 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 FibroMeterVirus3G 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 FibroMeterVirus3G 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 FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G 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 FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3).
The stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.
Core tip: Liver fibrosis assessment still poses a challenge when prioritizing hepatitis C treatment due to logistical and financial barriers in the use of direct acting antiviral drugs. We introduced a new stepwise combination of first generation fibrosis tests - aminotransferase-to-platelet ratio index (APRI) and Forns-followed by FibroMeterVirus3G whenever results remained unclassified after first generation tests to identify significant fibrosis. This combination presented similar accuracy to FibroMeterVirus3G used as the only test, reduced APRI and Forns grey zone, and spared FibroMeterVirus3G requirement in 50% of cases. This approach represents a lower-cost alternative to assess fibrosis, with no need for liver biopsy.