Overestimate of Fibrosis by FIBROSpect® II in African Americans Complicates the Management of their Chronic Hepatitis C

Abstract

Background: Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA).

Aims: This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays.

Methods: All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records.

Results: When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis.

Conclusions: The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.

Keywords: African Americans; Fibrosis; Fibrospect; Hepatitis c.

Fig. 1.. Distribution of fibrosis in patients with chronic hepatitis C (CHC).

Fibrosis score as either minimal (F0-F1) or significant (F2-4) was plotted as percentage of African Americans (AA) or Caucasians (Cau) with hepatitis C virus (HCV). The number of individuals with matched biopsy and FIBROSpect II (FSII), as indicated in the parenthesis, was 134 for AA and 15 for Cau. Some biopsy patients did not have the data required to calculate the aspartate amino transferase (AST) platelet ratio index (APRI) or FIB-4 index, which accounts for the difference in numbers.

Fig. 2.. Biopsy vs. FSII, APRI, and FIB-4 index for paired patients.

Biopsy and fibrosis assay results for paired patients are plotted by race, although the number of Cau (15) is inadequate for statistical analysis. The shaded area represents patients with high fibrosis values but minimal biopsy defined fibrosis (F0-F1) (i.e., over-scored patients).

Fig. 3.. Receiver operating characteristic (ROC) curves of panels of markers of fibrosis (FSII, APRI, and FIB-4 index) among AA with CHC compared with biopsy METAVIR (as “gold standard”) to define true positive.

Area under the curve (AUC) and the cutoff are defined using the ROC tables, as generated by the statistical program and represented by the tangent line in the graph. FSII (AUC = 0.69, Cutoff 52, Over-scored 24%), APRI (AUC = 0.66, Cutoff 0.8, Over-scored 10%), and FIB-4 (AUC = 0.64, Cutoff 1.9, Over-scored 20%). The over-scored percentage represents the number of patients who are scored as positive (significant fibrosis F2-F4) by the assay but are known negative (minimal fibrosis F0-F1) based on biopsy results divided by the total population.

Fig. 4.. APRI and FIB-4 index for individual AA with CHC stratified by biopsy defined FSII scores.

Patients were first divided into four groups using their FSII score and the true fibrosis value by biopsy. The four categories were: true negative (Fibrosis Accurate Low; FAccL), false positive (Fibrosis over-scored; FOver), true positive for significant fibrosis (FAccurateHigh; FAccH), or false negative (minimal fibrosis scored as high; Fibrosis Under; FUnder). The line represents the literature cutoff for separating F0-F1 from F2-F4 for the APRI and FIB-4 assays. The oval identifies patients, based on biopsy results, were over-scored in the FSII assay but correctly scored as minimal fibrosis in the APRI or FIB-4 assay. The rectangular box represents patients with biopsy proven significant fibrosis who were underscored by FSII but correctly scored as significant fibrosis by APRI or FIB-4.