Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C

Abstract

Background: Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations.

Methods: Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients.

Results: In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (FM) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10-3) in single expert pathologist. Significant discrepancy (≥ 2FM vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter2G: 5.6%, local pathologists: 4.9%, FibroMeter3G: 0.5%, expert pathologist: 0% (p < 10-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter2G (0.30 ± 0.55) and FibroMeter3G (0.14 ± 0.37, p < 10-3) or Fibrotest (0.84 ± 0.80, p < 10-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter2G: 68.7% (68.2%), FibroMeter3G: 77.1% (83.4%), p < 10-3 (p < 10-3). Significant discrepancy (≥ 2 FM) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter2G: 5.7% (6.0%), FibroMeter3G: 0.9% (0.9%), p < 10-3 (p < 10-3).

Conclusions: The accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter3G. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test.

Figure 1

Summary of different available fibrosis classifications in population #2. Metavir stages by liver biopsy (A), significant fibrosis by FibroMeter^2G (FM) (B), fibrosis class classification by FibroMeter^2G (C) or FibroMeter^3G (D) or by Fibrotest (FT) (E). The central figure within the pie chart indicates the number of fibrosis classes. Sectors correspond to patient proportions. The figures in the external circle of panels reflect the values of blood test scores. F_M denotes the Metavir fibrosis stages estimated by the classification.

Figure 2

Rates of discrepancy grade of fibrosis class classifications by diagnostic tests in populations #2 (top) or #3 (bottom). The figure indicates the difference in the number of fibrosis stage(s) between the blood test and liver biopsy. Thus, the grade 0 (green pie sector) indicates agreement with liver biopsy.

Figure 3

Discrepancy between fibrosis class classifications by non-invasive tests and liver biopsy staging. Results (Y axis) are expressed as a function of Metavir fibrosis (F) stage (X axis) in population #3. The left panel A indicates the mean score. The right panels show the details of discrepancy grades for each diagnostic test: Fibrotest (B), Fibroscan (C), FibroMeter^2G (D) and FibroMeter^3G (E). The grade indicates the difference in the number of fibrosis stage(s) between the blood test and liver biopsy. FT: Fibrotest, FS: Fibroscan, FM2: FibroMeter^2G, FM3: FibroMeter^3G.

Figure 4

Mean Metavir fibrosis score as a function of Metavir-based fibrosis class classifications. Results (± standard deviation, Y axis) are expressed as a function of classifications (X axis) for: FibroMeter^2G (panels A and C, 6 classes), Fibrotest (panels B and D, 8 classes) or Fibroscan (panel E, 6 classes) in populations #2 (top) or #3 (bottom). P by weighted Bonferroni test. The global relationship is indicated by Spearman's correlation coefficient (r_s).

Figure 5

Meaning of blood test score (in grey rectangles) in different Metavir fibrosis (F_M) stages within the same class of fibrosis class classification. Example of F_M2 and F_M1 stages in FibroMeter^3G in population #2. Sectors correspond to patient proportions. The figures on the top of the external circle reflect the values (mean ± SD) of the blood test score for a single F_M stage. The significant difference between F_M stages of contiguous classes was mathematically expected contrary to that observed within a single class.

Figure 6

Schematic reliability of diagnostic means. In clinical practice, a blood test is more reliable than liver pathology since the blood test is based on an algorithm that was calculated with expert pathologist as reference (black arrow with red background). There is little procedure variability for blood tests due to excellent interlaboratory reproducibility, contrary to the large inter-observer disagreement for liver pathology and, to a lesser degree, for elastometry. The size of observers is proportional to published observer variability.