Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: Proof of concept and first application in a large population

Background & Aims: Time-dependent statistics have been used to assess liver fibrosis progression (LFP) in liver diseases from birth to first biopsy, in a limited number of patients. Non-invasive biomarkers such as FibroTest (FT) should allow the estimation of LFP on larger populations. We aimed at validating this concept by comparing LFP using FT vs. biopsy (P1) and then at applying the non-invasive method to a large population (P2). Methods: In P1, LFP was assessed using biopsy and FT in 2472 untreated patients: 770 with chronic hepatitis C, 723 with hepatitis B, 761 with non-alcoholic fatty liver disease (NAFLD), and 218 with alcoholic fatty liver disease (ALD). In P2, 342,346 interpretable FT prospectively measured were used. LFP was estimated using transition rates (cumulative hazard rate) to cirrhosis (F4) or to minimal fibrosis (>F0). Results: In P1, there was a significant concordance between FT and biopsy estimates of hazards with intraclass correlation (ICC) = 0.961 (95% CI 0.948-0.970) and 0.899 (95% CI 0.135-0.969) for F4 and >F0, respectively. This concordance persisted according to the disease and the gender. The more rapid LFP to F4 (biopsy/FT) was observed for men with ALD (1.44/1.62), and the slower for women with NAFLD (0.09/0.02). In P2, the LFP started to increase for men at the age of 30 years. The cumulative fibrosis progression rate to minimal fibrosis in women crossed the "man curve" around the age of 80 years. The following factors were associated with LFP to F4 (all p <0.0001): male gender (Relative Risk = 3.29), HIV co-infection (2.33), and residency in Middle East (2.67) or Eastern Europe (2.15). Conclusions: Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.