The evolution of non-invasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

J. Vergniol¹, J. Boursier^2,4, C. Coutzac¹,  S. Bertrais⁴, J. Foucher¹, C. Angel², F. Chermak¹, I. Fouchard Hubert^2,4, W. Merrouche¹, F. Oberti^2,4, V. de Lédinghen^1,3, P. Calès^2,4

DOI: 10.1002/hep.27069

Copyright © 2014 American Association for the Study of Liver Diseases

Publication History
Accepted manuscript online: 12 FEB 2014 05:58AM EST
Manuscript Accepted: 6 FEB 2014
Manuscript Revised: 25 JAN 2014
Manuscript Received: 29 SEP 2013

Keywords: hepatitis C;  survival;  prognosis;  fibrosis;  cirrhosis;  liver stiffness;  FibroScan;  blood fibrosis test

Abstract

Introduction: No data are available about the prediction of long-term survival using repeated non-invasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), APRI, and FIB-4 evolution in CHC.

Patients and methods: CHC patients with two LSM (1000-1500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM.

Results: 1025 patients were included. Median follow-up after fLSM was 38.0 months (IQR: 27.7-46.1) during which 35 patients died (14 liver-related death) and 7 had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (p≥0.24) whereas FIB-4 provided more accurate prognostic models than APRI (p=0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and SVR. Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with increase (≥1 kPa/year) in 7-14 kPa bLSM, or decrease (≤0 kPa/year) in ≥14 kPa bLSM (p=0.949 between these two groups). Patients with increase (>0 kPa/year) in ≥14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significant different prognosis.

Conclusion: Three-year evolution of non-invasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. (Hepatology 2014;)

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