June 26, 2011

Role of a cirrhosis risk score for the early prediction of fibrosis progression in hepatitis C patients with minimal liver disease ☆

Journal of Hepatology
Volume 55, Issue 1, Pages 38-44 (July 2011)

Eric Trépo 12†, Andrej Potthoff 6† , Pierre Pradat 345, Rakesh Bakshi 6, Bradford Young 7, Robert Lagier8, Christophe Moreno 12, Laurine Verset8, Richard Cross 9, Delphine Degré 12, Arnaud Lemmers 12, Thierry Gustot 12, Pascale Berthillon 45, William Rosenberg 10, Christian Trépo 345, John Sninsky7, Michael Adler 2, Heiner Wedemeyer 6

Received 20 April 2010; received in revised form 22 September 2010; accepted 1 October 2010. published online 09 December 2010.

Background & Aims
Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test.

Methods
Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0–F1 at baseline were included. Patients were classified as progressors if they showed an increase 2 fibrosis stages at the second histological evaluation after a follow-up 5years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex® 200TM and computer analysis.

Results
In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p=0.050 in Brussels; p=0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p=0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (odds-ratio=2.23, 95%CI 1.21–4.11 p=0.01).

Conclusions
Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC.

See Editorial, pages 3–4

Abbreviations: HCV, hepatitis C virus, CHC, chronic hepatitis C, CRS, cirrhosis risk score, ELF, enhanced liver fibrosis, BMI, body mass index, OR, odds ratio, CI, confidence interval

Keywords: Hepatitis C, Cirrhosis risk score (CRS), Fibrosis progression, Minimal liver disease

1 Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
2 Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium
3 Hospices Civils de Lyon, Hôtel Dieu, Service d’hépatogastroentérologie, Lyon, France
4 INSERM, U871, Lyon, France
5 Université Lyon 1, IFR62 Lyon-Est, Lyon, France
6 Department of Gastroenterology and Hepatology, Medizinische Hochschule, Hannover, Germany
7 Celera, Alameda, CA, USA
8 Department of Pathology, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium
9 iQur Ltd., Southampton General Hospital, Southampton, UK
10 Centre for Hepatology, University College London, London, UK

Corresponding author. Address: Department of Hepatogastroenterology, Hôpital de la Croix-Rousse, 103 grande rue de la Croix-Rousse, 69317 Lyon Cedex 4, France. Tel: +33 4 26 73 27 15

☆ Orally presented in part at the Digestive Disease Week May 30–June 4 2009 in Chicago – USA.

† These authors contributed equally to this work.
PII: S0168-8278(10)01078-0
doi:10.1016/j.jhep.2010.10.018
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

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