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Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C

Authors

  • Julien Vergniol,

    1. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France
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  • Jérôme Boursier,

    1. Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France
    2. Laboratoire HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
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  • Clélia Coutzac,

    1. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France
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  • Sandrine Bertrais,

    1. Laboratoire HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
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  • Juliette Foucher,

    1. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France
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  • Camille Angel,

    1. Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France
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  • Faiza Chermak,

    1. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France
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  • Isabelle Fouchard Hubert,

    1. Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France
    2. Laboratoire HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
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  • Wassil Merrouche,

    1. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France
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  • Frédéric Oberti,

    1. Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France
    2. Laboratoire HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
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  • Victor de Lédinghen,

    Corresponding author
    1. Centre d'Investigation de la Fibrose hépatique, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France
    2. INSERM U1053, Université Segalen, Bordeaux, France
    • Address reprint requests to: Prof. Victor de Lédinghen, Centre d'Investigation de la Fibrose hépatique, Service d'Hépato-Gastroentérologie, Hôpital Haut-Lévêque, 33604 Pessac, France. E-mail: victor.deledinghen@chu-bordeaux.fr; fax: + 33 5 57 65 64 45.

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  • Paul Calès

    1. Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France
    2. Laboratoire HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
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  • Potential conflict of interest: Victor de Lédinghen: Echosens consultant; Paul Calès: Biolivescale consultant; no other authors have a potential conflict of interest. We disclosed to study participants potential investigator conflicts of interest.

Abstract

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 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. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven 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 sustained virological response (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 an 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 an increase (>0 kPa/year) in ≥14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. Conclusion: Three-year evolution of noninvasive 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;60:65-76)

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