Sustained virological response prevents the development of insulin resistance in patients with chronic hepatitis C

Authors

  • Alessio Aghemo,

    Corresponding author
    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
    • A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy
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    • *

      These authors contributed equally to this work

    • fax: +39-0250320410

  • Gian Maria Prati,

    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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    • *

      These authors contributed equally to this work

  • Maria Grazia Rumi,

    1. Liver Unit, San Giuseppe Hospital, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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  • Roberta Soffredini,

    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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  • Roberta D'Ambrosio,

    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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  • Emanuela Orsi,

    1. Endocrinology and Diabetology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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  • Stella De Nicola,

    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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  • Elisabetta Degasperi,

    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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  • Valeria Grancini,

    1. Endocrinology and Diabetology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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  • Massimo Colombo

    1. A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
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  • Potential conflict of interest: Nothing to report.

  • Massimo Colombo has received grant and research support from Merck, Roche, BMS, and Gilead Science, has served on advisory committees for Merck, Roche, Novartis, Bayer, BMS, Gilead Science, Tibotec, Vertex, and Achillion, and has worked in speaking and teaching roles for Tibotec, Roche, Novartis, Bayer, BMS, Gilead Science, and Vertex. Maria Grazia Rumi has worked in speaking and teaching roles for Roche, has served on advisory committees for Jannsen, and has received travel support from Roche. Alessio Aghemo has received grant and research support from Roche and Gilead Sciences, has worked in speaking and teaching roles for Roche and Janssen, and has received travel support from BMS, GlaxoSmithKline, Bayer, Janssen, and Roche.

Abstract

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), which is a condition known to influence the progression of liver fibrosis and the response to pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. We aimed to assess whether a sustained virological response (SVR) after antiviral therapy prevents the development of IR in the long term. Members of the Milan Safety Tolerability study cohort, who received PEG-IFNα2a/RBV or PEG-IFNα2b/RBV, underwent a homeostasis model assessment (HOMA) at the baseline and 24 months after treatment completion. For all patients (n = 431), a liver biopsy sample was scored for grading, staging (Ishak), and steatosis. At the baseline, IR (HOMA value > 2) was detected in 48 patients (12%), and it was associated with body weight (P = 0.03), an HCV load < 0.6 × 106 IU/L (P = 0.006), fibrosis staging ≥ 4 (P = 0.01), and moderate to severe steatosis (P = 0.03). IR did not influence the rates of end-of-treatment response (75% versus 69%, P = 0.4), SVR (63% versus 60%, P = 0.8), or relapse (19% versus 24%, P = 0.5). After treatment, IR developed in 49 of the 384 nondiabetic patients (14%). Although the mean baseline and posttreatment HOMA values were similar in SVR patients (1.11 ± 0.8 versus 1.18 ± 1.1, P = 0.25), patients experiencing treatment failure showed a significant increase in the mean HOMA value at the follow-up visit (1.20 ± 0.85 versus 1.49 ± 1.3, P = 0.007), and there was an increased rate of de novo IR in non-SVR patients versus SVR patients (17% versus 7%, P = 0.007). According to a logistic regression analysis, treatment failure (odds ratio = 2.81, 95% confidence interval = 1.39-5.67, P = 0.004) and a 10% body mass index increase (odds ratio = 6.42, 95% confidence interval = 1.69-24.3, P = 0.006) were significantly associated with the development of de novo IR. Conclusion: In nondiabetic patients with chronic HCV, the achievement of SVR with PEG-IFN and RBV prevents the development of de novo IR. (HEPATOLOGY 2012;56:1681–1687)

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