Prospective study of liver transplant recipients with HCV infection: Evidence for a causal relationship between HCV and insulin resistance

Authors

  • Aymin Delgado-Borrego,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
    2. Divisions of Gastroenterology and Clinical Research, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL
    3. Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, MA
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  • Yun-Sheen Liu,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
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  • Sergio H. Jordan,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
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  • Saurabh Agrawal,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
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  • Hui Zhang,

    1. Biostatistics Center, Department of Medicine, Massachusetts General Hospital, Boston, MA
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  • Marielle Christofi,

    1. Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, MA
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  • Deborah Casson,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
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  • A. Benedict Cosimi,

    1. Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Boston, MA
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  • Raymond T. Chung

    Corresponding author
    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
    2. Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Boston, MA
    • 55 Fruit Street, Gastrointestinal Unit, GRJ 724, Massachusetts General Hospital, Boston, MA 02114
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    • Telephone: (617) 724-7562; FAX: (617) 643-0446


Abstract

An association between hepatitis C virus (HCV) infection and insulin resistance (IR) has been recently reported. However, causality has not been established. The cross-sectional nature of most reported studies and varying degrees of fibrosis have limited definitive conclusions about the independent role of HCV in development of IR. We sought to evaluate whether HCV induces IR by prospectively analyzing a cohort of adult liver transplant (LT) recipients. A total of 34 adults (14 HCV(+) and 20 HCV(−)) who underwent consecutive LT were followed during the first year posttransplantation. IR was estimated using the homeostasis model assessment (HOMA). Univariate and multivariate repeated measures analyses and Cox regression models were used. There were no significant differences between the groups with respect to age, body mass index (BMI), family history of diabetes, alcohol consumption, or laboratory indices. The cohort had no or minimal fibrosis. There was lower prednisone use in the HCV(+) group, and no difference in the use of tacrolimus between the two groups was found. IR was 77% higher in HCV(+) subjects during the first year post-LT when controlling for BMI (P = 0.035). Subjects with high HCV ribonucleic acid (RNA) levels reached high HOMA-IR significantly earlier than those with lower HCV RNA (P = 0.03). Following the first month post-LT, HCV(+) subjects were 4 times more likely to become diabetic than HCV(−) controls (P < 0.01). In conclusion, there is significantly higher IR in the HCV(+) group during the first year post-LT. This cannot be explained by differences in BMI, medications used, alcohol consumption, or degree of fibrosis. Higher HCV RNA levels were associated with earlier elevations in HOMA-IR. Collectively, these results provide strong evidence that HCV induces the development of IR. Liver Transpl, 2007. © 2007 AASLD.

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