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Letters: Comments and Responses

Glucose Abnormalities in Patients With Hepatitis C Virus Infection: Epidemiology and Pathogenesis

Response to Lecube et al.

  1. Umberto Vespasiani Gentilucci, MD,
  2. Antonio Picardi, PHD and
  3. Paolo Pozzilli, MD
  1. From the Department of Internal Medicine and Hepatology, University Campus Bio-Medico, Rome, Italy
  1. Address correspondence to Umberto Vespasiani Gentilucci, MD, University Campus Bio-Medico, Via E. Longoni, 83, I-00155 Rome, Italy. E-mail: u.vespasiani{at}unicampus.it
Diabetes Care 2006 Nov; 29(11): 2558-2559. https://doi.org/10.2337/dc06-1374
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Response to Lecube et al.

We read with great interest the review article by Lecube et al. (1) on the pathogenic factors specifically linking hepatitis C virus (HCV) infection and glucose abnormalities. After analyzing the different mechanisms by which HCV is thought to contribute to the development of type 2 diabetes, Lecube et al. focus their attention on the role of proinflammatory cytokines, in particular tumor necrosis factor (TNF)-α and interleukin-6. They suggest that the activation of the TNF-α system in HCV-infected patients, which has been directly related to insulin resistance in their recent study (2), could be related to the T-helper (Th)1 immune response observed in the course of HCV infection. Accordingly, as shown in Fig. 1 of their review article, the activation of the TNF-α system following the Th1 immune-mediated response is central to the pathogenesis of both liver fibrosis and insulin resistance associated with HCV infection.

However, an apparent paradox is raised by an attempt to fit such interpretation with well-acquired data and the most recent evidence from literature. Indeed, a vigorous Th1 cytokine response has been classically observed in patients who clear their HCV infection, either spontaneously (3) or in response to antiviral treatment (4,5). By contrast, recent studies have demonstrated that insulin resistance is independently associated with a poor response to antiviral therapy in HCV patients (6,7), consistent with previous observations on the lower success rate of interferon alone or interferon plus ribavirin in obese and diabetic patients. Therefore, it is difficult to understand how an increased Th1 immune response, which is protective in relation to viral clearance, can be, at the same time, the major determinant of insulin resistance and responsible for a poor response to antiviral treatment.

Footnotes

  • DIABETES CARE

References

  1. ↵
    Lecube A, Hernandez C, Genesca J, Simo R: Glucose abnormalities in patients with hepatitis C virus infection: epidemiology and pathogenesis. Diabetes Care 29:1140–1149, 2006
    OpenUrlFREE Full Text
  2. ↵
    Lecube A, Hernandez C, Genesca J, Simo R: Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients: a case-control study. Diabetes Care 29:1096–1101, 2006
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Pape GR, Gerlach TJ, Diepolder HM, Gruner N, Jung M, Santantonio T: Role of the specific T-cell response for clearance and control of hepatitis C virus. J Viral Hepat 6(Suppl. 1):36–40, 1999
    OpenUrl
  4. ↵
    Sarobe P, Jauregui JI, Lasarte JJ, Garcia N, Civeira MP, Borras-Cuesta F, Prieto J: Production of interleukin-2 in response to synthetic peptides from hepatitis virus E1 protein in patients with chronic hepatitis C: relationship with the response to interferon treatment. J Hepatol 25:1–9, 1996
    OpenUrlCrossRefPubMed
  5. ↵
    Cramp ME, Rossol S, Chokshi S, Carucci P, Williams R, Naoumov NV: Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C. Gastroenterology 118:346–355, 2000
    OpenUrlCrossRefPubMedWeb of Science
  6. ↵
    Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J: Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 128:636–641, 2005
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    D’Souza R, Sabin CA, Foster GR: Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy. Am J Gastroenterol 100:1509–1515, 2005
    OpenUrlCrossRefPubMedWeb of Science
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Diabetes Care: 29 (11)

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November 2006, 29(11)
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Glucose Abnormalities in Patients With Hepatitis C Virus Infection: Epidemiology and Pathogenesis
Umberto Vespasiani Gentilucci, Antonio Picardi, Paolo Pozzilli
Diabetes Care Nov 2006, 29 (11) 2558-2559; DOI: 10.2337/dc06-1374

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Glucose Abnormalities in Patients With Hepatitis C Virus Infection: Epidemiology and Pathogenesis
Umberto Vespasiani Gentilucci, Antonio Picardi, Paolo Pozzilli
Diabetes Care Nov 2006, 29 (11) 2558-2559; DOI: 10.2337/dc06-1374
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