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

Response to Lecube et al.

From the Department of Internal Medicine and Hepatology, University Campus Bio-Medico, Rome, Italy

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

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)- and interleukin-6. They suggest that the activation of the TNF- 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- 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.

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[Free 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[Abstract/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
   
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[Medline]
   
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[Medline]
   
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[Medline]
   
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[Medline]
   

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				R. Simo Glucose Abnormalities in Patients With Hepatitis C Virus Infection: Epidemiology and Pathogenesis: Response to Gentilucci et al. Diabetes Care, November 1, 2006; 29(11): 2559 - 2560. [Full Text] [PDF]

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gentilucci, U. V. Articles by Pozzilli, P. Search for Related Content PubMed PubMed Citation Articles by Gentilucci, U. V. Articles by Pozzilli, P. Social Bookmarking                What's this?