Levels of TNF-α, IL-1β, TGF-β, and IL-6 in patients with chronic hepatitis C virus infection and hyperinsulinemia

Luis A. Salazar, Xóchitl García-Samper, Susana Alcázar-Leyva, Patricia Gorocica, Eduarda Cerón, María Cristina Negrete-García, Luis F. Montaño, Noé Alvarado-Vásquez

Department of Biochemistry, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico.
Department of Cell and Tissue Biology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Department of Gastroenterology, H.R. “Lic. Adolfo López Mateos”, Institute of Security and Social Services for State Workers, Mexico City, Mexico.
Institute of Scientific Research “Hans Selye”, Querétaro, Mexico.

DOI: 10.4236/oji.2013.31003                

Abstract

Background: Previous evidences support to inflammatory process associated with the IR those important factors in the development of fibrosis and hepatic damage in patients with HCV infection. Objectives: Determine the presence of immunological or histological differentces between hyperinsulinemic and non-hyperinsulinemic chronic HCV-infected patients with at least 10 years of evolution. Material and Methods: The body mass index, Child-Puigh score, liver function tests, and biochemical profile were evaluated in 30 control, 40 chronic HCV-infected patients with hyperinsulinemia, and in 40 normoinsulinemic chronic HCV-infected patients with at least 10 years of evolution. In addition, HCV genotype and viral load were established with the Amplicor System. In addition, nitrites in plasma, and TNF-α, IL-1β, TGF-β, IL-6, and insulin levels were determined. Results: No differences were found in BMI, Child-Pugh “A” scores, ALT, viral load, or genotype between the hyperinsulinemic (>25 IU/ml) and normoinsulinemic (<25 IU/ml) patients. Hyperinsulinemia patients had a higher HOMA- IR value (13.6) than normoinsulinemia patients (3.4), and none had a glycemia > 126 mg/dl. Cy- tokines concentration did not show differences with respect to controls. Nitrites showed a slight increase only in patients with HCV infection. Conclusions: Absence of changes in the proinflammatory cytokines concentration or in some inflammation markers in chronic HCV patients with hyperinsulinemia suggests that long-term insulin levels, in presence of HCV, cannot explain by themselves the hepatic alterations observed in the patient with HCV infection, the presence of others elements (alcoholism, cirrhosis, etc.) is necessary to onset hepatic damage in these patients.

Keywords

Hepatitis C; Inflammation; Hyperinsulinemia; Nitric Oxide; Type 2 Diabetes Mellitus

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Imazeki, F., Yokosuka, O., Fukai, K., Kanda, T., Kojima, H. and Saisho, H. (2008) Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: Comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Liver International, 28, 355-362. doi:10.1111/j.1478-3231.2007.01630.x
[2]	Nieto-Vazquez, I., Fernandez-Veledo, S., Kramer, D.K., Vila-Bedmar, R., Garcia-Guerra, L. and Lorenzo, M. (2008) Insulin resistance associated to obesity: The link TNFalpha. Archives of Physiology and Biochemistry, 114, 183-194. doi:10.1080/13813450802181047
[3]	Oliveira, B.R., Magalh?es, O., Furlanetto, T.W. and Bertoluci, M.C. (2008) Increased insulin resistance and hyperinsulinemia in patients with type 2 diabetes and chronic hepatitis C. Diabetes Research and Clinical Practice, 19, e11-e12. doi:10.1016/j.diabres.2007.08.003
[4]	Moucari, R., Asselah, T., Cazals-Hatem, D., et al. (2008) Insulin resistance in chronic hepatitis C: Association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology, 134, 416-423. doi:10.1053/j.gastro.2007.11.010
[5]	White, D.L., Ratziu, V. and El-Serag, H.B. (2008) Hepatitis C infection and risk of diabetes: A systematic review and meta-analysis. Journal of Hepatology, 49, 831-844. doi:10.1016/j.jhep.2008.08.006
[6]	Sersté, T., Nkuize, M., Moucari, R., et al. (2010) Metabolic disorders associated with chronic hepatitis C: Impact of genotype and ethnicity. Liver International, 30, 1131-1136. doi:10.1111/j.1478-3231.2010.02291.x
[7]	Lecube, A., Hernández, C., Genescà, J., Esteban, J.I., Jardí, R. and Simó, R. (2004) High prevalence of glucose abnormalities in patients with hepatitis C virus infection: A multivariate analysis considering the liver injury. Diabetes Care, 27, 1171-1175. doi:10.2337/diacare.27.5.1171
[8]	Ohmura, E., Hosaka, D., Yazawa, M., et al. (2007) Association of free fatty acids (FFA) and tumor necrosis factor-alpha (TNF-α) and insulin-resistant metabolic disorder. Hormone and Metabolic Research, 39, 212-217. doi:10.1055/s-2007-970421
[9]	Hokari, A., Zeniya, M., Esumi, H., Ishikawa, T., Kurasima, Y. and Toda, G. (2005) Role of nitric oxide (NO) in interferon-alpha therapy for hepatitis C. Journal of Infection, 51, 47-53. doi:10.1016/j.jinf.2004.08.025
[10]	Milner, K.L., van der Poorten, D., Trenell, M., et al. (2010) Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance. Gastroenterology, 138, 932-941. doi:10.1053/j.gastro.2009.11.050
[11]	Basaranoglu, M. and Basaranoglu, G. (2011) Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis. World Journal of Gastroenteroogy, 17, 4055-4062. doi:10.3748/wjg.v17.i36.4055
[12]	Cardona-Mu?oz, G., Noriega-Arellano, J., HernándezChávez A, et al. (2003) Effect of ramipril on the glucose/ insulin coefficient and the ventricular mass index in patients with light to moderate arterial hypertension. Archivos de Cardiologia de Mexico, 73, 24-30.
[13]	Yokoyama, H., Emoto, M., Fujiwara, S., et al. (2004) Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose. The Journal of Clinical Endocrinology and Metabolism, 89, 1481-1484. doi:10.1210/jc.2003-031374
[14]	Balogun, W.O., Adeleye, J.O., Akinlade, K.S., Kuti, M. and Otegbayo, J.A. (2006) Low prevalence of hepatitis-C viral seropositivity among patients with type-2 diabetes mellitus in a tertiary hospital. Journal of the National Medical Association, 98, 1805-1808.
[15]	Petta, S., Cammà, C., Di Marco, V., et al. (2008) Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. The American Journal of Gastroenterology, 103, 1136-1144. doi:10.1111/j.1572-0241.2008.01813.x
[16]	De Torres, M. and Poynard, T. (2003) Risk factors for liver fibrosis progression in patients with chronic hepatitis C. Annals of Hepatology, 2, 5-11.
[17]	Hotamisligil, G.S. (2003) Inflammatory pathways and insulin action. International Journal of Obesity and Related Metabolic Disorder, 27, S53-S55. doi:10.1038/sj.ijo.0802502
[18]	Tanaka, N., Nagaya, T., Komatsu, M., et al. (2008) Insulin resistance and hepatitis C virus: A case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase. Liver International, 28, 1104-1111. doi:10.1111/j.1478-3231.2008.01737.x
[19]	Hung, C.H., Lee, C.M., Chen, C.H., et al. (2009) Association of inflammatory and anti-inflammatory cytokines with insulin resistance in chronic hepatitis C. Liver International, 29, 1086-1093. doi:10.1111/j.1478-3231.2009.01991.x
[20]	Lawson, A. (2010) Hepatitis C virus-infected patients with a persistently normal alanine aminotransferase: Do they exist and is this really a group with mild disease? Journal of Viral Hepatitis, 17, 51-58.
[21]	Ohmura, E., Hosaka, D., Yazawa, M., et al. (2007) Association of free fatty acids (FFA) and tumor necrosis factor-alpha (TNF-α) and insulin-resistant metabolic disorder. Hormone and Metabolic Research, 39, 212-217. doi:10.1055/s-2007-970421
[22]	Patton, H.M., Patel, K., Behling, C., et al. (2004) The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. Journal of Hepatology, 40, 484-490. doi:10.1016/j.jhep.2003.11.004
[23]	Knobler, H., Zhornicky, T., Sandler, A., Haran, N., Ashur, Y. and Schattner, A. (2003) Tumor necrosis factor-alphainduced insulin resistance may mediate the hepatitis C virus-diabetes association. The American Journal of Gastroenterology, 98, 2751-2756.
[24]	Behrendt, C.E. and Ruiz, R.B. (2006) Hyperglycemia among persons with hepatitis C: Not the classical diabetic phenotype. Diabetes Research and Clinical Practice, 71, 68-74. doi:10.1016/j.diabres.2005.04.005
[25]	Capeau, J. (2008) Insulin resistance and steatosis in humans. Diabetes and Metabolism, 34, 649-657. doi:10.1016/S1262-3636(08)74600-7
[26]	Halfon, P., Pénaranda, G., Carrat, F., et al. (2009) Influence of insulin resistance on hepatic fibrosis and steatosis in hepatitis C virus (HCV) mono-infected compared with HIV-HCV co-infected patients. Alimentary Pharmacology & Therapeutics, 30, 61-70. doi:10.1111/j.1365-2036.2009.03995.x