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Presenters: Kate Ueland and DeeAnna VanReken

Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus – related chronic disease Himoto , Yoneyama H, Kurokohchi K, Inukai M, Masugata H, Goda F, et al . Nutrition Research . 2011: (31):829-835. Presenters: Kate Ueland and DeeAnna VanReken.

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Presenters: Kate Ueland and DeeAnna VanReken

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  1. Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus – related chronic diseaseHimoto, Yoneyama H, Kurokohchi K, Inukai M, Masugata H, Goda F, et al. Nutrition Research. 2011: (31):829-835. Presenters: Kate Ueland and DeeAnna VanReken

  2. Background • Hepatitis C virus • Infected person may carry many variants – quasi-species which have high multiplicity rate • Incubation period of 2-26 weeks • Asymptomatic in 75% of cases • Cirrhosis develops in 20% of cases • Statistics • A major cause of liver disease • Worldwide carrier rate is est. at 175 million people • Most frequently requires liver transplant in U.S. • No vaccine is currently available

  3. Background What is the role of Selenium (Se)? • Essential constituent of selenoproteins • Notably glutathione peroxidase (GPx) • Previous studies have shown that serum Se levels frequently decline in pts with type 2 diabetes mellitus (T2DM)

  4. Author’s Hypothesis Serum Se levels decline in proportion to the severity of hepatic fibrosis in patients with Hepatitis C virus-related chronic liver disease (HCV-CLD), and the decrease in Se levels contribute to insulin resistance in those patients.

  5. Methods • Study population • Experimental group: 52 non-diabetic patients with HCV-RNA in sera along with histological signs ranging from chronic hepatitis to liver cirrhosis. • Control group: 11 normal healthy patients/no Se supplementation • Assays • Glutathione Peroxidase levels in sera ELISA • Insulin Resistance  HOMA-IR

  6. Methods • Histological Assessments • Liver tissue stained with hematoxylin and eosin • Inuyama classification system • F0 = no fibrosis in liver • F1 = fibrous portal expansion • F2 = bridging fibrosis • F3 = bridging fibrosis with lobular destruction • F4 = liver cirrhosis

  7. Results Himoto et al. Nutrition Research. 2011

  8. Results Himoto et al. Nutrition Research. 2011

  9. Author’s conclusions • Decrease in serum Se levels was associated with severity of hepatic fibrosis in pts with HCV-CLD • An inverse correlation was found between serum Se concentration and insulin resistance • Insulin resistance was associated with severity of Se deficiency in pts with HCV-related CLD • Se deficiency may eventually facilitate oxidative stress in the liver of patients with HCV-CLD

  10. Study Limitations • Efficacy of Se supplementation not confirmed • Determine optimal dose of Se supplementation to attenuate insulin resistance • Selenium deficiency not properly defined • Mucosal abnormalities were suggested • Inadequate data to explain the link between insulin resistance and Se deficiency • Insulin mimetic properties were suggested

  11. Question for the audience Selenium is an essential constituent in what antioxidant enzyme?

  12. References • Abdel-Azziz MY, Zalata KR, El-Bendary MM. Insulin resistance and liver fibrosis progression in patients with chronic hepatitis C virus infection. Arab Journal of Gastroenterology. 2010: (11): 30-34. • Czuczejko, J. Zachara, B.A. Staubach-Topczewska, E. Halota, W, et. al. Selenium, glutathione and gluatathioneperoxidases in blood of patients with chronic liver diseases. ActaBiochimicaPolonica. 2003; 50:1147-1154. • Guo CH, Chen PC, Lin KP, Shih MY. Trace metal imbalance assosciated with oxidative stress and inflammatory status in anti-hepatitis C virus antibody positive subjects. Enviromental toxicology and pharmacology. (2012): (33): 288-296. • Higdon J. Linus Pauling Institute Micronutrient Information Center: Selenium. http://lpi.oregonstate.edu/infocenter/minerals/selenium/. Updated 01/22/2009. Accessed February 28, 2012. • Himoto T, Yoneyama H, Kurokohchi K, Inukai M, Masugata H, Goda F, et al. Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus-related chronic liver disease. Nutrition research. 2011: (31): 829-835. • Kumar V, Abbas AK, Fausto N, Mitchell RN. Robbins Basic Pathology 8th ed. Philadelphia: Saunders Elsvier, 2007. • Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. Clinical Nutrition. 1987: (1): 441-445. • Naota T, Ichikawa T, Hamasaki K, Nakao K, Nishimura D, Goto T, et al. Association Between Liver Fibrosis and Insulin Sensitivity in Chronic HCV: Discussion. The American Journal of Gastroenterology. 2006: 101(12): 2752-2759. • Negro, F. Mechanisms of hepatitis C virus-related insulin resistance: Mini Review. Clinics and Research in Hepatology and Gastroenterology. 2011: (35): 358-363.

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