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

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

BackgroundWhat 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)

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.

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

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

Results

Himoto et al. Nutrition Research. 2011

Results

Himoto et al. Nutrition Research. 2011

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

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

Question for the audience

Selenium is an essential constituent in what antioxidant

enzyme?

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Czuczejko, J. Zachara, B.A. Staubach-Topczewska, E. Halota, W, et. al. Selenium, glutathione and gluatathione peroxidases in blood of patients with chronic liver diseases. Acta Biochimica Polonica. 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.