Presenters: Kate Ueland and DeeAnna VanReken
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Hepatitis C virus
 Infected person may carry many variants – quasispecies 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
What is the role of Selenium (Se)?
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Essential constituent of selenoproteins
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Notably glutathione peroxidase (GPx)
Previous studies have shown that serum Se
levels frequently decline in pts with type 2
diabetes mellitus (T2DM)
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.
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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
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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
Himoto et al. Nutrition Research. 2011
Himoto et al. Nutrition Research. 2011
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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
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Efficacy of Se supplementation not confirmed
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Selenium deficiency not properly defined
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Determine optimal dose of Se supplementation to
attenuate insulin resistance
Mucosal abnormalities were suggested
Inadequate data to explain the link between
insulin resistance and Se deficiency
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Insulin mimetic properties were suggested
Selenium is an essential constituent in
what antioxidant enzyme?
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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 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.