Oxidative Stress and Fatty Acids in Hepatitis C
Hepatitis C virus infection (HCV) is a major health concern in Canada and worldwide. Chronic HCV can cause progressive liver damage leading to inflammation, scarring and, in some cases, cirrhosis or liver cancer. It has been shown that fat accumulation in the liver can accelerate the disease progression and is therefore a risk factor in HCV patients.
However, the exact mechanism(s) by which fat accumulation in the liver is involved in disease progression are not clear yet. It is possible that the presence of fat provides a liver susceptible to a second injurious process which leads to scarring. Candidates for this second "hit" may include insulin resistance, leading to accumulation of fat within the liver cells and secondly oxidation of these lipids. In turn, lipid peroxidation can lead to production of reactive oxygen species (unstable molecules that can damage cells) and cytokines (signal molecules that promote inflammation) resulting in more oxidative stress and liver damage.
Aim of the study is to find out, whether patients with HCV and fatty liver have increased oxidative stress and inflammation than patients with HCV without fatty liver, and whether this is associated with a different nutritional status.
|Study Design:||Observational Model: Case-Only
Time Perspective: Cross-Sectional
|Official Title:||Hepatitis C Infection With Liver Steatosis Compared to Hepatitis C Infection Without Liver Steatosis: Is There a Difference in Lipid Peroxidation and Indicators of Inflammation?|
- Lipid peroxidation (LPO) in the liver [ Time Frame: Single time point ]LPO by commercially available kit
- Hepatic fatty acid composition [ Time Frame: Single time point ]Fatty acid and lipid composition measured by gas chromatography and mass spectrometry
- Antioxidant power in the liver [ Time Frame: Single time point ]Antioxidant power (AOP) measured by test kit
- Plasma vitamin C [ Time Frame: Single time point ]Plasma vitamin C by colorimetric assay
- Tocopherols in plasma [ Time Frame: Single time point ]alpha- and gamma-tocopherol in plasma by gas chromatography
- Insulin resistance [ Time Frame: Single time point ]Homeostasis model assessment of insulin resistance
- Dietary intake [ Time Frame: single time point ]Macro- and micronutrient intake by 3-day food protocols
|Study Start Date:||July 2005|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Hepatitis C - Steatosis
Patients with chronic Hep C infection undergoing liver biopsy with >=5% steatosis on liver biopsy
Hepatitis C - no steatosis
Patients with chronic Hep C infection without steatosis on liver biopsy (<5% of hepatocytes involved)
Hypothesis: Patients with Hepatitis C and steatosis are more oxidatively stressed than those without steatosis. This is associated with 1) increased liver lipid peroxides and cytokines (TNF-alpha, TGF-beta); 2) altered unsaturated fat status (intake, tissue storage as measured in red blood cells); 3) reduced antioxidant status.
Objectives: To assess oxidative stress and nutritional status in patients with Hepatitis C and steatosis on liver biopsy and to compare the results to the same parameters measured in patients with Hepatitis C and no steatosis.
Primary outcome: Liver lipid peroxides (LPO)
Liver: TNF-alpha; liver pathology and immunohistochemistry for adducts of malondialdehyde (MDA), a product of lipid peroxidation (LP), alpha-smooth muscle actin (alpha-SMA), a marker of hepatic stellate cell activation; and transforming growth factor (TGF-beta), a profibrogenic cytokine involved in fibrogenesis, liver fatty acid composition (substrate for lipid peroxidation).
Oxidative stress and nutrition: Plasma lipid peroxides, plasma antioxidant vitamins, antioxidant status and power, and red blood cell fatty acid composition, 7 day food record, anthropometry.
Insulin resistance parameters such as blood glucose, insulin, c-peptide, hemoglobin A1c (HbA1c) Blood lipid profile, liver enzymes (as part of standard medical assessment) Subject demographics and medical history will also be recorded.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00444002
|University Health Network (Toronto General Hospital & Toronto Western Hospital)|
|Toronto, Ontario, Canada|
|Principal Investigator:||Johane P Allard, MD, FRCPC||University Health Network, Toronto General Hospital|