Oxidative Stress and Fatty Acids in Hepatitis C

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.

Measurements:

Primary outcome: Liver lipid peroxides (LPO)

Secondary outcomes:

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.

Other measurements:

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.

Inclusion criteria

• Male and female patients, age >18 y
• Established hepatitis C infection as confirmed by positive serology and positive hepatitis C RNA in serum
• Convincing evidence of negligible alcohol consumption (<20g of ethanol per day) obtained from a detailed history, confirmed by at least one close relative
• Absence of any other possible cause for liver dysfunction.
• Undergoing routing liver biopsy (usually pre-treatment)

Exclusion criteria

• Findings highly suggestive of liver disease of other etiology (e.g. other viral hepatitis, auto-immune chronic hepatitis, primary biliary cirrhosis and genetic liver diseases such as hemochromatosis, alpha-1 antitrypsin deficiency, Wilsons disease and biliary obstruction)
• Anticipated need for liver transplantation in one year or complications of liver disease such as recurrent variceal bleeding, spontaneous porto- systemic encephalopathy, resistant ascites or bacterial peritonitis
• Concurrent medical illnesses contraindicating a liver biopsy (history of unexplained bleeding, hemophilia or abnormal coagulation results as per routine laboratory work-up or other reasons judged by the hepatologist to contraindicate a percutaneous liver biopsy)
• Medications known to precipitate steatohepatitis (corticosteroids, high dose estrogens, methotrexate, amiodarone, calcium channel blockers, sulfasalazine or cloxacillin) in the 6 months prior to entry
• Antioxidant vitamin or n-3 supplementation, ursodeoxycholic acid or any other experimental drug in the 6 months prior to study entry
• Pregnant or lactating