Cytokines and lipid peroxidation in alcoholics with chronic hepatitis C virus infection

Servicios de Medicina Interna, Hospital Universitario, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
Alcohol and Alcoholism (Impact Factor: 2.89). 01/2008; 43(2):137-42. DOI: 10.1093/alcalc/agm171
Source: PubMed


A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-beta)), and IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-alpha (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-beta (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-alpha, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-alpha was significantly related to albumin and prothrombin activity, whereas TGF-beta was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-beta.

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Available from: Francisco Santolaria Fernández, Jun 09, 2015
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    • "In the setting of HCV monoinfection, heavy alcohol use has a synergistic effect on HCVrelated liver injury, with a higher likelihood of persistent infection (Thimme et al., 2002), greater viral replication (McCartney and Beard, 2010), more cytotoxicity, and increased oxidative stress (Bellentani et al., 1997; Castellano-Higuera et al., 2008). Moreover, heavy alcohol use induces an impaired immune response (Szabo et al., 2006) that has been related to a lower likelihood of sustained response to HCV antiviral therapy (Siu et al., 2009). "
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