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: 2.09). 01/2008; 43(2):137-42. DOI: 10.1093/alcalc/agm171
Source: PubMed

ABSTRACT 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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    ABSTRACT: Introduction Although it is known that alcoholic liver disease is associated with bone disease, there are few studies that analyze bone alterations in chronic hepatitis C virus (HCV) infection. Material and methods Twenty-eight consecutive patients affected by HCV infection admitted to the Internal Medicine Service of the Hospital Universitario de Canarias were included. Biochemical markers of bone turnover (cortisol, PTH, 1.25 dihydroxyvitamin D, IGF1, osteocalcin) were measured. Nutritional status was assessed by anthropometry, and fat mass, bone mineral density, and lean mass were all determined by densitometry (DEXA). These data were compared with those of a control group of similar age. Results Our patients had decreased body mass (BMD) values compared to the controls, especially intense among HIV co-infected individuals. We found significant differences between HIV infected and not infected patients in relation to right rib (T = 2.26, p = 0.037), lumbar spine (T = 2.45, p = 0.025) and pelvis (T = 2.23, p = 0.04). There was a significant relation between BMD in the right arm and brachial perimeter (p = 0.019) and between lean mass at different levels and BMD (total lean mass at left arm r = 0.69, at right arm r = 0.71, thoracic spine r = 0.79, lumbar spine r = 0.53). We found a significant inverse relation between BMD and Knodell index (relation between BMD at right rib and Knodell, p = 0.041, and BMD at lumbar spine and Knodell index, p = 0.033). Conclusions In patients with chronic HCV infection, there is a reduction of bone mass, particularly in HIV co-infected patients. This reduction is related to a reduction of the lean mass but not to fat mass, and maintains a relationship with viral load and histological activity.
    Revista Española de Enfermedades Metabólicas Óseas 03/2009; 18(1). DOI:10.1016/S1132-8460(09)70766-4
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