Treatment of Chronic Hepatitis C Virus Infection via Antioxidants

Liver Unit, Department of Medicine, Hebrew University, Hadassah Medical Center, Jerusalem, Israel.
Journal of Clinical Gastroenterology (Impact Factor: 3.5). 10/2005; 39(8):737-42. DOI: 10.1097/01.mcg.0000174023.73472.29
Source: PubMed


The pathogenesis of chronic hepatitis C virus (HCV) infection is associated with a defective host antiviral immune response and intrahepatic oxidative stress. Oxidative stress and lipid peroxidation play major roles in the fatty liver accumulation (steatosis) that leads to necro-inflammation and necrosis of hepatic cells. Previous trials suggested that antioxidative therapy may have a beneficial effect on patients with chronic HCV infection.
To determine the safety and efficacy of treatment of chronic HCV patients via a combination of antioxidants.
Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks. Patients were monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of quality of life was performed using the SF-36 questionnaire.
In one of the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score), a combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted.
These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.

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    • "In addition, chronic HCV infection is associated with decreased plasma levels of the antioxidant contents due to their inefficient intracellular synthesis.[1112] Therefore, host antioxidant defenses, such as GSH, catalase, superoxide dismutase (SOD), and hemo-oxygenase-1 are subnormal in Chronic hepatitis C (CHC) disease. "
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    ABSTRACT: Background/Aims: Oxidative stress and hepatocellular pathological changes are common associations with chronic hepatitis C virus (CHC) disease. The aim of this study was to assess serum antioxidant-oxidant (Redox) balance in patients with CHC infection before and after intake of the traditional antiviral therapy (pegylated interferon α-2b and oral ribavirin). Patients and Methods: Blood samples from 50 biopsy-proven CHC patients, with no prior anti-viral treatment and persistently elevated serum transaminase levels for 6 months, as well as 15 age- and sex-matched healthy subjects were used for determination of the antioxidants: reduced glutathione (GSH), superoxide dismutase (SOD), α tocopherol and ascorbic acid as well as lipid peroxidation (LPO) index (malondialdehyde [MDA]). The measurements were repeated in the diseased group 25 weeks after pegylated interferon α-2b and ribavirin combination therapy. Results: Serum levels of bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly higher in CHC patients than in the control group (P < 0.05). Pretreatment serum MDA values were significantly higher in patients with CHC infection than the control group (P < 0.001), while serum antioxidant levels were significantly lower (P < 0.001). Responders (10 patients) had lower pretreatment serum levels of MDA than non-responders (35 patients) (P < 0.001). Both groups were comparable for the antioxidant serum levels. There was significant negative correlation between serum MDA and serum SOD, GSH, α tocopherol, and ascorbic acid concentrations in CHC patients. On the other hand, there was no correlation between the studied parameters and serum bilirubin, albumin, ALT, and AST. Conclusions: Redox imbalance was detected in patients with CHC. Responders had significantly lower levels of MDA than non-responders. Serum MDA may be used as a pretreatment predictor of response to antiviral treatment in patients with CHC.
    No preview · Article · Nov 2012 · Saudi Journal of Gastroenterology
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    • "Silymarin has been reported to protect liver cells from a wide variety of toxins, including acetaminophen, ethanol, carbon tetrachloride, and D-galactosamine, as well as from ischemic injury, radiation, iron toxicity, and viral hepatitis [81][82]. A combination of antiviral and antioxidative therapies, including silymarin, ascorbic acid, lipoic acid, and alpha-tocopherol, may enhance the overall response rate in the patients with chronic hepatitis C [83]. Resveratrol, a dietary polyphenol, has been shown to possess potent antioxidant as well as anti-inflammatory properties and to mediate induction of antioxidant enzymes and modulate lipid metabolism while attenuating hepatic lipid peroxidation [84]. "
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    ABSTRACT: Oxidative damage due to oxidative stress is the failure of the cell's defense against the deleterious effects of harmful agents by means of its numerous autoprotective mechanisms. oxidative stress is a key impairment induced by various conditions, including atherosclerosis, hypertension, ischemia-reperfusion, hepatitis, pancreatitis, cancer, and neurodegenerative diseases. Oxidative stress is a common pathogenetic mechanism contributing to the initiation and progression of hepatic damage in cases of inflammatory liver disorders, including acute and chronic hepatitis. Antioxidant administration is a good therapeutic strategy for the treatment of hepatitis. Our comprehensive review of the literature revealed that contradictory results have been obtained with many antioxidants and antioxidant agents. Since clinical studies to date have generally involved testing of the effects of antioxidant mixtures containing more than 2 antioxidants and also have been limited because of toxic effects of high doses of some antioxidants, antioxidant therapy for acute and chronic hepatitis needs further study.
    Full-text · Article · Mar 2012 · Hepatitis Monthly
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    • "Infection with hepatitis C virus (HCV) is a serious public health problem worldwide [1] and is considered the major cause of chronic liver disease, cirrhosis, and death in the final stages of liver disease in the United States and in most Western countries. It is estimated that approximately 180 million people around the world are infected with HCV [2]. "
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    ABSTRACT: Infection with hepatitis C virus (HCV) is a serious public health problem worldwide. In clinical studies, weight loss has been reported in 11% to 29% of patients treated with pegylated interferon-α-2a/2b. Few reports have tried to explain such a weight loss. The aim of this study was to evaluate nutritional status, body composition, and resting energy expenditure (REE) in patients with chronic hepatitis C before and during treatment with pegylated interferon and ribavirin. This was a prospective study with the evaluation of patients with hepatitis C virus before and after 12 wk of treatment with pegylated interferon and ribavirin. The evaluation consisted of anthropometry (weight, height, body mass index, and waist circumference), and body composition was determined by bioelectrical impedance analysis. The REE of each individual was obtained by indirect calorimetry. To compare the two phases of treatment, the Wilcoxon test was used. The significance level was 5%. Subjects had significant weight loss during treatment with a consequent decrease in body mass index. This weight decrease was accompanied by a significant decrease in body fat and no decrease in fat-free mass. There was a significant decrease in energy intake as assessed by 24-h recall. However, there was no change in REE and in REE corrected for fat-free mass. Our study of patients with hepatitis C treatment showed that these patients had significant weight loss and this was not associated with changes in energy expenditure. However, we observed a significant decrease in energy intake, pointing to a possible need for intervention measures to decrease the damage.
    Full-text · Article · Dec 2011 · Nutrition
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