4-hydroxy-2-nonenal and Hepatitis-C--Chronic

The role of zinc (Zn) in hepatic steatosis of patients with HCV-related chronic liver disease (CLD-C) remains uncertain, although persistent HCV infection often evokes hepatic steatosis. The primary purpose of this study was to elucidate the contribution of Zn deficiency to hepatic steatosis in patients with CLD-C. Fifty nondiabetic patients with CLD-C were enrolled. Hepatic 4-hydroxy-2-nonenal (4-HNE) expression was examined using an immunohistochemical procedure as a marker for lipid peroxidation. Serum ferritin levels were assessed for iron overload. Insulin resistance was evaluated using the values of the homeostasis model for assessment of insulin resistance (HOMA-IR). The severity of hepatic steatosis was graded on the classification system proposed by Brunt and colleagues. Serum Zn levels were inversely correlated with serum ferritin levels in the patients with CLD-C (r = -0.382, p = 0.0062). Serum ferritin levels were strongly associated with the HOMA-IR values (r = 0.476, p = 0.0005). Therefore, Zn deficiency resulted in insulin resistance through iron overload. Moreover, serum Zn levels were significantly decreased in proportion to the level of hepatic 4-HNE expression, which was enhanced as hepatic steatosis developed. Then, Zn deficiency eventually seemed to exacerbate hepatic steatosis by way of an increase in lipid peroxidation. However, the serum Zn levels were not associated with either loads of HCV-RNA or HCV genotypes. These data suggest that, in patients with CLD-C, Zn deficiency promotes insulin resistance by exacerbating iron overload in the liver and induces hepatic steatosis by facilitating lipid peroxidation.

Topics: Adult; Aged; Aldehydes; Fatty Liver; Female; Ferritins; Hepatitis C, Chronic; Humans; Insulin Resistance; Lipid Peroxidation; Liver; Male; Middle Aged; Zinc

To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).. In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO).. In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150000/microL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFalpha, and IL-6, and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150000/microL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen.. The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.

Topics: Adult; Aged; Aged, 80 and over; Aldehydes; Biomarkers; Blood Platelets; Case-Control Studies; Cysteine; Female; Glutathione; Hepatitis C, Chronic; Humans; Interleukin-6; Male; Malondialdehyde; Middle Aged; Nitric Oxide; Nitrites; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Platelet Function Tests; S-Nitrosoglutathione; S-Nitrosothiols; Thrombocytopenia; Tumor Necrosis Factor-alpha

To evaluate whether chronic therapy with probiotics affects plasma levels of cytokines and oxidative/nitrosative stress parameters, as well as liver damage, in patients with various types of chronic liver disease.. A total of 22 nonalcoholic fatty liver disease (NAFLD) and 20 alcoholic liver cirrhosis (AC) patients were enrolled in the study and compared with 36 HCV-positive patients with chronic hepatitis without (20, CH) or with (16, CC) liver cirrhosis. All patients were treated with the probiotic VSL#3. Routine liver tests, plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and -10, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE), S-nitrosothiols (S-NO), were evaluated on days -30, 0, 90, and 120.. Treatment with VSL#3 exerted different effects in the various groups of patients: in NAFLD and AC groups, it significantly improved plasma levels of MDA and 4-HNE, whereas cytokines (TNF-alpha, IL-6, and IL-10) improved only in AC patients. No such effects were observed in HCV patients. Routine liver damage tests and plasma S-NO levels were improved at the end of treatment in all groups.. Results of the study suggest that manipulation of intestinal flora should be taken into consideration as possible adjunctive therapy in some types of chronic liver disease.

Topics: Adult; Aldehydes; Analysis of Variance; Chronic Disease; Cytokines; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Liver Diseases, Alcoholic; Liver Function Tests; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Probiotics; S-Nitrosothiols; Statistics, Nonparametric

Oxidative stress contributes to the pathogenesis of chronic hepatitis C. The aim of this study was to assess the peroxidation of n-3 polyunsaturated fatty acids (PUFAs) in the liver and its relation to hepatic steatosis in chronic hepatitis C.. We immunohistochemically detected malondialdehyde (MDA)-, 4-hydroxy-2-nonenal (HNE)-, and 4-hydroxy-2-hexenal (HHE)-protein adducts in liver biopsy specimens from 55 patients with chronic hepatitis C. Cells stained positively for HHE-protein adducts were quantified using computer-based image analysis. Fatty-acid composition was determined, by gas chromatography, for the noncancerous portions of resected livers, with or without steatosis, obtained from two patients with hepatitis C virus-associated hepatocellular carcinoma.. The detection rate of HHE-protein adducts (63.6%) was significantly higher than that of MDA-protein adducts (21.8%; P < 0.001) or HNE-protein adducts (29.1%; P < 0.001). Areas positively stained for HHE-protein adducts (HHE-positive areas) were significantly larger in 18 patients with steatosis (6.2 +/- 3.6%) than in 17 patients without steatosis (3.4 +/- 2.6%; P = 0.01). Resected liver tissue with steatosis showed a larger HHE-positive area (18.6%) and higher ratio of n-6 PUFA content to n-3 PUFA content (3 : 1) than liver tissue without steatosis (7.2%; 2 : 3). On multivariate analysis, the HHE-positive area (odds ratio, 1.55; 95% confidence interval [CI], 1.08-2.23; P = 0.019) was a factor associated with the presence of hepatic steatosis.. HHE-protein adducts, which are a good marker for oxidative stress, are associated with steatosis in chronic hepatitis C.

Topics: Adult; Aged; Aged, 80 and over; Aldehydes; Biomarkers; Biopsy; Chromatography, Gas; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Immunohistochemistry; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Severity of Illness Index; Triglycerides

Oxidative stress (OS) plays a major role in chronic hepatitis C. Various OS markers have been found to be elevated in hepatitis C virus (HCV)-related liver disease. This study detected the presence of OS in serum and liver biopsy specimens of HCV patients. Reactive oxygen molecules (ROM) in sera of 54 HCV patients were compared with 23 controls. OS markers 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal, malondialdehyde, and thioredoxin were measured in liver biopsy specimens of 18 HCV patients with fibrosis staging F1 (six); F2 (two), F3 (four), and F4 (six). The interferon (IFN) response and hepatocellular carcinoma (HCC) occurrence in the presence of OS markers were also evaluated. The level of ROM in HCV patients was 318 +/- 56.7 Carr compared with 248 +/- 40.8 Carr in controls (p=0.032). Multivariate analysis found age (p=0.0236) to be the only independent variable associated with increase in ROM in sera. In liver biopsy specimens, OS markers were found mainly around the area of piecemeal necrosis or the periportal area. The presence of OS markers seemed to increase with fibrosis staging, although not significantly. The OS DNA damage marker 8-OHdG was detected in the nucleus of hepatocytes. Thirteen patients received IFN therapy. During the 4-year follow-up period, HCC developed in four nonresponders to IFN and in one untreated patient. OS markers were stained in both HCC cells and non-HCC cells in HCC patients. OS markers were found in serum and liver specimens of HCV-associated liver disease and in HCC tissue. Detection of OS markers may be important for monitoring disease progression in HCV patients. Antioxidant therapy in combination with antiviral therapy may minimize liver damage and aid in the prevention and subsequent development of HCC.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Aldehydes; Biomarkers; Carcinoma, Hepatocellular; Deoxyguanosine; Disease Progression; Female; Hepatitis C, Chronic; Humans; Immunohistochemistry; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Malondialdehyde; Oxidative Stress; Reactive Oxygen Species; Thioredoxins

The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hydroxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated as markers of oxidative stress in 145 CHC patients with different alcohol consumption, 20 HCV-free heavy drinkers (HD) without liver disease, and 50 healthy controls. Anti-MDA IgG was increased in CHC patients irrespective of alcohol intake as well as in the HD group. CHC patients with moderate alcohol intake (<50 g ethanol/d), but not HD, also had significantly higher values of anti-AAHP-HSA, anti-HNE-HSA, and anti-Ox-CL IgG (P <.05) than controls. A further elevation (P <.001) of these antibodies was evident in CHC patients with heavy alcohol intake (>50 g ethanol/d). Anti-AAHP and anti-Ox-CL IgG above the 95th percentile in the controls were observed in 24% to 26% of moderate and 58% to 63% of heavy drinkers but only in 6% to 9% of the abstainers. The risk of developing oxidative stress during CHC was increased 3-fold by moderate and 13- to 24-fold by heavy alcohol consumption. Heavy drinking CHC patients had significantly more piecemeal necrosis and fibrosis than abstainers. Diffuse piecemeal necrosis was 4-fold more frequent among alcohol-consuming patients with lipid peroxidation-related antibodies than among those without these antibodies. In conclusion, even moderate alcohol consumption promotes oxidative stress in CHC patients, suggesting a role for oxidative injury in the worsening of CHC evolution by alcohol.

Topics: Adult; Alcohol Drinking; Aldehydes; Arachidonic Acid; Autoantibodies; Biomarkers; Cardiolipins; Female; Hepatitis C, Chronic; Humans; Hydrogen Peroxide; Immunoglobulin G; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Serum Albumin

Hepatic iron deposition has been reported in chronic hepatitis C (CH-C), and iron-induced lipid peroxidation may be involved in the pathogenesis of CH-C. The aims of the present study were: 1) to determine whether patients with CH-C have evidence of enhanced hepatic lipid peroxidation and to evaluate its relation to iron status, compared with that in patients with chronic hepatitis B (CH-B); and 2) to assess the effect of interferon (IFN) therapy on hepatic iron and lipid peroxidation.. In the liver biopsies of 40 patients with CH-C and 26 patients with CH-B, immunohistochemical detection of 4-hydroxy-2-nonenal (HNE)-protein adducts for evaluation of lipid peroxidation was performed, and hepatic iron status was biochemically and histologically assessed. In 16 CH-C patients with normal serum transaminases and undetectable serum HCV-RNA >6 months after the end of IFN treatment (responders) and in 11 nonresponders, hepatic HNE-protein adducts and siderosis were evaluated in pre- and posttreatment liver biopsies.. Hepatocytic HNE-protein adducts and iron deposits were more abundant in the patients with CH-C than in those with CH-B. No correlation was found between the levels of hepatocytic HNE-protein adducts and hepatic iron status in either of the two groups. In the responders to IFN treatment for CH-C, hepatocytic HNE-protein adducts disappeared or attenuated with improvement of hepatic siderosis after the treatment, whereas IFN treatment did not improve hepatocytic expression of HNE-protein adducts and hepatic siderosis in the nonresponders.. Patients with CH-C have evidence of enhanced hepatic iron accumulation and lipid peroxidation compared to those with CH-B. In CH-C, hepatic siderosis and lipid peroxidation are improved with successful IFN treatment. These results suggest that hepatic lipid peroxidation and iron may potentially play contributory roles in the pathogenesis of CH-C.

Topics: Adult; Aged; Aldehydes; Biopsy; Cross-Linking Reagents; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Interferons; Iron; Lipid Peroxidation; Liver; Liver Function Tests; Male; Middle Aged