In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features.

Paradis, Valérie; Mathurin, Philippe; Köllinger, M; Imbert‐Bismut, Françoise; Charlotte, Frédéric; Piton, A; Opolon, P; Holstege, Axel; Poynard, Thierry; Bédossa, Pierre

doi:10.1136/jcp.50.5.401

Cited by 185 publications

(138 citation statements)

References 24 publications

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“…[9][10][11][12][13][14] Moreover, immunohistochemistry has documented the presence of MDA and 4-hydroxynonenal protein adduct in liver biopsy specimens from CHC patients. 13,30 The measurement of the antibodies against the different lipid peroxidation-related antigens confirms these observations, revealing that elevated titers of IgG against MDA adducts are evident in 38% to 55% of the CHC patients, independent of the alcohol consumption. However, the combination of HCV infection and alcohol intake promotes the immune response toward other lipid peroxidation products, including HNE, arachidonic acid hydroperoxide (AAHP), and oxidized cardiolipin.…”

Section: Discussionsupporting

confidence: 54%

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C

et al. 2003

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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. (HEPATOLOGY 2003; 38:42-49.)

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Section: Discussionsupporting

confidence: 54%

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C

et al. 2003

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“…34 Lipid peroxidation is associated with stellate-cell activation and synthesis of collagen type 1. 35 In chronic hepatitis C infection, steatosis correlates with lipid peroxidation 34 and active fibrogenesis, 36 but the link has not been sufficiently evaluated. The results of our study seem to suggest that alcohol exerts a synergistic effect with steatosis in accelerating the progression of hepatic disease, even at a low intake (from 10 to 30 g/d), whereas in the absence of steatosis it does not aggravate the liver damage.…”

Section: Discussionmentioning

confidence: 99%

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

et al. 2001

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The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy-proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg/m 2 ), distribution of body fat, HCV genotype, and levels of HCV RNA. Eighty six (48%) patients showed steatosis, and a higher prevalence was observed in genotype 3a infection (P < .01). A correlation between the grade of steatosis and fibrosis was observed (P < .001). Fibrosis was also associated with age (P < .001). After adjusting for age, the association between steatosis and fibrosis remained significant. The grade of steatosis also correlated with the HAI (P < .007) with a significant increase in periportal necrosis. No relation was found between steatosis and age, gender, iron storage, or levels of HCV RNA. Patients with a high grade of steatosis (>30%) showed higher serum levels of ␥-GT and ALT (P < .001). Overall, steatosis was not significantly associated to BMI. Analysis by single genotype showed a significant association between the grade of steatosis and BMI in type 1 infection r ‫؍‬ .689; P < .001) and with levels of HCV RNA in type 3a infection r ‫؍‬ .786; P < .001). Visceral fat distribution rather than BMI proved to be associated with steatosis (P < .001). Data obtained from patients with a known date of infection confirmed that steatosis grades 3-4 were associated with a higher annual rate of fibrosis progression, and showed that alcohol and steatosis act together in increasing fibrosis (P < .05). Our data indicate that steatosis is an important cofactor in increasing liver necroinflammatory activity and in accelerating fibrosis in CHC. Visceral obesity and genotype 3a play a role in the development of steatosis. (HEPATOLOGY 2001;33: 1358-1364

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“…Patients infected with HCV show increases in lipid peroxidation levels in liver samples, serum, and peripheral blood mononuclear cells [72,[75][76][77][78][79][80]. In addition, other indicators of oxidative stress such as 4-hydroxynonenal and 8-hydroxydeoxyguanosine were found to be increased in HCV [72,74,[80][81][82][83]. The content of GSH decreased in the blood, liver, and lymphatic system, whereas that of GSSG increased, indicating a high glutathione turnover [83].…”

Section: Viral Hepatitis and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features.

Cited by 185 publications

References 24 publications

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

Role of free radicals in liver diseases

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