Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C

Vidali, Matteo; Tripodi, Marie‐Francoise; Ivaldi, A.; Zampino, Rosa; Occhino, G.; Restivo, Luciano; Sutti, Salvatore; Marrone, Aldo; Ruggiero, Giuseppe; Albano, Emanuele; Adinolfi, Luigi Elio

doi:10.1016/j.jhep.2007.10.011

Cited by 98 publications

(72 citation statements)

References 55 publications

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“…Similar antibodies have also been observed in ~40% of adult NAFLD patients, as well as in subjects with advanced alcoholic liver disease (ALD) and chronic hepatitis C, two other liver diseases characterized by the involvement of oxidative stress (26,27,(33)(34)(35)(36). Moreover, ~35% of ALD patients also have circulating CD4…”

Section: Discussionmentioning

confidence: 57%

Oxidative stress parameters in paediatric non-alcoholic fatty liver disease

Nobili

Parola

Alisi³

et al. 2010

Int J Mol Med

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Abstract.We have investigated the presence and the possible clinical implications of oxidative stress in children with nonalcoholic fatty liver disease (NAFLD). The present study was an observational study of oxidative stress parameters in the progression of paediatric NAFLD. We observed the role of oxidative stress in children diagnosed with NAFLD by evaluating: serum protein carbonyls, hepatic expression of 8-hydroxy-2-deoxyguanosine (8-OHG), and circulating antibody against malondialdehyde adducted human serum albumin (MDA-HSA). Forty consecutive children with biopsy-proven NAFLD (27 male; 13 female) referred to Bambino Gesù Children's Hospital, Rome, Italy, from January 2007 to April 2008 were included in the study. Serum variations of protein carbonyls, 8-OHG, and circulating antibody against MDA-HSA were evaluated. Elevated protein carbonyls were evident in 33 subjects (83%) irrespective of obesity and insulin resistance. Moreover, liver biopsies of NAFLD patients positive for circulating protein carbonyls also showed a significant increase in the nuclear staining for 8-OHG (p=0.006; 95% CI 3.1-17.7). Anti-MDA-HSA IgG above control threshold was detected in 25 (63%) children. Although protein carbonyl levels were unrelated with disease severity, patients with elevated anti-MDA-HSA IgG had scores for lobular inflammation significantly higher (p=0.019) than subjects with antibodies within the control range, while steatosis, hepatocyte ballooning and fibrosis were similar. High anti-MDA-HSA reactivity was also associated with a 13-fold increased risk (OR=12.9; 95% CI 1.5-113.8; p=0.013) of a NAFLD activity score (NAS) ≥5. These results demonstrate that oxidative stress has an high prevalence in children with NAFLD and is associated with an increased severity of steatohepatitis.

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Section: Discussionmentioning

confidence: 57%

Oxidative stress parameters in paediatric non-alcoholic fatty liver disease

Nobili

Parola

Alisi³

et al. 2010

Int J Mol Med

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“…However the interactions between oxidative stress, IR, metabolic syndrome and steatosis are complex, with each potentially influencing the other. A recent study showed that in patients infected with HCV genotype non-3, HOMA-IR (P < 0.01), fibrosis (P < 0.01) and oxidative stress (P < 0.05) were independently associated with steatosis, whereas steatosis was independently associated with oxidative stress (P < 0.03) and HOMA-IR (P < 0.02) [94] . The authors concluded that in genotype non-3 infection "oxidative stress and IR contribute to steatosis, which in turn exacerbates both IR and oxidative stress and accelerates the progression of fibrosis" [94] .…”

Section: Oxidative Stress and Irmentioning

confidence: 98%

Molecular mechanisms of insulin resistance in chronic hepatitis C

Douglas

George²

2009

WJG

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It is now widely recognized that chronic hepatitis C (CHC) is associated with insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1, in contrast to hepatic steatosis, which is associated with genotype 3 infection. Apart from the well-described complications of diabetes, IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma. More recently, it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined. This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

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“…[14][15][16][17][18] HCV-mediated oxidative stress has been suggested as a possible causative mechanism leading to both HCV-associated hepatic steatosis and IR, and has also been linked to cholesterol regulation. 15,19 Finally, from the host perspective, it is not known why compensatory regulation to increase cholesterol synthesis appears inadequate to resolve HCV-associated hypolipidemia.…”

mentioning

confidence: 99%

Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner

et al. 2012

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Hepatitis C virus (HCV) subverts host cholesterol metabolism for key processes in its lifecycle. How this interference results in the frequently observed, genotype-dependent clinical sequelae of hypocholesterolemia, hepatic steatosis, and insulin resistance (IR) remains incompletely understood. Hypocholesterolemia typically resolves after sustained viral response (SVR), implicating viral interference in host lipid metabolism. Using a targeted cholesterol metabolomic platform we evaluated paired HCV genotype 2 (G2) and G3 patient sera for changes in in vivo HCV sterol pathway metabolites. We compared HCV genotypic differences in baseline metabolites and following antiviral treatment to assess whether sterol perturbation resolved after HCV eradication. We linked these metabolites to IR and urine oxidative stress markers. In paired sera from HCV G2 (n 5 13) and G3 (n 5 20) patients, baseline sterol levels were lower in G3 than G2 for distal metabolites (7-dehyrocholesterol (7DHC) 0.017 versus 0.023 mg/dL; P adj 5 0.0524, cholesterol 140.9 versus 178.7 mg/dL; P adj 5 0.0242) but not the proximal metabolite lanosterol. In HCV G3, SVR resulted in increased levels of distal metabolites (cholesterol [D55.2 mg/dL; P adj 5 0.0015], 7DHC [D0.0075 mg/dL; P adj 5 0.0026], lathosterol [D0.0430 mg/dL P adj 5 0.0405]). In contrast, lanosterol was unchanged after SVR (P 5 0.9515). Conclusion: HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms. (HEPATOLOGY 2012;56:49-56)

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Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C

Cited by 98 publications

References 55 publications

Oxidative stress parameters in paediatric non-alcoholic fatty liver disease

Oxidative stress parameters in paediatric non-alcoholic fatty liver disease

Molecular mechanisms of insulin resistance in chronic hepatitis C

Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner

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