Steatosis Accelerates the Progression of Liver Damage of Chronic Hepatitis C Patients and Correlates With Specific Hcv Genotype and Visceral Obesity

Adinolfi, Luigi Elio; Gambardella, Michele; Andreana, A; Tripodi, Marie‐Francoise; Utili, Riccardo; Ruggiero, Giuseppe

doi:10.1053/jhep.2001.24432

Cited by 971 publications

(904 citation statements)

References 33 publications

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“…Our finding of HCV G3-specific perturbation of cholesterol metabolism is consistent with the clinical observations of increased prevalence of metabolic sequelae relative to other HCV genotypes, including more significant hypocholesterolemia, and increased rates and severity of hepatic steatosis 5,10 that also inversely correlate with lower cholesterol for HCV G3 10 and differing effects on host metabolic gene expression. 13 In keeping with our observation of an association between HCV RNA and low cholesterol in HCV G3, intrahepatic G3 HCV RNA has also been shown to correlate directly with other metabolic consequences of infection such as steatosis, further supporting a possible direct viral pathogenic effect.…”

Section: Discussionsupporting

confidence: 88%

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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Section: Discussionsupporting

confidence: 88%

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

et al. 2012

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“…The observation that some obese individuals presented a liver disease histologically indistinguishable from alcoholic liver disease itself had long been recognized. [42][43][44][45][46][47][48][49] Interestingly, it has been recently demonstrated that obesity also increases the risk of liver disease induced by either alcohol 50 or chronic hepatitis C. [51][52][53] In a literature survey of 41 original articles comprising information on liver morphology in 1515 morbidly obese patients, liver biopsy was considered as normal in only 12% of the cases. 54 The most frequent abnormality reported was fatty changes present in 80% of the biopsies; portal inflammation was also common (33%) while portal or periportal fibrosis was observed in 29%.…”

Section: The Association Of Nash With Obesitymentioning

confidence: 99%

Obesity and liver disease

Scheen

Luyckx

2002

Best Practice & Research Clinical Endocrinology & Metab

119

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Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.

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“…[8][9][10][11][12] In the few general population-based surveys conducted, the prevalence of liver disease, particularly hepatic steatosis (fatty liver disease), also appears to be higher in heavier people. 13,14 However, as has been highlighted, 15 interpretation of these findings is complicated by the issue of reverse causality.…”

Section: Introductionmentioning

confidence: 99%

Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study

et al. 2008

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Obesity has been implicated in the aetiology of liver disease. However, to date, evidence is largely drawn from cross-sectional studies, where interpretation is hampered by reverse causality, and from studies on clinical populations that have limited generalisability. In this prospective cohort study, data on body mass index (BMI) and covariates were collected at baseline on 18 863 male government employees (aged 40-69 years). Respondents were then followed up for a maximum of 38 years of age. Mortality surveillance gave rise to 13 129 deaths, 122 of which were due to liver disease (57 cancers; 65 non-cancers). In ageadjusted analyses, BMI was positively related to total liver disease mortality (hazards ratio per 1 s.d. increase in BMI; 95% confidence interval (CI): 1.36; 1.14, 1.62) in a graded fashion across the weight categories (P-value for trend: 0.01). The magnitude of this association was somewhat stronger for non-cancer liver disease deaths (1.47; 1.16, 1.86) than for cancer liver disease deaths (1.25; 0.96, 1.62). Excluding deaths in the first 10 years of follow-up somewhat strengthened the BMIFnoncancer liver disease association. Adjustment for socioeconomic position, other candidate confounders and mediating factors led to the modest attenuation of these associations. Further investigation in prospective cohort studies with more detailed data on liver disease, for instance using biochemical tests of liver function or hepatic ultrasonography, is warranted.

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Steatosis Accelerates the Progression of Liver Damage of Chronic Hepatitis C Patients and Correlates With Specific Hcv Genotype and Visceral Obesity

Cited by 971 publications

References 33 publications

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

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

Obesity and liver disease

Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study

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