Insulin Resistance in Chronic Hepatitis C: Association With Genotypes 1 and 4, Serum HCV RNA Level, and Liver Fibrosis

Moucari, Rami; Asselah, Tarik; Cazals–Hatem, Dominique; Voitot, Hélène; Boyer, Nathalie; Ripault, Marie–Pierre; Sobesky, Rodolphe; Martinot‐Peignoux, Michèle; Maylin, Sarah; Nicolas–Chanoine, Marie–Hélène; Paradis, Valérie; Vidaud, Michel; Valla, Dominique; Bédossa, Pierre; Marcellin, Patrick

doi:10.1053/j.gastro.2007.11.010

Cited by 496 publications

(471 citation statements)

References 61 publications

Supporting

Mentioning

386

Contrasting

Unclassified

Order By: Relevance

“…In 2003, Hui et al [27] first reported that IR is increased in patients infected with HCV, particularly genotype 1 and that this may form the basis for the earlier observations regarding the association with T2DM. Subsequent studies have confirmed this association, including for genotype 4 [28] and possibly also genotype 2a [29] . Since liver fibrosis irrespective of etiology can of itself cause hyperinsulinemia, it is important to exclude patients with advanced fibrosis in any assessment of the relationship between HCV and IR.…”

Section: Chc and Irmentioning

confidence: 73%

“…A recent study found that in patients with CHB the HOMA-IR reflected their overall metabolic profile, but was not increased in people with CHB compared with matched healthy controls [33] . Another recent prospective study comparing patients with CHB and CHC confirmed that IR is a specific feature of hepatitis C genotype 1 and 4 infection, but not CHB; it was present in 35% of patients with CHC compared with only 5% with CHB [28] .…”

Section: Chc and Irmentioning

confidence: 92%

See 1 more Smart Citation

Molecular mechanisms of insulin resistance in chronic hepatitis C

Douglas

George²

2009

WJG

View full text Add to dashboard Cite

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.

show abstract

Section: Chc and Irmentioning

confidence: 73%

Section: Chc and Irmentioning

confidence: 92%

Molecular mechanisms of insulin resistance in chronic hepatitis C

Douglas

George²

2009

WJG

View full text Add to dashboard Cite

show abstract

“…Hsu et al [22] reported a correlation between HCV-RNA levels and HOMA-IR score. Even in nondiabetic patients, Moucari et al [23] reported IR in 32.4% of CHC patients. Also, despite being nonobese, nondiabetic, or prediabetic, 45% of our patients had IR >3, and the mean fasting insulin and HOMA-IR were significantly higher in the patients group in comparison with control subjects (20.15 ± 5.13 vs 13.15 ± 4.2, P = 0.001) and (4.49 ± 1.28 vs 2.72 ± 0.87, P = 0.001) respectively.…”

Section: Discussionmentioning

confidence: 99%

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Sagheer

Soliman

Ahmad

et al. 2018

Libyan Journal of Medicine

View full text Add to dashboard Cite

Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.

show abstract

“…The predominance of metabolic effects such as hypocholesteremia and hepatic steatosis with HCV genotype 3 (G3) infection, 10 and IR and diabetes with non-G3 genotypes such as HCV G2 11 and genotypes 1 and 4, 12 suggests viral genotype-specific differences in the nature of this interference. 13 Direct viral perturbation of cholesterol biosynthetic pathways and their regulation is suggested from experimental in vitro and animal models.…”

mentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

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)

show abstract

Insulin Resistance in Chronic Hepatitis C: Association With Genotypes 1 and 4, Serum HCV RNA Level, and Liver Fibrosis

Cited by 496 publications

References 61 publications

Molecular mechanisms of insulin resistance in chronic hepatitis C

Molecular mechanisms of insulin resistance in chronic hepatitis C

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

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

Contact Info

Product

Resources

About