Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease

Svegliati‐Baroni, Gianluca; Bugianesi, Elisabetta; Bouserhal, T; Marini, F; Ridolfi, F.; Tarsetti, F.; Ancarani, F.; Petrelli, Enzo; Peruzzi, Elena; Cascio, Marco; Rizzetto, Mario; Marchesini, Giulio; Benedetti, Antonio

doi:10.1136/gut.2006.107946

Cited by 66 publications

(79 citation statements)

References 45 publications

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“…Original magnification !400. (16), one could expect fetuin A, as a marker of insulin resistance, to increase in parallel with the degree of liver fibrosis. On the other hand, fetuin A is a known extracellular inhibitor of transforming growth factor b (17), the key profibrogenic stimuli in chronic liver disease (18).…”

Section: Discussionmentioning

confidence: 99%

Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies

Haukeland

Dahl

Yndestad

et al. 2012

European Journal of Endocrinology

164

122

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Objective: Fetuin A has been associated with insulin resistance and the metabolic syndrome. We therefore explored the role of fetuin A in nonalcoholic fatty liver disease (NAFLD). Design: Cross-sectional and intervention studies. Methods: We included 111 subjects with histologically proven NAFLD of whom 44 participated in a randomized, controlled trial with metformin. One hundred and thirty-one healthy subjects and 13 subjects undergoing hepatic surgery for metastatic cancer served as controls. Main outcome variables were circulating levels of fetuin A according to the presence of NAFLD, hepatic gene expression of fetuin A and key enzymes in glucose and lipid metabolism, and the effect of metformin on fetuin A levels in vivo and in vitro (HepG2 cells). Results: Fetuin A levels were significantly higher in NAFLD patients compared with controls (324G98 vs 225G75 mg/l, P!0.001). NAFLD was a significant predictor of elevated fetuin A levels (bZ174 (95% confidence interval: 110-234)) independent of body mass index, age, sex, fasting glucose, and triglycerides. Hepatic fetuin A mRNA levels correlated significantly with hepatic mRNA levels of key enzymes in lipid (sterol regulatory element-binding protein 1c, carnitine palmitoyltransferase 1) and glucose (phosphoenol pyruvate kinase 1, glucose-6-phosphatase) metabolism. Plasma fetuin A levels decreased significantly after metformin treatment compared with placebo (K40G47 vs 15G82 mg/l, PZ0.008). Metformin induced a dose-dependent decrease in fetuin A secretion in vitro. Conclusions: Fetuin A levels were elevated in NAFLD. Hepatic expression of fetuin A correlated with key enzymes in glucose and lipid metabolism. Metformin decreased fetuin A levels in vitro.

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Section: Discussionmentioning

confidence: 99%

Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies

Haukeland

Dahl

Yndestad

et al. 2012

European Journal of Endocrinology

164

122

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“…We recently reported that insulin resistance is associated with interferon signalling, which plays an important role in the clearance of chronic hepatitis C (CHC) during interferon therapy (4,5). Previous studies have demonstrated the association between metabolic syndrome and hepatic fibrosis in patients with hepatitis C (6)(7)(8)(9)(10)(11). Steatosis is a frequent histological finding in chronic hepatitis C virus infection, one that affects disease progression and occurrence of hepatocellular carcinoma (7,(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of the Fibrosis Scores in Patients with Chronic Hepatitis C Associated with Liver Fibrosis and Metabolic Syndrome

et al. 2011

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Objective We evaluated patients with chronic hepatitis C (CHC) and compared the clinical and pathological features of steatosis and metabolic syndrome to identify the risk factors for CHC with severe fibrosis. Methods One hundred seventy-one patients with biopsy-confirmed CHC were included in the study: 90 males and 81 females, age 56.2±12.8 years; 46 with obesity (BMI!25 kg/m 2 ); 51 with hypertension; 36 with type 2 diabetes mellitus; and 20 with hypertriglyceridemia. Results Steatosis was detected in 79 patients (46%); 92 patients (54%) showed no steatosis. Seventy-four patients (43%) showed mild fibrosis and 97 patients (56%) showed severe fibrosis. The variables that were significantly associated with steatosis were obesity [odds ratio 2. . Nagasaki (N) score (the total number of specific risk factors, namely an older age, obesity, and type 2 diabetes) was higher in the severe fibrosis group than in the mild fibrosis group (mild fibrosis: severe fibrosis=1.48±1.14 vs.2.66±94, p<0.001). Conclusion Metabolic syndrome factors, including obesity and diabetes, play a critical role in the pathogenesis of fibrosis in CHC. The N score was therefore found to be a significant predictor of severe fibrosis in CHC.

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“…Combination therapy with PegIFN and ribavirin has been recommended as standard therapy for patients with HCV infection with favorable efficacy (Hui et al, 2003;Petit et al, 2001;Svegliati-Baroni et al, 2007). It therefore provides a wide scope of view addressing the correlation between HCV infection and IR.…”

Section: The Characteristics Of Glucose Abnormalities In Patients Witmentioning

confidence: 99%

“…The prevalence of the MS in patients with CHC varied from 4.4% in Italy, 24.7% in Taiwan and 51% in US veterans (Huang et al, 2009a;Keane et al, 2009;Svegliati-Baroni et al, 2007), suggesting that host factors such as ethnic origin could play a role in the association between IR and CHC (Conjeevaram et al, 2007;Serste et al, 2010). Liangpunsakul et al examined the relationship between nondiabetic subjects with HCV infection and microalbuminuria by using NHANES III database which consisted of 15,336 adults from the United States.…”

Section: Metabolic Disordersmentioning

confidence: 99%

“…viral G-2 or -3, lower pretreatment viral load) (Hui et al, 2003;Petit et al, 2001;Strader et al, 2004;Svegliati-Baroni et al, 2007;Taura et al, 2006) and host factors (younger age, lower BMI, non-African-American or Asian races and interleukin-28B polymorphisms, etc.) (Fried et al, 2002;Strader et al, 2004;Svegliati-Baroni et al, 2007;Yu et al, 2009;Yu et al, 2011). Glucose abnormalities have also been suggested recently to be a risk factor for nonresponse (Muiret al, 2004).…”

Section: The Characteristics Of Glucose Abnormalities In Patients Witmentioning

confidence: 99%

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Metabolic Aspects of Hepatitis C Virus Infection

Huang¹,

Yu²,

Dai³

et al. 2012

Molecular Virology

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Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease

Abstract: Post-load insulin resistance (OGIS <9.8 mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease.

Cited by 66 publications

References 45 publications

Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies

Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies

Predictive Value of the Fibrosis Scores in Patients with Chronic Hepatitis C Associated with Liver Fibrosis and Metabolic Syndrome

Metabolic Aspects of Hepatitis C Virus Infection

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