Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: A meta-analysis

Deltenre, Pierre; Louvet, Alexandre; Lemoine, Maud; Mourad, Abbas; Fartoux, Lætitia; Moreno, Christophe; Henrion, Jean; Mathurin, Philippe; Serfaty, Lawrence

doi:10.1016/j.jhep.2011.03.010

Cited by 73 publications

(54 citation statements)

References 72 publications

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“…Clinical studies have drawn attention to a correlation between insulin and IFN sensitivities in individuals who are infected with hepatitis C virus (84). The expression levels of TNF-␣ are often increased in HCV-infected livers.…”

Section: In Tsc2mentioning

confidence: 99%

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

Burke

Platanias

Fish

2014

J Virol

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Section: In Tsc2mentioning

confidence: 99%

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

Burke

Platanias

Fish

2014

J Virol

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“…A proposed mechanism is that the HCV Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients GT1 core protein blocks the insulin signaling cascade protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase β-1 by increasing the expression of tumor necrosis factor α (TNF-α) and suppressor of cytokine signaling 3 (11,12). This may lead to inactivation of insulin receptor substrate 1 and block glucose entry into cells by preventing the activation of glucose transporters (13). GT1 and GT4 have been associated with a higher degree of IR in the presence or absence of type 2 diabetes (T2D) (14).…”

Section: Introductionmentioning

confidence: 99%

Effect of branched‑chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients

et al. 2017

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Abstract. The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P= 0.084 and P= 0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P= 0.017), role limitations due to emotional problems (P= 0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection.

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“…11 This observation with dual peginterferon/ribavirin therapy was further strengthened by two recent meta-analyses. 9,10 In the first one, 9 carried out on 17 studies, despite some heterogeneity among studies, SVR associated with peginterferon/ribavirin was significantly higher in patients with low HOMA-IR (i.e., <2) irrespective of HCV genotype (genotype 1, OR 5 2.16; genotype 2 and 3, OR 5 3.06; genotype 4, OR 5 6.65). The second metaanalysis 10 assessed 14 studies involving 2,732 patients, and concluded that HCV patients with IR have a 20% lower SVR rate than patients without IR, thereby hinting that baseline HOMA-IR index is a major determinant of SVR with peginterferon/ribavirin therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma HCV RNA was measured using the COBAS TaqMan assay, v. 2.0 (Roche, Switzerland; lower limit of quantification 25 IU/mL and lower limit of detection 10 IU/mL) at screening, baseline, day 3, during weeks 1, 2, 4, 5,6,8,10,12,14,16,20,24,36, and 48, at early discontinuation, at follow-up visits 4, 12, and 24 weeks after end of treatment and at week 72, even in patients who discontinued early. SVR was defined as having undetectable (<25 IU/mL undetectable) HCV RNA at 24 weeks after the last planned dose of study medication.…”

Section: Studymentioning

confidence: 99%

Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial

et al. 2013

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Baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR), a marker for insulin resistance, has been associated with poor virologic response to peginterferon alpha/ribavirin (PR) in chronic hepatitis C. We evaluated the association between baseline HOMA-IR and pretreatment factors on sustained virologic response (SVR) to telaprevir (TVR) in genotype 1 patients with hepatitis C and prior peginterferon/ribavirin (PR) treatment failure. Patients were randomized to 12 weeks of TVR (750 mg q8h) plus peginterferon (180 lg/week) and ribavirin (1,000-1,200 mg/day) (with or without a 4-week lead-in) followed by PR, or PR alone (PR48), for 48 weeks. Univariate and multiple logistic regression analyses explored the prognostic significance of baseline HOMA-IR alone and adjusted for other pretreatment factors and SVR. The TVR arms were pooled for the purposes of this analysis. In all, 662 patients were randomized; 578 had baseline HOMA-IR and other prognostic data and were included in this analysis. Median baseline HOMA-IR was 2.6 (interquartile range [IQR] 1.7-4.3); 207 (36%), 206 (36%), and 165 (29%) patients had baseline HOMA-IR <2, 2 to <4, and 4, respectively. Male gender, higher body mass index, triglycerides, gamma-glutamyl transpeptidase, maximum alanine aminotransferase/aspartate aminotransferase, and fibrosis stage were associated with higher baseline HOMA-IR. Baseline HOMA-IR was associated with SVR in univariate analysis, but not after adjustment for other baseline prognostic factors (TVR: OR 5 0.95, 95% confidence interval [CI]: 0.71,1.29; PR48: 0.60; 95% CI: 0.25,1.43). Conclusion: In patients with prior PR treatment failure, baseline HOMA-IR correlated with SVR in univariate but not multivariate analyses, suggesting other factors have a more direct causal relationship with virologic response to TVR-based therapy than HOMA-IR.

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Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: A meta-analysis

Cited by 73 publications

References 72 publications

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

Effect of branched‑chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients

Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial

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