The role of insulin resistance in HIV/hepatitis C virus-coinfected patients

Eslam, Mohammed; López‐Cortés, Luis F.; Romero–Gómez, Manuel

doi:10.1097/coh.0b013e32834bd21d

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…The role of IR is particularly controversial, as other studies have reported negative results . One meta‐analysis not including the most recent negative results reported by Butt and co‐workers confirmed the association between IR and virologic response in HIV/HCV .…”

Section: Introductionmentioning

confidence: 96%

Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV‐/HCV‐coinfected patients: the role of metabolic factors and elevated GGT levels

Mandorfer

Reiberger

Payer

et al. 2013

Journal of Viral Hepatitis

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Evaluation of metabolic factors and elevated γ-glutamyltransferase (GGT) levels as independent predictors of treatment failure in a thoroughly documented cohort of HIV-/HCV-coinfected patients (HIV/HCV). Sixty-four HIV/HCV patients treated with pegylated interferon-α-2a plus ribavirin (PEGIFN + RBV) at the Medical University of Vienna within a prospective trial were included in this study. In addition, 124 patients with HIV/HCV from the AIFA-HIV and AHIVCOS cohorts were included as a validation cohort. Advanced liver fibrosis, GGT elevation, insulin resistance (IR) and low CD4+ nadir were defined as METAVIR F3/F4, GGT levels >1.5× sex-specific upper limit of normal, homoeostasis model assessment of insulin resistance >2 and CD4+ nadir <350 cells/μL, respectively. HCV-genotype 1/4 (OR26.3; P = 0.006), advanced liver fibrosis (OR20.2; P = 0.009), interleukin 28B rs12979860 non-C/C SNP (OR8.27; P = 0.02) and GGT elevation (OR7.97; P = 0.012) were independent predictors of treatment failure, while both IR (OR3.51; P = 0.106) and low CD4 + nadir (OR2.64; P = 0.263) were not independently associated with treatment failure. A statistically significant correlation between GGT elevation and prior alcohol abuse (r = 0.259; P = 0.039), liver steatosis (r = 0.301; P = 0.034) and low-density lipoprotein-cholesterol (r = -0.256; P = 0.041) was observed. The importance of GGT elevation as an independent predictor of treatment failure was confirmed in a validation cohort (OR2.76; P = 0.026). While GGT elevation emerged as an independent predictor of treatment failure in both the derivation and the validation cohort, no independent associations between metabolic factors and treatment failure were observed. Thus, our findings suggest that GGT elevation is an independent predictor of treatment failure in HIV/HCV that can easily be incorporated into predictive algorithms.

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Section: Introductionmentioning

confidence: 96%

Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV‐/HCV‐coinfected patients: the role of metabolic factors and elevated GGT levels

Mandorfer

Reiberger

Payer

et al. 2013

Journal of Viral Hepatitis

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“…In this setting, chronic hepatitis C (CHC) has turned into an important comorbidity and a major cause of death in HIV/ hepatitis C virus (HCV) coinfected patients [2,3], because HIV infection accelerates the natural history of CHC [4][5][6]. Moreover, although the published data suggest that cART might be beneficial for HIV/HCV-coinfected patients [4], the interactions among HIV, HCV and cART are also associated with several metabolic disorders [7], including dyslipidaemia, lipodystrophy, steatosis, insulin resistance and type 2 diabetes mellitus [7,8].…”

Section: Introductionmentioning

confidence: 99%

FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients

et al. 2014

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BackgroundThe Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients.MethodsWe carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFNα/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ≥2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR).ResultsThe rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ≥27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ≥2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%.ConclusionsPatients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0198-y) contains supplementary material, which is available to authorized users.

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“…There are many pretreatment factors such as age, sex, ethnicity, BMI, insulin resistance, hepatic steatosis, degree of liver fibrosis, HCV genotype, and baseline viral load and viral kinetics during treatment, which can influence the response to the therapy with pegIFN and ribavirin in patients with chronic Prediction of response to pegINF Mohamed and Attalah 65 hepatitis C [21][22][23]. There are many pretreatment factors such as age, sex, ethnicity, BMI, insulin resistance, hepatic steatosis, degree of liver fibrosis, HCV genotype, and baseline viral load and viral kinetics during treatment, which can influence the response to the therapy with pegIFN and ribavirin in patients with chronic Prediction of response to pegINF Mohamed and Attalah 65 hepatitis C [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Prediction of response to pegylated interferon and ribavirin in Egyptian patients with chronic hepatitis C using serum neopterin

Mohamed¹,

Attalah²

2014

Egyptian Liver Journal

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The role of insulin resistance in HIV/hepatitis C virus-coinfected patients

Cited by 8 publications

References 43 publications

Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV‐/HCV‐coinfected patients: the role of metabolic factors and elevated GGT levels

Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV‐/HCV‐coinfected patients: the role of metabolic factors and elevated GGT levels

FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients

Prediction of response to pegylated interferon and ribavirin in Egyptian patients with chronic hepatitis C using serum neopterin

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