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

Younossi, Zobair M.; Negro, Francesco; Serfaty, Lawrence; Pol, Stanislas; Diago, M.; Zeuzem, Stefan; Andreone, Pietro; Lawitz, Eric; Roberts, Stuart K.; Focaccia, Roberto; Foster, Graham R.; Horban, Andrzéj; Lonjon–Domanec, Isabelle; Coate, Bruce; DeMasi, Ralph; Picchio, Gastón; Witek, James

doi:10.1002/hep.26437

Cited by 23 publications

(15 citation statements)

References 45 publications

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“…However, this is not sufficient to claim that improving insulin sensitivity may ameliorate response to therapy. More recently, Younossi and co‐workers found that baseline HOMA‐IR correlated with sustained virologic response in univariate but not multivariate analyses in patients chronically infected with HCV‐1 and undergoing triple therapy, suggesting other factors have a more direct causal relationship with virologic response to telaprevir‐based therapy than HOMA‐IR [Younossi et al, ].…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian Patients

El‐Wahab

Mikheal

Sidkey

et al. 2015

Journal of Medical Virology

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Prior assessment of insulin resistance by HOMA-IR is emerging as an important milestone in the treatment of patients with chronic hepatitis C. This cost-effective tool is recommended to individualize treatment duration, or to exclude those with low insulin sensitivity from being treated until ameliorating their state of insulin resistance (IR). The present work aims to elucidate further the effect IR state on early viral kinetic response to Chronic hepatitis C virus (HCV) therapy and the impact of HCV treatment and viral eradication on insulin sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All enrolled patients were treated with a dual therapy (pegylated interferon-alpha plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic response as well as the impact of treatment on insulin sensitivity throughout the early period of therapy. Of a total 392 chronic HCV cases, early virologic response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV patient of which 73.4% responded to treatment. Early virologic response among patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA-IR values ≤2.18 (P < 0.0001). IR was significantly associated with high baseline BMI. Steatosis and fibrosis correlated with IR but neither independently predicted early virologic response. Pretreatment IR < 2.18, low fasting blood glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were independent factors associated with early virologic response. IR interferes with early virologic response to the antiviral care. Clinical application of pretreatment HOMA-IR assessment could help in predicting early treatment outcome and thus enable treatment regimens to be optimized and individually tailored.

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Section: Discussionmentioning

confidence: 99%

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian Patients

El‐Wahab

Mikheal

Sidkey

et al. 2015

Journal of Medical Virology

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“…In such patients, overt diabetes may develop earlier than in HCV negative persons [103] . Glucose metabolism is altered by HCV at early stages of the infection, leading to insulin resistance [86] which, when combined with type 2 diabetes, accelerates liver disease progression [86,88] and reduces the response to combined pegylated interferon (PEGIFN) with Ribavirin (RBV) [104,105] , although the res ponse to regimens containing directacting antiviral (DAA) does not seem to be affected by glucose metabolism alterations [106] . Other extrahepaticassociated diseases include porphyria cutanea tarda, lichen planus, necrolytic acral erythema, sialadenitis, sicca syndrome, and autoimmune thyroiditis [96] .…”

Section: Extrahepatic Manifestationsmentioning

confidence: 99%

Hepatitis C genotype 4: The past, present, and future

Abdel-Ghaffar

Sira

Naghi

2015

WJH

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Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% (15-18 million) of total global HCV infection. It is prevalent in Northern and Equatorial Africa and the Middle East, and is also present in some countries in Europe. GT-4 (and subtype 4a in particular) dominates the HCV epidemic in Egypt. In underdeveloped countries, risk factors associated with HCV infection may be due to unsafe medical practices or other factors such as familial transmission, mother's HCV status, or illiteracy. HCV prevention and control programs should include health education, increased community awareness towards the disease, controlling infection distribution in healthcare centers, proper sterilization of medical and dental instruments, and ensuring safe supply of blood and blood-products. Response rates to a 48-wk combined pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment range from 40%-69%, and HCV-GT-4 has been considered better than GT-1 but worse than GT-2 and GT-3 in treatment with PEG-IFN/RBV. However, with the introduction of the HCV-GT-1 effective protease inhibitors boceprevir and telaprevir in 2011, HCV-GT-4 became the "most difficult (GT) to treat". Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir, and daclatasvir have been recommended in triple regimens with PEG-IFN/RBV for the treatment of HCV-GT-4. An IFN-free regimen will be available for treatment of all genotypes of HCV in the near future. To date, several DAAs have been developed and are currently being evaluated in various combinations in clinical trials. As new regimens and new agents are being approved by the Food and Drug Administration, we can expect the guidelines for HCV treatment to be changed. The availability of shorter, simpler, and more tolerable treatment regimens can reduce the morbidity and mortality associated with HCV infection. With such a large number of therapeutic agents available, we can end up with a range of choices that we can select from to treat patients.

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“…Other studies confirmed these findings and showed a correlation between the degree of fibrosis and IR (13,14) . T2DM and IR were observed to be independent predictors of liverrelated mortality (15,16) , moreover IR was associated with fibrosis progression and the stage of fibrosis (12) .…”

Section: Introductionmentioning

confidence: 99%

Insulin Resistance Reduction After Sustained Virological Response With Direct Acting Antiviral:not Every Population Improves

Andrade

Yamashiro

Oliveira

et al. 2018

Arq. Gastroenterol.

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BACKGROUND: Hepatitis C virus (HCV) infection is a serious public health problem, that affects approximately 170 million people worldwide. Chronic HCV infection is associated with hepatic insulin resistance and an increased risk of diabetes HCV-infected patients has been well documented. OBJECTIVE: To assess the homeostasis model assessment of insulin resistance (HOMA-IR) index in patients treated with direct acting antiviral (DAAs) medication in the sustained virological response (SVR), categorized by the presence or absence of cirrhosis. METHODS: A prospective study was conducted. Data were collected at the beginning of treatment (t-base) and in the twelfth week after the completion of treatment (t-SVR12). The inclusion criteria were presence of: HCV infection (RNA-HCV positive), age ≥18 years, completion of DAAs’ therapy, and presence of diabetes with use of oral hypoglycemic agents. All samples were collected during the study period. The exclusion criteria were: presence of HBV/HIV co-infection, hepatocellular carcinoma at baseline, diabetic patients taking insulin and transplanted patients (liver/kidney). Fibrosis was assessed by hepatic elastography or biopsy (METAVIR). Cirrhosis was determined by clinical results or imaging. HOMA-IR was calculated as fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5) The patients were divided into two groups: the general study population (all patients, including the diabetic patients) and the special population (patients with normal values of HOMA-IR, which is >2.5, and without diabetes). The delta HOMA-IR value was calculated as: HOMA-IR at t-base - HOMA-IR at t-SVR12. For the descriptive statistical analysis, the paired t-test and generalized linear model assuming the log binding function were performed. A P value of < 0.05 was considered significant. RESULTS: We included 150 patients, and 75 were cirrhotic. The mean age was 55.3±9.97 and body mass index was 27.4±5.18. Twenty-two (14.67%) were diabetic patients using oral hypoglycemic agents, and 17 (11%) were cirrhotic. In the general study population, the mean glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. Delta HOMA-IR was negative at t-SVR12, but there was no significant difference. Excluding diabetic patients and those with normal HOMA-IR values (<2.5), mean glucose, insulin and HOMA-IR decreased at t-SVR12. Delta HOMA-IR decreased significantly at t-SVR12 (P: 0.02). CONCLUSION: In the general population, glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. In the special population, glucose, insulin, HOMA-IR and Delta HOMA-IR decreased at t-SVR12.

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

Cited by 23 publications

References 45 publications

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian Patients

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian Patients

Hepatitis C genotype 4: The past, present, and future

Insulin Resistance Reduction After Sustained Virological Response With Direct Acting Antiviral:not Every Population Improves

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