Meta-analysis: Insulin resistance and sustained virological response in hepatitis C

Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
Alimentary Pharmacology & Therapeutics (Impact Factor: 5.73). 05/2011; 34(3):297-305. DOI: 10.1111/j.1365-2036.2011.04716.x
Source: PubMed


A higher baseline homeostasis model assessment of insulin resistance (HOMA-IR) score has sometimes predicted a poorer sustained virological response (SVR) rate to peginterferon/ribavirin therapy in treatment-naïve chronic hepatitis C patients.
To perform a meta-analysis to evaluate the impact of HOMA-IR on SVR in hepatitis C.
Relevant studies were identified by searching Medline and EMBASE. We identified 17 publications that addressed the influence of insulin resistance on SVR. The random effect model of Der Simonian and Laird method were used for heterogeneous studies using the Meta-Disc software 1.4, Madrid, Spain.
Normal insulin sensitivity was associated with a higher rate of SVR [odds ratio (OR) 2.86 (95%CI: 1.97-4.16)] in comparison with insulin resistance. Moreover, in separate analysis by genotype selecting studies that used HOMA-IR > 2 as cut-off defining insulin resistance, SVR was higher in patients with HOMA-IR < 2 in all genotypes: HCV-1 [OR: 2.16 (95%CI: 1.51-3.08)], HCV-2&3 [OR: 3.06 (95%CI: 1.06-8.82)] and HCV-4 [OR: 6.65(95%CI: 2.51-17.61)]. Studies reporting no association between HOMA and SVR included easy-to-cure cohorts, analysed variables strongly related with insulin resistance like body mass index, steatosis, hyper γGT, age and fibrosis and reported differences in handling and interpretation of HOMA-IR.
Elevated HOMA-IR was associated with a lower cure rate of patients with hepatitis C treated with Peg-IFN-α/ribavirin irrespective of genotype, and the more difficult-to-treat cohort, the better the HOMA-IR prediction. HOMA-IR is, as a surrogate marker of insulin resistance, susceptible to some biases derived from both handling and interpretation.

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Available from: Mahmoud Khattabm, Jul 01, 2014
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    • "A recent meta-analysis indicated that insulin resistance reduces the antiviral effect of IFN-based therapy, regardless of HCV genotype [43, 44]. Therefore, before starting antiviral therapy, it is better to improve some metabolic disorders including obesity and insulin resistance by diet therapy and exercise therapy. "
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    ABSTRACT: The dietary intake of patients with nonalcoholic fatty liver disease (NAFLD) is generally characterized by high levels of carbohydrate, fat, and/or cholesterol, and these dietary patterns influence hepatic lipid metabolism in the patients. Therefore, careful investigation of dietary habits could lead to better nutrition therapy in NAFLD patients. The main treatment for chronic hepatitis C (CHC) is interferon-based antiviral therapy, which often causes a decrease in appetite and energy intake; hence, nutritional support is also required during therapy to prevent undernourishment, treatment interruption, and a reduction in quality of life. Moreover, addition of some nutrients that act to suppress viral proliferation is recommended. As a substitutive treatment, low-iron diet therapy, which is relatively safe and effective for preventing hepatocellular carcinoma, is also recommended for CHC patients. Some patients with liver cirrhosis (LC) have decreased dietary energy and protein intake, while the number of LC patients with overeating and obesity is increasing, indicating that the nutritional state of LC patients has a broad spectrum. Therefore, nutrition therapy for LC patients should be planned on an assessment of their complications, nutritional state, and dietary intake. Late evening snacks, branched-chain amino acids, zinc, and probiotics are considered for effective nutritional utilization.
    Full-text · Article · Nov 2012 · Gastroenterology Research and Practice
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    • "This is an important finding since some studies have shown that the largest proportion of cellular infiltrate found in a liver with chronic hepatitis C is TH1 cells, such as IL-1b, IL-2, IL-6, IL-8, TNF-α and IFN [26]. On the other hand, a recent meta-analysis has demonstrated that sustained virological response is lower in patients with higher HOMA (>2) [27]. HCV-induced insulin resistance is considered to be more peripheral than hepatic shown by Milner et al. [28] in 29 nonobese infected patients. "
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    ABSTRACT: Aims. To determine lymphocyte IRS (IRS1 cells) in HCV patients, correlating it to liver IRS (IRS 1liver) and HOMA-IR. This study tested the hypothesis that IRS1 cells expression can be used as insulin resistance (IR) marker in HCV-infected patients. IRS1 cells were not studied before in HCV infection. Materials and Methods. HCV chronically infected patients, naïve, nonobese, noncirrhotic, and nondiabetic were prospectively included and compared to controls (blood donors). Blood was taken, and leukocytes were separated. IRS1 was determined by real-time PCR. Liver tissue was obtained from transplant donors as controls. Results. 41 HCV-positive patients were included, 26 males (60.5%); mean age of 45 (±7.9); 33 (80.5%) from genotype 1. 6 out of 12 controls were males (50%); mean age was 26.7 (±3.2). There was expression of IRS1 in leukocytes. The median IRS1 cells (HCV) were 0.061 (0.004 to 0.469); the median IRS 1liver (HCV) was 0.0003 (0.00002 to 0.0186)-lower than in controls (resp., P = 0.005 and P = 0.018). HOMA-IR had an inverse correlation with IRS 1liver (P = 0.04). There was no correlation between IRS1 liver and IRS1 cells (P = 0.930). Conclusions. There was expression of IRS1 in leukocytes. IRS1 cells and IRS1 liver were lower in HCV patients than in controls.
    Full-text · Article · Jul 2012
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    • "Hepatic steatosis and insulin resistance are negative predictors for sustained virological response (SVR) in patients with CH-C treated with peg-IFNα plus ribavirin combination therapy [53, 54]. In recent meta-analyses, HOMA-IR, a marker of insulin resistance, is negatively correlated with SVR, irrespective of viral genotype [55, 56]. Therefore, lifestyle modifications, such as weight reduction by exercise and nutritional management, are recommended to enhance the effects of antiviral treatments. "
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    ABSTRACT: It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C.
    Full-text · Article · Jun 2012
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