Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.
ABSTRACT We evaluated the effect of insulin resistance and viral factors on sustained virological response in patients with chronic hepatitis C treated with peginterferon plus ribavirin.
Patients (n=159; 94 men; age, 41.7 +/- 11.1 years) with chronic hepatitis C (genotype 1, n=113; non-1 genotype, n=46) received treatment with interferon plus ribavirin. Serum levels of leptin and insulin were measured, and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index were calculated.
A sustained virological response was associated with lower age, insulin resistance index, body mass index, and gamma-glutamyltranspeptidase and serum leptin levels. There was no association with viral load, sex, type of interferon, or cholesterol levels. A sustained virological response was achieved in 43.4% (46/113) of genotype 1 and 89% (32/36) of genotype 2 and 3 (P=.0001) patients. Necroinflammatory activity and steatosis were not associated with the sustained virological response rate. Multivariate regression analysis indicated that the independent variables related to sustained virological response were genotype (odds ratio, 3.57; 95% confidence interval, 1.49-8.3; P=.001), insulin resistance index (odds ratio, 1.82; 95% confidence interval, 1.08-3.06; P=.012), and fibrosis (odds ratio, 1.36; 95% confidence interval, 1.01-1.84; P=.029). A sustained virological response in patients with genotype 1 and insulin resistance (HOMA-IR > 2) occurred in 23 of 70 (32.8%; 95% confidence interval, 21.9%-43.9%) patients, vs. 26 of 43 (60.5%; 95% confidence interval, 45.9%-75.1%) genotype 1 patients without insulin resistance (P=.007; odds ratio, 3.12, 95% confidence interval, 1.42-6.89).
Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.
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ABSTRACT: Hepatitis C virus (HCV) is considered as a foremost cause affecting numerous human liver-related disorders. An effective immuno-prophylactic measure (like stable vaccine) is still unavailable for HCV. We perform an in silico analysis of nonstructural protein 5B (NS5B) based CD4 and CD8 epitopes that might be implicated in improvement of treatment strategies for efficient vaccine development programs against HCV. Here, we report on effective utilization of knowledge obtained from multiple sequence alignment and phylogenetic analysis for investigation and evaluation of candidate epitopes that have enormous potential to be used in formulating proficient vaccine, embracing multiple strains prevalent among major geographical locations. Mutational variability data discussed herein focus on discriminating the region under active evolutionary pressure from those having lower mutational potential in existing experimentally verified epitopes, thus, providing a concrete framework for designing an effective peptide- based vaccine against HCV. Additionally, we measured entropy distribution in NS5B residues and pinpoint the positions in epitopes that are more susceptible to mutations and, thus, account for virus strategy to evade the host immune system. Findings from this study are expected to add more details on the sequence and structural aspects of NS5B protein, ultimately facilitating our understanding about the pathophysiology of HCV and assisting advance studies on the function of NS5B antigen on the epitope level. We also report on the mutational crosstalk between functionally important coevolving residues, using correlated mutation analysis, and identify networks of coupled mutations that represent pathways of allosteric communication inside and among NS5B thumb, finger, and palm domains.Journal of Molecular Recognition 02/2015; · 2.34 Impact Factor
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ABSTRACT: Unhealthy food intake, specifically fructose, has been associated to metabolic alterations and to the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C(G1CHC), we tested the association of fructose intake with the severity of liver histology. Anthropometric and metabolic factors, including waist circumference(WC), waist-to-hip ratio(WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. All biopsies were scored by an experienced pathologist for staging and grading(Scheuer classification), and graded for steatosis, which was considered moderate-severe if ⩾20%. Features of nonalcoholic steatohepatitis(NASH) in CHC were also assessed(Bedossa classification). Mean daily intake of total, industrial and fruit fructose was 18.0 ± 8.7 g, 6.0 ± 4.7 g, and 11.9 ± 7.2 g, respectively. Intake of industrial, not fruit fructose, was independently associated with higher WHR(p=0.02) and hypercaloric diet(p<0.001). CHC patients with severe liver fibrosis(⩾F3) reported a significantly higher intake of total(20.8 ± 10.2 vs. 17.2 ± 8.1 g/day; p=0.04) and industrial fructose(7.8 ± 6.0 vs. 5.5 ± 4.2; p=0.01), not fruit fructose(12.9 ± 8.0 vs. 11.6 ± 7.0; p=0.34). Multivariate logistic regression analysis showed that older age(OR 1.048, 95%CI 1.004-1.094, p=0.03), severe necroinflammatory activity(OR 3.325, 95%CI 1.347-8.209, p=0.009), moderate-severe steatosis(OR 2.421, 95%CI 1.017-6.415, p=0.04), and industrial fructose intake(OR 1.147, 95%CI 1.047-1.257, p= 0.003) were independently linked to severe fibrosis. No association was found between fructose intake and liver necroinflammatory activity, steatosis, and the features of NASH. The daily intake of industrial, not fruit fructose is a risk factor for metabolic alterations and the severity of liver fibrosis in patients with G1CHC.Journal of Hepatology 08/2013; DOI:10.1016/j.jhep.2013.07.037 · 10.40 Impact Factor
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ABSTRACT: Background. HCV infection is associated with lipid disorders because this virus utilizes the host lipid metabolism to sustain its life cycle. Several studies have indicated that higher concentrations of serum cholesterol and LDL before treatment are important predictors of higher rates of sustained virological response (SVR). However, most of these studies involved patients infected with HCV genotype 1. Thus, we performed a multi-institutional clinical study to evaluate the impact of lipid profiles on SVR rates in patients with HCV genotype 2. Methods. A total of 100 chronic hepatitis C patients with HCV genotype 2 who received peg-IFN alfa-2b and ribavirin therapy were consecutively enrolled. The significance of age, sex, BMI, AST level, ALT level, WBC, hemoglobin, platelet count, gamma-glutamyltransferase, total cholesterol level (TC), LDL level, HCV RNA, and histological evaluation was examined for SVR using logistic regression analysis. Results. The 100 patients infected with HCV genotype 2 were divided into 2 groups, an SVR group and a non-SVR group. Characteristics of each group were subsequently compared. There was no significant difference in the level of HCV RNA, BMI, platelet, TG, or stage of fibrosis between the groups. However, there were significant differences in the levels of TC and LDL-C. In multivariate logistic regression analysis using baseline characteristics, high TC level was an independent and significant risk factor (relative risk 18.59, P = 0.015) for SVR. Conclusion. Baseline serum total cholesterol levels should be considered when assessing the likelihood of sustained treatment response following the course of peg-IFN and ribavirin therapy in patients with chronic HCV genotype 2 infection.Gastroenterology Research and Practice 11/2012; 2012:317580. DOI:10.1155/2012/317580 · 1.50 Impact Factor