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Association of TNF-? and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

ABSTRACT: AIM OF THE STUDY:To evaluate the role of potential genetic predictors -308G/A TNF-? and -403G/A CCL5 in treatment for HCV 1 genotype. MATERIAL AND METHODS:Treatment results of 130 patients with chronic hepatitis C 1 genotype according to different genotypes of IL28B, CCL5, and TNF-? were analysed using multiple logistic regression. RESULTS:IL28B genotypes CC/CT/TT were found in 27 (20.8%), 74 (56.9%), and 29 (22.3%) patients. Genotypes GG/GA/AA of -308G/A TNF-? were revealed in 98 (75.4%), 30 (23.1%), and 2 (1.5%) patients. Genotypes GG/GA/AA of -403G/A CCL5 were revealed in 86 (66.2%), 39 (30%), and 5 (3.8%) patients, respectively. The previously known effect of IL28B was observed. IL28B TT genotype decreased end of treatment response (EOTR) rates by a factor of 29.0 (95% CI: 6.4-183). The combination of CCL5 GG and IL28B CT genotypes increased the risk of failure to achieve EOTR by a factor of 28.5 (95% CI: 7.2-160). Genotypes GA and AA of TNF-? (-308) G/A SNP increased the risk of relapse in patients who achieved EOTR (OR = 9.4; 95% CI: 2.4-48). CONCLUSIONS:Practitioners may benefit from using these predictors when considering indications for the antiviral therapy and deciding on the treatment regimen.

SUBMITTER: Danilau D

PROVIDER: S-EPMC5497450 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Association of TNF-α and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

Danilau Dzmitry D Litvinchuk Dzmitry D Solovey Nikita N Krasko Olga O Karpov Igor I

Clinical and experimental hepatology 20170120 1

<h4>Aim of the study</h4>To evaluate the role of potential genetic predictors -308G/A TNF-α and -403G/A CCL5 in treatment for HCV 1 genotype.<h4>Material and methods</h4>Treatment results of 130 patients with chronic hepatitis C 1 genotype according to different genotypes of IL28B, CCL5, and TNF-α were analysed using multiple logistic regression.<h4>Results</h4>IL28B genotypes CC/CT/TT were found in 27 (20.8%), 74 (56.9%), and 29 (22.3%) patients. Genotypes GG/GA/AA of -308G/A TNF-α were reveale ...[more]

PMID: 28856285

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Project description:BACKGROUND:Abnormal serum lipid profiles have been noted in patients with chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b infection who have an unfavorable response to pegylated interferon (peg-IFN) plus ribavirin (RBV) combination therapy. However, after the discovery of single nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent predictive factors affecting the response to peg-IFN plus RBV, lipid factors are thought to be confounding factors. OBJECTIVES:To re-examine the significance of lipoprotein profiles on virological response to peg-IFN plus RBV combination therapy in patients with chronic HCV G1b infection, we examined cholesterol and triglyceride concentrations in each lipoprotein fraction separated by high performance liquid chromatography. PATIENTS AND METHODS:Lipoprotein profiles were examined using fasting sera from 108 patients infected with HCV G1b who had chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles and clinical data, including IL28B genotype and amino acid substitution at aa70 of HCV G1b, were compared between patients with a sustained virological response (SVR) and non-SVR or a non-virological response (NVR) and virological responses other than NVR (non-NVR). In addition, significant predictive factors independently associated with virological response to peg-IFN?-2b plus RBV were determined by logistic regression analysis. RESULTS:An increased ratio of cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917 (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In contrast, lipid factors were not elucidated as independent predictive factors for NVR. CONCLUSIONS:Examination of the fasting lipid profile has clinical importance in predicting the efficacy of peg-IFN-?-2b plus RBV combination therapy for patients with HCV G1b even after the discovery of the IL28 genotype as a potent predictive factor.

Dataset Information

Association of TNF-? and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

Publications

Association of TNF-α and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

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