Background: Recent genome wide association studies (GWAS) have shown important roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28 (IL28B) gene in spontaneous and drug-induced Clearance of hepatitis C virus (HCV) in genotype 1 HCV infection.Objectives: This meta-analysis was designed to determine the world-wide distribution patterns of IL28B genotypes and alleles, and to find possible linkages between IL28B and HCV genotypes.Patients and Methods: Manual and electronic databases were searched. Critical appraisal was performed. According to the results of heterogeneity tests, we used fix/random model for the analysis. The data concerning patients’ ethnicity and HCV genotypes were analyzed by using statistical analysis software.Results: A total of 255 articles were found. After article review and quality assessment, 50 studies, including 18662 patients and 1313 healthy subjects, were analyzed. Presence of HCV genotype 3 versus genotype 1 was significantly associated with a higher frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI: 1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV infected patients. Prevalence of rs12979860 TT genotype in the African-American genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)], and significantly different compared to all other ethnicities.Conclusions: There were significant linkages between HCV genotypes and IL28B genotypes/alleles. Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a better chance to clear HCV in the acute phase.

Background and Objectives: Viral Clearance studies are an essential part of a manufacturer's plan to ensure the safety of an injectable biologic product. In this way, Viral safety is a critical quality attribute for biologics such as monoclonal antibodies (Mabs). Evaluation of virus purification by downstream processes is a key component of risk mitigation. In this study, the capability of continuous monoclonal antibody purification steps was evaluated in the process of instant monoclonal antibody purification in different stages of purification, and the amount of reduction or inactivation of each step was determined. Materials and Methods: Four enveloped and non-enveloped Viral models VSV, Reovirus, EMCV, and HSV1 were used for spiking in selected samples in the designated tests, to have a comprehensive examination of the ability to clear the virus such as the type of genetic material, chemical resistance, and particle size. A TCID50 and qPCR methods were used to measure Viral reduction. Two cell lines, Vero (African green monkey kidney) and L929 (Mouse fibroblast) were used for 4 model viruses propagation. The steps that were evaluated included 4 steps monoclonal antibody purification,cation exchange chromatography, acidic pH treatment, affinity chromatography, and nanofiltration. Results: The nano-filter stage showed the highest Viral reduction and cation exchange chromatography showed the lowest reduction. The cumulative decrease using TCID50 is equal to 19. 27 [log10] for all steps and for the qPCR method is equal to 12. 47 [log10] in three steps of nano-filter, affinity chromatography, and ion exchange chromatography. Conclusion: The overall average reduction coefficient for all four model viruses is significantly high, which indicates the high capacity of the monoclonal antibody production process in inactivating and removing viruses leads to reducing the load of all four model viruses.

Background: Polymorphisms in the interferon l (INF l) genes on chromosome 19 have been associated with Clearance of hepatitis C virus (HCV) induced by interferon and ribavirin therapy however there is no such data available for Pakistani patients with HCV infection.Objectives: In this study, the effects of single nucleotide polymorphisms (SNPs) have been investigated in response to treatment with interferon-a and ribavirin in a cohort of 75 HCV genotype 3a patients.Patients and Methods: A total number of 50 SNPs from the Interferon l region on chromosome 19 were genotyped to investigate allelic associations with the treatment response in HCV type 3a patients. Thirteen SNPs were associated with HCV Clearance, with the most significant alleles being RS8109886 (Fisher's P=0.0001), RS8113007 (Fisher's P=0.0001) and RS12979860 (Fisher's P=0.0002).Results: These SNPs were found to be the most suitable SNPs for predicting treatment response in the present study. These findings support those reported previously. This could be used to improve HCV treatment strategies and suggest that Pakistani patients should be genotyped for the relevant SNPs to identify the patients who are more likely to respond to interferon and ribavirin therapy.Conclusions: This therapy is costly and can be accompanied by several adverse side-effects, hence pre-treatment prediction of patients who are most likely to benefit would have both economic and patient benefits in the long term.