A study of pharmacogenomics for therapeutic and prognostic guidance towards hepatitis C virus (HCV) for patients co-infected with HIV

• Main Authors: Yuen, King-tai, 袁敬弟
• Language: English
• Published: The University of Hong Kong (Pokfulam, Hong Kong) 2014
• Subjects: Hepatitis C - Treatment; Hepatitis C - Prognosis
• Online Access: http://hdl.handle.net/10722/193555

The cost effectiveness of using novel HCV treatment option, telaprevir and boceprevir, should depend on patients’ respond to conventional PEG-INFα and ribavirin therapy. The study of pharmacogenomics, interleukin-28B (IL-28B) polymorphisms, accompanied with the information of HCV genotypes are suggested to have the strongest predictive value of treatment outcomes and prognosis of disease in individuals infected with HCV who are undergoing conventional PEG-INFα and ribavirin therapy. It is extremely valuable in HCV/HIV co-infected patients as these groups of patients require a complex treatment regimen and demonstrate poor sustained viral response (SVR) rate. The development of a fast and promising IL-28B genotyping assay is urgently needed. A total of 47 blood samples randomly selected from HCV and HIV co-infected patients were used in this investigation. The aims of this study are to evaluate and compare the performance of newly developed IL-28B HybProbe real-time PCR assay using LightCycler® system against Sanger Sequencing method in determining IL-28B polymorphisms on rs12979860 and rs8099917 and to estimate the prevalence of IL-28B polymorphisms among HCV/HIV co-infected patients in Hong Kong. In addition, the genotypic distribution of HCV among the same patient group is identified by using in-house Sanger Sequencing method. It was found that the newly developed IL-28B real-time HybProbe assay resulted in 100% concordance with the traditionally used Sanger Sequencing method. The allele frequencies of C and T were 96% and 4% in rs12979860 and T and G were 97% and 3% in rs8099917 respectively. The CC and TT wild type are predominating in rs12979860 and rs8099917 with frequencies of 93.62% and 95.74% respectively. The most favorable compound genotype CC/TT with both homozygous wild types on both SNPs was the most predominant type with a high prevalence of 93.61%. Among all the samples, 50% samples were found to be HCV genotype 1, 41.18% were genotype 6 and 8.82% were genotype 3. A simple and efficient IL-28B real-time HybProbe assay was developed in this study and proved to show excellent performance on IL-28B genotyping although further optimization is suggested before it can be applied in the clinical setting. The favourable wild type genotypes of rs12979860 and rs8099917 accounted for the most predominant genotypes which is similar to other findings obtained from an Asian population. A comparatively high prevalence of HCV genotype 6 was found in the HCV/HIV co-infected group. Future study with the information of treatment outcomes (HCV viral load) can further evaluate the predictive value of IL-28B polymorphisms on SVR in different HCV genotypes. === published_or_final_version === Medical Sciences === Master === Master of Medical Sciences