Prospective Study
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World J Gastroenterol. Aug 14, 2014; 20(30): 10599-10605
Published online Aug 14, 2014. doi: 10.3748/wjg.v20.i30.10599
Early viral kinetics during hepatitis C virus genotype 6 treatment according to IL28B polymorphisms
Srunthron Akkarathamrongsin, Sunchai Payungporn, Vo Duy Thong, Kittiyod Poovorawan, Phisit Prapunwattana, Yong Poovorawan, Pisit Tangkijvanich
Srunthron Akkarathamrongsin, Vo Duy Thong, Yong Poovorawan, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Sunchai Payungporn, Phisit Prapunwattana, Pisit Tangkijvanich, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Kittiyod Poovorawan, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Author contributions: Akkarathamrongsin S, Payungporn S, Poovorawan Y and Tangkijvanich T conceived and designed the experiments; Akkarathamrongsin S and Thong VD performed the experiments; Akkarathamrongsin S, Poovorawan K and Tangkijvanich P analyzed the data; Akkarathamrongsin S and Tangkijvanich P wrote the paper; Prapunwattana P and Poovorawan Y revised the manuscript for important intellectual content.
Supported by Chulalongkorn University, No. RES560530155; Thailand Research Fund, No. BRG5580005, and No. DPG5480002; Joint Research Program between National Research Council of Thailand and Japan Society for the Promotion of Science, Centenary Academic Development Project, No. CU56-HR01; Ratchadapiseksompotch Fund (Faculty of Medicine), Integrated Innovation Academic Center and Postdoctoral of Ratchadaphiseksomphot Endowment Fund, Chulalongkorn University; Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, No. HR1155A
Correspondence to: Pisit Tangkijvanich, MD, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, 254 Phayathai Road, Bangkok 10330, Thailand. pisittkvn@yahoo.com
Telephone: +662-256-4482 Fax: +662-256-4482
Received: December 27, 2013
Revised: February 21, 2014
Accepted: May 28, 2014
Published online: August 14, 2014
Processing time: 234 Days and 5 Hours
Abstract

AIM: To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy.

METHODS: Sixty-five patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon and ribavirin (PEG-IFN/RBV) were included, of whom 15 (23.1%), 16 (24.6%) and 34 (52.3%) patients were infected with hepatitis C genotype 1 (HCV-1), genotype 3 (HCV-3) and genotype 6 (HCV-6), respectively. Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy. DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism (SNP) rs12979860 by polymerase chain reaction and direct sequencing.

RESULTS: During the first 4-wk of therapy, the mean viral decline for patients with HCV-6 (5.55 ± 1.82 log10IU/mL) was comparable to that of patients with HCV-3 (5.55 ± 1.82 log10IU/mL vs 5.86 ± 1.02 log10IU/mL, P = 0.44) and was significantly higher than patients with HCV-1 (5.55 ± 1.82 log10IU/mL vs 4.23 ± 1.99 log10IU/mL, P = 0.04). In the HCV-6 group, the first phase (days 0-2) viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes (2.46 ± 1.01 log10IU/mL/wk vs 1.70 ± 0.67 log10IU/mL, respectively, P = 0.045). A statistically insignificant decrease in the second-phase (days 7-28) decline was also found in patients with the CC genotype than those with the non-CC genotype, though not significantly different (1.24 ± 0.64 log10IU/mL/wk vs 0.80 ± 0.65 log10IU/mL/wk, respectively, P = 0.172). At baseline, the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response.

CONCLUSION: The IL28B genotype was linked to an impact on early viral kinetics in response to PEG-IFN/RBV therapy in HCV-6 infected patients.

Keywords: Hepatitis C virus; Genotype 6; Interleukin-28B; rs12979860; Early viral kinetics

Core tip: Assessment of the early viral kinetics of hepatitis C virus (HCV) RNA during pegylated interferon/ribavirin therapy correlates with a specific interleukin-28B polymorphism, potentially revealing insights about the virus-host dynamics. This is the first study to report that single nucleotide polymorphism rs12979860 is well correlated with early viral kinetics in the response to antiviral therapy and leads to a higher rate of rapid virological response in HCV-6 infected patients.