Abstract
Background and AimsRecently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography.MethodsSeven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping.ResultsCCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients.ConclusionThis study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.
Highlights
Hepatitis C virus (HCV) infects 170 million people worldwide [1] and is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma [2]
Several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in the 19q13 region, in close proximity to three genes (IL28A, IL28B, and IL29) encoding cytokines of the interferon-l family, predict spontaneous clearance of hepatitis C virus (HCV) infection [3,4] as well as sustained virological response (SVR) following pegylated-interferon and ribavirin therapy among patients infected with HCV genotype 1 [3,5,6,7]
Among HCV genotype 1 infected patients this translates into higher frequencies of achieving both rapid virological response (RVR) and SVR among carriers of the favorable SNP alleles [9,15], and concomitant assessment of pretreatment levels of systemic IP-10 augments the predictive value of IL28B genetic variants [17,18]
Summary
Hepatitis C virus (HCV) infects 170 million people worldwide [1] and is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma [2]. Several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in the 19q13 region, in close proximity to three genes (IL28A, IL28B, and IL29) encoding cytokines of the interferon-l (i.e. type III interferon) family, predict spontaneous clearance of HCV infection [3,4] as well as sustained virological response (SVR) following pegylated-interferon (peg-IFN) and ribavirin therapy among patients infected with HCV genotype 1 [3,5,6,7]. Several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography
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