Predictive Value of IL28B Gene Polymorphisms on Retreatment Outcome of Chronic Hepatitis C

Chronic hepatitis C infection (CHC) is a leading cause of decompensated cirrhosis and hepatocellular carcinoma. Forty-eight-weekly pegylated interferon (PEG-IFN)plus weight-based ribavirin (RBV) has been the current standard of care (SOC) for CHC genotype 1 in Asia-Pacific region and can only achieve an overall sustained virologic response (SVR) of 60-70%.The single nucleotide polymorphism (SNP) near the interleukin-28B (IL28B) is associated with spontaneous or treatment-induced viral clearance in untreated patients. It remains unclear for the efficacy of current SOC and influence of IL28B SNP in re-treating Taiwan CHC relapsers.
In Taiwan, since November 2009, we consecutively enrolled 103 CHC relapsers into this study. We evaluated the IL28B SNPs, virologic kinetics, and biochemical responses of CHC patients receiving 48-weekPEG-IFN plus RBV. Only 75 CHC genotype 1 relapsers (73%) were included for analysis. The overall viral kinetics was 37%,73% and 52% in rapid virologic response (RVR), end-of-treatment viral response (EOT-VR) and SVR respectively. Relapse rate was 29%.Patient with TT IL28B had higher rate of RVR (P=0.0002), EOT-VR (P=0.0001) and SVR (P<0.0001) in comparison with GT. Achieving a RVR ensured a higher SVR rate (P<0.0001) and lower relapse rate (P=0.0034). In combination of week 4 viral negativity (i.e. RVR) with IL28B genotype, a high positive and negative predictive value of SVR achieved as equally good as week 12 viral negativity.
About half of the CHC relapsers in Taiwan would achieve SVR under current SOC. IL28B SNP would influence the on-treatment viral kinetics, SVR and relapse rate in retreatment. There might be the individualized therapy according to the IL28B SNP and RVR in the future, especially the early stopping rule.