STAT4 variant predicts HBV IFNα response

By Shreeya Nanda, Senior medwireNews Reporter

Variation in the STAT4 gene is associated with response to interferon (IFN)α therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, suggests research published in Hepatology.

Specifically, patients with the GG genotype of the STAT4 rs7574865 genetic variant receive significantly less benefit from IFNα treatment than their counterparts harbouring the GT or TT genotype.

Therefore, genotyping HBeAg-positive chronic HBV patients for this variant could help to optimise IFN-α treatment in this patient population, say De-Ke Jiang (Fudan University, Shanghai, China) and fellow researchers.

They explain that STAT4 rs7574865 was selected for evaluation in this study as it has previously been linked with an increased risk of not only HBV, but also HBV-related liver cirrhosis and hepatocellular carcinoma.

After 48 weeks of therapy and 24 weeks of follow-up, the rate of sustained virological response (SVR) – defined as HBeAg seroconversion plus HBV DNA level <2000 copies/mL – was 30.4% for the 224 patients who received IFNα-2b therapy and a comparable 28.9% for the 242 patients treated with pegylated-IFNα-2a (PEG-IFNα-2a).

When patients were stratified by STAT4 rs7574865 genotype, the SVR rate was significantly lower for those with the GG than the GT or TT genotype in the IFNα-2b and the PEG-IFNα-2a groups, at 21.1% versus 37.2% (p=0.01) and 18.0% versus 41.2% (p=9.74x10^-5), respectively.

The difference between genotypes remained significant in the overall cohort, such that the SVR rate of 19.3% for GG carriers was approximately half that observed for participants with the GT or TT genotype, at 39.1% (p=4.15x10^-6).

And multivariate analysis showed that the rs7574865 GG genotype was a significant predictor of SVR in patients treated with IFNα-2b (odds ratio [OR]=0.45; p=0.01), those given PEG-IFNα-2a (OR=0.22; p=1.24x10^-4) and in the overall study population (OR=0.34; p=1.30x10^-5).

By contrast, clinical factors such as gender, age and baseline HBV levels “did not show a consistently significant association with response to IFNα treatment” in this study, leading the authors to suggest that “STAT4 rs7574865 is a stronger predictor for [chronic HBV] patients’ responses to IFNα therapy than any of the previously proposed clinical factors.”

They note, however, that their findings need to be confirmed in other populations, such as patients with HBeAg-negative HBV and those of other ethnic origins.

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