Background Some hepatitis B extracellular antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in their immune active phase can clear the virus spontaneously and enter into an inactive hepatitis B virus (HBV) carrier state,indicating a benign prognosis.In this study,the association between cytokine-inducibie SRC homology 2 domain protein (C/SH) gene polymorphisms at-292 (rs414171) and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated.Methods Seventy HBeAg-positive CHB patients in the immune active phase were followed up for 76 weeks without antiviral therapy.The alanine transaminase,aspartate transaminase,HBV DNA,HBeAg and hepatitis B extracellular antibody levels were tested regularly.At week 76,27 patients were classified into group A (HBV DNA level below 2 104 IU/ml and the value of HBeAg declined below 10％ of the baseline at week 76),and 43 patients were classified into group B (HBV DNA level higher than 2×104 IU/ml or the value of HBeAg did not decline substantially at week 76).CISH (rs414171) polymorphisms were also tested using the iPLEX system.Results The HBV DNA levels at week 12 were significantly greater in group B compared with group A (group A:(6.87±1.40) log10IU/ml; group B:(7.61±1.38) log10IU/ml,P=0.034) and the HBeAg values were greater in group B at week 28 compared with group A (P=0.001).The differences in HBV DNA and HBeAg values increased between the groups over time.Sixteen patients in group A and 11 in group B were genotype AA.Those with genotype AT or TT included 11 in group A and 31 in group B (AA vs.AT and TT,odds ratio 4.10 (95％ confidence interval:1.462-11.491),P=0.006).Conclusion CISH gene polymorphisms at-292 (rs414171) are associated with HBV clearance in HBeAg-positive CHB patients in the immune active phase,and AA is a favorable genotype for this effect.