Song Guangjun, Rao Huiying, Feng Bo, Wei Lai
Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University, Beijing 100044, China.
Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University, Beijing 100044, China. Email:
Chin Med J (Engl). 2014;127(9):1691-5.
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-inducible SRC homology 2 domain protein (CISH) gene polymorphisms at -292 (rs414171) and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated.
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 2×10(4) IU/ml or the value of HBeAg did not decline substantially at week 76). CISH (rs414171) polymorphisms were also tested using the iPLEX system.
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).
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.
一些处于免疫活跃期的乙肝e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者可自发清除病毒并进入乙肝病毒（HBV）非活动携带者状态，提示预后良好。本研究调查了细胞因子诱导的Src同源2结构域蛋白（CISH）基因-292（rs414171）位点多态性与免疫活跃期HBeAg阳性CHB患者HBV自发清除之间的关联。
对70例免疫活跃期的HBeAg阳性CHB患者进行76周的随访，期间不进行抗病毒治疗。定期检测丙氨酸转氨酶、天冬氨酸转氨酶、HBV DNA、HBeAg和乙肝e抗体水平。在第76周时，27例患者被分为A组（HBV DNA水平低于2×10⁴IU/ml且第76周时HBeAg值下降至低于基线值的10%），43例患者被分为B组（HBV DNA水平高于2×10⁴IU/ml或第76周时HBeAg值未显著下降）。还使用iPLEX系统检测CISH（rs414171）多态性。
第12周时，B组的HBV DNA水平显著高于A组（A组：（6.87±1.40）log₁₀IU/ml；B组：（7.61±1.38）log₁₀IU/ml，P = 0.034），且第28周时B组的HBeAg值高于A组（P = 0.001）。随着时间推移，两组间HBV DNA和HBeAg值的差异增大。A组有16例患者和B组有11例患者为AA基因型。A组中基因型为AT或TT的有11例，B组中有31例（AA与AT和TT相比，比值比为4.10（95%置信区间：1.462 - 11.491），P = 0.006）。
-292（rs414171）位点的CISH基因多态性与免疫活跃期HBeAg阳性CHB患者的HBV清除相关，AA是产生此效应的有利基因型。
