恩替卡韦对慢性乙型肝炎外周血Th9细胞动态变化的影响研究

The effect of entecavir on the dynamic changes of peripheral blood Th9 cell population in patients with chronic hepatitis B and its clinical significance

目的观察恩替卡韦对慢性乙型肝炎(chronic hepatitis B,CHB)外周血辅助性T淋巴细胞9(Th9)细胞动态变化的影响。方法回顾性分析2014年1~3月杭州市红十字会医院接受恩替卡韦抗病毒治疗(0.5 mg/d)的乙型肝炎e抗原(HBeAg)阳性CHB患者30例,根据丙氨酸氨基转移酶(alanine transaminase,ALT)水平分为2×ULN<ALT≤4×ULN(8例),4×ULN<ALT≤6×ULN(13例),ALT>6×ULN(9例)三组,分别检测Th9细胞频数,同时选择健康志愿者30名作为健康对照组。在治疗前及治疗12周、24周、36周时,分别检测Th9细胞频数,乙型肝炎病毒(hepatitis B virus,HBV)标志ALT值及HBV-DNA。结果CHB患者Th9细胞频数高于健康对照组,差异有统计学意义(t=4.96,P<0.05)。随着炎性反应程度的加重,Th9细胞频数逐渐升高,三组比较差异有统计学意义(F=27.21,P<0.05)。恩替卡韦抗病毒治疗12周、24周、36周后,Th9细胞频数分别为(1.41±0.54,1.12±0.50,0.82±0.42)%,呈逐步下降趋势,且与治疗前比较差异均有统计学意义(t=8.55,14.37,16.33,P<0.05);治疗12周后30例患者中ALT恢复正常11例(36.67%),HBV-DNA转阴19例(63.33%),Th9频数较治疗前下降但均未恢复至正常水平;24周后ALT恢复正常26例(86.67%),HBV-DNA全部转阴30例,Th9频数恢复至正常水平5例;36周后全部恢复正常30例,Th9频数均恢复至正常水平。治疗期间未发现HBsAg转阴,治疗36周后出现HBeAg血清学转换5例(16.67%),其Th9频数于24周时恢复至正常水平。结论Th9与乙肝病毒感染炎性反应密切相关,恩替卡韦抗病毒治疗能降低CHB患者外周血Th9频数,治疗早期Th9频数下降的患者HBeAg血清学转换率更高。

Objective To observe the effect of entecavir on the dynamic changes of peripheral blood Th9 cell population in patients with chronic hepatitis B(CHB)and to discuss its clinical significance.Methods 30 CHB cases with positive HBeAg and treated with entecavir in Hangzhou Red Cross Hospital from January to march,2014 were enrolled into our study.Based on their serum ALT levels,they were divided into low(2×ULN<ALT≤4×ULN,8 cases),medium(4×ULN<ALT≤6×ULN,13 cases)and high(ALT>6×ULN,9 cases)ALT groups.Meanwhile,30 volunteers were selected as healthy controls.Blood samples were collected before treatment as well as at 12,24 and 36 weeks after treatment for the determination of Th9 cell count,HBV biomarkers,serum ALT levels and HBV-DNA.Results The overall Th9 cell count was significantly higher in CHB patients than in healthy controls(t=4.96,P<0.05),and was the highest in patients with high ALT level(F=27.21,P<0.05).The Th9 cell population gradually decreased in CHB patients with12,24 and 36 weeks of entecavir treatment(1.41±0.54%,1.12±0.50%,0.82±0.42%,P<0.05).At 12 weeks of treatment,the serum levels of ALT in 11 patients(36.67%)went back to normal and 19 patients(63.33%)became negative for HBV-DNA.At weeks of 24 after treatment,the cell counts of Th9 in 5 cases were in the normal range and all 30 cases were negative for HBV-DNA.While by the week of 36,all 30 patients had normal level of ALT and normal cell counts of Th9.During the treatment,no case was found to become HBsAg negative.The sero-conversion of HBeAg occurred in 5 cases(16.67%)after 36 weeks of treatment,and their Th9 cell counts went back to normal at 24 weeks.Conclusions The Th9 cell population in the peripheral blood of CHB patients is elevated and closely correlated with hepatic inflammation.Entecavir treatment may reduce the number of Th9 cells and the rate of HBeAg sero-conversion increases in patients with early Th9 cell drop after treatment.