ALT正常肝组织学轻度异常的慢性乙型肝炎患者经恩替卡韦抗病毒治疗的效果分析

Clinical effect of entecavir antiviral therapy in chronic hepatitis B patients with persistently normal alanine aminotransferase and mild liver histological abnormalities

目的对ALT正常肝组织学轻度异常的慢性乙型肝炎患者给予恩替卡韦治疗,探讨其抗病毒治疗的可行性。方法回顾性纳入2008年1月—2018年1月广西医科大学第一附属医院收治的HBV感染者181例。入组患者中基线ALT正常者归入研究组(n=61),基线ALT 1~2×ULN归入对照1组(n=62),基线ALT>2×ULN归入对照2组(n=58),经恩替卡韦抗病毒治疗至少1年,对比3组间临床疗效。采用寿命表法计算病毒学应答、HBeAg血清学应答和病毒学突破的累积进展率以及年发生率。计量资料多组间比较采用单因素方差分析,两两比较采用SNK法;计数资料多组间比较采用χ^(2)检验。结果181例中男性124例(68.5%),HBeAg阳性80例(44.2%),平均随访时间3.63年。3组病毒学应答年均发生率分别为74.37%、71.89%、74.21%(χ^(2)=2.91,P=0.371),3组病毒学突破年发生率分别为3.48%、5.17%、2.73%(χ^(2)=1.72,P=0.097)。3组HBeAg阳性患者年均阴转率分别为9.79%、37.16%、38.24%(χ^(2)=1.37,P=0.01),3组HBeAg年均转换率分别为9.10%、31.35%、36.74%(χ^(2)=5.61,P=0.021),研究组HBeAg年均阴转率及HBeAg年均转换率均低于对照1组和2组(P值均<0.05)。结论ALT正常的HBV感染者经恩替卡韦抗病毒治疗可以获得理想的病毒学应答,但免疫学应答有待提高。

Objective To investigate the clinical effect of entecavir antiviral therapy in chronic hepatitis B(CHB)patients with persistently normal alanine aminotransferase(PNALT)and mild liver histological abnormalities.Methods A retrospective analysis was performed for 181 patients with hepatitis B virus(HBV)infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from January 2008 to January 2018,and according to the baseline ALT level,they were divided into study group(61 patients with PNALT at baseline),control group 1[62 patients with an ALT level of(1-2)×upper limit of normal(ULN)],and control group 2(58 patients with an ALT level of>2×ULN).Entecavir antiviral therapy was given for at least 1 year,and clinical outcome was compared between the three groups.The life-table method was used to calculate the cumulative progression rates and annual incidence rates of virologic response,HBeAg serological response,and virologic breakthrough.An analysis of variance was used for comparison of continuous data between groups,and the SNK method was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between groups.Results Among the 181 patients enrolled in this study,there were 124 male patients(68.5%)and 80 patients with positive HBeAg(44.2%),with a mean follow-up time of 3.63 years.The three groups had a mean annual incidence rate of virologic response of 74.37%,71.89%,and 74.21%,respectively(χ^(2)=2.91,P=0.371)and an annual incidence rate of virologic breakthrough of 3.48%,5.17%,and 2.73%,respectively(χ^(2)=1.72,P=0.097).For the patients with positive HBeAg,the three groups had a mean annual clearance rate of 9.79%,37.16%,and 38.24%,respectively(χ^(2)=1.37,P=0.01)and a mean annual HBeAg seroconversion rate of 9.10%,31.35%,and 36.74%,respectively(χ^(2)=5.61,P=0.021);the study group had significantly lower mean annual clearance rate and seroconversion rate of HBeAg than the control groups 1 and 2(all P<0.05).Conclusion CHB patients with PNALT level can obtain satisfactory virologic response after entecavir antiviral therapy,while immunological response needs to be further improved.