摘要
目的探索糖皮质激素(以下简称激素)治疗乙型肝炎病毒(hepatitis B virus,HBV)相关性慢加急性(亚急性)肝衰竭(acute-on-chronic liver failure,ACLF)早期患者的疗效,探索伏立康唑预防HBV相关性ACLF并发肺部曲霉菌感染的作用及安全性。方法纳入2016年1月至2018年12月在南昌大学第一附属医院感染科治疗的232例HBV相关性ACLF患者,其中未使用激素组104例,单用激素组74例,激素联合伏立康唑(200 mg/d)组54例。观察期为4个月,比较3组患者基线肝功能、并发肺曲霉菌感染的发生率、观察期内存活率、其他并发症的发生率,观察伏立康唑的不良反应,探索最佳预防剂量。计量资料采用方差分析或秩和检验,计数资料采用卡方检验或Fisher确切概率法。结果3组间患者基线肝功能指标比较,差异均无统计学意义(均P>0.05)。单用激素组肺部曲霉菌感染率为22.97%(17/74),高于未使用激素组[5.77%(6/104)]和激素联合伏立康唑组[1.85%(1/54)],差异均有统计学意义(χ^2=11.373、9.843,均P<0.01)。HBV相关性ACLF合并肺曲霉菌病总病死率达79.2%(19/24)。未使用激素组生存率[37.50%(39/104)]与单用激素组存活率[39.19%(29/74)]之间比较差异无统计学意义(χ^2=0.052,P=0.819);而激素联合伏立康唑组存活率[66.67%(36/54)]高于其他2组,差异均有统计学意义(χ^2=12.126、9.431,均P<0.01)。随机监测激素联合伏立康唑组16例患者伏立康唑的血药浓度范围为0.82~5.38 mg/L,所有口服伏立康唑片剂患者均未见明显不良反应。结论激素治疗HBV相关性ACLF早期患者有效,伏立康唑能有效降低激素治疗时感染肺曲霉菌的发生率,从而提高HBV相关性ACLF患者的生存率;口服伏立康唑200 mg/d在患者中血药浓度稳定,不良反应少见,具有较好的安全性。
Objective To explore the efficacy of glucocorticoid(GC)therapy on hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF),and the effectiveness and safety of voriconazole(VCZ)in preventing pulmonary Aspergillus infection in HBV-ACLF patients treated with GC.Methods Two hundred and thirty-two patients with HBV-ACLF were enrolled from January 2016 to December 2018 in the First Affiliated Hospital of Nanchang University.They were divided into non-GC group(104 cases),GC group(74 cases),and GC+VCZ group(54 cases).The observation period was four months.The baseline liver function,the incidence of pulmonary Aspergillus infection,the survival rate during observation period,and the incidence of complications were compared among the three groups.The adverse reactions of VCZ were observed to identify the best dose for prevention.Quantitative data were analyzed by analysis of variance or rank sum test.Count data were analyzed by chi-square test or Fisher exact test.Results The baseline liver functions were not significantly different among the three groups(all P>0.05).The incidence of pulmonary Aspergillus infection in the GC group(22.97%(17/74))was both higher than that in the non-GC group(5.77%(6/104))and GC+VCZ group(1.85%(1/54)),the differences were both statistically signifrcant(χ^2=11.373 and 9.843,respectively,both P<0.01).The overall mortality rate of HBV-ACLF patients with pulmonary Aspergillus infection was 79.2%(19/24).The survival rate in non-GC group(37.5%(39/104))showed no statistical difference with that in GC group(39.19%(29/74),χ^2=0.052,P=0.819).The survival rate of GC+VCZ group(66.67%(36/54))was significantly higher than that in GC group and non-GC group(χ^2=12.126 and 9.431,respectively,both P<0.01).The blood concentrations of VCZ were randomly measured in 16 patients from the GC+VCZ group,and the range was 0.82-5.38 mg/L,with no evident adverse reactions.Conclusions The GC treatment is effective in HBV-ACLF patients in early stage.The VCZ treatment effectively reduces the incidence of pulmonary Aspergillus infection in HBV-ACLF patients receiving GC treatment and increases the survival rate.Oral VCZ(200 mg/d)treatment has a stable blood concentration in HBV-ACLF patients,with rare adverse reactions and good safety.
作者
余婷婷
张伦理
葛善飞
李小鹏
张文峰
Yu Tingting;Zhang Lunli;Ge Shanfei;Li Xiaopeng;Zhang Wenfeng(Department of Infectious Diseases,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China)
出处
《中华传染病杂志》
CAS
CSCD
2019年第9期534-539,共6页
Chinese Journal of Infectious Diseases
基金
江西省科技厅人才资助计划(20161BCD40015)
江西省教育课题(GJJ170043)。
