利福昔明间断性及规律性给药预防肝性脑病及全因住院的对照研究

A controlled study of intermittent and regular administration of rifaximin for the prevention of hepatic encephalopathy and all-cause hospitalisation

摘要:

目的 探究临床中间断性使用利福昔明预防肝性脑病（hepatic encephalopathy， HE）复发的效果是否不劣于规律给药，利福昔明治疗后是否可降低患者因HE及全因住院的次数。方法 该研究为单中心前瞻性病例对照研究，将纳入的HE患者根据给药方案不同分为2组：间断给药组（利福昔明 400 mg tid，每周连续给药2 d）30例，其中最短给药时间4周，18例疗程3个月；规律给药组（利福昔明 400 mg tid，每天服用）25例，其中24例疗程3个月。比较2组患者在不同给药时间及给药前后因HE及全因住院的差异。结果 间断给药组与规律给药组相比，服药4周因HE及全因住院的概率差异均无统计学意义（P>0.05），服药3个月因HE及全因住院的次数差异均无统计学意义（P>0.05）。利福昔明给药后3个月与给药前3个月相比，因HE住院的平均住院次数减少［（0.52±0.86）次vs.（1.12±1.04）次，P=0.000］、全因住院的平均住院次数减少［（0.90±0.98）次vs.（1.60±1.08）次，P=0.000］。亚组分析发现，间断给药组及规律给药组在给药后3个月与给药前3个月相比较，因HE及全因住院的次数均减少，差异有统计学意义（P<0.05）。规律给药组患者大便含真菌的比例更高（4/7 vs. 1/10），但差异无统计学意义（P=0.101）。结论 间断使用利福昔明预防HE不劣于规律给药。间断或规律使用利福昔明，给药后均可减少患者因HE及全因住院的次数。临床中长期用药需警惕真菌感染风险。

Abstract:

Objective To compare whether intermittent use of rifaximin in clinical practice is no less effective than regular dosing in preventing recurrence of hepatic encephalopathy（HE） and whether rifaximin treatment before and after reduces the number of patients hospitalized for HE and all-cause illness.Methods The study was a single-center prospective case-control study in which enrolled HE patients were divided into 2 groups according to different dosing regimens，with a minimum duration of 4 weeks，including intermittent dosing group（rifaximin 400 mg tid， 2 days a week），with 30 patients，18 of whom were treated for 3 months；regular dosing group （rifaximin 400 mg tid， daily），with 25 patients，24 of whom were treated for 3 months. The differences in HE and all-cause hospitalization between the two groups were compared at different dosing times and before and after dosing.Results There was no statistically significant difference in the probability of hospitalization for HE and all-cause hospitalization in the intermittent dosing group compared to the regular dosing group at 4 weeks of dosing（P>0.05）， and there was either no statistically significant difference in the number of hospitalizations for HE and all-cause hospitalization at 3 months of dosing（P>0.05）. The mean times of hospitalizations for HE ［（0.52±0.86） vs. （1.12±1.04），P=0.000］ and all-cause hospitalizations［（0.90±0.98） vs. （1.60±1.08），P=0.000］ were reduced in the 3 months following rifaximin administration compared to the 3 months prior to administration. Subgroup analysis revealed a statistically significant difference in the number of hospitalizations for he and all-cause hospitalizations in both the intermittent and regular dosing groups at 3 months after dosing compared to 3 months before dosing（P<0.05）. Patients in the regular dosing group had a higher proportion of stools containing fungi（4/7 vs. 1/10），but the difference was not statistically significant（P=0.101）.Conclusion Intermittent use of rifaximin for the prevention of HE is non-inferior to regular use. Both intermittent and regular use of rifaximin can reduce the number of patients hospitalized for HE and all-cause hospitalization after dosing. Long-term use in the clinic requires caution about the risk of fungal infection.