菌群移植3932例治疗效果和并发症的5年随访分析

A five-year follow-up analysis of efficacy and complications of 3 932 cases of fecal microbiota transplantation treatment

目的观察菌群移植的长期疗效和并发症的发生率,不同移植途径和疗程对菌群移植疗效的影响。方法前瞻性收集2012年4月至2020年4月自愿接受菌群移植治疗的3932例(南京军区南京总医院804例,同济大学附属第十人民医院3128例)患者的资料,观察所有患者在菌群移植第1疗程结束后第1、12、24、36、48和60个月的随访率、有效率,以及5年并发症发生情况。根据首次移植途径的不同,将3932例患者分为鼻肠管组(2604例)、胶囊组(873例)、结肠镜组(268例)和灌肠组(187例),观察4组不同移植途径患者菌群移植1个月后的有效率和并发症发生情况。同时将菌群移植≤4疗程的1813例患者分为1疗程组(369例)、2疗程组(568例)、3疗程组(497例)和4疗程组(379例),观察4组不同疗程患者治疗结束后6个月的有效率。统计学方法采用卡方检验。结果3932例患者在菌群移植第1疗程结束后第1、12、24、36、48和60个月的随访率分别为93.67%(3683/3932)、82.30%(2307/2803)、82.17%(1825/2221)、62.41%(978/1567)、59.85%(559/934)和60.84%(289/475),1、12、24、36、48和60个月的总有效率分别为67.23%(2476/3683)、64.20%(1481/2307)、59.29%(1082/1825)、59.71%(584/978)、55.81%(312/559)和59.17%(171/289),菌群移植期间各类并发症总发生率为34.49%(1356/3932),随访期间各并发症总发生率为4.22%(166/3932),均无消化道穿孔、多重耐药菌感染、器官功能衰竭和死亡等严重并发症事件发生。鼻空肠管组、胶囊组、结肠镜组和灌肠组患者菌群移植后1个月的有效率分别为67.18%(1668/2483)、68.63%(549/800)、67.23%(158/235)、61.21%(101/165),4组间的差异无统计学意义(P>0.05);其中鼻空肠管组、胶囊组和结肠镜组中慢性便秘患者的有效率均高于灌肠组[67.82%(1043/1538)、67.98%(138/203)和62.96%(17/27)比26.67%(8/30)],差异均有统计学意义(χ2=22.55、19.07、7.60,P均<0.01)。鼻空肠管组、胶囊组、结肠镜组和灌肠组患者菌群移植期间的并发症总发生率分别为35.22%(917/2604)、30.24%(264/873)、42.54%(114/268)、32.62%(61/187),4组间差异有统计学意义(χ2=18.84,P<0.01);其中鼻空肠管组、胶囊组、结肠镜组和灌肠组患者的腹泻[分别为4.49%(117/2604)、4.58%(40/873)、7.83%(21/268)和5.35%(10/187)]、咽喉部疼痛[分别为5.30%(138/2604)、0.69%(6/873)、2.99%(8/268)和1.07%(2/187)]、消化道出血[分别为0、0、1.87%(5/268)和0.53%(1/187)]和肠源性感染发生率[分别为0、0、1.49%(4/268)和0.53%(1/187)]比较,差异均有统计学意义(χ2=8.24、39.24、63.13、49.68,P均<0.05)。1疗程组、2疗程组、3疗程组和4疗程组患者治疗结束后6个月的有效率分别为63.94%(211/330)、61.93%(301/486)、65.75%(286/435)和72.54%(251/346),不同疗程组间差异有统计学意义(χ2=10.70,P=0.01);其中4疗程组患者的有效率高于1疗程组、2疗程组和3疗程组,差异均有统计学意义(χ2=5.78、10.18、4.14,P均<0.05)。4疗程组患者的慢性便秘和孤独症有效率均高于1疗程组和2疗程组[72.73%(136/187)比55.47%(71/128)和58.71%(155/264),72.73%(40/55)比6/15和47.83%(11/23)],3疗程组患者的孤独症有效率高于1疗程组[69.05%(29/42)比6/15],差异均有统计学意义(χ2=10.05、9.39、5.60、4.44、3.94,P均<0.05)。结论菌群移植治疗肠道菌群紊乱相关的肠道疾病和合并肠道功能异常的肠道外疾病长期疗效确切,无严重不良事件发生。菌群移植疗效与移植途径和疗程有关,菌群移植并发症发生率与移植途径有关。针对不同疾病应制定不同的移植途径和疗程。

Objective To observe the long-term efficacy and complication rate of fecal microbiota transplantation(FMT)and the effects of different ways of transplantation and treatment courses on the efficacy of FMT.Methods From April 2012 to April 2020,the data of 3932 patients(804 cases of Nanjing General Hospital of Nanjing Military Command and 3128 cases of Tenth People′s Hospital of Tongji University)who voluntarily received FMT treatment were prospectively collected.After the first course of transplantation,the follow-up rate and efficacy and complications in 5 years were observed at the 1st,12th,24th,36th,48th and 60th month.According to the different ways of the first transplantation,3932 patients were divided into nasointestinal tube group(2604 cases),capsule group(873 cases),colonoscopy group(268 cases)and enema group(187 cases).One month after transplantation,the effective rate and complication were observed.At the same time,the 1813 patients with FMT less than four courses were divided into 1 treatment course group(369 cases),2 treatment courses group(568 cases),3 treatment courses group(497 cases)and 4 treatment courses group(379 cases).The effective rates of patients in four groups with different treatment courses were observed 6 months after finishing the treatment.Chi square test was used for statistical analysis.Results Among 3932 patients,the follow-up rates at 1st,12th,24th,36th,48th and 60th month after the first course of FMT were 93.67%(3683/3932),82.30%(2307/2803),82.17%(1825/2221),62.41%(978/1567),59.85%(559/934)and 60.84%(289/475),respectively.The total effective rates at 1st,12th,24th,36th,48th and 60th month were 67.23%(2476/3683),64.20%(1481/2307),59.29%(1082/1825),59.71%(584/978),55.81%(312/559)and 59.17%(171/289),respectively.During FMT period,the total incidence of different complications was 34.49%(1356/3932).During follow-up period,the total rate of complication was 4.22%(166/3932).There were no serious adverse events such as gastrointestinal perforation,multi-drug resistant bacterial infection,organ failure and death.One month after FMT,the effective rates of nasojejunal tube group,capsule group,colonoscopy group,and enema group were 67.18%(1668/2483),68.63%(549/800),67.23%(158/235),61.21%(101/165),respectively.There was no significant difference among the four groups(P>0.05).The effective rates of patients with chronic constipation in nasal jejunal tube group,capsule group and colonoscopy group were all higher than that of enema group(67.82%,1043/1538;67.98%,138/203 and 62.96%,17/27 vs.26.67%,8/30),and the differences were statistically significant(χ2=22.55,19.07 and 7.60,all P<0.01).During the period of FMT,the total incidence of complications of nasojejunal tube group,capsule group,colonoscopy group and enema group were 35.22%(917/2604),30.24%(264/873),42.54%(114/268)and 32.62%(61/187),respectively.The difference was statistically significant among four groups(χ2=18.84,P<0.01).Among nasojejunal tube group,capsule group,colonoscopy group and enema group,there were significant differences in the incidence of diarrhea(4.49%,117/2604;4.58%,40/873;7.83%,21/268 and 5.35%,10/187,respectively),throat pain(5.30%,138/2604;0.69%,6/873;2.99%,8/268 and 1.07%,2/187,respectively),gastrointestinal bleeding(0;0;1.87%,5/268 and 0.53%,1/187,respectively)and enterogenous infection(0;0;1.49%,4/268 and 0.53%,1/187,respectively)(χ2=8.24,39.24,63.13 and 49.68,all P<0.05).At the 6th month after treatment,the effective rates of 1 treatment course group,2 treatment courses group,3 treatment courses group and 4 treatment courses group were 63.94%(211/330),61.93%(301/486),65.75%(286/435)and 72.54%(251/346),respectively.There were statistically significant differences among groups with different treatment courses(χ2=10.70,P=0.01).The effective rate of the four treatment courses group was significantly higher than those of the one treatment course group,two treatment courses group and three treatment courses group,and the differences were statistically significant(χ2=5.78,10.18 and 4.14,all P<0.05).The effective rates of in chronic constipation and autism in 4 treatment courses group were significantly higher than those in 1 treatment course group and 2 treatment courses group(72.73%(136/187)vs.55.47%(71/128)and 58.71%(155/264),72.73%(40/55)vs.6/15 and 47.83%(11/23)),the effective rate of autism in 3 treatment courses group was higher than that in 1 treatment course group(69.05%(29/42)vs.6/15),and the differences were statistically significant(χ2=10.05,9.39,5.60,4.44 and 3.94,all P<0.05).Conclusions The long-time efficacy of FMT is definite in the treatment of intestinal flora derangement related intestinal diseases and extraintestinal diseases complicated with intestinal disfunction and there are no serious adverse events.The efficacy of FMT is related to the way of transplantation and treatment.The incidence of complications of FMT is related to the way of transplantation.Different ways of transplantation and treatment courses should be formulated for different diseases.