抗结核药物诱导肝损伤后三种不同再次给药方案的比较研究

Comparison of safety among three different reintroduction regimens after development of anti-tuberculosis drug-induced hepatotoxicity

目的观察抗结核药物诱导肝损伤后三种不同再次给药方案的临床效果。方法临床纳入因抗结核药物诱导肝损伤患者135例,按数字法随机分配到A、B、C三组。A组于肝功能恢复正常后,在乙胺丁醇治疗的基础上予以异烟肼、利福平、吡嗪酰胺,按逐步增加药物种类的方法,B组在肝功能恢复正常后,在乙胺丁醇和左氧氟沙星治疗基础上予以异烟肼、利福平逐步增加药物剂量及种类的方法,C组于出现ATDH后予以乙胺丁醇、链霉素、左氧氟沙星替代治疗,当肝功能恢复正常后予以异烟肼、利福平逐步增加药物剂量及种类,于利福平、异烟肼治疗耐受后,撤除链霉素,观察比较不同治疗方案药物性肝损伤再发率及抗结核疗效。结果 A、B、C组药物性肝损伤再发率分别为22.22%、17.78%和4.44%。C组患者药物性肝损伤再发率明显低于A、B组,差异均有显著性(P<0.05)。A、B组再次肝损伤后分别有10例、8例患者接受C组治疗方案,均顺利完成治疗,无再次发生肝功能损伤。结论临床A组采用含有吡嗪酰胺的再次抗结核方案,容易导致再次肝损伤的发生。而采用不含有吡嗪酰胺,并且逐步提高异烟肼、利福平给药剂量的治疗方案,能够明显降低再次肝损伤的发生率,值得推广。

Objective To compare the safety of 3 different reintroduction regimens for patients with anti-tuberculosis drug-induced hepatotoxicity. Methods A total of 135 patients with anti-tuberculosis DIH were randomly divided into 3 groups. The group A received isoniazid,rifampicin,and pyrazinamide simultaneously at full dosage from day 1,the group B was given isoniazid,rifampicin,and pyrazinamide simultaneously with gradually increasing the dosage of the drugs,and the group C was given isoniazid and rifampicinby gradually increasing the number and dosage of the drugs on the basis of ethambutol,levofloxacin and streptomycin. In the group C,streptomycin was stopped when isoniazid and rifampicin were tolerated. Results The rate of recurrence of hepatotoxicity was 22. 2%,17. 8% and 4. 44% respectively in the groups A,B and C（ P〈0. 05）. There were 10 recurrence cases in the group A and 8 recurrence cases in the group B,who all received the same re-treatment protocol as the group C and cured.Conclusion The recurrence rate of hepatotoxicity in the re-treatment of tuberculosis is higher in the re-introduction of a full-dose regimen including pyrazinamide,which causes more hepatotoxicity than gradual re-introduction of a regimen without pyrazinamide.