Wada M
Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Kekkaku. 1997 Oct;72(10):587-95.
Six-month short course regimen had been accepted all over the world since early 1980s. In Japan this short course regimen had not been accepted as a standard regimen for treatment of pulmonary tuberculosis until April 1996. The reason why this was not accepted is resumably due to hepatotoxicity of pyrazinamide. The situation around tuberculosis were changing in Japan especially in urban areas. Incidence of tuberculosis in younger generations is higher in urban areas than in rural areas. More effective and shorter course regimen were needed. Efficacy of pyrazinamide were briefly described first, then results of six-month regimen with pyrazinamide in Fukujuji Hospital since 1991 January were discussed. Pyrazinamide can kill tubercle bacilli in acidic environment. It works bacericidally during the early treatment phase. It can kill not only replicating bacilli but also semidormant ones. The results of many six-month regimens showed that only pyrazinamide containing regimens were acceptable for standard regimen in pulmonary tuberculosis with less than a few percent of relapse. Newly accepted standard chemotherapy included 2HRZ with or without S or E/4HRE, 6HRS or E/3HR, and 6HR. Among 429 tuberculosis patients treated at Fukujuji Hospital with pyrazinamide-containing regimens, the negative conversion rate after two months of chemotherapy was 95 percent and similar to those of Western, African and Asian tuberculosis trials. Six of 290 evaluable cases have relapsed. (relapse rate; 2%) Noticeably all relapsed cases were complicated with diabetes mellitus. The higher percent of patients, 8.2 had elevated serum transaminase levels 5 times of upper limit of normal level or more compared with that of patients without pyrazinamide, 6.6 percents, but this difference is not statistically significant. One patient whose pretreatment liver function was abnormal with unknown origin died from hetatoxicity of anti-tuberculous drugs. The risk factors of hepatotoxicity included HCV carrier, elderly more than 80 years old, but HB carrier, alcohol drinking and hepatic diseases were not risk factors. Less patients, 5.6% defaulted from regimen compared with that with 9-month regimen without pyrazinamide (8.6%), but this difference is not statistically significant. The efficacy of the regimen was 90.3% higher than that of 9-month regimen, 86.0% In summary, six-month regimen containing pyrazinamide is highly effective. The incidence and severity of hepatotoxicity must be further studied in Japan.
自20世纪80年代初以来，六个月短程疗法已在全球范围内被接受。在日本，直到1996年4月，这种短程疗法才被接受为治疗肺结核的标准疗法。未被接受的原因可能是吡嗪酰胺的肝毒性。日本尤其是城市地区的结核病情况正在发生变化。城市地区年轻一代的结核病发病率高于农村地区。需要更有效且疗程更短的疗法。首先简要描述了吡嗪酰胺的疗效，然后讨论了自1991年1月以来富士寿寺医院使用含吡嗪酰胺的六个月疗法的结果。吡嗪酰胺可在酸性环境中杀死结核杆菌。它在治疗早期发挥杀菌作用。它不仅能杀死正在繁殖的杆菌，还能杀死半休眠的杆菌。许多六个月疗法的结果表明，只有含吡嗪酰胺的疗法可作为肺结核的标准疗法被接受，复发率不到百分之几。新接受的标准化疗方案包括2HRZ（含或不含S或E）/4HRE、6HRS或E/3HR以及6HR。在富士寿寺医院接受含吡嗪酰胺疗法治疗的429例结核病患者中，化疗两个月后的痰菌转阴率为95%，与西方、非洲和亚洲的结核病试验结果相似。290例可评估病例中有6例复发（复发率为2%）。值得注意的是，所有复发病例均合并糖尿病。与未使用吡嗪酰胺的患者（6.6%）相比，使用吡嗪酰胺的患者中血清转氨酶水平升高至正常上限5倍及以上的比例更高，为8.2%，但这种差异无统计学意义。一名治疗前肝功能异常且病因不明的患者死于抗结核药物的肝毒性。肝毒性的危险因素包括丙型肝炎病毒携带者、80岁以上的老年人，但乙肝携带者、饮酒和肝脏疾病不是危险因素。与不含吡嗪酰胺的9个月疗程相比，该疗法的患者脱落率较低，为5.6%（9个月疗程为8.6%），但这种差异无统计学意义。该疗法的疗效比9个月疗程高90.3%，为86.0%。总之，含吡嗪酰胺的六个月疗程非常有效。日本必须进一步研究肝毒性的发生率和严重程度。
