Isoniazid를 제외한 Rifampicin과 Pyrazinamide 병합치료의 간독성 빈도

Hepatotoxicity of Rifampicin and Pyrazinamide Treatment Excluding Isoniazid

  • 최익수 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 박이내 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 홍상범 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 오연목 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 임채만 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 이상도 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 고윤석 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김우성 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김동순 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김원동 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 심태선 (울산대학교 의과대학 서울아산병원 호흡기내과)
  • Choi, Ik Su (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Park, I-Nae (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Hong, Sang-Bum (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Oh, Yeon-Mok (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lim, Chae-Man (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lee, Sang Do (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Koh, Younsuck (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Woo Sung (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Dong Soon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Won Dong (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Shim, Tae Sun (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center)
  • 투고 : 2005.10.12
  • 심사 : 2005.12.05
  • 발행 : 2006.01.30

초록

연구배경 : RMP과 PZA 병합 잠복결핵치료는 2개월만 치료하여도 된다는 장점이 있으나 중증 간독성이 보고됨에 따라 미국흉부학회 지침에서 특별한 사유가 있지 않는 한 잠복결핵의 치료에 사용하지 말도록 권고하였다. 그러나 한국인에서도 RMP/PZA 병합요법이 높은 빈도로 중증 간독성을 유발하는지에 대한 보고가 아직은 없어서 이를 확인하고자 본 연구를 시행하였다. 방 법 : 1990년 1월부터 2003년 12월까지 서울아산병원에서 INH 단독내성(256명)으로 진단된 결핵환자 중 표준치료를 시행하다가 INH 내성 확인 후 INH를 제외하고 RMP/PZA가 포함된 처방으로 변경한 64명(RZ+군)을 대상으로 의무기록을 후향적으로 분석하였다. 같은 기간에 결핵진단 후 INH/RMP/PZA를 포함한 표준치료를 시행한 146명을 무작위로 추출하여(HRZ+군) 대조군으로 하였다. 양 군에서 나이, 성별, 기저 간질환 유무, 해당 약제의 치료기간 및 간독성발생률을 조사하였다. 결 과 : RZ+군 64명의 평균나이는 $50.2{\pm}16.2$세, 남녀비는 36:28이었다. HIV 검사를 시행한 20명 모두 음성이었다. RZ+군과 HRZ+군에서 각각 기저 간질환의 빈도는 10.9%(7/64), 4.1%(6/146)으로 차이가 없었다. RZ+군과 HRZ+군에서 각각 RMP/PZA, INH/RMP/PZA를 포함한 치료를 시행한 기간은 각각 $5.5{\pm}4.8$, $2.7{\pm}2.3$ 개월로 RZ+군에서 의미있게 길었음에도 불구하고(p<0.05) 기저간질환이 없는 환자 57명과 140명 중 각각 2명(3.5%, 모두 경증), 10명(7.1%, 모두 경증)에서 간독성이 발생하여 양 군간에 차이가 없었다. RZ+군 중 기저간질환이 있었던 5명 모두 간독성은 발생하지 않았다. 결 론 : 한국인에서 INH 를 제외하고 RMP과 PZA가 포함된 병합치료를 시행한 군에서 간독성의 발생률은 3.5%로 모두 경증이었고 4제 표준치료요법에 비하여 높지 않았다. 향후 RMP/PZA 병합요법을 우리나라에서 잠복결핵의 치료요법으로 사용하기 위해서는 많은 수의 환자를 대상으로 한 전향적인 연구가 필요할 것으로 생각된다.

Background : Even though two-month rifampicin (RMP, R) and pyrazinamide (PZA, P) treatment has some advantages over isoniazid (INH, H) treatment for latent tuberculosis infection (LTBI), it was withdrawn from the list of treatment regimens for LTBI because of reported cases of severe hepatotoxicity. The purpose of this study was to estimate the frequency of hepatotoxicity of RMP and PZA treatment excluding INH in a Korean population. Method : TIn order to recruit patients who were prescribed RMP and PZA excluding INH, 256 INH-resistant tuberculosis patients were investigated through retrospective medical record analysis. A standard four-drug regimen was changed to a RMP/PZA-containing regimen excluding INH in 64 patients (RZ+ group). In the same study period, 146 patients who were prescribed an INH/RMP/PZA-containing standard regimen were randomly selected as a control (HRZ+ group). Clinical characteristics including liver diseases and the frequency of drug-induced hepatitis were compared between the RZ+ and HRZ+ groups. Result : The mean age of patients in the RZ+ group was 50.2 (${\pm}16.2$) and the male-to-female ratio was 36:28. The frequency of underlying liver diseases was 10.9% (7/64), which was not significantly different from that of the HRZ+ group (4.1%, 6/146). Even though the treatment duration of RZ+ ($5.5{\pm}4.8months$) was longer that than that of HRZ+ ($2.7{\pm}2.3months$), the frequency of toxic hepatitis was not significantly different between RZ+ and HRZ+ groups, 3.5% (2/57) and 7.1% (10/140), respectively. Conclusion : Hepatotoxicity was mild and occurred in a minor proportion of patients in a Korean population prescribed an RMP/PZA-containing regimen. A future prospective study including more patients is needed.

키워드

참고문헌

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