TB Drug-Induced Mixed Liver Injury /F.Nomi et al. 651

Abstract　[Background] Liver injury is the most common and clinically significant adverse reaction to anti-tuberculosis drugs, sometimes resulting in a fatal outcome. It has been reported that liver injury induced by isoniazid and pyrazin-amide, which has the potential to cause hepatocellular injury, has a risk of becoming severe; while an injury induced by rifampicin, which has the potential to cause cholestatic injury, rarely becomes severe. However, mixed liver injury has not been studied thoroughly.　[Methods] Of 321 tuberculosis patients who were admitted and treated in our hospital over the past 5 years, 7 patients (2.1％) who developed mixed liver injury due to the use of anti-tuberculosis drugs were clinically investigated through their medical records.　[Results] There were 4 male patients and 3 female patients, with a mean age of 66.7 (59_85) years. The mean duration from the start of oral anti-tuberculosis drugs to the onset of mixed liver injury was 28.5 days. In 2 of the patients, the event occurred within 2 weeks. Two of them had a total bili-

rubin level of ＞5 mg/dl at the time of diagnosis. In 6 of the 7 patients, the liver injury improved on discontinuation of the anti-tuberculosis drugs. In the remaining 1 patient, the liver injury progressed even after discontinuation of the oral treat-ment, leading to death.　[Conclusion] Since mixed liver injury sometimes results in a fatal outcome, it is necessary to take adequate precautions.

Key words : Pulmonary tuberculosis, Anti-tuberculosis agents, Adverse reactions, Drug-induced liver injury, Mixed liver injury

1Misato Central General Hospital, 2Saiseikai Kawaguchi Gen-eral Hospital

Correspondence to: Fumiko Nomi, Misato Central General Hospital, 745 Koubou, Misato-shi, Saitama 341_8526 Japan. (E-mail : fnoumi@gmail.com)

－－－－－－－－Original Article－－－－－－－－

A CLINICAL INVESTIGATION OF SEVEN PATIENTS WITH PULMONARY TUBERCULOSIS WHO DEVELOPED MIXED LIVER INJURY

DURING ORAL ANTI-TUBERCULOSIS TREATMENT

1Fumiko NOMI, 2Kiminori HOSAKA, and 2Takayuki KUROSAWA

結核 第88巻 第 9 号 2013年 9 月658

Abstract　[Purpose] To evaluate the efficacy of regular exam-ination (primarily by chest radiography) following treatment for latent tuberculosis infection (LTBI), we attempted to estimate the frequency and time to onset of active tuberculosis after completion of LTBI treatment. 　[Objects & Methods] From the Japanese national surveil-lance data of 2008_2011, we extracted and analyzed the number of active tuberculosis cases after the end of LTBI treatment that was registered during 2008_09. 　[Results] Among LTBI cases registered during 2008_09 (n＝8951), 56 active tuberculosis cases following LTBI treat-ment were detected by the end of 2011. Frequency of onset of active tuberculosis by the end of the second year after registra-tion of LTBI cases were as follows: 0.57％ (51/8951), all active tuberculosis cases; 0.10％ (9/8951), smear-positive lung tuberculosis cases; and 0.22％ (20/8951), all bacteria-positive lung tuberculosis cases. In 37 active tuberculosis cases for which the date of completion of LTBI treatment was available, 12 cases were diagnosed within 1 year and 22 within

2 years of the completion of LTBI treatment. 　[Conclusion] The frequency of onset of active tuberculosis after completion of LTBI treatment was relatively low, but it did not decrease with time in the following 2 years. Hence, the validity of regular examination should be assessed, rather than specifying the duration of regular examinations after comple-tion of LTBI treatment.

Key words : Tuberculosis, Latent tuberculosis infection, Follow-up examination, Chest radiograph, Surveillance

Department of Epidemiology and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association

Correspondence to: Kunihiko Ito, Department of Epidemiol-ogy and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan. (E-mail : ito@jata.or.jp)

－－－－－－－－Original Article－－－－－－－－

USE OF REGULAR CHECK-UPS AFTER COMPLETION OF TREATMENT FOR LATENT TUBERCULOSIS INFECTION

Kunihiko ITO

5. 総　括

　本調査からも文献的にも，LTBI治療終了後の結核発

病率が治療終了後 1年目に高くその後低減するといった

事実は確認されず，むしろ終了後 2年間は少なくとも同

様の発病率で推移する可能性が高いものと推測される。

もしLTBI治療後の管理健診 ⁄経過観察施行の妥当性が発病率のみで規定されるのであれば，治療終了後 1年目の

管理健診 ⁄経過観察の施行を妥当とするなら同時に 2年目も妥当とされるべきであろう。しかし推定発病率その

ものは，治療中断者まで含めたデータであっても，登録

年次次年末までで全結核で 0.57%，塗抹陽性肺結核で

0.10%，全菌陽性肺結核で0.22%と著しく低い。したが

って問題とするのであれば，LTBI治療終了後の管理健

診 ⁄経過観察期間の妥当性よりも，LTBI治療終了後の管理健診 ⁄経過観察そのものの要不要であろうと思われる。　付記：本稿は平成24年度新型インフルエンザ等新興・

再興感染症研究事業「地域における効果的な結核対策の

強化に関する研究（主任研究者 石川信克）」の研究費補

助を受けて作成されている。

　著者のCOI（conflicts of interest）開示：本論文発表内

容に関して特になし。

文　　　献

1 ） 阿彦忠之：「感染症法に基づく結核接触者健康診断の手引き」改訂第4版, 結核予防会, 東京, 2010.

2 ） WHO: Treatment of tuberculosis : guidelines for national tuberculosis programs. 4th ed, Geneva, 2010.

3 ） Julius K, Solomon K, Vytautas D, et al. : Effect of isoniazid upon the reactivation of inactive tuberculosis. American Review of Respiratory Disease. 1965 ; 91 : 345‒350.

4 ） Abraham F, George FF: Prophylaxis with isoniazid in inac-tive tuberculosis A Veterans Administration Cooperative Study XII. Chest. 1978 ; 73 : 44‒48.

5 ） International Union Against Tuberculosis Committee on Prophylaxis. : Efficacy of various durations of isoniazid preventive therapy for tuberculosis : five years follow-up in IUAT trial. Bull WHO. 1982 ; 60 : 555‒564.

6 ） Comstock GW, Ferebee SH, Hammes LM: A controlled trial of community-wide isoniazid prophylaxis in Alaska. American Review of Respiratory Disease. 1967 ; 95 : 935‒943.

Homeless Patients with TB/K.Matsumoto et al. 665

Abstract　[Purpose] We conducted a study on factors related to treatment outcome and medication support in homeless patients with tuberculosis. 　[Methods] Participants were 433 homeless patients with tuberculosis newly registered in Osaka City between 2007 and 2009. We investigated factors related to treatment outcome (e.g., length of hospital stay, scheduled duration of outpatient treatment, and type of DOTS). Controls were 3,047 non-homeless patients with pulmonary tuberculosis newly regis-tered in Osaka City during the same period. 　[Results] Regarding medication support, 219 (70.4％) of the 311 patients with successful treatment received DOTS and completed the treatment during their hospital stay. Thirty-five (72.9％) of the forty-eight patients who did not complete treatment left the hospital at their own discretion, resulting in treatment failure/default. The rate of treatment failure/default in the homeless patients with pulmonary tuberculosis was 11.0％, significantly higher than that of non-homeless patients with pulmonary tuberculosis (6.5％; P＜0.001). Among the 102 patients receiving community DOTS, medication compli-ance occurred at least 5 days a week in 66 patients (64.7％) and treatments failed or were interrupted in 10 patients (9.8％). The mean hospital stay was 2.0±1.6 months in patients with failed/defaulted treatment and 4.4±2.5 months in those with successful treatment. The scheduled duration of outpatient treatment was 7.9±2.7 months in patients with failed/defaulted

treatment and 3.6±2.1 months in those with successful treatment. Shorter length of hospital stay and longer scheduled duration of outpatient treatment were associated with a higher rate of treatment failure/default (P＜0.01). 　[Conclusion] Homeless patients with tuberculosis had a higher rate of treatment failure/default, most likely due to leaving the hospital at their own discretion. Patients with successful treatment generally completed treatment during their hospital stay. In contrast, patients who received commu-nity DOTS after discharge from the hospital had a higher rate of treatment failure/default, despite receiving medication at least 5 days a week. This suggests the need for adequate support, particularly in patients with a shorter hospital stay and those with a longer scheduled duration of outpatient treatment.

Key words : Tuberculosis, Homeless patient, DOTS, Treat-ment outcome, Duration of treatment, Self-discharge

1Osaka City Public Health Office, 2Health Bureau, Osaka City, 3Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (JATA)

Correspondence to: Kenji Matsumoto, Osaka City Public Health Office, 1_2_7_1000, Asahimachi, Abeno-ku, Osaka-shi, Osaka 545_0051 Japan.(E-mail : ke-matsumoto@city.osaka.lg.jp)

－－－－－－－－Original Article－－－－－－－－

MEDICATION SUPPORT AND TREATMENT OUTCOME IN HOMELESS PATIENTS WITH TUBERCULOSIS

1Kenji MATSUMOTO, 1Jun KOMUKAI, 1Sachi KASAI, 1Asami MORIKOCHI, 1Hideki YOSHIDA, 1Satoshi HIROTA, 1Shinichi KODA, 2Kazuhiko TERAKAWA,

and 3Akira SHIMOUCHI

結核 第88巻 第 9 号 2013年 9 月670

と考えられた。この課題に対しては，LTBI治療終了後

のフォローアップ期間の延長と有症状時早期受診の啓発

の二つの方策が考えられる。LTBI治療終了後のフォロ

ーアップ期間については，平成22年の結核活動性分類

の改正にともない，LTBI治療者も治療終了後 2年間ま

でフォローアップ期間が延長されるようになった。しか

し，少数ではあるがこのフォローアップ期間以降にも発

病する者がおり，そのことを念頭においたLTBI治療終

了者への有症状時早期受診の啓発が必要と考えられる。

　本論文の要旨は第88回日本結核病学会総会（千葉）

にて発表した。

　著者のCOI（conflicts of interest）開示：本論文発表内

容に関して特になし。

文　　　献

1） 豊田　誠, 森岡茂治：高知市中学校における結核集団

感染―感染要因と化学予防の効果に関する検討. 結核.2001 ; 76 : 625‒634.

2） 深澤啓治：クォンティフェロン第二世代の結核対策への応用と課題. 結核. 2007 ; 82 : 53‒59.

3） International Union Against Tuberculosis Committee on Prophylaxis : Efficacy of various durations of isoniazid pre-ventive therapy for tuberculosis : five years of follow-up in the IUAT trial. Bull WHO. 1982 ; 60 : 555‒564.

4） 公益財団法人結核予防会：日本版DOTSの改正.「結核の統計2012」, 結核予防会, 東京, 2012, 18.

5） Comstock GW: How much is isoniazid needed for preven-tion of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis. 1999 ; 3 : 847‒850.

6） 豊田　誠：若年者を中心に複数の経路で拡大した結核集団感染. 結核. 2012 ; 87 : 757‒763.

Abstract　[Purpose] To evaluate the efficacy of treatment for latent tuberculosis infection and delayed reactivation of tuberculosis.　[Method] During a large tuberculosis outbreak, 129 indi-viduals who were in close contact with tuberculosis patients and subsequently tested strongly positive by the tuberculin skin test were followed up for 10 years after identification of the source case.　[Result] Of the 129 individuals, 105 received treatment for latent tuberculosis infection for 6 months as per recommenda-tion, while the remaining 24 did not receive treatment, because most of them were above 30 years of age and were therefore discouraged from receiving treatment, as was done in the earlier times in Japan. Of the 105 individuals, 5 (4.8％) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 53 months. Of the 24 individuals who did not receive treatment for latent tuberculosis infection, 6 (25.0％)

were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 8.2 months.　[Conclusion] The risk of active tuberculosis was reduced by 81.0％ with treatment for latent tuberculosis infection, compared with that without treatment. Delayed reactivation of tuberculosis was observed among patients treated with isoniazid for latent tuberculosis infection for 6 months.

Key words : Tuberculosis, Outbreak, Latent tuberculosis infec-tion, Efficacy of LTBI, Delayed reactivation of tuberculosis

Kochi City Public Health Center

Correspondence to: Makoto Toyota, Kochi City Public Health Center, 1_7_45, Marunouchi, Kochi-shi, Kochi 780_0850Japan. (E-mail : kc-140200@city.kochi.lg.jp)

－－－－－－－－Short Report－－－－－－－－

EFFICACY OF THE TREATMENT FOR LATENT TUBERCULOSIS INFECTION AND DELAYED REACTIVATION OF TUBERCULOSIS

Makoto TOYOTA

686 結核 第88巻 第 9 号 2013年 9 月

－－－－－－－－Report and Information－－－－－－－－

TUBERCULOSIS ANNUAL REPORT 2011─ (4) Tuberculosis Treatment and Treatment Outcomes─

Tuberculosis Surveillance Center (TSC), RIT, JATA

Abstract　The frequency of re-treatment among newly notified tuberculosis (TB) patients might be an indicator of inadequate prior treatment. In 2011, 22,681 patients were notified with TB, of which, 1,687 patients had received prior TB treatment (7.6％ of those patients who presented with unknown treatment history were excluded). Nearly half of the re-treatment cases had received previous treatment after 2000 (n＝766). 　A standardized treatment regimen is the key to TB control. As for the initial treatment regimen, a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol (or streptomycin) is recommended; this regimen was initially used for the treatment of approximately ≧85％ of all forms of TB in patients aged 15_54 years (patients with an unknown treatment regimen were excluded). Of the 11,556 patients who underwent TB treatment regimen with pyrazinamide and completed the course of treatment by the end of 2011, approximately 10％ were unable to complete the 2-month-long regimen with pyrazinamide. 　In 2011, 17,519 patients were newly notified with pulmo-nary TB (PTB). The proportion of patients who were hospi-talized on the commencement of anti-TB treatment increased as the age increased above 30 years. 　The median duration of hospitalization among newly noti-fied TB patients in 2010 was 70 days for new sputum-smear positive PTB patients, 71 days for re-treatment sputum-smear positive PTB patients, 43 days for other bacteriologically positive PTB patients, 41.5 days for bacteriologically negative and other patients, and 46 days for extra-pulmonary TB patients. As of end-of-year 2011, the median treatment duration

for all forms of TB patients, newly notified in 2010, was 272 days. 　The treatment success rates for new sputum-smear-positive PTB patients (n＝8,242), re-treatment PTB patients (n＝794), other bacteriologically positive PTB patients (n＝6,358), and bacteriologically negative and other patients (n＝2,883), registered in 2010 were 52.0％, 42.7％, 59.6％, and 60.4％, respectively. 　The proportion of new sputum-smear-positive PTB patients, registered in 2009 and 2010, who died by the end of the following years were 26.9％ and 27.8％, respectively. 　The cause of death among TB patients, usually determined by physicians, has been collected through a TB surveillance system in Japan. The proportion of deaths caused by TB within one month of registration, among both the newly notified TB patients and the new sputum-smear-positive PTB patients, tended to be higher than that caused by other reasons (48.5％ vs. 17.3％ and 51.5％ vs. 19.7％, respectively).

Key words : Tuberculosis, Treatment history, Treatment status, Duration of treatment, Treatment outcomes

Research Institute of Tuberculosis (RIT), Japan Anti-Tubercu-losis Association (JATA)

Correspondence to: Tuberculosis Surveillance Center (TSC), Research Institute of Tuberculosis (RIT), JATA, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan. (E-mail : tbsur@jata.or.jp)