Metabolomics and microbiomes for discovering biomarkers of antituberculosis drugs-induced hepatotoxicity

Shouquan Wu ◽  
Minggui Wang ◽  
Miaomiao Zhang ◽  
Jian-Qing He
The Lancet ◽  
1996 ◽  
Vol 348 (9028) ◽  
pp. 688
Elizabeth Tayler

2020 ◽  
Vol 20 (1) ◽  
Gen Shimizu ◽  
Ryota Amano ◽  
Itaru Nakamura ◽  
Akane Wada ◽  
Masanobu Kitagawa ◽  

Abstract Background Intravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. Case presentation A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. Conclusions We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

2018 ◽  
Vol 51 (1) ◽  
pp. 88-93 ◽  
Cheng-Yu Kuo ◽  
Wen-Hung Wang ◽  
Chung-Hao Huang ◽  
Yen-Hsu Chen ◽  
Po-Liang Lu

2015 ◽  
Vol 41 (1) ◽  
pp. 77-89 ◽  
Laíse Soares Oliveira Resende ◽  
Edson Theodoro dos Santos-Neto

This review sought to identify the available scientific evidence on risk factors associated with adverse reactions to antituberculosis drugs. We performed a systematic review of studies published in the 1965-2012 period and indexed in the MEDLINE and LILACS databases. A total of 1,389 articles were initially selected. After reading their abstracts, we selected 85 studies. Of those 85 studies, 16 were included in the review. Risk factors for adverse reactions to antituberculosis drugs included age > 60 years, treatment regimens, alcoholism, anemia, and HIV co-infection, as well as sodium, iron, and albumin deficiency. Protective factors against hepatic adverse effects of antituberculosis drugs included being male (combined OR = 0.38; 95% CI: 0.20-0.72) and showing a rapid/intermediate N-acetyltransferase 2 acetylator phenotype (combined OR = 0.41; 95% CI: 0.18-0.90). There is evidence to support the need for management of adverse reactions to antituberculosis drugs at public health care facilities.

Tubercle ◽  
1964 ◽  
Vol 45 (3) ◽  
pp. 181-187 ◽  
Sister M. Aquinas

2017 ◽  
Vol 29 (7) ◽  
pp. 1583-1586 ◽  
P. Mishra ◽  
A. Durgbanshi ◽  
R.P. Pawar

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