Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China.

Penghui Shang,Yuan Zhang,Xiaoting Li,Yan Chen,Xiaozhen Lv,Na Li,Li Yang,Yu Ma,Siyan Zhan,Lin Zhou,Shaowen Tang,Shiming Cheng,Zheng Shu,Paul Garner,Zhirong Yang,Peiyuan Deng,Dafang Chen,Weiwei Gao,Yixin Chen,Feiying Liu,Pingping He,Dehua Tu,Yingjian He,Shanshan Wu,Xiaomeng Wang,Feng Sun,Daiyu Hu,Hongyuan Wang,Yanli Yuan,Yuqing Xia ,Li-Zhen Zhu

doi:10.1371/journal.pone.0021836

Abstract

BackgroundAnti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China.Methodology/Principal FindingsIn a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%–3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69–15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI,1.23–3.60) risk of prolonged intensive treatment phase.Conclusions/SignificanceATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.

Highlights

Tuberculosis (TB) continues to be a major health problem, with 9.4 million incident cases and 1.7 million deaths globally in 2009 [1]
More research and efforts are warranted in order to enhance the diagnosis and the prevention of Anti-tuberculosis drug induced liver injury (ATLI)
After starting anti-TB treatment, 206 patients had greater than 1 time of UNL elevation of ALT, 58 patients had greater than 1 time of UNL elevation of AST, and 9 patients had greater than 1 time of UNL elevation of total bilirubin (TBil) (Table 2)

Summary

Introduction

Tuberculosis (TB) continues to be a major health problem, with 9.4 million incident cases and 1.7 million deaths globally in 2009 [1]. The key component of DOTS strategy is the standard anti-TB short course chemotherapy regimen, which requires continually taking drug combinations of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E) and Streptomycin (S) every other day for 6–9 months [4]. These anti-TB drugs have shown that they are able to contain and kill Mycobacterium tuberculosis effectively, they are known to induce various adverse effects, including liver injury, skin reactions, gastrointestinal and neurological disorders [5,6]. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China

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Conclusion