Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China

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.

Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors

“…Low frequency of TB DILI (5%) was reported in a meta-analysis from the west [23] Pulmonary TB was the commonest form of TB in this study whereas an earlier study [24] had lesser frequency of pulmonary TB. Nausea, anorexia, and vomiting are the main clinical presentation of TB DILI in this study which is congruent to the former studies [25] [26]. All three types of DILI were observed here including asymptomatic patients with raised aminotransferase, symptomatic with raised aminotransferase and patients with acute liver failure/encephalopathy.…”

“…The difference in DILI severity from above study to ours was owing to different cut off values for transaminases used in those two studies. A large Chinese study also showed similarly severe TB DILI [25] Locally published study on TB DILI showed severity according to elevated level of trans- [27]. DILI was also documented after reintroduction of ATT in this study.…”

Drug Induced Hepatotoxicity of Antituberculosis Drugs and Their Serum Levels

“…In this study the incidence of DIH was similar to the rates reported in previous studies (5,6,20,21). Several risk factors for anti-TB DIH, such as old age, female gender, malnutrition, alcoholism, underlying liver disease, extensive pulmonary parenchymal disease, and HIV infection, have been reported in previous studies (5,6,22,23).…”

Preventive use of a hepatoprotectant against anti‐tuberculosis drug‐induced liver injury: A randomized controlled trial

“…20 This condition has been emerging as a threat to tuberculosis control in China, although limited data are available at the population level. 21 As ATLI can only be diagnosed without any other causes of liver injury, it is frequently underdiagnosed, 22 although high rates of hepatotoxicity have been reported worldwide. [23][24][25] In China, the reported incidence of ATLI varies from 2.6% to 7.5%.…”