Prospective cohort design is adopted to comprehensively analyze the adverse reactions occurred in Chinese tuberculosis patients during first-line anti-tuberculosis treatment in order to provide reference for preparing and improving the policies of anti-tuberculosis drug prevention and control. The embedded case control is adopted to investigate the genomics of the drug-induced liver injury of anti-tuberculosis drug so as to provide scientific evidence for early recognition and prevention of the liver injury, clinical classification, prognosis predictation and preparation of personalized treatment scheme.
General Information of Study
Name China National Tuberculosis Prevention and Control Scheme Study (ADACS) Project Number CCC2017051401 Website None Investigators Institutions Peking University Contacts Funding Global Foundation Program-"China National Tuberculosis Prevention and Control Scheme Study" (TB07-030), Natural Science Foundation of China-"Study on Genetic Polymorphism of Drug Metabolic Enzyme and Hereditary Susceptibility of Liver Damage Caused by Anti-tuberculosis Drugs" (30771847), "Study on the Genomic Epidemiology of the Drug-induced Liver Injury in the Anit-tuberculosis Cohort Population" (81072387); Natural Science Foundation of Beijing-"Study on the Genomic Epidemiology of the Medicamentous Liver Lesion in the Anit-tuberculosis Cohort Population" (7111006) Objectives Prospective cohort design is adopted to comprehensively analyze the adverse reactions occurred in Chinese tuberculosis patients during first-line anti-tuberculosis treatment in order to provide reference for preparing and improving the policies of anti-tuberculosis drug prevention and control. The embedded case control is adopted to investigate the genomics of the drug-induced liver injury of anti-tuberculosis drug so as to provide scientific evidence for early recognition and prevention of the liver injury, clinical classification, prognosis predictation and preparation of personalized treatment scheme. Start Date October, 2007 End Date December, 2014
Number of Participants 4,488 Age Range All ages Geographic Distribution 52 counties from Zhejiang, Jilin, Guangxi Zhuang Autonomous Region and Chongqing General Information of Study Design and Sample Methods Stratification, clustering and sampling with certain ratio to the specification Inclusion Criteria 1. Primary or repeated tuberculosis patients with positive sputum smear;
2. Patients receivig standard short-term chemotherapy recommended by CNTS in the local CDC;
3. Patients who voluntarily participate in the study and sign the informed consent
Exclusion Criteria 1. Patients with mental diseases that can interfere the questionnaire;
2. Patients with severe diseases and the prognoss is shorter than 6 months;
3. Patients having difficulty in signing the informed consent;
Key Achievements 1. The total incidence rate of adverse reaction of anti-tuberculosis drug is 15.08% with 2.55% liver injury (95%CI, 2.04-3.06), and about 1/3 patients have liver injury without any symptoms;
2. The affecting factors of liver injury include positive hepatitis B surface antigen (HBsAg), concurrent disease and male;
3. The relative risk of extended reinforcement period of liver injury patient is 2.11 compared with the non-liver injury patients and that of the non-cure or completing the treatment course is 9.25;
4. Prophylactic administration of liver-protective drug shows no obvious effect during the anti-tuberculosis treatment;
5. Complete the relative economic evaluation of the adverse reaction;
6. Obtain the frequency distribution of 70 SNPs polymorphism from 30 important genes in I, II, and III phase reaction and immunity reaction pathway of Chinese tuberculosis patients;
7. Screen out 5 hereditary susceptibility sites of liver injury patients in Chinese anti-tuberculosis treatment population;
8. The results demonstrate initially the relationship between the polymorphism of relative genes and ATLI in the three-phase reaction and immunity reaction as well as the effect of environmental factor, genetic factor and the interaction on ATLE so as to provide sientific evidence for the early recognition and prevention of ATLI, clinical classification, prognosis and preparation of personalized treatment scheme.
Marker Papers 1. YY Xia, DY Hu, FY Liu, XM Wang, YL Yuan, H Tu de, YX Chen, L Zhou, LZ Zhu, WW Gao, HY Wang, F Chen da, L Yang, PP He, XT Li, YJ He, F Sun, SY Zhan. Design of the anti-tuberculosis drugs induced adverse reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS). BMC Public Health 2010; 10:267.
2. P Shang, Y Xia, F Liu, X Wang, Y Yuan, D Hu, D Tu, Y Chen, P Deng, S Cheng, L Zhou, Y Ma, L Zhu, W Gao, H Wang, D Chen, L Yang, P He, S Wu, S Tang, X Lv, Z Shu, Y Zhang, Z Yang, Y Chen, N Li, F Sun, X Li, Y He, P Garner, S Zhan. Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China. PLoS One 2011; 6(7):e21836.
3. SW Tang, XZ Lv, Y Zhang, SS Wu, ZR Yang, YY Xia, DH Tu, PY Deng, Y Ma, DF Chen, SY Zhan. CYP2E1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: a nested case-control study. J Clin Pharm Ther 2012; 37(5):588-93.
4. Wu S, Xia Y, Lv X, Tang S, Yang Z, Zhang Y, Wang X, Hu D, Liu F, Yuan Y, Tu D, Sun F, Zhou L, Zhan S. Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti-tuberculosis agents in a large cohort of Chinese patients. J Gastroenterol Hepatol. 2015;30(3):540-5
5. Chen R, Wang J, Zhang Y, Tang S, Zhan S. Key factors of susceptibility to anti‑tuberculosis drug‑induced hepatotoxicity. Arch Toxicol. 2015; 89(6):883-897.
Strength The extraction method of Whatman Corporation on FTA stored DNA is optimized by the research group and the whole gene amplification is improved. The haplotype analysis, principal component analysis and multifactor dimension reduction is used to investigate the gene-gene and gene-environment interaction during the developmnt of ATLI. For the representative large sample, cluster sampling is used for the cohort. Weakness Only the dry blood filter paper is available so GWAS study cannot be initiated.
General Information of Baseline Investigation
Variables of Baseline Investigation
General Information of Follow-up Investigation
Variables of Follow-up Investigation