Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST

ABSTRACT Setting: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH).DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. Objective: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. Design: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. Results: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. Conclusion: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p = 0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.

Diagnosis of the pulmonary tuberculosis by polymerase chain reaction: a comparative study between HIV - positive and - negative individuals

This study was performed to assess the efficiency of polymerase chain reaction (PCR) directly from sputum for the diagnosis of pulmonary tuberculosis by comparison between HIV-positive and HIV-negative individuals. Sputum samples were collected from hospitalized patients admitted with a clinical diagnosis of pulmonary tuberculosis, and subjected to smear microscopy, culture on LJ medium and detection of M. tuberculosis by PCR. Sensitivity, specificity, and predictive values (positive and negative) were calculated using smear and/or culture at day 42 as the gold standard, by comparing the yield in HIV-positive and HIV-negative individuals. Regardless of serostatus, the technique's yield had 62% sensitivity, 70% specificity, 79% positive predictive value, 50% negative predictive value, and 65% accuracy. HIV-negative had 64% sensitivity, 74% specificity, 75% positive predictive value, 63% negative predictive value, and 68% accuracy. HIV-positive had 59% sensitivity, 33% specificity, 87% positive predictive value, 10% negative predictive value, and 56% accuracy. The PCR showed a higher yield in HIV-negative individuals compared to HIV-positive individuals.

Serum adenosine deaminase in pulmonary tuberculosis, malignancy and non-tubercular respiratory diseases.

The study has been conducted to find out the serum ADA levels in 120 patients with various pulmonary diseases which included patients with tubercular pleural effusion (n = 86), lung cancer (n = 10) and patients with non-tubercular pulmonary diseases like pneumonia, etc (n = 24). Twenty healthy individuals served as control subjects. The mean (+/- SD) of ADA activity was 23.38 (4.47), 7.29 (1.08), 12.71 (1.95) and 2.23 (1.00) units/litre in tuberculosis, malignancy, non-tubercular pulmonary diseases and healthy controls respectively with significant difference between each other (P less than 0.001). Patients with tuberculosis (100%) fall in 97% sensitivity range with a lower cut off limit at 17 units/litre ADA activity, while for malignancy and non-tubercular respiratory diseases, the sensitivity was 90% and 83% respectively. Within the sensitivity limits, the serum ADA activity can be used for the differential diagnosis of pulmonary diseases.

Evaluación de la actividad de la adenosin deaminasa sérica en el diagnóstico de la tuberculosis pulmonar activa / Evaluation of serum adenosine deaminase activity in diagnosing active pulmonary tuberculosis

Se evalúa la utilidad de la determinación de la Adenosin Deaminasa (A.D.A.) sérica en el diagnóstico de la tuberculosis pulmonar activa. Se estudió una serie de enfermos con TBC pulmonar activa confirmada bacteriológicamente y sin tratamiento (n=19), y se lo comparó con un grupo control de sujetos sanos (n=20) y un grupo de pacientes dados de alta inactivos de TBC (n=20). Igual determinación se hizo en un grupo de pacientes portadores de cáncer pulmonar (n=20) y en otra serie de pacientes con neumopatía aguda (n=20). Se encontró que los niveles de A.D.A. sérica en los pacientes con TBC pulmonar activa sin tratamiento son significativamente mayores (p<0.001) que en los demás grupos, por lo que se considera que éste examen es útil en el diagnóstico de la TBC pulmonar