Objective
To investigate the changes of eosinophil VCS parameters and further its potential value in monitoring hepatotoxicity of anti-tuberculosis (anti-TB) drugs.
Methods
The eosinophil counts(EO#), percentage of eosinophil (EO%), the VCS parameters and standard deviation (SD), of 633 TB patients and 500 healthy controls , were measured by the Coulter LH-750 analyzer.Alanine aminotransferase (ALT) was measured simultaneously. The changes of VCS and ALT parameters of 426 TB patients including 376 case controls and 50 with drug induced liver injury (DILI）[ALT>2×upper limit of normal value] before and after treatment were statistically analyzed and the receiver operating characteristic (ROC) were depicted, so as to assess the value of eosinophil VCS parameters in predicting the sensitivity and specificity of hepatotoxicity of antituberculosis drugs in intensive phase.
Results
The parameters ALT，EO%，MEV and MEV-SD did not show significant difference before treatment in case controls and DILI group [(17.28±5.82)U/L, (2.20±0.74)%, (162.54±7.05)fl,（15.66±3.67)；(17.32±5.79)U/L, (2.26±0.72 )%, (163.05±7.365) fl, 15.63±3.70] compared to health controls[(17.07±5.61)U/L, (2.07±0.71)%, (161.93±7.30)fl, 15.57±3.82; t=-0.830, -1.121, -0.598, -1.659；-1.908, -1.189, -1.023, -1.462; P>0.05]. The incidence of increased EO% in DILI group [36.0% (18/50)]was significantly higher than case-controls [6.6% (25/376), x2=14.45, P<0.05]. There were also no statistically significances between parameters prior to treatment and after [ (17.50±5.86) U/L, (2.34±0.69)%, (163.11±8.21)fl, 15.70±3.69; t=0.618, -1.178, -1.750, -0.618; P>0.05]. The MEV, MEV-SD during the week before ALT elevated [(165.01±7.64) fl, (15.89±3.27)]were significantly larger than those prior to treatment (t=-2.545,-3.021; P<0.05). When DILI happened，the changes were more significant[(166.87±8.92) fl, (16.37±3.66); t=-10.616, -9.727; P<0.01]. The receiver operating characteristics analysis reveals the MEV and MEV-SD had the largest areas under curves ( 0.894, 0.815 prior to DILI). Using the cutoff point≥163.15 fl for MEV and ≥17.11 for MEV-SD, the sensitivities of 81% and 72% and specificities of 82% and 80%, were respectively greater than EO%(50%, 71%) and ALT (54%, 76%). In addition，the effect of combined diagnosis was better than one single.The sensitivity and specificity of ALT+EO%+MEV+MEV-SD were up to 84% and 91%.
Conclusions
The MEV and MEV-SD change significantly when liver injury is induced by anti-TB drugs and are further significantly increase before the increase of ALT. The effect of combined diagnosis with ALT and EO% could improve the sensitivity and specificity of DILI diagnosis, which may provide help for predicting hepatotoxicity of anti-TB drugs and early diagnosis of DILI.