Study Of The Antituberculosis Drug-induced Hepatotoxicity And The Ifn-γ,il-10 Levels In Such Patients

Objective:1.To investigate the incidence of multi-drug antituberculosis regimens induced hepatotoxicity,to clarify clinical risk factors associated with the development of hepatotoxicity during antituberculosis chemotherapy.2.By detecting the levels of IFN-γ, IL-10 in Antituberculosis drug-induced hepatotoxicity,to explore the cellular immune status and its significance in such patients.Method:1.In a retrospective analysis in my hospitle, the medical material of 658 patients who received antituberculosisc hemotherapy between December 2008 and December 2009 were surveyed.All patients had normal serum alanine transferase (ALT), aspartate transferase (AST) and bilirubin. Serum hepatitis B viral markers (HBVM), consisting of HBeAg and HBeAb, were measured by enzyme-linked immunoassay HBsAg,(ELISA).HBcAb HBVM was considered positive when one or more of the markers was/were positive.2.60 secondary pulmonary tuberculosis patients are gathered, divided them into 4 groups: 1. Control group, 10 cases: no HBV infection in patients with secondary pulmonary tuberculosis, take anti-tuberculosis drugs 2 months and does not appear liver injury. 2. group 1, 20 cases: no HBV infection but have liver injury; 3. group 2, 17 cases: HBSAG positive, no reactivation of hepatitis B virus, liver injury,;4. group3, 13 cases: HBSAG positive, with hepatitis B virus reactivation, liver injury. Taken fasting blood 3ml in the morning, to separate serum and stored at -70℃refrigerator. At last, the levels of IFN-γ, IL-10 are examined together by ELISA. The liver function,hepatitis markers and HBV-DNA are detected by the hospital clinical laboratory ,were used the methods of enzyme, double-antibody sandwich ELISA, and immunofluorescence- PCR.Results:1.Hepatotoxicity Developed in 164 of 658 patients(24.9%).The rates of hepatotoxicity in male was less than in female(15.4% vs 21.3%,P<0.05).There were 122 patients with HBVM positive [HBV infectious group], and the other 536 patients with HBVM negative [non-HBV infectious group]. The incidence of antituberculosis drug-induced hepatototxicity in HBV infectious group was significantly higher than in non-HBV infectious group (48.3% vs 12.7%, P<0.001). Among patients with hepatotoxicity, HBV infectious group had significantly higher aminotransferase levels than non-HBV infectious group (P<0.01). The frequency of hepatotoxicity increased from 15.2% for those aged younger than 40 to 23.0% at age 40-60 and to 35.6% for those aged 60 and over,with the increasing of the age,the rate of drug-induced hepatotoxicity was significantly higher.About 90% of hepatotoxicity occurred with in the first 3 months of treatment.2.Compared with the control group, the level of peripheral blood IFN-γin group 1 and group 2 are obviously higher(P<0.01),The IL-10 level are lower (P <0.01);while in group 3 the IFN-γlevel is lower(P<0.01),the IL-10 level is higher(P<0.01), Compared group 3 with group 1 and group 2, the level of IFN-γis lower (P<0.01), the level of IL-10 is higher (P <0.01), but compared group 1 with group 2, the level of IFN-γand IL-10 are no significant difference (P>0.05).The therapeutic time of patients take anti-TB drugs when liver injury occurs has no correlation with the levels of IFN-γand IL-10. with the ALT elevated, IFN-γare rising, compared ALT <200U/L group with ALT200-400U/L group and ALT>400U/L group,the difference was statistically significant (P<0.01),compared ALT>400U/L group with ALT200-400U/L group, the difference was statistical significance (P<0.05); IL-10 are shown a declining tendency, but no statistically significant difference (P> 0.05).Conclusions:1.Age and HBV infection are the important risk factors for the development of hepatotoxicity during antituberculosis treatment.Female and HBV-DNA positive patients are easier occurred hepatotoxicity,we must monitoring liver status.2. This study examined the levels of IFN-γand IL-10 in patients with Drug-induced hepatitis, initially confirmed these cytokines in such patients are unbalanced. suggesting their cellular immune function is disrupted. 3. For the patients with pulmonary tuberculosis combined HBV infection, when HBV reactivated, the IFN-γ, IL-10 levels are different with no HBV-reactivated group and non-HBV infection group. HBV-reactivated has the negative effect to the production of IFN-γand has the positive effect to the production of IL-10 .4. The duration of patients take anti-TB drugs when liver injury occurs has no correlation with the levels of IFN-γand IL-10. IFN-γhas the positive effect to the production of ALT.