脱氧核苷酸钠防治初治继发性肺结核合并乙型肝炎患者药物性肝损伤的效果

Clinic observations of sodium deoxy nucleotide on prevention and control of drug-induced liver injury in new pulmonary tuberculosis patients with Hepatitis B antigen positive

目的 观察和评价脱氧核苷酸钠注射液防治初治继发性肺结核合并乙型肝炎抗原阳性患者抗结核药物性肝损伤的疗效.方法 选取2012年1月至2014年3月广东省汕头市结核病防治所门诊就诊、经实验室和临床诊断为初治继发性肺结核合并乙型肝炎抗原阳性的患者112例,按数字表法随机分为实验组和对照组,各56例.对照组的治疗方案为：2 HRZE/4 HR,并常规应用肝泰乐片（葡醛内酯片）进行保肝治疗;实验组在上述治疗方案的基础上在强化期加用脱氧核苷酸钠注射液,疗程为1个月,比较两组患者的肝损伤情况及细胞免疫功能指标.采用SPSS 11.0软件进行数据处理和分析,计量资料以“（x）±s”表示,组间比较采用t检验,“率”的比较采用χ2检验,以P＜0.05为差异有统计学意义.结果 治疗后第2、4周,实验组肝损伤的发生率分别为10.71％（6/56）和23.21％（13/56）,明显低于对照组的32.14％（18/56）和48.21％（27/56）,差异有统计学意义（χ2值分别为7.64、7.62,P值均＜0.01）;实验组中度肝损伤1例（1.79％,1/56）,而对照组中、重度肝损伤有11例（19.64％,11/56）.在肝功能指标方面,治疗后第2周,对照组丙氨酸转氨酶[（45±23）U/L]、天冬氨酸转氨酶[（46±18）U/L]较实验组[分别为（24±12）U/L、（20±13）U/L]明显升高（t值分别为6.06、8.76,P值均＜0.01）;血清总胆红素[对照组：（9.6±4.7） μmol/L;实验组：（8.7±4.5）μmol/L]和血清白蛋白[对照组：（40.9±4.2）g/L;实验组：（41.3±4.6）g/L]差异无统计学意义（t值分别为1.04、0.48,P值均＞0.05）.治疗后第4周,对照组丙氨酸转氨酶[（102±36）U/L]、天冬氨酸转氨酶[（94±39）U/L]、血清总胆红素[（36.1±10.5） μmol/L]均明显高于实验组[分别为（33±16）U/L、（32±12）U/L、（9.8±5.1） μmol/L],血清白蛋白则明显下降[对照组：（32.7±5.3）g/L;实验组：（40.7±3.9）g/L],两组比较差异均有统计学意义（t值分别为13.11、11.38、16.88、9.11,P值均＜0.01）.在细胞免疫方面,治疗4周后,实验组CD4＋T淋巴细胞[（39.5±8.1）％]、CD4＋/CD8＋值（1.5±0.3）明显高于治疗前[分别为（33.5±5.2）％、1.2±0.2],而CD8＋T淋巴细胞则明显降低[治疗前后分别为（33.1±4.8）％、（30.3±4.7）％]（t值分别为4.67、3.12、6.25,P值均＜0.01）,且与对照组[治疗4周后分别为（33.5±5.9）％、（33.4±6.2）％、1.2±0.6]比较,差异也有统计学意义（t值分别为4.48、2.98、3.33,P值均＜0.01）.结论 脱氧核苷酸钠注射液能改善肺结核合并乙型肝炎抗原阳性患者在抗结核治疗中出现的肝损伤,且能增强机体的细胞免疫功能.

Objective To observe and evaluate the effect of sodium deoxy nucleotide injection on prevention and control of anti-TB drugs-induced liver damage in new pulmonary tuberculosis（PTB） patients with Hepatitis t3 antigen （HBsAg） positive. Methods One hundred and twelve new PTB patients with HBsAg positive diagnosed by laboratory tests and clinical features sought care in Anti-TB Institute of Shantou were selected, and were random- ly divided into experimental group and control group. The treatment regimen for control group was 2HRZE/4HR, Gan Tai Le tablet （Glucurolactone） was used regularly to protect liver. For the experimental group, on the basis of the control group regimen, Sodium deoxy nueleotide injection was added during the intensive phase for one month. The liver damage severity and indicators of immune cell function of the two groups were compared. SPSS 11.0 soft- ware was used for data processing and analysis, t test was used for quantitative data and Chi-square test was appliedfor rate comparison. P〈0.05 was considered statistically significant. Results The incidence of liver damage after 2 weeks and 4 weeks treatment in experimental group were 10.71% （6/56） and 23.21%（13/56） respectively, which were significantly lower than the control group （ 32.14 % （ 18 / 56） and 48. 21 % （27 / 56） ）, there were statisti- cally significant differences （χ2 = 7.64 and 7.62, P〈0.01）. There was 1 patient in experimental group suffered from moderate liver damage （1.79%, 1/56）, while in control group there were 11 patients suffered from moderate and severe liver injury （19.64%, 11/56）. In the aspect of liver function, after two weeks treatment, alanine ami- motransferase （ALT） and aspartate aminotransferase （AST） in the control group （（45±23）U/L and （46±18）U/L） were significantly higher than the experimental group （（24 ± 12）U/L and （20±13）U/L） （t = 6.06 and 8.76, P〈 0. 01）. There was no significant differences on serum total hilirubin （STB） and serum albumin （ALB） between the two groups （control group.. （9.6±4. 7）μmol/L and （40. 9±4. 2） g/L; experimental group. （8. 7±4. 5） μmol/L and （41.3±4.6）g/L）（t=1. 04 and 0.48, P〉0.05）. After 4 weeks treatment, ALT, AST and STB in the control group （（102±36）U/L, （94±39）U/L and （36.1±10. 5） μmol/L） were significantly higher than the experimental group （（33±16）U/L, （32±12） U/L and （9.8±5.1） μmol/L）. ALB decreased significantly in the control group. There were statistically significant differences between 2 groups （t= 13.11, 11.38, 16.88 and 9.11, P〈0. 01）. In the aspect of cell-mediated immunity, after 4 weeks treatment, in the experimental group CD4＋ lymphocyte （（39.5±8.1） % vs （33.5±5.2） %）, CD4＋/CD8＋ ratio （1.5±0. 3 vs 1.2±0. 2） obviously elevated while CD8＋ lymphocyte （（30.3±4. 7）% vs （33.1±4.8）%） significantly decreased （t=4.67, 3.12 and 6.25, P〈0. 01）, with significant differences contrast with the control group （（33.5±5.9）%, （33.4±6.2）% and 1.2±0.6） （t=4. 48, 2.98 and 3.33, P〈0.01）. Conclusion Sodium deoxy nucleotide injection can improve liver damage occurred in new PTB patients incorporated with Hepatitis B antigen positive during initial treatment, and can enhance immune function as well.