抗结核药物致急性肝损伤和中性粒细胞减少

Acute liver injury and neutropenia due to antitubercular agents

1例30岁女性患者因肺结核给予口服利福平0.5625g(早餐前)和异烟肼0.4g(晚餐后)。服药前,患者血常规及肝功能指标未见异常。服药3d后,患者出现乏力、恶心和呕吐症状。次日实验室检查示白细胞计数1.1×10^9/L,中性粒细胞计数0.32×10^9/L,血红蛋白(Hb)120g/L,血小板计数(PLT)149×10^9/L;丙氨酸转氨酶(ALT)368U/L,天冬氨酸转氨酶(AST)1333U/L,总胆红素(TBil)19.7μmol/L,直接胆红素(DBil)6.6μmol/L。诊断为肝损伤,中性粒细胞减少。考虑当前用药所致,停用利福平和异烟肼,并给予保肝和对症治疗。停药第4天,患者症状改善,中性粒细胞计数1.50×10^9/L;ALT163U/L,AST139U/L,TBil9.0μmol/L,DBil3.7μmol/L。停药第7天,患者肝功能好转(ALT75U/L,AST33U/L,TBil6.4μmol/L,DBil3.3μmol/L),中性粒细胞计数1.60×10^9/L。出院1周后复查,患者中性粒细胞计数1.70×10^9/L;ALT30U/L,AST34U/L,TBil10.0μmol/L,DBil4.2μmol/L。

A 30-year-old female patient received oral rifampicin 0.562 5 g (before breakfast) and isoniazid 0.4 g (after dinner) for pulmonary tuberculosis. There were no abnormalities in her blood routine and liver function indexes before medication. Three days after the medication, the patient developed fatigue, nausea, and vomiting. The next-day laboratory tests showed white blood cell count 1.1×10^9/L, neutrophil count 0.32×10^9/L, hemoglobin (Hb) 120 g/L, platelet count (PLT) 149×10^9/L, alanine aminotransferase (ALT) 368 U/L, aspartate aminotransferase (AST) 1 333 U/L, total bilirubin (TBil) 19.7 μmol/L, and direct bilirubin (DBil) 6.6 μmol/L. Liver injury and neutropenia were diagnosed. Considering the reason from current medication, rifampicin and isoniazid were discontinued and liver-protective and symptomatic treatments were given. On day 4 of the withdrawal, the patient′s symptoms improved and laboratory tests showed neutrophil count 1.50×10^9/L, ALT 163 U/L, AST 139 U/L, TBil 9.0 μmol/L, and DBil 3.7 μmol/L. On day 7 of the withdrawal, the patient′s liver function improved (ALT 75 U/L, AST 33 U/L, TBil 6.4 μmol/L, and DBil 3.3 μmol/L) and her neutrophil count was 1.60×10^9/L. One week after discharge, the neutrophil count was 1.70×10^9/L;the levels of ALT, AST, TBil, and DBil were 30 U/L, 34 U/L, 10.0 μmol/L, and 4.2 μmol/L, respectively .