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目的:评价临床常见肺癌化疗方案所致药物性肝损伤(DILI)的影响因素及保肝药物使用的合理性。方法:选择我院2018年2月1日-2019年1月31日接受常见化疗方案的肺癌患者资料,回顾性分析不同化疗方案所致DILI的发生情况、相关影响因素并评价保肝药物使用的合理性。结果:共纳入325例患者,其中有126例患者(38.77%)出现DILI,包括1级109例(33.54%)、2级17例(5.23%)。常见化疗方案包括依托泊苷+顺铂、吉西他滨+顺铂、多西他赛+铂类、培美曲塞二钠+铂类。DILI临床分型为肝细胞损伤型44例(14.52%)、胆汁淤积型38例(12.54%)、混合型37例(12.21%)。有174例患者(53.54%)在化疗时使用保肝药物,其中有49例(28.16%)出现1级DILI,6例(3.45%)出现2级DILI,总发生率为31.61%;未使用保肝药物的患者中有60例(39.74%)出现1级DILI,11例(7.28%)出现2级DILI,总发生率为47.02%,显著高于使用保肝药物患者(P<0.05)。使用保肝药物的患者中有23例(13.22%)为不合理用药,包括3种及3种以上保肝药物联用5例(2.87%),相同作用机制的保肝药物重复用药3例(1.72%),3种及3种以上保肝药物联用与相同作用机制保肝药物重复用药同时存在11例(6.32%),违反禁忌证用药4例(2.30%)。影响因素相关性分析结果显示,化疗药物剂量、疗程和化疗前功能状态评分均与DILI的发生呈正相关(P<0.05)。结论:化疗药物剂量、疗程和化疗前功能状态评分是DILI发生的主要影响因素。我院保肝药的使用存在重复用药、联合用药品种数不合理、违反禁忌证用药等不合理情况。化疗时使用保肝药物能够降低DILI的发生风险,但临床医师需加强对保肝药物使用方法、适应证的认识,以提高用药的有效性和安全性。
OBJECTIVE: To evaluate the influential factors for drug-induced liver injury (DILI) caused by routine lung cancer chemotherapy plan and the rationality of hepatoprotective drugs. METHODS: The information of lung cancer patients receiving routine chemotherapy in our hospital from Feb. 1st, 2018 to Jan. 31st, 2019 were selected. The occurrence of DILI induced by different routine chemotherapy plans, the correlation of each influential factor with DILI and the rationality of hepatoprotective drugs were analyzed retrospectively. RESULTS: A total of 325 patients were involved in this study, among which 126 patients (38.77%) suffered from DILI, involving 109 first-level cases (33.54%) and 17 second-level cases (5.23%). Routine chemotherapy plan included etoposide+cisplatin, gemcitabine+cisplatin, docetaxel+platinum, pemetrexed disodium+platinum. The clinical classification of DILI included hepatocyte injury type 44 cases (14.52%), cholestasis type 38 cases (12.54%) and mixed type 37 cases (12.21%). Totally 174 patients (53.54%) received hepatoprotective drugs during chemo-therapy, among whom 49 patients (28.16%) suffered from first-level DILI and 6 patients (3.45%) second-level DILI, with total incidence of 31.61%. Among patients without hepatoprotective drugs, 60 patients (39.74%) suffered from first-level DILI, and 11 patients (7.28%) suffered from second-level DILI, with total incidence of 47.02%. The incidence of DILI in patients without hepatoprotective drugs was significantly higher than those with hepatoprotective drugs (P<0.05). Among patients with hepatoprotective drugs, 23 patients (13.22%) used hepatoprotective drugs unreasonably, including 5 patients (2.87%) received 3 kinds or more hepatoprotective drugs; 3 patients (1.72%) received drugs with same mechanism repeatedly; 11 patients (6.32%) received 3 kinds or more drugs and drug with same mechanism repeatedly; 4 patients (2.30%) used drugs contrary to contraindication. Influential factor correlation analysis showed that there was a positive correlation between DILI and the dosage of chemotherapeutic drugs, treatment course and KPS before chemotherapy (P<0.05). CONCLUSIONS: KPS before chemotherapy, dosage of chemotherapeutic agents and treatment course are the main factors of DILI. There is still unreasonable use of drugs such as repeated use, unreasonable drug combination, violation of drug contraindications. The use of hepatoprotective drugs during chemotherapy can reduce the risk of DILI occurrence. Clinicians should be more aware of the methods and indications of hepatoprotective drugs in order to improve the effectiveness and safety of drug use.
肺癌药物性肝损伤化疗方案影响因素保肝药物合理性评价
Lung cancerDrug-induced liver injuryChemotherapy planInfluential factorHepatoprotective drugsRationality evaluation
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