异甘草酸镁对化疗药物致初治胃肠道肿瘤患者肝损害的预防作用

Magnesium isoglycyrrhizinate prevention of chemotherapy-induced liver damage during initial treatment of patients with gastrointestinal tumors

目的 观察异甘草酸镁对化疗药物致初治胃肠道肿瘤患者急性药物性肝损伤的预防作用. 方法 采用前瞻性随机对照研究,选择经病理学诊断为胃肠道恶性肿瘤并且有全身化疗适应证的初治胃肠道肿瘤患者216例,分为异甘草酸镁预防（实验）组、谷胱甘肽预防（对照）组.化疗分别采用FOLFOX方案、XELOX方案.在第一周期化疗开始前1天及化疗停药后1周留取血清,即时采用全自动生物化学分析仪检测ALT、AST、碱性磷酸酶（ALP）、总胆红素（TBil）.计量资料数据比较采用t检验,计数资料采用x2检验. 结果 共216例次化疗,40例次出现肝功能生物化学指标异常,其中实验组12例次（10.53％）,对照组28例次（27.25％）,预防效果差异有统计学意义（x 2=10.219,P＜0.01）.实验组及对照组肝急性及亚急性毒性反应分度比较：其中0、I度肝损害在实验组分别为94.78％、5.3％,对照组分别为88.2％、11.8％（x2=6.99,P＜0.01）;均未出现Ⅱ度及Ⅱ度以上肝损害.实验组化疗后1周肝功能生物化学指标：ALT为（35.93±8.33）U/L,AST为（24.84±2.91） U/L,TBil为（13.29±5.89） μmol/L,ALP为（125.1±53.61） U/L,与对照组比较,P值均＜ 0.05.实验组化疗前后肝功能生物化学指标差值：ALT为（13.18±3.23）U/L,AST为（5.39±2.57） U/L,TBil为（2.79±0.23）μmol/L,ALP为（52.08±4.83）U/L,与对照组比较,P值均＜ 0.05.实验组化疗后1周：FOLFOX方案组与XELOX方案组肝功能生物化学指标及其化疗前后差值比较,P值均＞ 0.05.对照组化疗后1周肝功能生物化学指标：AST在FOLFOX、XELOX方案组分别为（26.24±3.50） U/L、（29.80±6.57） U/L,t=-2.431,P＜ 0.05,其余指标差异未见统计学意义;肝功能生物化学指标差值：ALP差值在FOLFOX、XELOX方案组分别为（53.44±2.47）U/L、（56.58±6.70） U/L,t=-2.201,P＜0.05,其余指标差值的差异未见统计学意义. 结论 异甘草酸镁是预防初治胃肠道肿瘤患者化疗后药物性肝损伤的有效药物.

Objective To investigate the preventive effect of magnesium isoglycyrrhizinate against acute drug-induced liver damage from initial chemotherapy treatment in patients with gastrointestinal cancer.Methods A total of 216 cases with early stage gastric cancer and indications for systemic chemotherapy that had been diagnosed with gastrointestinal malignant tumors by pathology in our hospital were enrolled for study during the period of January 2011 to June 2013.Using a prospective randomized controlled study design,differences were assessed between groups treated with glycyrrhizic acid magnesium （experimental group; n =114） or glutathione （control group; n =102） and the FOLFOX regimen （n =104） or the XELOX regimen （n =112）.Patients in the FOLFOX group received intravenous infusion of L-OHP （85 mg/m2） at day 1,followed by a bolus injection of 5-FU （400 mg/m2） at days 1-2 and continuous intravenous infusion of 5-FU （600 mg/m2） for 22 h at days 1-2,with one cycle comprising 2 weeks.Patients in the XELOX group received intravenous infusion of L-OHP （130 mg/m2） at day 1,followed by capecitabine （1 000 mg/m2） oral twice a day at days 1-14,with one cycle comprising 3 weeks.In the first cycle of chemotherapy,serum was extracted from the patients at 1 day before chemotherapy and 1 week after chemotherapy.An automated biochemistry analyzer was used to measure alanine aminotransferase （ALT）,aspartate aminotransferase （AST）,total bilirubin （TBil） and alkaline phosphatase （ALP）.Differences between groups were statistically analyzed by the t-test andx2 test.Results Among the total 216 cases treated with chemotherapy,40 showed hepatic biochemical abnormalities （12 cases in the experimental group,28 cases in the control group）,and the effect of prevention was significantly different between the two groups （10.53% vs.27.25%;x2 =10.219,P 〈 0.005）.The acute and subacute hepatic toxicity reaction degrees for the experimental and the control groups were：0：94.78% vs.88.2%; 1：5.3% vs.11.8% （x2 =6.99,P 〈 0.01）.One week after chemotherapy,the liver biochemical indexes in the experimental group （ALT：35.93±8.33 U/L; AST：24.84±2.91 U/L; TBil：13.29±5.89 μmol/L; ALP：125.1±53.61 U/L） were statically different from those in the control group （all P 〈 0.05）.The liver biochemical indexes before and after chemotherapy were also significantly different between the experimental group （ALT：13.18t3.23 U/L; AST：5.39±2.57 U/L; TBil：2.79±0.23 μmol/L; ALP：52.08±4.83 U/L） and the control group （all P 〈 0.05）.One week after chemotherapy in the experimental group,the groups treated with the FOLFOX regimen or the XELOX regimen showed no statistical differences in the liver biochemical indexes.One week after chemotherapy in the control group,though,the groups treated with the FOLFOX regimen showed significantly lower AST （26.24±3.50 U/L vs.29.80±6.57 U/L,t =-2.431,P 〈 0.05）,but the residual liver biochemical indexes were not significantly different.In the experimental group,the FOLFOX group showed significantly lower ALP （53.44±2.47 U/L vs.56.58±6.70 U/L,t =-2.201,P 〈 0.05）,AST （6.48±3.15U/L vs.9.88±4.57 U/L,t =-5.223,P 〈 0.05）,but the residual liver biochemical index was not significantly different.Conclusion Magnesium isoglycyrrhizinate is an effective drug for the prevention of drug-induced liver damage after initial chemotherapy in patients with early stage gastrointestinal cancer.