摘要
背景：慢加急性肝衰竭（acute-on-chronicliverfailure，ACLF）是在慢性肝病基础上，在急性诱因作用下，出现的以黄疸、凝血障碍、腹水和（或）肝性脑病等为主要临床表现的一种严重的临床综合征，病死率达65％-93％。对如此严重的疾病，进行随机对照临床试验研究，涉及伦理问题。因此，在探索新的中西医结合治疗方案时，可进行前瞻性队列研究设计。目的：对大剂量清热化瘀中药治疗乙型肝炎相关性ACLF热毒瘀结证进行疗效和安全性评价。设计、场所、受试者和干预措施：采用前瞻性队列研究方法，收集成都中医药大学附属医院感染科住院病房中符合纳入标准的乙型肝炎相关性ACLF患者，全部病例均行“经典的西医综合治疗”方案，以是否自愿接受中医药辨证治疗分为治疗组（，2=：=66）及对照组（72-32）。两组均干预12周。主要结局指标：评价治疗后3个月（治疗结束时）两组非肝移植患者的生存率。观察治疗前及治疗4、8和12周后的非肝移植患者的总胆红素（totalbilirubin，TBiL）、白蛋白（albumin，ALB）、丙氨酸氨基转移酶（alanineaminotransferase，ALT）、门冬氨酸氨基转移酶（aspartate aminotransferase，AST）及凝血酶原活动度（prothrombinactivity，PTA）等，并观察治疗前及治疗结束时的中医证候积分、并发症情况及安全性。结果：治疗组（n=66）死亡21例（31．8％），对照组（n-32）死亡19例（59．49／5），两组存活及死亡病例数比较，差异有统计学意义（x^26．775，P〈0．01）。在治疗12周期间，治疗组和对照组估计平均生存时间分别为69。9、47．2d；治疗组累积生存率高于对照组，经log-rank检验比较，差异有统计学意义（P〈0．01）。治疗4、8、12周时，治疗组血TBiL、ALT、AST、ALB、PTA等指标均改善，且均优于对照组（P〈0．01或P〈0．05）。治疗12周后，治疗组（n=45）中医证候积分平均为（7．52±2．41）分，低于对照组（n=13）的（18．34±4．36）分（t8．784，P〈0．01）。治疗组、对照组腹水发生率分别为22．229／6（10／45）、69．23％（9／13），感染发生率分别为8．89％（4／45）、53．85％（7／13），肝性脑病发生率分别为11．11％（5／45）、46．15％（6／13）；两组不良反应发生率分别为0．00％和12．50％，差异均有统计学意义（P〈0．05或P〈O．01）；治疗过程中，两组血、尿、大便常规，肾功能及心电图等检查均未见异常。结论：大剂量清热化瘀中药可显著改善乙型肝炎相关性ACLF热毒瘀结证患者的肝功能和凝血功能等，减少并发症，提高疗效，降低病死率。
BACKGROUND： Hepatitis Brelated acuteonchronic liver failure （ACLF） is a severe clinical syndrome characterized by jaundice, coagulopathy, ascites and hepatic encephalopathy and with a high mortality rate of 65% to 93%. It involves significant ethical issues when a randomized, doubleblinded, placebocontrolled clinical study is conducted to such a serious disease. Therefore, a prospective cohort study design was utilized to explore a new treatment modality of applying integrated traditional Chinese and Western medicine.
OBJECTIVE： To evaluate the efficacy, safety and recent survival rates of highdose herbs with the function of clearing heat and resolving stasis, named Qingre Huayu, in patients with hepatitis Brelated ACLF with heat toxin stagnation syndrome.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： A matched, prospective cohort study was conducted. Participants who met the inclusion criteria were recruited from the Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. Patients were assigned to either an integrated medicine group or a Western medicine group according to their own preference and received either a regime of classic Western medical treatment （control group） or a regime of classic Western medical treatment 131us Qingre Huayu herbs （treatment group）. The regimes were conducted for 12 weeks.
MAIN OUTCOME MEASURES： Survival rates of nonliver transplantation patients were evaluated after12-week treatment. The levels of total bilirubJn （TBiL）, albumin （ALB）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and prothrombin activity （PTA） were detected at baseline and weeks 4, 8 and 12. Scores of traditional Chinese medicine （TCM） syndrome and complications were evaluated at baseline and study completion. Adverse events were recorded.
RESULTS： All patients were followed up to the deadline for this study. There were 21 cases （31.8%） who died in the treatment group （n：66） and 19 cases （59. 4%） in the control group （n-32）. Significant difference （x^2=6. 775, P〈0.01） was found in comparing the survival and death rates between the two groups by X^2 test. At 12 weeks, mean survival time of the two groups was 69.9 and 47.2 d respectively; cumulative survival rate of patients in the treatment group was higher than that of patients in the control group （P〈0.01）. Levels of TBiL, ALT, AST, ALB and PTA at weeks 4, 8 and 12 in the treatment group were superior to those in the control group with statistical significance （P〈0. 01 or P〈：0. 05）. In comparison of the TCM syndrome scores at week 12, the average score of the TCM syndrome of the treatment group （n=45） was 7.52±2.41, lower than 18.34±4.36 of the control group （n=13）, and the difference was significant （t=8.784, P〈：0. 01）. Complication incidences after 12 weeks of treatment were statistically different between the treatment group （n=45） and the control group （n=13） by Z2 test （P〈：0.05 or P〈：0.01）. Incidence rates of ascites, infection and hepatic encephalopathy accounted for 22.22% （10/45） and 69.23% （9/13）, 8.89% （4/45） and 53.85% （7/13）, and 11.11% （5/45） and 46.15% （6/13） in the two groups respectively. The incidence rates of adverse events in the treatment group and the control group were 0.00 % and 12.50% respectively and the difference was statistically significant （x^2=5,705, P〈0.05）. No drugrelated adverse events were found in blood, urine and stool routine tests, renal function test and electrocardiography.
CONCLUSION：High doses of Qingre Huayu herbs can significantly improve liver function and coagulation function, reduce complications, and reduce mortality in patients with hepatitis Brelated ACLF.
出处
《中西医结合学报》
CAS
2012年第2期176-185,共10页
Journal of Chinese Integrative Medicine
基金
国家科技重大专项"十一五"计划资助项目(No.2009ZX10005
2008ZX10005)
四川省科技厅重大科技招标基金资助项目(No.310312)
关键词
中草药
肝功能衰竭
清热化瘀
存活率
证候
并发症
队列研究
前瞻性研究
drugs, Chinese herbal
liver failure
clearing heat and resolving stasis
survival rate
syndrome
complications
cohort studies
prospective studies
