慢性乙型肝炎慢加急性肝衰竭患者应用不同抗病毒药物治疗后的临床疗效观察

发布时间：2018-10-23 11:08

【摘要】：研究目的观察拉米夫定（Lamivudin，LAM）、恩替卡韦（Entecavir，ETV）、拉米夫定联合阿德福韦酯（Adefovir dipivoxi，ADV）（以下简称联合）治疗慢性乙型肝炎慢加急性肝衰竭（hepatitis B virus related acute-on-chronic liver failure，HBV-ACLF）早、中期患者的24周临床疗效。以期找到更合理、更经济、更安全有效的抗病毒治疗方案，快速控制HBV感染所致慢加急性肝衰竭患者的病情，为后期治疗及肝脏细胞再生赢得时间，降低肝衰竭患者的死亡率。研究方法收集并采用回顾性分析2010年12月至2013年6月期间在我院感染科确诊并治疗的89例HBV-ACLF早、中期患者的临床数据及随访记录。其中25例患者接受恩替卡韦抗病毒治疗，42例患者接受拉米夫定治疗，22例患者接受联合治疗，比较三组患者在治疗前后0、4、8、12、24周的临床生化指标改善程度、病毒载量的下降幅度、出现各种并发症的几率以及短期内生存率和死亡率等方面综合判断三种不同抗病毒方案的优劣。结果 1.三组患者的人口学特征及初始治疗时临床指标的比较，差异均无统计学意义（P0.05） 2.与本组治疗前基线相比较，3组患者24周后ALT均明显下降，差异有统计学意义（P0.001）。 3.与本组治疗前基线相比较，3组患者TBil水平在治疗第2、4周时均有所上升，治疗4周后开始下降，24周后TBil水平明显下降，差异有统计学意义（P0.001）。 4.与本组治疗前基线相比较，3组患者24周后PTA均明显上升，差异有统计学意义（P0.05）。 5.与本组治疗前基线相比较，3组患者HBV-DNA滴度在治疗4周后均快速下降，差异有统计学意义（P0.001）。 6.24周后恩替卡韦治疗组与联合治疗组相比，HBV-DNA滴度明显降低，2组间差异有统计学意义（P=0.0022）。 7.比较随访结束时恩替卡韦治疗组HBV-DNA低于检测下限即转阴率为62.5%，，拉米夫定治疗组转阴率为25%，联合组转阴率为16.7%，三组转阴率差异有统计学意义（P 0.05）。 8.24周后，恩替卡韦治疗组死亡9例，死亡率为36%；拉米夫定治疗组死亡10例，死亡率为23.8%；联合治疗组死亡10例，死亡率为45.5%，差异无统计学意义,在死亡原因分析中,三组患者死于各类并发症的比较,差异无统计学意义（P0.05）。 9.随访结束时恩替卡韦治疗组存活16例，存活率为64%，拉米夫定治疗组存活32例，存活率为76.2%，联合治疗组存活12例，存活率为54.5%，三组患者生存曲线比较，差异无统计学意义（P0.05），两两比较无统计学意义（P0.05）。结论三种抗病毒方案均能快速下降慢性乙型肝炎慢加急性肝衰竭患者的ALT、TBil以及HBV-DNA等临床指标，促进肝功能的恢复，24周内患者的死亡率及累计存活率在三组之间差别无统计学意义，但从长远来看，恩替卡韦可能会达到更好的病毒学应答。
[Abstract]:Objective to observe the 24 week clinical efficacy of lamivudine (Lamivudin,LAM), entecavir (Entecavir,ETV), lamivudine and adefovir (Adefovir dipivoxi,ADV) in the treatment of chronic hepatitis B (CHB) with acute hepatic failure (hepatitis B virus related acute-on-chronic liver failure,HBV-ACLF). In order to find a more reasonable, more economical, more safe and effective antiviral treatment, to quickly control the condition of patients with chronic and acute liver failure caused by HBV infection, to buy time for later treatment and liver cell regeneration, and to reduce the mortality of patients with liver failure. Methods the clinical data and follow-up records of 89 cases of HBV-ACLF diagnosed and treated in our hospital from December 2010 to June 2013 were collected and analyzed retrospectively. Among them, 25 patients received entecavir antiviral therapy, 42 patients received lamivudine treatment, 22 patients received combined treatment. The improvement degree of clinical biochemical indexes and the decrease of viral load were compared between the three groups before and after treatment. The probability of various complications, short-term survival rate and death rate were used to judge the merits and demerits of three different antiviral protocols. Result 1. The demographic characteristics of the three groups of patients and the initial treatment of clinical indicators, the differences were not statistically significant (P0.05) 2. 5. Compared with baseline before treatment, ALT decreased significantly in the three groups after 24 weeks (P0.001). Compared with the baseline before treatment, the level of TBil in the three groups increased at the 2nd week, began to decrease after 4 weeks of treatment, and decreased significantly after 24 weeks of treatment (P0.001). The difference was statistically significant (P0.001). Compared with the baseline before treatment, the PTA of the 3 groups increased significantly after 24 weeks, the difference was statistically significant (P0.05). Compared with baseline before treatment, the titer of HBV-DNA in the three groups decreased rapidly after 4 weeks of treatment. After 6.24 weeks, the titer of HBV-DNA in the entecavir group was significantly lower than that in the combined treatment group, and the difference between the two groups was statistically significant (P0. 0022). At the end of follow-up, the HBV-DNA of the treatment group was lower than the lower detection limit (62.5%), the negative conversion rate of lamivudine group was 25%, and the negative conversion rate of the combined group was 16.7%. There was significant difference among the three groups after 8. 24 weeks (P < 0. 05). There were 9 deaths in the entecavir group with a mortality rate of 36; 10 deaths in the lamivudine group with a mortality rate of 23.80.The combined treatment group had 10 deaths, with a mortality rate of 45.5. The difference was not statistically significant. Three groups of patients died from various complications, the difference was not statistically significant (P0.05). At the end of follow-up, 16 cases survived in entecavir group (64%), 32 cases survived in lamivudine group (76.2%), 12 cases survived in combination group (54.5%). The difference was not statistically significant (P0.05), pairwise comparison had no statistical significance (P0.05). Conclusion all three antiviral regimens can rapidly decrease the ALT,TBil and HBV-DNA in patients with chronic hepatitis B and acute liver failure. There was no significant difference in mortality and cumulative survival rate between the three groups within 24 weeks, but in the long run, entecavir might achieve a better virological response.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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