核苷（酸）类似物治疗乙肝病毒相关慢加急性肝功能衰竭的临床研究

发布时间：2018-06-03 19:46

本文选题：乙肝病毒相关慢加急性肝功能衰竭 + 抗病毒治疗　；参考：《华中科技大学》2013年博士论文

【摘要】：【背景】乙肝病毒相关的慢加急肝功能衰竭（HBV related acute-on-chronic liver failure,HBV-ACLF）是一类预后差病死率高的临床综合征，在亚洲和太平洋地区有较高的发病率。尽管高载量的HBV并不直接损伤肝细胞，但使用核苷（酸）类似物抗HBV治疗在HBV-ACLF患者的综合治疗中具有非常重要的意义。2009年，，亚太肝病学会慢加急肝衰竭工作小组正式推荐对于HBV-ACLF应尽早使用核苷（酸）类似物进行抗病毒治疗。临床上缺乏能有效预测肝衰竭预后的模型。研究组前期针对HBV-ACLF建立了同济预后预测模型（Tongji prognostic predictor model，TPPM），本研究对同济预后预测模型进行了验证。【目的】比较核苷（酸）类似物恩替卡韦、替比夫定及拉米夫定治疗HBV-ACLF的安全性和有效性。验证同济预后预测模型（TPPM）对HBV-ACLF预后的预测价值优于终末期肝病模型（MELD）。【方法】本研究回顾性分析了283例HBV-ACLF患者，均接受内科标准治疗和核苷（酸）类似物抗HBV治疗。其中100例患者使用恩替卡韦抗病毒治疗，85例患者使用替比夫定，98例患者使用拉米夫定。三组患者的基线临床特征在病毒学、临床生化等均无显著差异。收集并随访患者的存活时间、生化指标、凝血功能、血液常规检查和并发症等临床资料，比较恩替卡韦、替比夫定及拉米夫定的临床效果及安全性。最后，比较TPPM和MELD对HBV-ACLF（HBV-ACLF）预后的预测价值。【结果】恩替卡韦、替比夫定或拉米夫定三组抗病毒治疗的HBV-ACLF患者第4周和第12周的生存率无显著差异，4周生存率分别为79.00%,81.18%和86.73%，12周生存率分别为67.00%,65.88%和73.47%。观察抗病毒治疗后四周内，三组患者的MELD评分均有改善。通过Hosmer和Lemeshow检验，验证了同济预后预测模型优于MELD模型，对HBV-ACLF的预后预测有更好的拟合度。针对本研究中283例HBV-ACLF的预后进行ROC曲线分析和比较，检验TPPM和MELD评分体系对HBV-ACLF患者的预后预测能力，TPPM预测12周死亡率的曲线下面积为0.787，优于MELD的曲线下面积0.726；TPPM预测4周死亡率的曲线下面积为0.733，再次优于MELD的曲线下面积0.67。评分以0.22为截断值，TPPM预测HBV-ACLF12周死亡率，阳性预测值为49.66%，阴性预测值为89.55%。【结论】 1.恩替卡韦，替比夫定和拉米夫定三种核苷（酸）类似物均可以阻止或延缓HBV-ACLF的病情快速进展并提高患者的近期生存率。 2.存在肝硬化的肝脏基础疾病患者，由于肝脏储备功能下降或门脉高压状态，更容易出现各类并发症。 3.本研究验证了TPPM模型优于MELD模型，对HBV-ACLF预后有更好的预测价值。
[Abstract]:[background] Hepatitis B virus associated chronic acute liver failure HBV-ACLF is a kind of clinical syndrome with poor prognosis and high mortality. It has a high incidence in Asia and the Pacific. Although high-load HBV does not directly damage hepatocytes, the use of nucleoside analogues against HBV is of great significance in the comprehensive treatment of HBV-ACLF patients. The Asia-Pacific Society for liver Disease working Group on chronic Acute liver failure formally recommends the early use of nucleoside (acid) analogue for antiviral treatment of HBV-ACLF. There is a lack of clinical models that can effectively predict the prognosis of liver failure. Tongji prognostic predictor model (Tongji prognostic predictor model) was established to predict the prognosis of HBV-ACLF. [purpose] To compare the safety and efficacy of nucleoside analogues entecavir, tibivudine and lamivudine in the treatment of HBV-ACLF. The predictive value of Tongji prognostic model (TPPM) for HBV-ACLF was better than that for end-stage liver disease. [methods] In this study, we retrospectively analyzed 283 patients with HBV-ACLF who received standard medical treatment and nucleoside (acid) analogue anti HBV therapy. Among them, 100 cases were treated with entecavir antiviral therapy and 85 cases were treated with tibivudine. 98 cases were treated with lamivudine. There were no significant differences in virology and clinical biochemistry among the three groups. To compare the clinical efficacy and safety of entecavir, tibivudine and lamivudine, the survival time, biochemical parameters, coagulation function, blood routine examination and complications were collected and followed up. Finally, the prognostic value of TPPM and MELD in HBV-ACLF (HBV-ACLF) was compared. [results] There was no significant difference in the 4th and 12th week survival rates among the HBV-ACLF patients treated with entecavir, tibivudine or lamivudine. The four-week survival rates were 79.00% and 81.18%, respectively. The 12-week survival rates were 67.00% and 73.47%, respectively. The MELD scores of the three groups were improved within four weeks after antiviral therapy. The results of Hosmer and Lemeshow test showed that Tongji prognostic prediction model was superior to MELD model and had a better fit for HBV-ACLF prognosis prediction. The prognosis of 283 cases of HBV-ACLF in this study was analyzed and compared by ROC curve. To test the prognostic ability of TPPM and MELD scoring system in predicting the prognosis of HBV-ACLF patients, the area under the curve of predicting 12-week mortality was 0.787, and the area under the curve of MELD was 0.733, and the area under the curve of MELD was 0.67. The HBV-ACLF12 mortality was predicted with 0.22 truncation value, 49.66 positive predictive value and 89.55 negative predictive value. [conclusion] 1. Entecavir, tibivudine and lamivudine can all prevent or delay the rapid progression of HBV-ACLF and improve the short-term survival rate. 2. Patients with liver underlying diseases with liver cirrhosis are more likely to have complications due to decreased liver reserve function or portal hypertension. 3. This study verifies that TPPM model is superior to MELD model and has better prognostic value for HBV-ACLF.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R512.62;R575.3

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