本文選題：乙肝病毒相關慢加急性肝功能衰竭 + 抗病毒治療�。� 參考：《華中科技大學》2013年博士論文

【摘要】：【背景】 乙肝病毒相關的慢加急肝功能衰竭（HBV related acute-on-chronic liver failure,HBV-ACLF）是一類預后差病死率高的臨床綜合征，在亞洲和太平洋地區(qū)有較高的發(fā)病率。盡管高載量的HBV并不直接損傷肝細胞，但使用核苷（酸）類似物抗HBV治療在HBV-ACLF患者的綜合治療中具有非常重要的意義。2009年，，亞太肝病學會慢加急肝衰竭工作小組正式推薦對于HBV-ACLF應盡早使用核苷（酸）類似物進行抗病毒治療。臨床上缺乏能有效預測肝衰竭預后的模型。研究組前期針對HBV-ACLF建立了同濟預后預測模型（Tongji prognostic predictor model，TPPM），本研究對同濟預后預測模型進行了驗證。 【目的】 比較核苷（酸）類似物恩替卡韋、替比夫定及拉米夫定治療HBV-ACLF的安全性和有效性。驗證同濟預后預測模型（TPPM）對HBV-ACLF預后的預測價值優(yōu)于終末期肝病模型（MELD）。 【方法】 本研究回顧性分析了283例HBV-ACLF患者，均接受內(nèi)科標準治療和核苷（酸）類似物抗HBV治療。其中100例患者使用恩替卡韋抗病毒治療，85例患者使用替比夫定，98例患者使用拉米夫定。三組患者的基線臨床特征在病毒學、臨床生化等均無顯著差異。收集并隨訪患者的存活時間、生化指標、凝血功能、血液常規(guī)檢查和并發(fā)癥等臨床資料，比較恩替卡韋、替比夫定及拉米夫定的臨床效果及安全性。最后，比較TPPM和MELD對HBV-ACLF（HBV-ACLF）預后的預測價值。 【結(jié)果】 恩替卡韋、替比夫定或拉米夫定三組抗病毒治療的HBV-ACLF患者第4周和第12周的生存率無顯著差異，4周生存率分別為79.00%,81.18%和86.73%，12周生存率分別為67.00%,65.88%和73.47%。觀察抗病毒治療后四周內(nèi)，三組患者的MELD評分均有改善。通過Hosmer和Lemeshow檢驗，驗證了同濟預后預測模型優(yōu)于MELD模型，對HBV-ACLF的預后預測有更好的擬合度。針對本研究中283例HBV-ACLF的預后進行ROC曲線分析和比較，檢驗TPPM和MELD評分體系對HBV-ACLF患者的預后預測能力，TPPM預測12周死亡率的曲線下面積為0.787，優(yōu)于MELD的曲線下面積0.726；TPPM預測4周死亡率的曲線下面積為0.733，再次優(yōu)于MELD的曲線下面積0.67。評分以0.22為截斷值，TPPM預測HBV-ACLF12周死亡率，陽性預測值為49.66%，陰性預測值為89.55%。 【結(jié)論】 1.恩替卡韋，替比夫定和拉米夫定三種核苷（酸）類似物均可以阻止或延緩HBV-ACLF的病情快速進展并提高患者的近期生存率。 2.存在肝硬化的肝臟基礎疾病患者，由于肝臟儲備功能下降或門脈高壓狀態(tài)，更容易出現(xiàn)各類并發(fā)癥。 3.本研究驗證了TPPM模型優(yōu)于MELD模型，對HBV-ACLF預后有更好的預測價值。
[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.
【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2013
【分類號】：R512.62;R575.3

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