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慢性乙型肝炎肝損傷與肝再生失衡評估模型構建研究

發(fā)布時間:2018-06-18 19:45

  本文選題:慢性乙型肝炎 + 肝損傷; 參考:《湖北中醫(yī)藥大學》2017年碩士論文


【摘要】:目的 本研究旨在針對部分早期無癥狀的慢性乙型肝炎患者,通過建立慢性乙型肝炎肝損傷與肝再生失衡狀態(tài)的生物學評價指標體系,構建肝損傷與肝再生失衡狀態(tài)的量化評估模型,為“無癥可辨”的慢性乙型肝炎患者提供臨床監(jiān)測和中醫(yī)藥干預依據(jù),防止病情進一步發(fā)展。方法 結合文獻計量學方法和Delphi專家咨詢法構建慢性乙型肝炎肝損傷與肝再生失衡狀態(tài)評價生物學指標體系。在此基礎上,根據(jù)納入、排除標準,從湖北省某三甲醫(yī)院中西醫(yī)結合治療慢性乙型肝炎病例中篩選數(shù)據(jù)納入研究,采用單因素方差分析和Logistic回歸方法篩選特征變量;結合研究數(shù)據(jù)實際問題(樣本量小,變量共線性問題),從多種分級評估算法中篩選兩種合適的算法構建模型,并根據(jù)靈敏度、準確度、特異度三個指標比較兩種模型預估結果,獲得最優(yōu)模型。在臨床上納入多例慢性乙型肝炎“肝腎精虛”證患者,進行為期一年的治療和動態(tài)監(jiān)測,分別在首診、半年和一年后對患者進行肝臟穿刺,同時利用模型對患者的肝損傷與肝再生失衡程度進行量化評估,與以“肝穿”為金標準的結果比較,檢驗模型預測的靈敏度/準確度。結果 本研究在546篇臨床試驗研究文獻計量結果基礎上,制定了Delphi專家咨詢表,其中涵蓋了25個與肝損傷和肝再生失衡狀態(tài)相關的生物學評價指標備選項,結合5位臨床肝病專家的問卷調查結果和意見,形成了評價慢性乙型肝炎肝損傷與肝再生失衡狀態(tài)的生物學指標體系,該體系包含肝損傷評價與肝再生評價兩個指標集,共納入ALT、AST、TNF-α、IL-6等16項指標,可有效反映肝損傷與肝再生失衡狀態(tài)評價的6個要素(肝組織病變程度、保肝作用、抗氧化能力、降酶作用、抗炎作用、肝再生能力)。本研究共納入慢性乙型肝炎患者114例,其中86例納入模型構建訓練集,其余28例為驗證集。模型構建納入ALT、ALB、TBIL、PDGF-B、G-CSF、TNF-α、IL-6和IL-18八個危險因素,分別采用Fisher判別算法和主成分回歸算法構建模型,比較預估結果獲得最優(yōu)模型——Fisher判別模型(靈敏度:97.06%、特異度:100%、準確度:97.67%),該模型的非標準化典型判別函數(shù)為:(1)F1=-0.514*Ln(ALT_(實測值))+4.826*Ln(ALB_(實測值))-1.454*Ln(TBIL_(實測值))-0.403*Ln(PDGF-B_(實測值))+0.239*Ln(G-CSF_(實測值))-0.118*SQRT(TNF-α_(實測值))+0.549*Ln(IL-6_(實測值))-0.121*Ln(IL-18_(實測值))-15.556;(2)F2=-0.166*Ln(ALT_(實測值))+0.391*Ln(ALT_(實測值))+0.087*Ln(TBIL_(實測值))+0.328*(PDGF-B_(實測值))-0.878*Ln(G-CSF_(實測值))+0.021*SQRT(TNF-α_(實測值))+0.934*Ln(IL-6_(實測值))-0.077*Ln(IL-18_(實測值))-5.152;實證研究中,與“肝穿刺”金標準判斷結果相比,模型對慢性乙型肝炎“肝腎精虛”證患者在首診、半年和一年后的肝損傷與肝再生失衡程度量化評估準確度為82.14%(23/28)、85.71%(24/28)和89.29%(25/28)。結論本研究建立的慢性乙型肝炎肝損傷與肝再生失衡狀態(tài)評價生物學指標體系具有結構簡單、覆蓋率高、重復率低等特點,涉及指標易于獲得,便于臨床采用。構建的慢性乙型肝炎肝損傷與肝再生失衡狀態(tài)評估Fisher判別模型在訓練和實證研究階段對慢性乙型肝炎患者肝損傷和肝再生失衡狀態(tài)分級診斷的準確性較高,可為后續(xù)深入研究提供基礎性依據(jù)。但由于本次納入研究樣本量較少,模型穩(wěn)定性不夠高,后續(xù)研究除需擴大樣本量外,還可通過改變Fisher算法判別準則或引入權重因子等方法進一步改進,以提升模型的穩(wěn)定性和準確率。
[Abstract]:Objective to establish a quantitative evaluation model for the unbalanced state of liver injury and liver regeneration by establishing a biological evaluation index system of the unbalanced state of liver injury and liver regeneration in chronic hepatitis B patients with asymptomatic hepatitis B, and to provide clinical monitoring for the patients with "symptomless discrimination" of chronic hepatitis B. Based on the Bibliometrics and Delphi expert consultation, the biological index system of the evaluation of liver injury and liver regeneration in chronic hepatitis B was constructed by bibliometrics and Delphi expert consultation. Based on the inclusion and exclusion criteria, the treatment of chronic hepatitis B from a three a hospital in Hubei province was combined with Chinese and Western Medicine. Screening data in hepatitis cases were included in the study. Single factor analysis of variance and Logistic regression were used to screen feature variables. Combined with the actual data of research data (small sample size, variable colinearity), two kinds of appropriate algorithms were selected from a variety of classification evaluation algorithms, and three index ratios were based on sensitivity, accuracy and specificity. The optimal model was obtained from the two models. Many patients with chronic hepatitis B, "liver kidney essence deficiency", were included in the treatment and dynamic monitoring for one year. The patients were punctured in the first visit, half a year and one year later, and the model was used to quantify the degree of liver injury and the imbalance of liver regeneration. The evaluation, compared with the results of the "liver wear" as the gold standard, tested the sensitivity / accuracy of the model prediction. Results based on the bibliometric results of 546 clinical trials, a Delphi expert consultation table was developed, covering 25 biological assessment options related to liver injury and liver regeneration imbalance, and 5 The results and suggestions of the questionnaire survey of clinical liver disease experts have formed a biological index system to evaluate the unbalanced state of liver injury and liver regeneration in chronic hepatitis B. This system includes two indexes of evaluation of liver injury and evaluation of liver regeneration, including 16 indexes such as ALT, AST, TNF- A and IL-6, which can effectively reflect the imbalance of liver injury and liver regeneration. The 6 elements of the evaluation (liver lesion degree, liver preservation, antioxidant capacity, antioxidation, anti-inflammatory, liver regeneration). This study included 114 patients with chronic hepatitis B, of which 86 were included in the model construction training set and the other 28 were the validation set. The model construction was included in ALT, ALB, TBIL, PDGF-B, G-CSF, TNF- a, IL-6 and IL-18. Risk factors, using the Fisher discriminant algorithm and the principal component regression algorithm to construct the model respectively, compare the prediction results to obtain the optimal model Fisher discriminant model (sensitivity: 97.06%, specificity: 100%, accuracy: 97.67%), and the model's non standardized typical discriminant function is (1) F1=-0.514*Ln (ALT_ (measured value)) +4.826*Ln (ALB_ (measured value)) -1.454* Ln (TBIL_ (measured value)) -0.403*Ln (measured value)) +0.239*Ln (G-CSF_ (measured value)) -0.118*SQRT (TNF- alpha) +0.549*Ln (IL-6_ (measured value)) -0.121*Ln (IL-18_ (measured value)); (2) (measured value)) +0.021*SQRT (measured value)) +0.934*Ln (IL-6_ (measured value)) -0.077*Ln (IL-18_ (measured value)) -0.077*Ln (measured value)) -5.152. In the empirical study, compared with the results of "liver puncture" gold standard, the model was used to quantify the quantitative assessment of the imbalance of liver injury and liver regeneration after the first diagnosis of the patients with "liver kidney essence deficiency" in the first diagnosis. The accuracy was 82.14% (23/28), 85.71% (24/28) and 89.29% (25/28). Conclusion the biological index system for the evaluation of liver injury and liver regeneration in chronic hepatitis B has the characteristics of simple structure, high coverage and low repetition rate, which are easy to obtain and facilitate clinical use. The Fisher discriminant model of regenerative imbalance state is more accurate for the diagnosis of liver injury and liver regeneration in chronic hepatitis B patients during the training and empirical study stage, which can provide a basic basis for further research. However, because the sample size is less, the stability of the model is not high, and the follow-up study needs to be expanded. Besides, large sample size can be further improved by changing the criterion of Fisher algorithm or introducing weighting factors to improve the stability and accuracy of the model.
【學位授予單位】:湖北中醫(yī)藥大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R259

【參考文獻】

相關期刊論文 前10條

1 李游;顏迎春;王妍;田霞;張明香;;慢性乙型肝炎中醫(yī)治療研究進展[J];遼寧中醫(yī)藥大學學報;2016年05期

2 李瀚e,

本文編號:2036652


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