本文關鍵詞： 肝炎 乙型 急性 肝衰竭 發(fā)熱 前驅期 前核心區(qū) 病毒變異　出處：《山東大學》2013年碩士論文　論文類型：學位論文

【摘要】：研究背景及目的：2006年全國乙型肝炎流行病學調查結果顯示,1～59歲一般人群中乙肝表面抗原(hepatitis B surface antigen, HBsAg)攜帶率為7.18%。HBV感染后,由于人體免疫功能強弱,可出現亞臨床感染(隱性感染)、顯性感染甚至出現急性肝衰竭。免疫功能健全成人感染HBV后,由于機體免疫系統(tǒng)強力清除病毒,可造成肝臟損傷,嚴重時由于肝細胞壞死廣泛,可導致重型肝炎甚至急性肝衰竭(ALF)。在中國及世界范圍內其他HBV流行區(qū),急性乙型肝炎仍然是急性肝衰竭最重要乃至最常見的原因。 發(fā)熱是最常見的臨床癥狀之一。發(fā)熱反應可以解釋許多疾病的發(fā)病機理,臨床表現,甚至判斷疾病預后；前驅期發(fā)熱以及體溫的高低與疾病嚴重程度及某些傳染性疾病的診斷密切相關。急性乙型肝炎患者前驅期出現發(fā)熱并不常見,且通常表現輕微,我們對于前驅期發(fā)熱是否在急性乙型肝炎臨床病程中存在作用尚不清楚。 本研究的目的是調查急性乙型肝炎患者中前驅期出現發(fā)熱癥狀的可能影響因素以及其在急性肝衰竭進展過程中作用 方法：1.調查了2006年1月至2010年12月間于濟南市傳染病醫(yī)院確診并住院的618例急性乙型肝炎患者。急性乙型肝炎診斷標準符合2000年西安會議修訂的《病毒性肝炎防治方案》；急性肝衰竭診斷標準符合我國《肝衰竭診療指南》(2012年版)；前驅期發(fā)熱界定為體溫測量值大于37.5℃或者患者自覺發(fā)熱(即無客觀測量數據)。 2.本研究比較了急性乙型肝炎患者中出現或不出現前驅期發(fā)熱癥狀的人群以及是否發(fā)生急性肝衰竭人群的人口學數據、臨床表現、血清生化學和病毒學指標。3.統(tǒng)計方法：分類變量使用卡方檢驗；連續(xù)型變量視不同情況分別使用t檢驗或Mann-Whitney U檢驗或Kruskal-Wallis檢驗。使用多因素logistic回歸分析急性乙型肝炎患者前驅期出現發(fā)熱癥狀以及發(fā)生急性肝衰竭的危險因素。P值小于0.05具有統(tǒng)計學意義。所有數據分析應用SPSS16.0(SPSS Inc., Chicago,IL,USA)統(tǒng)計學軟件進行. 結果：1.急性乙型肝炎出現前驅期發(fā)熱癥狀患者的臨床特征 發(fā)熱與未發(fā)熱組患者的平均年齡、性別比例、戶籍、吸煙飲酒史、自疾病起始至入院前時間(天)及至第1次化驗檢查的時間(天)相近,無明顯統(tǒng)計學差異。發(fā)熱組患者的谷丙轉氨酶(ALT)、膽紅素、國際標準化比值(INR)中位數明顯高于未發(fā)熱組；而白蛋白、血小板水平明顯低于未發(fā)熱組,差異具有統(tǒng)計學意義。發(fā)熱組HBsAg250IU/mL以及HBeAg陽性率明顯低于未發(fā)熱組(P≤0.001)。且兩組間HBeAg陽性率的不同只有當HBV DNA≥1000copies/ml時具有顯著的統(tǒng)計學差別。發(fā)熱組急性肝衰竭的發(fā)生率和病死率明顯高于未發(fā)熱組患者(P＜0.001)。 2.急性乙型肝炎患者前驅期出現發(fā)熱癥狀的的危險因素 多因素logistic回歸分析表明,在調整了多因素后,白蛋白40g/L,血小板＜150×109/L,INR＞1.1,入院時HBeAg陰性是急性乙型肝炎患者前驅期出現發(fā)熱癥狀的獨立危險因素。比值比(95%可信區(qū)間)分別為1.9(1.2-3.2),2.3(1.3-4.0),1.9(1.1-3.1)和2.4(1.4-4.2)。 3.急性乙型肝炎患者中,前驅期發(fā)熱癥狀與急性肝衰竭的關系。 618例患者中,41例(6.6%)出現急性肝衰竭。其中25例(61%)患者死亡,16例(39%)存活。與未出現急性肝衰竭組相比,急性肝衰竭組患者前驅期發(fā)熱的比例更高(46.3%vs.14.4%,P＜0.001)。同樣,體溫測量值T≥38℃比例更高(41.5%vs.7.6%,P＜0.001)。急性肝衰竭組患者具有更高的TBIL、INR水平(P＜0.001)以及較低的白蛋白、血小板水平,HBsAg2501U/ml比例較低(P＜0.001)。調整多項指標后,多因素logistic]回歸分析顯示前驅期發(fā)熱(體溫測量值＞37.5℃或自覺發(fā)熱)及T≥38℃是急性乙型肝炎患者發(fā)生急性肝衰竭的獨立危險因素；比值比(95%可信區(qū)間)分別為3.5(1.4-8.6)和7.1(2.6-19.7)。4.出現急性肝衰竭及前驅期發(fā)熱急性乙型肝炎患者的臨床特點. 出現發(fā)熱的急性肝衰竭患者中,男性性別比例明顯高于未發(fā)熱組(100%vs.77.3%,P=0.03)。自疾病起始進展至肝性腦病的平均時間明顯低于未發(fā)熱組(6.6±3.5vs.15.2±7.5,P＜0.001)。兩組患者的病死率相近,發(fā)熱組HBeAg陽性率明顯低于未發(fā)熱組(15.8%vs59.1%,P=0.005). 結論： 1.急性乙型肝炎患者中,前驅期發(fā)熱癥狀的流行率為16.5%。 2.前驅期發(fā)熱與感染致使HBeAg表達丟失的前核心區(qū)變異的HBV病毒株有關。 3.前驅期發(fā)熱是急性乙肝患者發(fā)生肝衰竭的獨立危險因素。
[Abstract]:Background and objective: 2006 national epidemiological survey showed that hepatitis B, hepatitis B surface antigen 1~59 in the general population (hepatitis B surface antigen, HBsAg) carrying rate of 7.18%.HBV after infection, the immune function of human body strength, there may be subclinical infection (infection), apparent infection or even acute liver failure of immune function. Adult after HBV infection, because the immune system strong clear virus, can cause serious liver damage, due to extensive hepatocyte necrosis, can cause severe hepatitis and acute liver failure (ALF). In China and throughout the world, other HBV epidemic areas, acute hepatitis B is still the most important and the most common acute liver failure the reason.
Fever is one of the most common clinical symptoms. Fever reaction can explain the pathogenesis of many diseases, clinical manifestation, prognosis and diagnosis; prodromal fever and body temperature level and severity of disease and certain infectious diseases are closely related. In patients with acute hepatitis B liver precursor fever is not common, and usually mild we for prodromal fever in the clinical course of acute hepatitis B in effect is not clear.
The purpose of this study is to investigate the possible influencing factors of febrile symptoms in patients with acute hepatitis B and its role in the progression of acute liver failure.
Methods: 1. survey from January 2006 to December 2010 in Jinan Infectious Disease Hospital and the hospital diagnosed 618 cases of acute hepatitis B patients. Acute hepatitis B prevention scheme revised diagnostic criteria in line with the Xi'an conference of 2000 > > viral hepatitis; diagnostic criteria for acute liver failure in line with China's "guidelines for diagnosis and treatment of liver failure" (2012 Edition); prodromal fever is defined as the temperature measurement value is greater than 37.5 degrees or the patient subjective fever (i.e. no objective measurements).
2. this study compared the demographic data of patients with acute hepatitis B in the presence or absence of prodromal symptoms of fever and whether people prevalence of acute liver failure in clinical manifestation, chemical and virological indicators of.3. statistical methods: Serum categorical variables using chi square test; continuous variables according to different circumstances respectively using t test or Mann-Whitney U test or Kruskal-Wallis test. Using logistic regression analysis of acute hepatitis B patients with prodromal fever symptoms and risk factors of acute liver failure.P value less than 0.05 was statistically significant. All data was analyzed using the SPSS16.0 (SPSS Inc., Chicago, IL, USA) statistical software.
Results: 1. the clinical characteristics of patients with prodromal fever symptoms in acute hepatitis B
Fever and non fever patients mean age, sex ratio, household smoking, drinking history, since before the time of disease onset to admission (first days) and test time (days) were similar, no statistically significant difference in patients with fever. Alanine aminotransferase (ALT), bilirubin, international standard the median ratio (INR) was significantly higher than in nonfebrile; and albumin, platelet levels were significantly lower than that of non fever group, the difference was statistically significant. The fever group HBsAg250IU/mL and the positive rate of HBeAg was lower than that of the non fever group (P = 0.001). And the two groups of HBeAg positive rate among the different DNA only when HBV is not less than 1000copies/ml with statistically significant difference a significant incidence of fever group. Acute liver failure and mortality rate was significantly higher than in nonfebrile patients (P < 0.001).
2. the risk factors for the onset of fever in patients with acute hepatitis B
Multivariate logistic regression analysis showed that after adjustment for multiple factors, albumin 40g/L, platelet < 150 * 109/L, INR > 1.1, HBeAg negative admission is an independent risk factor of acute hepatitis B patients with prodromal fever symptoms. The odds ratio (95% confidence interval) were 1.9 (1.2-3.2), 2.3 (1.3-4.0) 1.9, (1.1-3.1) and 2.4 (1.4-4.2).
3. the relationship between prodromal fever and acute liver failure in patients with acute hepatitis B.
In 618 patients, 41 cases (6.6%) suffered from acute liver failure. 25 cases (61%) patients died, 16 cases (39%). Survival and non acute liver failure group, higher acute liver failure patients with prodromal fever ratio (46.3%vs.14.4%, P < 0.001). Similarly, temperature the T value of more than 38 DEG C higher proportion (41.5%vs.7.6%, P < 0.001). Acute liver failure patients have higher TBIL, INR levels (P < 0.001) and albumin, low platelet levels, a low proportion of HBsAg2501U/ml (P < 0.001). The adjustment of a number of indicators, the multi factor Logistic regression. Analysis showed that prodromal fever (measured body temperature value is higher than 37.5 DEG C or consciously fever) of more than 38 DEG C and T are independent risk factors in patients with acute hepatitis B incidence of acute liver failure; odds ratio (95% confidence interval) were 3.5 (1.4-8.6) and 7.1 (2.6-19.7).4. acute liver failure and prodromal fever acute hepatitis hepatitis The clinical characteristics of the person.
Acute liver failure patients with fever, the proportion of male gender was significantly higher than in nonfebrile (100%vs.77.3%, P=0.03). The average time from disease onset to progression of hepatic encephalopathy was significantly lower than in nonfebrile (6.6 + 3.5vs.15.2 + 7.5, P < 0.001). The mortality rate in two groups were similar. The positive rate of fever group HBeAg was lower than that of the non fever group (15.8%vs59.1%, P=0.005).
Conclusion:
1. of the patients with acute hepatitis B, the prevalence of fever symptoms in the prodrome is 16.5%.
2. fever and infection in the prodrome are related to the HBV virus strain of the former core region of the HBeAg expression.
3. prodromal fever is an independent risk factor for liver failure in patients with acute hepatitis B.

【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R512.62;R575.3

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本文編號：1524694