急性乙型肝炎前驱期发热与肝衰竭的相关性研究

发布时间：2018-02-22 15:26

本文关键词： 肝炎乙型急性肝衰竭发热前驱期前核心区病毒变异　出处：《山东大学》2013年硕士论文　论文类型：学位论文

【摘要】：研究背景及目的：2006年全国乙型肝炎流行病学调查结果显示,1～59岁一般人群中乙肝表面抗原(hepatitis B surface antigen, HBsAg)携带率为7.18%。HBV感染后,由于人体免疫功能强弱,可出现亚临床感染(隐性感染)、显性感染甚至出现急性肝衰竭。免疫功能健全成人感染HBV后,由于机体免疫系统强力清除病毒,可造成肝脏损伤,严重时由于肝细胞坏死广泛,可导致重型肝炎甚至急性肝衰竭(ALF)。在中国及世界范围内其他HBV流行区,急性乙型肝炎仍然是急性肝衰竭最重要乃至最常见的原因。发热是最常见的临床症状之一。发热反应可以解释许多疾病的发病机理,临床表现,甚至判断疾病预后；前驱期发热以及体温的高低与疾病严重程度及某些传染性疾病的诊断密切相关。急性乙型肝炎患者前驱期出现发热并不常见,且通常表现轻微,我们对于前驱期发热是否在急性乙型肝炎临床病程中存在作用尚不清楚。本研究的目的是调查急性乙型肝炎患者中前驱期出现发热症状的可能影响因素以及其在急性肝衰竭进展过程中作用方法：1.调查了2006年1月至2010年12月间于济南市传染病医院确诊并住院的618例急性乙型肝炎患者。急性乙型肝炎诊断标准符合2000年西安会议修订的《病毒性肝炎防治方案》；急性肝衰竭诊断标准符合我国《肝衰竭诊疗指南》(2012年版)；前驱期发热界定为体温测量值大于37.5℃或者患者自觉发热(即无客观测量数据)。 2.本研究比较了急性乙型肝炎患者中出现或不出现前驱期发热症状的人群以及是否发生急性肝衰竭人群的人口学数据、临床表现、血清生化学和病毒学指标。3.统计方法：分类变量使用卡方检验；连续型变量视不同情况分别使用t检验或Mann-Whitney U检验或Kruskal-Wallis检验。使用多因素logistic回归分析急性乙型肝炎患者前驱期出现发热症状以及发生急性肝衰竭的危险因素。P值小于0.05具有统计学意义。所有数据分析应用SPSS16.0(SPSS Inc., Chicago,IL,USA)统计学软件进行. 结果：1.急性乙型肝炎出现前驱期发热症状患者的临床特征发热与未发热组患者的平均年龄、性别比例、户籍、吸烟饮酒史、自疾病起始至入院前时间(天)及至第1次化验检查的时间(天)相近,无明显统计学差异。发热组患者的谷丙转氨酶(ALT)、胆红素、国际标准化比值(INR)中位数明显高于未发热组；而白蛋白、血小板水平明显低于未发热组,差异具有统计学意义。发热组HBsAg250IU/mL以及HBeAg阳性率明显低于未发热组(P≤0.001)。且两组间HBeAg阳性率的不同只有当HBV DNA≥1000copies/ml时具有显著的统计学差别。发热组急性肝衰竭的发生率和病死率明显高于未发热组患者(P＜0.001)。 2.急性乙型肝炎患者前驱期出现发热症状的的危险因素多因素logistic回归分析表明,在调整了多因素后,白蛋白40g/L,血小板＜150×109/L,INR＞1.1,入院时HBeAg阴性是急性乙型肝炎患者前驱期出现发热症状的独立危险因素。比值比(95%可信区间)分别为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,前驱期发热症状与急性肝衰竭的关系。 618例患者中,41例(6.6%)出现急性肝衰竭。其中25例(61%)患者死亡,16例(39%)存活。与未出现急性肝衰竭组相比,急性肝衰竭组患者前驱期发热的比例更高(46.3%vs.14.4%,P＜0.001)。同样,体温测量值T≥38℃比例更高(41.5%vs.7.6%,P＜0.001)。急性肝衰竭组患者具有更高的TBIL、INR水平(P＜0.001)以及较低的白蛋白、血小板水平,HBsAg2501U/ml比例较低(P＜0.001)。调整多项指标后,多因素logistic]回归分析显示前驱期发热(体温测量值＞37.5℃或自觉发热)及T≥38℃是急性乙型肝炎患者发生急性肝衰竭的独立危险因素；比值比(95%可信区间)分别为3.5(1.4-8.6)和7.1(2.6-19.7)。4.出现急性肝衰竭及前驱期发热急性乙型肝炎患者的临床特点. 出现发热的急性肝衰竭患者中,男性性别比例明显高于未发热组(100%vs.77.3%,P=0.03)。自疾病起始进展至肝性脑病的平均时间明显低于未发热组(6.6±3.5vs.15.2±7.5,P＜0.001)。两组患者的病死率相近,发热组HBeAg阳性率明显低于未发热组(15.8%vs59.1%,P=0.005). 结论： 1.急性乙型肝炎患者中,前驱期发热症状的流行率为16.5%。 2.前驱期发热与感染致使HBeAg表达丢失的前核心区变异的HBV病毒株有关。 3.前驱期发热是急性乙肝患者发生肝衰竭的独立危险因素。
[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.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62;R575.3

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