本文選題：肝衰竭 + 巨細(xì)胞病毒��； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景肝衰竭是多種因素導(dǎo)致的肝功能嚴(yán)重障礙,其臨床表現(xiàn)通常包括肝功能異常、肝臟生化指標(biāo)異常、凝血功能障礙,部分可進(jìn)展為肝性腦病、多器官功能衰竭和發(fā)生死亡。肝衰竭可并發(fā)多種嚴(yán)重的并發(fā)癥,預(yù)后極差,在病程中可出現(xiàn)類似膿毒血癥的炎癥因子風(fēng)暴及免疫麻痹等免疫紊亂現(xiàn)象,容易繼續(xù)各種感染(包括病毒、細(xì)菌及真菌)。巨細(xì)胞病毒(Cytomegalovirus,CMV)與EB病毒(Epstein-Barr virus,EBV)均屬于皰疹病科中的DNA病毒,均具有潛伏-活化的病毒學(xué)特點,人體感染上兩種病毒后,病毒不能完全從體內(nèi)清除,由于其特殊的病毒學(xué)特性可逃過宿主的免疫監(jiān)視從而長期潛伏在機(jī)體內(nèi),但均具有潛在的再活化的風(fēng)險。在人體免疫力低下時上述兩種病毒可出現(xiàn)再活化,比如獲得性免疫缺陷的患者、長期服用免疫抑制劑的患者、及某些腫瘤患者等。我們前期工作中已證明男同性戀的群體體內(nèi)CMV及EBV的再活化率較正常人高。研究發(fā)現(xiàn)膿毒血癥患者體內(nèi)CMV的再活化較多,且CMV活化感染可增加膿毒血癥患者的死亡率。亦有報道在慢性乙型病毒性肝炎患者、及肝衰竭患者體內(nèi)CMV再活化率明顯高于正常人,但對肝衰竭患者體內(nèi)EBV的活化研究甚少。巨細(xì)胞病毒及EB病毒再活化是否導(dǎo)致病情加重目前尚無報道。因此本研究擬對肝衰竭患者住院治療期間CMV、EBV感染狀態(tài)進(jìn)行監(jiān)測,觀察了解肝衰竭患者體內(nèi)CMV和(或)EBV的再活化是否加重病情,影響患者的預(yù)后。同時對肝衰竭患者的部分炎癥因子進(jìn)行檢測,了解在肝衰竭患者體內(nèi)的免疫狀態(tài)以及與這兩種病毒再激活的相關(guān)性。目的肝衰竭患者體內(nèi)巨細(xì)胞病毒(Cytomegalovirus,CMV)和(或)EB病毒(Epstein-Barr virus,EBV)的再活化是否加重病情,影響患者的預(yù)后。方法1.收集2015年9月-2016年9月在我院診斷為肝衰竭患者35例,診斷標(biāo)準(zhǔn)參照2012年《肝衰竭診治指南》。在患者入院時及入院治療2周收集患者的外周靜脈血離心后取上層血清備用,同時在患者入院治療2周統(tǒng)計患者肝功及凝血象;同時收集我院25例健康體檢者的血清作為對照組。對各組的血清進(jìn)行病毒定量及病毒相關(guān)抗體的檢測,凡是能檢測到CMV和(或)EBV定量擴(kuò)增陽性或Ig M抗體陽性均考慮為病毒活化感染。將35例肝衰竭患者按有無病毒活化分為病毒活化組及無病毒活化組。將在住院期間死亡的與病情危重自動放棄治療均視為死亡。2.采用ELISA法檢測各分組中血清樣本的CMV-Ig G、CMV-Ig M抗體及EBV-VCA-Ig M、EBV-VCA-Ig G抗體;采用熒光實時定量法測定血清中巨細(xì)胞病毒及EB病毒的擴(kuò)增量;采用ELISA法測定入院治療2周肝衰竭血清及健康對照組中4種細(xì)胞因子的濃度,分別為IL-4,IL-10,IL-17及IFN-r。3.采用統(tǒng)計學(xué)分析軟件SPSS 23.0進(jìn)行數(shù)據(jù)分析,不符合正態(tài)分布的數(shù)據(jù)均用中位數(shù)(M)及四分位數(shù)間距(Q)表示。秩和檢驗用于各組之間的比較,當(dāng)P0.05時差異具有統(tǒng)計學(xué)意義。各組間率之間的比較采用四格表的行×列卡方檢驗,當(dāng)n≤40或最小理論頻數(shù)T1時采用Fisher確切概率法檢驗;當(dāng)n40且最小理論頻數(shù)1≤T5時采用連續(xù)性校正卡方檢驗,以P0.05表示差異具有統(tǒng)計學(xué)意義。結(jié)果1、肝衰竭組共35例,存在CMV和(或)EBV病毒再活化的肝衰竭患者共7例,無病毒活化的共28例,肝衰竭組中病毒活化率為20%,健康對照組病毒活化率為0,肝衰竭組患者體內(nèi)CMV和(或)EBV再活化率較健康對照組顯著升高(P0.05)。2、有CMV和(或)EBV病毒活化的肝衰竭組病死率為71.4%,無病毒活化的肝衰竭組病死率為17.85%,存在病毒活化的肝衰竭組的病死率顯著升高,差異具有統(tǒng)計學(xué)意義(P0.05)。3、有CMV和(或)EBV病毒活化的肝衰竭組患者的ALT、TB、INR均較無病毒活化的肝衰竭組明顯升高(P0.05),有病毒活化的肝衰竭組患者的PTA、白蛋白較無病毒活化的肝衰竭組顯著降低(P0.05),有病毒活化的肝衰竭組與無病毒活化的肝衰竭組比較AST差異無統(tǒng)計學(xué)意義(P0.05)。4、有CMV和(或)EBV病毒活化的肝衰竭組患者血清中IL-4、IL-10、IL-17三種細(xì)胞因子的濃度比健康對照組顯著增高(P0.05);無病毒活化的肝衰竭組患者血清中的IL-10、IL-17的濃度較健康對照組顯著增高(P0.05);有病毒活化的肝衰竭組患者血清中的IL-4、IL-10濃度比無病毒活化的肝衰竭組顯著增高(P0.05);有病毒活化的肝衰竭組患者血清中IL-17細(xì)胞因子的濃度與無病毒活化的肝衰竭組之間對比無差異無統(tǒng)計學(xué)意義(P0.05);有病毒活化的肝衰竭組、無病毒活化的肝衰竭與健康對照組體內(nèi)IFN-r濃度三者無明顯差異(p0.05)。結(jié)論1、35例肝衰竭患者CMV-Ig G抗體及EBV-VCA-Ig G抗體均陽性,說明體內(nèi)均有潛伏的CMV及EBV,且肝衰竭患者容易繼發(fā)CMV和(或)EBV的再活化。2、CMV和(或)EBV的再活化可能會加重肝衰竭患者的病情,并與患者的病死率密切相關(guān)。3、再次證實了在肝衰竭患者體內(nèi)存在促炎癥反應(yīng)及抗炎癥反應(yīng)的相互作用,同時IL-4與IL-10的升高可能與CMV和(或)EBV活化感染密切相關(guān)。
[Abstract]:Background liver failure is a serious obstacle to liver function caused by a variety of factors. Its clinical manifestations usually include abnormal liver function, abnormal biochemical indexes of the liver, coagulation dysfunction, partial progression to hepatic encephalopathy, multiple organ failure and death. Liver failure can be complicated with many severe complications, and the prognosis is extremely poor and similar in the course of the disease. The inflammatory factors such as the inflammatory factor storm and immune paralysis of sepsis are easy to continue various infections (including viruses, bacteria and fungi). Cytomegalovirus (CMV) and EB virus (Epstein-Barr virus, EBV) all belong to the DNA virus in the herpes department, which have latent and activated virological characteristics and two diseases of human infection. After the virus, the virus can not be completely removed from the body. Because of its special virological characteristics, the virus can escape from the host's immune surveillance and lurk in the body for a long time, but it has a potential reactivation risk. The above two viruses can be reactivated when the human immunity is low, such as those who have acquired immune deficiency, for long-term use of immunosuppression. We have shown that the reactivation rate of CMV and EBV in the male homosexual population is higher in our earlier work. The study found that the reactivation of CMV in the patients with sepsis is more, and the CMV activation infection can increase the death rate of the patients with sepsis. The reactivation rate of CMV in patients with liver failure is significantly higher than that of normal people, but the activation of EBV in patients with liver failure is rarely studied. It is not reported that the reactivation of cytomegalovirus and EB virus has not been reported. Therefore, this study is to monitor the status of CMV and EBV infection during the hospitalization of patients with liver failure and observe the liver failure. Whether the reactivation of CMV and / or EBV in the exhaustive patients will aggravate the condition and affect the prognosis of the patients. At the same time, the partial inflammatory factors of the patients with liver failure are detected, the immune state in the patients with liver failure and the correlation with the reactivation of these two viruses. And (Cytomegalovirus, CMV) in the patients with liver failure (CMV) and ( Whether or not the reactivation of the EB virus (Epstein-Barr virus, EBV) aggravates the condition and affects the patient's prognosis. Method 1. collect 35 cases of liver failure diagnosed in our hospital in September -2016 September 2015. The diagnostic criteria refer to the guidelines for the diagnosis and treatment of liver failure in 2012. At the same time, the liver function and Hemogram of the patients were counted for 2 weeks, and the serum of 25 healthy persons in our hospital was collected as the control group. The serum of each group was detected by virus quantitative and virus related antibodies, and all the CMV and / or EBV quantitative positive or Ig M antibody positive were considered for the virus activation Infection. 35 patients with liver failure were divided into virus activation group and non viral activation group according to the activation of virus without virus. The death of the patients during hospitalization and the critical automatic abandonment treatment were all considered as death.2., and the serum samples of CMV-Ig G, CMV-Ig M, EBV-VCA-Ig M, EBV-VCA-Ig G antibody were detected by ELISA. The amplification of cytomegalovirus and EB virus in serum was measured by quantitative method, and the concentration of 4 cytokines in the 2 weeks liver failure serum and the healthy control group were measured by ELISA. The statistical analysis software SPSS 23 was used to analyze the data of IL-4, IL-10, IL-17 and IFN-r.3., and the median (M) did not conform to the normal distribution. And the four quantile spacing (Q). The rank sum test is used for the comparison between each group. The difference between P0.05 is statistically significant. The comparison between the rates of each group uses a row x column test of the four lattice, when the N < 40 or the minimum theoretical frequency T1 is tested by the exact probability method of Fisher; and the continuity correction is adopted when N40 and the minimum theoretical frequency 1 are less than T5. A total of 35 cases of liver failure in the liver failure group, 7 cases of liver failure with CMV and / or EBV reactivation, 28 cases of no virus activation, 20% in the liver failure group, 0 in the healthy control group and 0 in the healthy control group, and the reactivation rate of CMV and / or EBV in the liver failure group were 1. The fatality rate of the liver failure group with CMV and (or) EBV virus activation was 71.4%, the fatality rate of the liver failure group without virus activation was 17.85%, the mortality rate of the virus activated liver failure group was 17.85%, the mortality rate of the virus activated liver failure group was significantly higher, the difference was statistically significant (P0.05).3, with CMV and (or) EBV virus activated liver failure group patients with CMV and / or EBV virus activated liver failure group. ALT, TB and INR were significantly higher than those in the non viral activated liver failure group (P0.05). The PTA of the patients with viral activated liver failure was significantly lower than that of the non viral activated liver failure group (P0.05). There was no significant difference between the virus activated liver failure group and the non viral activated liver failure group than the AST (P0.05).4, CMV and / or EBV disease (P0.05). The concentration of three cytokines in serum IL-4, IL-10 and IL-17 in the patients with toxic activated liver failure was significantly higher than that in the healthy control group (P0.05). The concentration of IL-10 and IL-17 in the serum of the patients with no virus activated liver failure was significantly higher than that in the healthy control group (P0.05), and the concentration of IL-10 in the serum of the patients with virus activated liver failure group was less than that of the disease. There was no significant difference between the concentration of IL-17 cytokine in the serum of the patients with virus activated liver failure and the non virus activated liver failure group (P0.05), and there was no virus activated liver failure group, no virus activated liver failure and the IFN-r concentration of three in the healthy control group of three patients with virus activated liver failure. Significant differences (P0.05). Conclusion the CMV-Ig G antibody and EBV-VCA-Ig G antibody in patients with 1,35 liver failure are both positive, indicating that there are latent CMV and EBV in the body, and that the patients with liver failure are prone to secondary reactivation of CMV and / or EBV, and the reactivation of CMV and / or reactivation may aggravate the condition of the patients with liver failure and be closely related to the mortality of the patients. The interaction of proinflammatory and anti inflammatory reactions in patients with liver failure is confirmed, and the increase of IL-4 and IL-10 may be closely related to the activation of CMV and / or EBV.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R575.3

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