HBsAg自然转阴的慢性HBV感染临床特征分析

发布时间：2018-04-10 04:03

本文选题：HBsAg自然转阴　切入点：乙肝血清标志物　出处：《延安大学》2017年硕士论文

【摘要】：【目的】探索乙型肝炎病毒表面抗原(Hepatitis B surface antigen,HBsAg)自发性血清清除的慢性乙型肝炎病毒(Hepatitis B virus,HBV)感染者的临床特点。包括表面抗原定量数值与其阴转的关系;不同年龄、性别的患者在发生HBsAg自然阴转过程中是否存在显著性差异;同时明确此过程的影响因素,包括促进HBsAg阴转和阻碍HBsAg阴转的相关因素,比如家族史、饮酒史、性别、年龄是否会对这一进程产生正性或负性作用;并对HBsAg转阴的患者进行随访,评估其预后。【方法】纳入85例HBsAg自发清除的慢性HBV感染者,这些患者来源于延大附院感染科病房及门诊,就诊时间为2014年9月—2017年2月。慢性乙型肝炎(Chronic hepatitis B,CHB)诊断依据我国慢乙肝防治指南2015年版标准,除外药物治疗导致的HBsAg转阴病例(干扰素或核苷类药物)。并设置对照组,收集患者的一般资料,包括年龄、性别、乙肝家聚史、饮酒史,回顾性收集患者既往乙型肝炎病毒标志物(Hepatitis B virus Markers,HBV M),包括HBsAg,乙型肝炎病毒表面抗体(Hepatitis B surface antibody,HBsAb),乙型肝炎病毒e抗原(Hepatitis B e antigen,HBeAg),乙型肝炎病毒e抗体(Hepatitis B e antibody,HBeAb),乙型肝炎病毒核心抗体(Hepatitis B core antibody,HBcAb)、乙型肝炎病毒脱氧核糖核酸(Hepatitis B virus deoxyribonucleic acid,HBV DNA)定量、腹部B超、肝功、甲胎蛋白(Alpha-fetoprotein,AFP)、肝纤维化指标、肝纤维化无创检测值,肝癌患者收集其上腹部增强核磁共振。并对其进行随访,随访内容包括患者以上各指标的变化。随访终点为启动抗病毒治疗、患者因病情进展死亡及随访时间截止2017年2月。应用相应的统计学方法进行分析处理。【结果】1.随访时间为2-42年,随访时间平均值(17.5±9.5)年。hbsag转阴时间(14.6±9.6)年,3例病人hbv基因分型为c型,3例病人启动抗病毒治疗。2.85例hbsag自然转阴的慢性hbv感染者中男性57例(67.1%),女性28例(32.9%)。年龄21-73岁,平均年龄(47.7±12.1)岁。3.hbsag转阴后复现患者3例(3.5%),均为男性。在随访时间内,其中hbsag复现后再未消失者1例(1.2%),hbsag复现后转阴者2例(2.3%)。男性复发与女性复发率fisher精确概率法p值0.05。4.85例hbsag自然转阴的慢性hbv感染者中随访起始hbeag阳性者6例(7.0%),hbeag阴性者65例(76.5%)。情况不详者14例(16.5%)。5.hbsag转阴时hshbvdna(highsensitivehbvdna)定量:0-197iu/ml。6.hbsab的值与谷丙转氨酶(alanineaminotransferance,alt)相关性分析r=-0.013,p=0.894。hbsab的值与(aspartateaminotransferase,ast)相关性分析:r=-0.075,p=0.712。7.hbcab的值与alt相关性分析:r=0.190,p=0.072。hbcab的值与ast相关性分析:r=-0.008,p=0.955。8.hbcab与hbsag相关性分析,r=-0.559,p=0.000。9.hbsag转阴时年龄≤50岁,共56例:上腹部b超、肝功正常者49例,肝硬化(livercirrhosis,lc)者7例,肝癌(hepatocellularcarcinoma,hcc)者0例。hbsag转阴时年龄50岁,共29例:9例患者腹部b超、肝功正常,16例出现肝硬化,4例患者发生hcc。χ2=29.509,p=0.000。≤50岁平均肝纤维化无创检测值6.3kpa,50岁9.9kpa,经t检验,p=0.003,差异具有统计学差异。10.对照组为hbsag未转阴的慢性hbv感染者80例,性别、家族史、饮酒史年龄的多分类logistic回归分析,其p值分别为:0.645、0.514、0.440、0.002。11.随访初期hbsag的均值:(75.93±12.40)iu/ml,95%置信区间(50.98,100.98)iu/ml。hbcab的均值:(173.8±22.6)s/co,95%置信区间(128.94,218.72)iu/ml。12.afp和肝纤四项中的层连蛋白(laminin,ln)的pearson相关系数为0.787,P=0.000。【结论】1.HBsAg自然阴转者中,男性所占百分比较多。2.HBsAg自然阴转后,仍然会有部分患者乙肝表面抗原再现,但其再现与患者性别无相关性。3.HBeAg阴性者较HBeAg阳性者出现HBsAg自然阴转的可能性大。4.HBsAg转阴时,血清中仍可测到HBV DNA,即乙肝表面抗原阴性,不能排除HBV感染。5.HBsAb的值与ALT、AST无相关性,提示HBsAb升高,不会预示肝功损伤;HBcAb的值与ALT、AST无相关性,提示HBcAb升高,不会预示肝功损伤。6.HBcAb与HBsAg呈负相关,前者升高,提示后者血清学清除的可能性。7.与50岁以后出现HBsAg自发清除患者比较,50岁以前即发生转阴者出现肝硬化、HCC的几率小。8.性别、家族史、饮酒史不是促进HBsAg转阴的因素,而对于乙肝表面抗原100IU/ml以下的患者,随着年龄增长,HBsAg转阴的可能性增大。9.AFP和肝纤四项中的LN具有相关性,AFP升高,LN会随着升高,两者具有相关性。
[Abstract]:[Objective] to explore the hepatitis B virus surface antigen (Hepatitis B surface antigen, HBsAg) spontaneous seroclearance in chronic hepatitis B virus (Hepatitis B, virus, HBV) the clinical features of infection. Including the relationship with negative quantitative surface antigen; different age, sex occurred in patients with HBsAg negative natural existence significant differences in the process; influence factors and define this process, including the promotion of related factors of HBsAg negative and HBsAg negative obstacles, such as family history, drinking history, gender, age, whether it will have a positive or negative role in this process; and the HBsAg negative patients were followed up to evaluate the prognosis [Methods]. Infection in 85 patients with spontaneous clearance of HBsAg in chronic HBV, these patients from Yanan University Affiliated Hospital infection wards and outpatient visits, time is September 2014 to February 2017. Chronic hepatitis B (Chron IC hepatitis B, CHB) on the basis of our diagnosis of chronic hepatitis B prevention and treatment guidelines in 2015 version of the standard, except the drug treatment resulted in HBsAg negative cases (interferon or nucleoside drugs). Control group was set, data were collected including age, gender, family history of hepatitis B, drinking history, history of hepatitis B patients were retrospectively collected. Hepatitis B virus markers (Hepatitis B, virus Markers, HBV M), including HBsAg, hepatitis B virus surface antibody (Hepatitis B surface antibody, HBsAb), hepatitis B virus e antigen (Hepatitis B e antigen, HBeAg), hepatitis B virus e antibody (Hepatitis B e antibody, HBeAb), hepatitis B virus core antibody (Hepatitis B core antibody, HBcAb), hepatitis B virus deoxyribonucleic acid (Hepatitis B virus deoxyribonucleic acid, HBV DNA) quantitative abdominal ultrasound, liver function, alpha fetoprotein (Alpha-fetoprotein, AFP), liver fibrosis index, Noninvasive detection of liver fibrosis in patients with hepatocellular carcinoma were collected on the value of enhanced abdominal MRI. The changes were followed up, the follow-up including the indexes above. End point for follow-up commencement of antiviral therapy, the patients died because of disease progression and follow-up time as of February 2017. By using relevant statistical methods were analyzed. [results] 1. follow-up of 2-42 years, the average follow-up time (17.5 + 9.5).Hbsag clearance time (14.6 + 9.6) years, 3 cases of HBV gene in patients with type C, 3 cases of patients starting antiretroviral therapy for.2.85 patients HBsAg negative chronic HBV infection in 57 cases of male, female 28 (67.1%) cases (32.9%). The age is 21-73 years old, the average age (47.7 + 12.1) of 3 cases of recurrent patients after.3.hbsag negative (3.5%), were male. During the follow-up period, of which HBsAg reappearance hasn't disappeared in 1 cases (1.2%), 2 cases of recurrence after HBsAg were negative (2.3%) male. Recurrent and the recurrence rate of female Fisher exact probability p 0.05.4.85 cases but HBsAg of chronic HBV infection in the follow-up of the initial HBeAg were positive in 6 cases (7%), 65 HBeAg negative patients (76.5%). 14 cases were unknown (16.5%).5.hbsag negative hshbvdna (highsensitivehbvdna): quantitative transaminase 0-197iu/ml.6.hbsab value with alanine (alanineaminotransferance, ALT). The correlation between r=-0.013, p=0.894.hbsab (aspartateaminotransferase, AST) and the value of correlation analysis: r=-0.075, p=0.712.7.hbcab value and ALT correlation analysis: r=0.190, AST and p=0.072.hbcab correlation value analysis: r=-0.008, p=0.955.8.hbcab and HBsAg correlation analysis, r=-0.559, p=0.000.9.hbsag negative aged less than 50 years. A total of 56 cases of upper abdominal B Ultrasound, 49 cases of normal liver function, liver cirrhosis (livercirrhosis, LC) in 7 cases of hepatocellular carcinoma (hepatocellularcarcinoma, HCC) in 0 cases of.Hbsag negative Age of 50 years, a total of 29 cases: 9 cases of patients with abdominal B Ultrasound, normal liver function, 16 cases of liver cirrhosis, 4 cases of patients with hcc. x 2=29.509, p=0.000. = 50 years average liver fibrosis non-invasive detection value of 6.3kpa, the 50 year old 9.9kpa, by t test, p=0.003, the difference is statistically significant in 80 cases,.10. infection in control group HBsAg non negative chronic HBV gender, family history, drinking history age classification logistic regression analysis, the P values were: mean HBsAg 0.645,0.514,0.440,0.002.11. early follow-up: (75.93 + 12.40) iu/ml, 95% confidence interval (50.98100.98): iu/ ml.hbcab (mean 173.8 + 22.6) s/co, 95% confidence interval (128.94218.72) iu/ml.12.afp and hepatic fibrosis four in laminin (laminin, LN) Pearson correlation coefficient is 0.787. [Conclusion] P=0.000. 1.HBsAg spontaneous negative-conversicn in male, the percentage is.2.HBsAg natural seroconversion, there will still be a part of patients with hepatitis B The surface antigen of reproduction, but its reproduction no correlation between.3.HBeAg negative and HBeAg positive patients were sex HBsAg spontaneous negative-conversicn likely.4.HBsAg negative, can still be detected HBV DNA in serum, the HBsAg negative value and ALT.5.HBsAb cannot exclude HBV infection, AST had no correlation, suggesting that HBsAb will not increase indicates that the liver injury; and ALT HBcAb, AST had no correlation, suggesting that HBcAb does not indicate increased, was negatively correlated with liver injury.6.HBcAb and HBsAg of the former increased possibility of.7. serological clearance after the age of 50 is the spontaneous clearance of HBsAg patients, which occurred before the age of 50 were negative for the presence of cirrhosis, family history of HCC the probability of a small.8. gender, drinking history, not to promote HBsAg negative factors, and for hepatitis B surface antigen 100IU/ml in patients below, with the increase of age, the possibility of the increase of.9.AFP and liver HBsAg. The LN in the four items of the fiber has a correlation, the AFP increases, and the LN will increase with the correlation.

【学位授予单位】：延安大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62

【参考文献】