肝炎病毒感染与肝外肿瘤相关性的临床研究

发布时间：2018-04-01 09:20

本文选题：肝脏疾病　切入点：疾病谱　出处：《南京医科大学》2017年博士论文

【摘要】：第一部分肝脏疾病住院患者疾病谱变化趋势目的:分析住院肝病患者的疾病谱变化,了解本医疗机构收治的病毒性肝炎患者趋势是否发生变化。方法:以2006年1月至2014年12月期间入住南京医科大学第一附属医院感染病科的患者为研究对象,回顾性分析肝病患者的病因变化、病毒性肝炎中不同肝炎病毒感染比例、不同年龄段乙型肝炎比例变化趋势等。结果:1、连续9年期间,住院患者中肝病的比例逐渐下降,最高为2006年达64.46%,最低为2013年降至39.89%,但患者数量有所增加,2006年为497人,而2014年达798人。前五位的肝病病因依次是病毒性肝炎、药物性肝病、自身免疫性肝病、酒精性肝病和非酒精性脂肪性肝病,总比例分别为62.61%、10.70%、4.96%、3.18%和1.90%,其中病毒性肝炎比例逐渐下降,而药物性肝病和自身免疫性肝病比例明显上升。2、病毒性肝炎患者中,乙型肝炎、丙型肝炎和戊型肝炎比例处于前三位,其中乙型肝炎稳定在70%左右,而丙型肝炎比例呈现上升趋势,由2006年8.45%上升至2014年的15.58%;乙型肝炎患者每年平均住院时间呈逐渐缩短趋势,差异具有明显的统计学意义(P0.001);乙型肝炎患者主要分布在31-60岁年龄段,合计比例在60%以上,同一年龄组各年份比例间差异无统计学意义,而14-23岁年龄段,乙型肝炎患者比例逐渐降低,差异有统计学意义(P=0.01)。结论:1、肝病在本机构感染病科的病种分布中依然占有重要地位;药物性肝病和自身免疫性肝病等非感染性的肝病应引起足够的重视和关注。2、本机构感染病科收治的病毒性肝炎住院患者中,乙型肝炎和丙型肝炎依然严重;乙型肝炎和丙型肝炎患者的发病趋势为其防治提出新的挑战。第二部分HBV或HCV感染与肝外肿瘤相关性研究目的:肝炎病毒与肝细胞肝癌具有相关性众所周知,国际上虽然已有研究显示与肝外肿瘤关联,但本地区的状况并不清楚。方法:1、2008年1月至2016年12月期间入住南京医科大学第一附属医院的患者,选取诊断为淋巴瘤、乳腺癌、甲状腺癌、肾癌和胰腺癌以及同期诊断为非肿瘤疾病的住院患者为研究对象。2、采用回顾性方法进行病例对照研究,以上五种肝外肿瘤患者设为研究组,同期住院非肿瘤疾病的患者为对照组,研究组和对照组依据性别、年龄等资料进行1:1完全匹配。3、以乙型肝炎表面抗原检测阳性为HBV感染标志物,丙型肝炎抗体检测阳性为HCV感染标志物。分析研究组和对照组之间乙型肝炎表面抗原、乙型肝炎表面抗体、乙型肝炎核心抗体、丙型肝炎抗体等阳性率的差异性,并计算比值比及其95%可信区间。同时,研究组检测数据资料与2006年全国HBV、HCV血清流行病学调查结果进行乙型肝炎表面抗原阳性率的比较分析。4、选取弥漫大B细胞淋巴瘤患者,研究HBV感染与HBV非感染者之间性别和发病年龄的分布差异性。结果:1、分析五种肝外肿瘤患者与医院非肿瘤住院患者对照人群HBV感染率的差异性,结果显示淋巴瘤中非霍奇金淋巴瘤(OR = 2.10;95%CI,1.72-2.56),非霍奇金淋巴瘤中的B细胞淋巴瘤(OR= 2.33;95%(CI,1.90-2.86),以及其亚型中的弥漫大B细胞淋巴瘤(OR = 2.07;95%CI,1.62-2.64)、滤泡性淋巴瘤(OR = 3.38;95%CI,2.28-5.00)、边缘区淋巴瘤(OR = 2.23;95%CI,1.37-3.62)、慢性淋巴细胞白血病/小淋巴细胞(OR=1.91;95%CI,1.03-3.55)、黏膜相关淋巴组织淋巴瘤(OR=1.85;95%CI,1.00-3.44)、脾边缘区淋巴瘤(OR = 5.86;95%CI,2.28-15.28)等HBV感染率均明显高于对照组,差异具有统计学意义。除胰腺癌(OR=1.40;95%CI,1.07-1.84)外,乳腺癌、甲状腺癌、肾癌HBV感染率与对照组相比,差异未见明显统计学意义(P值分别为0.873、0.308、0.331);但乳腺癌、甲状腺癌、肾癌以及胰腺癌抗-HBc阳性率均明显高于对照组,差异有明显统计学意义(P值分别为0.003、0.001、0.003)。2、以全国2006年HBV血清流行病学调查结果为对照,对HBV感染率差异性进行了进一步研究,B细胞非霍奇金淋巴瘤亚型的分析发现,男性群体中除边缘区淋巴瘤以及黏膜相关淋巴组织淋巴瘤HBV感染率与对照差异未见明显统计学意义外(P值分别为0.548、0.603),其余HBV感染率均明显高于对照。而对于女性群体,B细胞非霍奇金淋巴瘤亚型HBV感染率均明显高于对照,差异有统计学意义。对于乳腺癌、甲状腺癌、肾癌以及胰腺癌的研究,无论男性还是女性患者,并未发现HBV感染率与对照的差异有明显统计学意义。3、以弥漫大B细胞淋巴瘤亚型患者为研究对象,分析比较了弥漫大B细胞淋巴瘤中HBV感染者与非HBV感染者性别、发病年龄分布的差异性,结果均未发现二者差异有明显统计学意义(P值分别为0.941、0.232)。4、本研究入组的淋巴瘤、乳腺癌、甲状腺癌、肾癌和胰腺癌,其抗-HCV阳性率分别为0.75%、0.50%、0.33%、0.39%、0.75%,与各自住院患者对照组抗-HCV阳性率相比较,差异未见明显统计学意义;并且淋巴瘤的各亚型抗-HCV阳性率与住院患者对照组相比较,也未发现差异有明显统计学意义。在与全国2006年HCV血清流行病学调查结果比较时,男性群体中五种肝外肿瘤抗-HCV阳性率与全国数据比较,差异均未见明显统计学意义。在女性群体中,乳腺癌、甲状腺癌、肾癌和胰腺癌抗-HCV阳性率与全国数据比较,差异也未见明显统计学意义,而淋巴瘤亚型中的慢性淋巴细胞白血病/小淋巴细胞抗-HCV阳性率为5.56%,与全国数据比较差异均有明显统计学意义(P=0.001)。结论:1、非霍奇金淋巴瘤及其部分亚型、胰腺癌等的发生与HBV感染存在一定的相关性。2、弥漫大B细胞淋巴瘤患者中HBV感染与HBV非感染者,性别和发病年龄分布未见明显差异。3、女性患者慢性淋巴细胞白血病/小淋巴细胞淋巴瘤与HCV感染存在一定的相关性。
[Abstract]:Changing trends of inpatient disease spectrum to the first part: the analysis of liver disease spectrum changes of hospitalized patients with liver disease, to understand the trend of viral hepatitis patients admitted to medical institutions are changed. Methods: the First Affiliated Hospital of Nanjing Medical University Department of infection during the period from January 2006 to December 2014 were selected as the research object, a retrospective analysis of etiology changes in patients with liver disease different, hepatitis B virus infection of viral hepatitis in the proportion of different age of hepatitis B ratio trend. Results: 1, for 9 consecutive years, the proportion of hospitalized patients with liver disease decreased gradually, the highest reached 64.46% in 2006, the lowest for 2013 to 39.89%, but the number of patients increased 497 in 2006 and 2014. Up to 798 people. The etiology of liver disease before five were viral hepatitis, drug-induced liver disease, autoimmune liver disease, alcoholic liver disease and alcohol Fatty liver disease, the proportion of the total were 62.61%, 10.70%, 4.96%, 3.18% and 1.90%, the proportion of viral hepatitis decreased, and drug-induced liver disease and autoimmune liver disease significantly increased the proportion of.2 in patients with viral hepatitis, hepatitis B, hepatitis C and hepatitis E, the proportion of the top three, including B B stable at around 70%, and the proportion of hepatitis C showed a rising trend, up from 8.45% in 2006 to 15.58% in 2014; the annual average hospitalization time of patients with hepatitis B decreased, the difference is significant (P0.001); hepatitis B patients mainly distributed in 31-60 years of age, the proportion of the total is more than 60%, no significant the significance of each year the same age group the proportion difference, and 14-23 years of age, the proportion of patients with hepatitis B gradually decreased, the difference was statistically significant (P=0.01). Conclusion: 1. The mechanism of infectious diseases in liver disease Still occupies an important position in the distribution of diseases in the Department of medicine; liver disease and autoimmune liver diseases and non infectious disease should arouse enough attention and concern of.2, the mechanism of viral hepatitis infection diseases were hospitalized patients, hepatitis B and hepatitis C are still serious; hepatitis B and hepatitis C in patients with the incidence trend of it new challenges for its prevention and treatment. The second part studies the relationship between HBV or HCV infection and hepatic tumor Objective: hepatitis B virus and hepatocellular carcinoma associated with the world as everyone knows, although research has shown that tumor associated with liver, but the region's status is not clear. Methods: the patients in the First Affiliated Hospital of Nanjing Medical University during the period from January 12008 to December 2016 in selection, diagnosis of lymphoma, breast cancer, thyroid cancer, renal cell carcinoma and pancreatic cancer and the corresponding diagnosis for non tumor disease in hospital patients The research object of.2, using the method of retrospective case-control study, more than five patients with extrahepatic tumor for the study group, hospitalized non neoplastic disease patients as the control group, the study group and the control group according to gender, age,.3 1:1 complete data for the detection of hepatitis B surface antigen as a marker HBV infection, detection of hepatitis C virus antibody positive for markers of HCV infection. The analysis between the study group and the control group of hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, the difference of the positive rate of antibody to hepatitis C, and calculate the odds ratios and 95% confidence intervals. At the same time, the research group of testing data and 2006 the results of HBV, HCV positive rate of serum epidemiological survey of hepatitis B surface antigen.4 comparative analysis, selected patients with diffuse large B cell lymphoma, the infection of HBV and non HBV infection The distribution of the difference between gender and age. Results: 1, analysis of hospitalized patients with cancer were HBV infection rate of five patients with extrahepatic tumor hospital, showed non Hodgkin lymphoma lymphoma (OR = 2.10; 95%CI, 1.72-2.56), B cell lymphoma in non Hodgkin lymphoma (OR= 2.33 95%; (CI, 1.90-2.86), and its subtypes of diffuse large B cell lymphoma (OR = 2.07; 95%CI, 1.62-2.64), follicular lymphoma (OR = 3.38; 95%CI, 2.28-5.00), marginal zone lymphoma (OR = 2.23; 95%CI, 1.37-3.62), chronic lymphocytic leukemia / small lymphocytes (OR=1.91; 95%CI, 1.03-3.55), mucosa associated lymphoid tissue lymphoma (OR=1.85; 95%CI, 1.00-3.44), splenic marginal zone lymphoma (OR = 5.86; 95%CI, 2.28-15.28) HBV infection rate was significantly higher than that of control group, the difference was statistically significant. In addition to pancreatic cancer (OR=1.40; 95%CI, 1.07-1.84) and, Breast cancer, thyroid cancer, renal cell carcinoma HBV infection rate compared with the control group, the difference was significant (P = 0.873,0.308,0.331); breast cancer, thyroid cancer, renal cell carcinoma, pancreatic cancer, anti -HBc positive rate were significantly higher than the control group, the difference was statistically significant (P =.2, 0.003,0.001,0.003) in 2006 the national epidemiological survey of serum HBV as control, the infection rate of HBV difference was further studied, analysis of B cell non Hodgkin's lymphoma subtypes found in male group removal rate compared with no obvious statistical significance of marginal zone lymphoma of mucosa associated lymphoid tissue lymphoma and HBV infection (P = 0.548,0.603 the infection rate of HBV), were significantly higher than that of control. But for women, B cell non Hodgkin's lymphoma subtype HBV infection rate were significantly higher than that in control, the difference was significant Meaning. For breast cancer, thyroid cancer, renal cancer and pancreatic cancer, both men and women, did not find the HBV infection rate between the control and the statistically significant.3, diffuse large B cell lymphoma subtype patients as the research object, analysis and comparison of HBV infection in diffuse large B cell lymphoma and non HBV infection sex, age distribution sex differences, the results indicated that there were no statistically significant difference between the two groups (P = 0.941,0.232).4, the research group of lymphoma, breast cancer, thyroid cancer, renal cell carcinoma and pancreatic cancer, the anti -HCV positive rates were 0.75%, 0.50%, 0.33%, 0.39% 0.75%, with the respective control group, patients with anti -HCV positive rate comparison, no significant difference; and patients compared to the control group the positive rate of -HCV subtypes of lymphoma and anti, also found no statistically significant difference. In righteousness. And in 2006 the country HCV seroepidemiological survey results, male five extrahepatic tumor positive rate of anti -HCV and the data comparison, differences were no obvious statistical significance. In women, breast cancer, thyroid cancer, kidney and pancreatic cancer compared with anti -HCV positive rate and the data difference there is no statistically significant, while chronic lymphocytic leukemia / lymphoma subtypes in small lymphocyte anti -HCV positive rate was 5.56%, compared with the national data significantly differences were statistically significant (P=0.001). Conclusion: 1, non Hodgkin's lymphoma and its subtypes, and HBV pancreatic cancer such as.2 infection existed certain correlation. Diffuse infection in non HBV infected patients with HBV large B cell lymphoma, sex and age distribution showed no significant difference between.3 and female patients with chronic lymphocytic leukemia / small lymphocytic lymphoma There is a certain correlation with HCV infection.

【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R512.6

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