慢性HBV感染合并NAFLD炎症病理特征及无创临床模型研究

发布时间：2018-05-22 07:31

本文选题：慢性HBV感染 + 非酒精性脂肪性肝病　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:通过观察慢性乙型肝炎病毒(Hepatitis B Virus,HBV)感染合并非酒精性脂肪性肝病(Nonalcoholic Fatty Liver Disease,NAFLD)患者病理特征判别肝脏炎症原因,比较它们之间的临床特点,分析与其炎症相关的指标,进而探讨是否存在一种无创的方法比如公式识别这些炎症原因,从而建立慢性HBV感染合并NAFLD炎症无创临床诊断模型。方法:收集2014年01月至2016年12月就诊于天津市第二人民医院的慢性HBV感染合并NAFLD的患者,观察这些患者肝脏病理特征,分析炎症引起原因,根据病理特征的不同,分为HBV炎症组(HBV感染合并NAFLD患者有HBV感染相关炎症活动)和非HBV炎症组(HBV感染合并NAFLD患者无HBV感染相关炎症活动),单因素分析比较这两组患者一般特征和临床资料[包括肝肾功能、血脂、血糖、尿酸、胰岛素、乙肝五项、HBV-DNA、甲状腺功能、铁四项、免疫功能、血常规、B超、受控衰减参数(Controlled Attenuation Parameter,CAP)、FibroScan]等差异,纳入具有临床差异性的指标进行二元logistic回归分析肝脏炎症活动相关性指标,得出回归公式,评价及验证其准确性。结果:1.HBV炎症组的病理表现为:汇管区扩大,单个核为主的炎细胞浸润,或淋巴细胞集结浸润,有界面性炎症。非HBV炎症组病理表现为:无明显汇管区扩大及汇管区内炎细胞浸润,无界面性炎症。2.HBV炎症组平均年龄(41.8±9.9岁)高于非HBV炎症组平均年龄(36.42±10.49岁),差异有统计学意义(P0.05)。两组患者性别、体重指数(Body Mass Index,BMI)均无差别(P均0.05)。HBV炎症组炎症较非HBV炎症组的炎症及纤维化程度重,但肝脂肪变程度较非HBV炎症组轻,差异有统计学意义(P均0.05)。3.HBV炎症组ALT、AST、GGT、ALP均高于非HBV炎症组,差异有统计学意义(P均0.05)。HBV炎症组TP、ALB、UA均低于非HBV炎症组,差异有统计学意义(P均0.05)。两组的TBIL、BUN、CRE、TG、CHO、HDL、LDL差异无统计学意义(P均0.05)。4.两组HBsAg、HBeAg、HBe Ag阳性率、TT3、TT4、FT3、FT4、TSH、TGAB及胰岛素差异均无统计学意义(P均0.05)。HBV炎症组的HBV-DNA载量高于非HBV炎症组,差异有统计学意义(P0.05)。5.HBV炎症组补体C3水平低于非HBV炎症组,差异具有统计学意义(P0.05);两组补体C4、IgG、IgA、IgM、TFR、Fe、FER、TIBC、UIBC均无差别(P均0.05)。6.HBV炎症组WBC、NEUT、PLT均低于非HBV炎症组,差异有统计学意义(P均0.05),MPV、MCV均高于非活动性HBV组,差异有统计学意义(P均0.05)。两组LYMPH、RBC、HGB、HCT差异均无统计学意义(P均0.05)。7.HBV炎症组CAP值低于非HBV炎症组,肝硬度值高于非HBV炎症组,差异有统计学意义(P均0.05)。8.逐步logistic回归分析后,年龄、CAP、E、ALT等四个因子差异有统计学意义(P均0.05),所得的回归方程为Y=0.106×年龄-0.033×CAP+0.48×E+0.048×ALT-0.86,预测的整体正确率为83.1%。此公式相应的AUC=0.922,P0.001,cut-off值为0.534,灵敏度为80%,特异度为90.91%,阳性预测值为93.6%,阴性预测值为73.2%。9.公式Y=0.106×年龄-0.033×CAP+0.48×E+0.048×ALT-0.86在验证组正确率为63.64%,但所有的用公式诊断为活动性HBV组的(Y0.534)与病理结果诊断一致,符合率100%。结论:1.HBV感染合并NAFLD患者有HBV感染相关炎症活动(HBV炎症组)的特征为:血清学HBV标记物阳性,同时肝组织免疫组化HBs Ag、HBcAg、PreS1Ag至少一项阳性;肝组织脂肪变性符合NAFLD形态学特征;肝组织汇管区扩大,单个核为主的炎细胞浸润,或淋巴细胞集结浸润,至少有轻度的界面性炎症。2.HBV感染合并NAFLD患者无HBV感染相关炎症活动(非HBV炎症组)的特征为:血清学HBV标记物阳性,同时肝组织免疫组化HBsAg、HBcAg、PreS1Ag至少一项阳性;肝组织脂肪变性符合NAFLD形态学特征;肝脏组织汇管区扩大及汇管区内炎细胞浸润均不明显,无界面炎症;除外:a.明确的中央静脉周围炎,伴或不伴中央静脉周围网状支架塌陷b.肝窦内kuffer细胞腊样质沉积。慢性HBV感染合并NAFLD患者的肝脏炎症大部分是由HBV感染引起的。3.HBV炎症组较非HBV炎症组患者的肝脏炎症及纤维化比较明显。且这些患者年龄大,临床上常常ALT、AST、GGT、ALP、HBV-DNA水平升高,且FibroScan值大,CAP值小,血常规可出现WBC、NEUT、PLT等下降、MPV升高,这些简单的临床指标为HBV感染合并NAFLD患者炎症原因判别有一定预示意义。4.可以参考公式Y=0.106×年龄-0.033×CAP+0.48×E+0.048×ALT-0.86初筛,若Y值0.534,考虑肝脏炎症与HBV感染炎症有关,需高度重视HBV的问题,必要时行抗病毒治疗。当然,此公式的实用性有待进一步验证。
[Abstract]:Objective: to identify the causes of liver inflammation by observing the pathological features of patients with chronic hepatitis B virus (Hepatitis B Virus, HBV) infection combined with non-alcoholic fatty liver disease (Nonalcoholic, Liver Disease, NAFLD), compare the clinical characteristics between them, and analyze the indexes related to their inflammation, and then discuss the existence of a non-invasive prescription. Methods such as formulae identify these inflammatory causes and establish a noninvasive clinical diagnostic model for chronic HBV infection with NAFLD inflammation. Methods: to collect chronic HBV infection with NAFLD in Second People's Hospital of Tianjin from 01 months to December 2016, and observe the pathological features of these patients, analyze the causes of inflammation, and according to the pathology. The characteristics were divided into HBV inflammation group (HBV infection combined with NAFLD patients with HBV infection related inflammatory activity) and non HBV inflammation group (HBV infection with NAFLD patients without HBV infection related inflammatory activities). Single factor analysis compared the general characteristics and clinical data of these two groups [including liver and kidney function, blood lipid, blood sugar, uric acid, insulin, hepatitis B, hepatitis B, HBV, HBV, HBV, HBV, HBV -DNA, thyroid function, four iron, immune function, blood routine, B ultrasound, controlled attenuation parameters (Controlled Attenuation Parameter, CAP), FibroScan] and other differences, included in the index of clinical differential and logistic regression analysis of the correlation index of liver inflammation, regression formula, evaluation and verification of its accuracy. Results: 1.HBV The pathological features of the inflammatory group were: enlargement of sinks, infiltration of mononuclear inflammatory cells, or lymphocytic infiltration, and interfacial inflammation. The pathological manifestations of non HBV inflammatory groups were: no obvious enlargement of sinks and infiltration of inflammatory cells in the sinks, and the average age of 41.8 + 9.9 years in the group without interfacial inflammation (41.8 + 9.9 years) was higher than the average of non HBV inflammation group. Age (36.42 + 10.49 years), the difference was statistically significant (P0.05). There was no difference in sex, body mass index (Body Mass Index, BMI) in the two groups (P 0.05). The inflammation and fibrosis degree of.HBV inflammation group was more severe than that of non HBV inflammation group, but the degree of hepatic steatosis was less than that of non HBV inflammatory group, and the difference was statistically significant (P 0.05).3.HBV inflammatory group ALT. GT and ALP were higher than non HBV inflammatory groups (P 0.05).HBV inflammation group TP, ALB, UA were lower than non HBV inflammatory groups, and the difference was statistically significant (P 0.05). No statistical significance (P 0.05).HBV inflammation group was higher than non HBV inflammation group, the difference was statistically significant (P0.05).5.HBV inflammation group C3 level was lower than non HBV inflammation group, the difference was statistically significant (P0.05). In the non HBV inflammation group, the difference was statistically significant (P 0.05), MPV, MCV were higher than the non active HBV group, the difference was statistically significant (P 0.05). The difference of LYMPH, RBC, HGB, HCT was not statistically significant (P 0.05) in the two groups. After the stepwise logistic regression analysis, the four factors of age, CAP, E, ALT were statistically significant (P 0.05). The regression equation was Y=0.106 x -0.033 x CAP+0.48 x E+0.048 x ALT-0.86, the overall accuracy of the prediction was 83.1%., 0.534, the sensitivity was 80%, the specificity was 90.91%, and the positive rate was 90.91%. The predictive value was 93.6%, the negative predictive value was 73.2%.9. Y=0.106 x age -0.033 x CAP+0.48 x E+0.048 x ALT-0.86 in the verification group, the correct rate was 63.64%, but all the formula diagnosed as active HBV group (Y0.534) was consistent with the pathological diagnosis, and the coincidence rate was 100%. conclusion: 1.HBV infection combined NAFLD patients with HBV infection related inflammatory activities. The characteristics of inflammation group were: serological HBV markers positive, and liver tissue immunization of HBs Ag, HBcAg, PreS1Ag at least one positive; liver tissue fatty degeneration conformed to NAFLD morphological characteristics; liver tissue enlargement area, mononuclear mainly inflammatory cell infiltration, or lymphatic cell aggregation infiltration, at least mild interfacial inflammation.2.HBV infection NAFLD patients without HBV infection related inflammatory activities (non HBV inflammation group) were characterized by positive serological HBV markers, and at least one positive of HBsAg, HBcAg and PreS1Ag in liver tissue; fatty degeneration of liver tissue was conformed to NAFLD morphological characteristics, and the enlargement of liver tissue and the infiltration of inflammatory cells in the sinks were not obvious and no interface Inflammation; excepted: A. clear central phlebitis, with or without the collapse of the mesostatic stent around the central vein of Kuffer cell paranotic deposition in the B. hepatic sinusoid. The liver inflammation in patients with chronic HBV infection combined with NAFLD is most obvious in the.3.HBV inflammation group caused by HBV infection and in the liver inflammation and fibrosis in the patients with non HBV inflammation. Some patients are older, often ALT, AST, GGT, ALP, HBV-DNA, and FibroScan value, CAP value, WBC, NEUT, PLT and so on, and MPV increase. +0.048 x ALT-0.86 initial screening, if Y value 0.534, to consider the liver inflammation and HBV infection and inflammation, it is necessary to attach great importance to the problem of HBV, when necessary antiviral treatment. Of course, the practicality of this formula needs to be further verified.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62;R575

【参考文献】