低水平HBsAg患者纤维化分期特征及其与血小板的相关性分析

目的 了解低水平乙型肝炎表面抗原(HBsAg)慢性乙型肝炎(CHB)患者纤维化分期特征及其与血小板(PLT)计数的相关性.方法 选取珠海市人民医院2018年4月至2020年4月收治的136例低水平HBsAg CHB患者,依据肝纤维化分期将患者分为S1期组(n=28)、S2期组(n=37)、S3期组(n=40)、S4期组...     

HBeAg阳性慢性乙型肝炎不同肝组织炎症与纤维化时期血清HBsAg含量的动力学特点

目的:探讨乙型肝炎病毒e抗原(hepatitis B e antigen,HBeAg)阳性在慢性乙型肝炎(chronichepatitis B,CHB)自然病程中,不同肝组织炎症分级和肝纤维化分期时,血清HBsAg含量的动力学特点.方法:应用电化学发光法检测血清HBsAg含量.各自两两比较在肝组织炎症分级1、2、3和4级的四级之间、肝组织纤维化分期Ⅰ、Ⅱ、Ⅲ和Ⅳ期的四期之间血清HBsAg的含量.结果:HBeAg阳性CHB患者的血清HBsAg含量,在肝组织炎症1、2、3和4级时分别为2998 COI/mL±2515 COI/mL、4064 COI/mL±2468 COI/mL、5513 COI/mL±2390 COI/mL和5736 COI/mL±1838 COI/mL;在肝组织纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期时分别为3159COI/mL±2577 COI/mL、4075 COI/mL±2149 COI/mL、5670 COI/mL±2189 COI/mL和5976 COI/mL±2128 COI/mL.血清HBsAg含量在肝组织炎症分级四级之间、肝组织纤维化分期四期之间均存在差异(F=9.986,P<0.000和F=13.955,P<0.000).结论:HBeAg阳性CHB,其血清HBsAg含量随肝组织损伤程度的进展而增加.     

慢性乙型肝炎患者血清AFP水平与肝组织炎症分级和纤维化分期的关系

目的探讨慢性乙型肝炎自然病程中血清AFP水平变化与肝组织炎症分级和肝纤维化分期的关系。方法在189例慢性乙型肝炎患者行肝活检,并检测血清甲胎蛋白水平。结果在HBeAg阳性者,肝组织炎症1、2、3和4级血清AFP水平分别为4.09±1.94μg/L、6.51±3.42μg/L、19.71±23.72μg/L和33.88±24.29μg/L;在HBeAg阴性者,分别为3.99±2.65μg/L、6.74±4.22μg/L、22.21±23.83μg/L和40.02±45.32μg/L;在HBeAg阳性者,肝纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期血清AFP水平分别为5.28±3.00μg/L、6.97±3.46μg/L、18.16±20.26μg/L和35.06±28.56μg/L;在HBeAg阴性者,肝纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期血清AFP水平分别为4.89±3.20μg/L、5.62±3.40μg/L、19.51±23.00μg/L和32.89±37.88μg/L。结论在慢性乙型肝炎的自然病程中,血清AFP水平的轻度升高与肝组织炎症分级和肝纤维化分期相关,而与HBeAg状态无关。     

HBeAg阴性慢性乙型肝炎患者血清HBsAg水平在不同肝组织炎症分级和纤维化分期的变化

目的 探讨HBeAg阴性慢性乙型肝炎患者血清HBsAg水平以及经相同肝实质细胞体积(肝细胞数量)分摊后的血清HBsAg水平在不同肝组织炎症分级和纤维化分期的动态变化情况. 方法 对144例HBeAg阴性慢性乙型肝炎患者,应用电化学发光法检测血清HBsAg水平.分别两两比较肝组织炎症1、2、3和4级以及Ⅰ、Ⅱ、Ⅲ和Ⅳ期纤维化时血清HBsAg的水平以及经相同肝实质细胞体积分摊后的血清HBsAg水平.组间均数比较采用单因素方差分析,进一步两两比较采用LSD-t检验.结果 肝组织炎症1、2、3、4级时血清HBsAg水平(COI/ml)分别为6 036.4±2 729.4、6 704.6±2 457.5、6 332.2±2 409.0和6226.2±2 716.0,各组之间差异无统计学意义(F分摊前=0.564,P=0.640);但经相同肝实质细胞体积(肝细胞数量)分摊后,肝组织炎症1、2、3、4级时的血清HBsAg水平(COI/ml)分别为9 174.8±4 142.0、10743.1±3950.3、11 078.0±4 230.0和11 540.5±5 058.8,各组之间差异有统计学意义(F分摊后=27.354,P＜ 0.01).肝纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期时血清HBsAg水平(COI/ml)分别为6 222.1±2 665.4、6 706.8±2 623.8、6 004.5±2 625.5和6 455.6±2 344.4,各组之间差异无统计学意义(F分摊前=0.768,P=0.513);但经相同肝实质细胞体积(肝细胞数量)分摊后,肝纤维化Ⅰ、Ⅱ、Ⅲ和Ⅳ期时血清HBsAg水平(COI/ml)分别为9 417.5±4 034.2、10 093.3±4 183.4、10 177.1±4 445.0和12 166.6±4 418.5,各组之间差异有统计学意义(F分摊后=57.077,P＜ 0.01).结论 HBeAg阴性慢性乙型肝炎患者,相同肝实质细胞体积(肝细胞数量)分摊后的血清HBsAg水平,而非血清HBsAg水平,随肝组织病理进展而不断增加.     

综合预测模型FibroTest对慢性乙型肝炎肝纤维化的诊断价值

目的探讨综合预测模型FibroTest对慢性乙型肝炎肝纤维化的诊断价值。方法留取2002年8月至2005年12月北京大学第一医院、安阳市第五人民医院和无锡市传染病医院的123例行肝活检的慢性乙型肝炎患者的血清,检测α2-巨球蛋白、结合珠蛋白、载脂蛋白-AⅠ、记录总胆红素和谷氨酰转肽酶的数值,并根据其结果结合患者的年龄和性别计算出FibroTest的数值。根据肝纤维化分期设定3个判定点,分别为显著纤维化(S2~S4期),严重纤维化(S3~S4期)和肝硬化(S4期)。以肝活检病理结果为金标准绘制出FibroTest的受试者工作特征曲线,计算曲线下面积(AUC),并与用天冬氨酸转氨酶-血小板比值指数(APRI)计算出的AUC进行比较,评价其对慢性乙型肝炎肝硬化的诊断价值。结果123例肝活检患者中S0期25例(20.3%);S1期27例(22.0%);S2期31例(25.2%);S3期29例(23.6%);S4期11例(8.9%),即显著纤维化者(S2~S4期)71例(57.7%),严重纤维化者(S3~S4期)40例(32.5%),肝硬化者(S4期)11例(8.9%)。FibroTest对3个判定点的AUC值分别为0.814(95%CI:0.740~0.888,P<0.01),0.824(95%CI:0.749~0.898,P<0.01),0.723(95%CI:0.575~0.870,P=0.015)。而APRI对3种不同程度肝纤维化的AUC值分别为0.715(95%CI:0.625~0.805,P=0.001),0.725(95%CI:0.631~0.818,P=0.002)和0.646(95%CI:0.497~0.795,P>0.05)。结论Fi-broTest可以准确地估计慢性乙型肝炎患者有无显著纤维化,可使45.5%的患者避免进行肝脏活检,并保证87.5%的诊断准确率。     

慢性乙型肝炎儿童肝脏病理特征分析及其肝纤维化非侵入性指标探索

目的:分析总结儿童乙型肝炎患者肝脏病理学特征及其与临床指标间的相关性,进一步探索可用于儿童肝脏纤维化评估的非侵入性指标。方法:回顾性分析2011年至2020年住院的80例行肝活检的未经抗病毒治疗的乙型肝炎患儿资料。分析不同年龄段及不同性别患儿的炎症和纤维化特征,选取与肝纤维化分期相关性较好的变量建立儿童肝纤维化非侵入性...     

慢性乙型肝炎患者肝组织病理研究

目的:探讨慢性乙型肝炎(CHB)患者临床表现和病理诊断的相关性.方法:收集30例CHB患者的临床资料,分析临床表现与病理诊断的相关性.结果:肝组织的炎症和纤维化程度的相关性显著(r=0.659,P＜0.01),白蛋白/球蛋白比值(A/G)与肝脏炎症和纤维化分级显著负相关(r=-0.368,P＜0.05;r=-0.401,P＜0.05).年龄、性别及其他化验指标如ALT、AST、TP、ALB、GLO、TBil、PLT、PT、PTA、门静脉宽度、脾脏厚度等与肝组织炎症和纤维化分级无显著相关性(P＞0.05).结论:慢性乙型肝炎肝脏炎症和纤维化的严重程度密切相关,仅根据肝功能判断轻中度的CHB患者的肝脏炎症及纤维化程度有相当的局限性.     

慢性乙型肝炎患者实验室检查指标与肝纤维化程度的关系

目的探讨慢性乙型肝炎患者实验室检查指标与肝纤维化程度的关系。方法 90例慢性乙型肝炎肝纤维化患者,根据肝纤维化程度不同分为S1~S4期,分析白细胞、血红蛋白、血小板等实验室检查指标与肝纤维化分期的关系及危险因素。结果多因素Logistic回归分析发现,慢性乙型肝炎肝纤维化的独立性危险因素有血小板(OR=0.440,P=0.022)、透明质酸(OR=2.224,P=0.033)、Ⅲ型前胶原(OR=2.163,P=0.034)及Ⅳ型胶原(OR=2.133,P=0.036)。结论对于慢性乙型肝炎患者,尤其是血小板水平降低,血清透明质酸、Ⅲ型前胶原、Ⅳ型胶原水平持续升高时,应及时行肝脏组织学评估以便早期发现及治疗肝纤维化。     

慢性乙型肝炎患者临床和肝组织病理学特点及影响肝纤维化因素分析*

目的 分析HBeAg阴性与阳性慢性乙型肝炎（CHB）患者临床和肝组织病理学特点,探讨影响CHB患者发生明显肝纤维化的危险因素。方法 回顾性分析250例CHB患者血清HBV DNA水平、Fibroscan检测肝脏硬度（stiffness）值和肝穿刺组织病理学特点,应用多因素Logistic回归模型分析影响CHB患者发生明显肝纤维化的独立危险因素。结果 160例HBeAg阴性患者血清HBV DNA ≥1×10⁵ copies/ml者所占比例显著低于HBeAg阳性组（66.9%对99.4%,P<0.05）;HBeAg阴性组血清ALT和AST水平显著低于HBeAg阳性组（P<0.05）;血清HBeAg阴性组与阳性组肝组织炎症分级和纤维化分期总体分布差异无统计学意义（P>0.05）;多因素Logistic回归分析结果显示年龄≥40岁、HBV DNA水平高、PTA低和Stiffness水平高为CHB患者存在明显肝纤维化的独立危险因素。结论 血清HBeAg阴性与阳性CHB患者存在一些临床和肝组织病理学特征的差异,血清HBeAg阴性患者可能存在更为严重的临床和预后问题,需要给予特别的关注和管理。     

The association of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage in patients with chronic hepatitis B

The utility of measurement of serum immunoglobulin and complement in chronic hepatitis B (CHB) patients remains controversial. This study aimed to investigate the association of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage in CHB patients. A total of 687 patients with CHB who underwent liver biopsy were enrolled. Serum immunoglobulin and complement were measured before liver biopsy, and liver pathological results were recorded. Associations of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage were analysed. C3, C4, IgG and IgG1 had statistically significant differences among different fibrosis and different inflammation groups. Both C3 and C4 negatively correlated with fibrosis and inflammation stage, but IgG and IgG1 showed opposite results. C3, C4, IgG and IgG1 had statistical significance to predict ≥S2, ≥S3 and S4, and also had statistical significance to predict ≥G2, ≥G3 and G4. The area under curve (AUC) of the combination of C3, C4 and IgG (C3 + C4 + IgG) for predicting ≥S2, ≥S3 and S4 was 0.640 (95% CI: 0.603, 0.676), 0.674 (95% CI: 0.638, 0.709) and 0.744 (95% CI: 0.710, 0.776), respectively. The AUC of C3 + C4 + IgG for predicting ≥G2, ≥G3 and G4 was 0.723 (95% CI: 0.688, 0.756), 0.674 (95% CI: 0.638, 0.709) and 0.771 (95% CI: 0.738, 0.802), respectively. C3, C4, IgG and IgG1 are correlated with liver fibrosis and inflammation stage in CHB patients. C3, C4, IgG and IgG1 have diagnostic value for liver fibrosis and inflammation. C3 + C4 + IgG may improve diagnostic accuracy.     

慢性乙型肝炎肝纤维化分期与血清肝纤维化标志物的相关性分析

目的 探讨血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原等血清肝纤维化标志物与慢性肝炎肝组织炎症活动度及纤维化程度的相关性。方法 278例慢性肝炎患者经肝脏活栓后常规病理检查,肝活检前同时采血检测血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原,结果应用x^2检验及t检验进行统计学处理。结果 肝组织纤维化程度与炎症活动度呈正相关关系,透明质酸可反映中度以上慢性肝炎炎症活动度及纤维化程度,且呈正相关;肝脏存在纤维化时层粘蛋白水平升高,与纤维化程度正相关;Ⅲ型前胶原、Ⅳ型胶原水平升高与炎症活动度有关。结论 血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原可不同程度反映肝纤维纤维化程度,可作为血清肝纤维化检测指标,透明质酸更可反映肝硬化发展趋势。     

饮酒对慢性乙型病毒性肝炎患者肝脏炎症和纤维化的病理影响

目的:从病理角度研究饮酒对慢性乙型病毒性肝炎(CHB)患者肝脏炎症和纤维化的影响.方法:回顾性分析84例有肝活检的患者,分为单纯饮酒组、单纯CHB组、CHB合并饮酒组.以半定量的方法分析并评价肝穿活检病理的炎症活动度、纤维化程度及脂肪变性程度.结果:在饮酒的CHB患者的病理下炎症活动度、纤维化程度及脂肪变性程度(8.73±6.93,7.67±5.34,43.58±21.80)均显著高于单纯CHB组(5.20±3.41,5.40±3.94,6.83±12.81,P均<0.05).多元线性逐步回归分析显示,每日饮酒量分别与病理下炎症活动度及脂肪变性程度的加重相关(R2=0.673,P=0.000;R2=0.559,P=0.000),每日饮酒量和累积饮酒量与病理下纤维化程度的加重相关(R2=0.650,P=0.000).结论:饮酒、尤其每日饮酒量与肝细胞损害程度有关,可明显加重CHB的病情.     

慢性乙型肝炎患者肝组织学纤维化分期与血清肝纤维化相关指标的关系

目的 探讨慢性乙型肝炎(CHB)肝组织学纤维化程度与临床血清肝纤维化相关指标之间的关系.方法 对189例人院诊断为CHB的患者行肝穿刺.同时检测血清HA、LN、PCⅢ、ⅣC、肝功能和血常规,并按组织学的不同纤维化分期(S)进行比较和相关性回归分析.结果 从肝纤维化So至S4期,PC Ⅲ、γ-GT、TBil、γ-球蛋白和PT渐增,差异有统计学意义(F值分别为3.325、6.218、2.958、10.160和7.028,P＜0.05);胆碱酯酶(CHE)、总蛋白(TP)、Alb、PLT值渐减,差异有统计学意义(F值分别为15.984、3.786、14.919和4.737,P＜0.01);LN、ⅣC、ALT和AST值在S各期比较差异有统计学意义(F值分别为4.618、2.795、2.649和3.199,P＜0.05).S分期与LN、PCⅢ、ALT、AST、TBil、γ-GT、γ-球蛋白、PT呈正相关(rs值为0.200、0.306、0.1 72、0.273、0.153、0.402、0.415、0.269),与CHE、TP、Alb、PLT呈负相关(rs值为-0.502、-0.208、-0.413、-0.390);LN、ALT、CHE、PLT、γ-球蛋白为肝纤维化分期的独立影响因素(P＜0.05).结论 肝组织学纤维化分期与血清肝纤维化、肝功能、血常规指标有不同程度相关.综合多项临床资料可早期无创性诊断肝纤维化.     

慢性乙型肝炎患者肝纤维化程度与肝功能指标关系分析

目的 探讨慢性乙型肝炎肝纤维化程度与血清HBV DNA水平及肝功能的关系.方法 采用肝脏活体组织检查确定肝组织炎症活动度及纤维化程度,同时检测血清HBV DNA水平及肝功能.结果 肝组织病理的肝纤维化分级与炎症活动分期有关,肝脏炎症程度与纤维化程度呈正相关,P=0.000,rs=0.657.肝脏炎症分期与HBV DNA...     

HBeAg阴性慢性乙型肝炎获得HBsAg清除与血清白细胞介素17水平的关系

目的探讨聚乙二醇干扰素(PEG-IFN)治疗HBeAg阴性慢性乙型肝炎(CHB)发生HBsAg清除与血清白细胞介素(IL)17水平的关系。方法选择2012年1月-2015年1月于北京佑安医院就诊的HBeAg阴性CHB患者13例,经PEG-IFN治疗24周,其中6例获得HBsAg清除(R组),7例未获得HBsAg清除(NR组)。用Luminex技术检测患者基线、治疗12周和24周血清IL-17水平。同时检测10例健康人和6例急性乙型肝炎(AHB)患者发病时的血清IL-17水平。计量资料两组间比较采用t检验,多组间比较采用方差分析,进一步两两比较采用SNK-q检验;计数资料组间比较采用χ~2检验。结果 AHB组基线血清IL-17水平最高,其次是CHB组,健康对照组最低,3组间比较差异有统计学意义(P0.05)。CHB患者经PEG-IFN治疗24周后,IL-17水平较基线明显下降(P=0.044)。R组基线血清IL-17水平高于NR组,而且在PEG-IFN治疗后明显下降;而NR组IL-17升高或降低不明显。结论 PEG-IFN治疗HBeAg阴性CHB患者,IL-17基线高水平和治疗过程中明显降低可能有利于HBsAg清除。     

Clearance of HBsAg in seven patients with chronic hepatitis B.

The natural history of chronic hepatitis B patients who spontaneously cleared serum HBsAg was investigated. A total of 351 patients with chronic hepatitis B were observed in our hospital for at least 3 yr. Seven of these patients became HBsAg negative during the follow-up period. HBsAg disappeared within 6 mo (range = 11 to 169 days, mean = 70 days) after acute elevation of ALT. ALT levels as high as 500 IU were found in three patients, whereas such elevation was not demonstrated in the other four patients. After the disappearance of HBsAg, ALT levels returned to normal in all patients. With one exception, all patients seroconverted to antibody to HBsAg; however, hepatitis B virus DNA remained detectable in serum using the polymerase chain reaction in five patients. The titer of percent inhibition of antibody to HBcAg gradually decreased to less than 70% when a 1:200 dilution of the serum of six patients was used. Four of the patients had active liver disease develop: two had chronic active hepatitis and two had cirrhosis. Three of these four patients subsequently had hepatocellular carcinoma develop. These findings suggest that patients may suffer complications of chronic hepatitis even after normalization of transaminase activities and after the clearance of HBsAg. Thus hepatitis B virus should be considered as a possible factor associated with hepatocellular carcinoma even in the absence of HBsAg, particularly if serum hepatitis B virus DNA persists.     

e抗原阴性和阳性慢性乙型肝炎患者血清HBVDNA定量与肝组织病理学关系

目的研究HBeAg阴性和阳性慢性乙型肝炎（以下简称慢乙肝）患者血清HBVDNA定量与肝组织炎症活动度及纤维化程度的关系。方法选取慢乙肝患者68例,行肝穿刺病理检查,并检测血清HBVDNA定量,按照HBeAg阴性和阳性分组,进行相关性检验。结果HBeAg阴性患者血清HBVDNA定量与肝组织炎症活动度及纤维化程度之间呈明显正相关,r分别为0．706、0．689,P均小于0．05;HBeAg阳性者血清HBVDNA定量与肝组织炎症活动度及纤维化程度之间均无相关性,r分别为-0．119、-0．096,P均大于0．05。结论血清HBVDNA定量可作为HBeAg阴性慢乙肝患者肝组织损伤程度的预测指标之一。     

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.Liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan.Patients with liver inflammation activity≥2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage,whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity<2(all P<0.05).A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan,and the AUC was 0.701.CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage.A combination of other related noninvasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.