病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).     

肝纤维化磁共振扩散相关成像与病理学结果关系的对照研究

目的 :探讨磁共振体素内不相干运动(intravoxel incoherent motion,IVIM)及扩散峰度成像(diffusional kurtosis imaging,DKI)在轻中度肝纤维化诊断中的价值。方法 :23例弥漫性肝病患者行磁共振IVIM、DKI检查及CT引导下肝脏穿刺活检术。在磁共振图像上测得定量DKI相关指标和标准表观弥散系数(apparent diffusion coefficient,ADC)、快速ADC、慢速ADC、快速ADC/总ADC比例。以病理组织学诊断为金标准,统计分析各磁共振指标与肝纤维化分期、Knodell组织学活动指数(炎症评分)间的相关性,评估其诊断价值。结果:随着肝纤维化分期进展,MD、Dr、标准ADC、慢速ADC值均有逐渐下降的趋势,但差异尚无统计学意义。随着炎症评分程度加重,Dr值呈下降趋势,MK、Kr值呈上升趋势,但差异亦无统计学意义。MD、Dr值、快速ADC值与肝纤维化分期之间具有中度负相关性。快速ADC值与肝纤维化炎症评分之间具有中度负相关性。结论 :磁共DKI及IVIM在轻中度肝纤维化诊断中具有一定价值,其中DKI中MD、Dr指标和IVIM中快速ADC值有助于肝纤维化分期诊断。     

Survivin在肝脏疾病中的研究进展

存活素(Survivin)是新近发现的凋亡蛋白抑制物(inhibitor of apoptosis protein,IAP)基因家族的一个新成员,它选择性地表达于恶性肿瘤组织,在肿瘤的发生和发展过程中起重要作用,参与肝细胞的再生,在肝细胞损伤和修复中起重要作用。本文就Survivin在肝脏中的表达和作用作一简介,并讨论其作为靶点在肝脏疾病治疗中的应用前景。     

乙型肝炎相关肝功能衰竭患者预后危险因素及预后模型建立

目的 探讨影响乙型肝炎相关肝衰竭患者预后的危险因素并建立其预后模型.方法 回顾性收集2006年6月至2008年12月在我科收治的178例乙型肝炎相关肝衰竭患者的临床资料.采用x 2和t检验和非参数检验进行单因素分析,Logistic回归进行多因素分析.结果 年龄、腹水、感染、消化道出血、肝性脑病、肝肾综合征、甲胎蛋白、...     

Survivin在肝脏疾病中的研究进展

存活素(Survivin)是新近发现的凋亡蛋白抑制物(inhibitor of apoptosis protein,IAP)基因家族的一个新成员，它选择性地表达于恶性肿瘤组织，在肿瘤的发生和发展过程中起重要作用，参与肝细胞的再生，在肝细胞损伤和修复中起重要作用。本文就Survivin在肝脏中的表达和作用作一简介，并讨论其作为靶点在肝脏疾病治疗中的应用前景。     

FibroScan-AST评分对具有显著活动性和纤维化的非酒精性脂肪性肝炎患者的诊断效能

目的 验证FibroScan-AST(FAST)评分对非酒精性脂肪性肝病(NAFLD)活动性积分升高(NAS≥4)和显著纤维化(F≥2)的非酒精性脂肪性肝炎(高危NASH)患者的诊断效能,并与其他血清学模型进行比较。方法 回顾性纳入2015年1月—2020年12月在上海交通大学医学院附属瑞金医院住院并经肝组织病理学证实为NAFLD/NASH患者84例,患者于肝活检前后1周内完成FibroScan检查(包括肝脏硬度值和受控衰减参数)和血清生化指标检测。多组间比较采用Kruskal-Wallis H秩和检验。Spearman相关系数(r)用于分析变量之间的相关性。以肝组织病理学检查结果为“金标准”,绘制受试者工作特征曲线(ROC曲线),计算曲线下面积(AUC)。根据既往研究确定的分界值,计算灵敏度、特异度、阳性预测值(PPV)和阴性预测值(NPV)和分类准确性。亚组分析时,采用不同临床指标分组进而比较各模型的评估效能,用AUC(95%CI)表示。结果 84例患者中有高危NASH患者43例。所有患者FAST是0.54(0.04～0.93),F0～4不同肝纤维化分期的FAST依次为0.26(0...     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).     

D-氨基半乳糖联合脂多糖诱导急性肝功能衰竭小鼠血清微小核糖核酸的表达

目的 探讨D氨基半乳糖联合脂多糖诱导急性肝功能衰竭小鼠血清微小核糖核酸(miRNA)的表达变化以及与肝组织miRNA的相关性.方法 Balb/C清洁级小鼠40只分为两组,模型组32只,对照组8只.模型组应用D-氨基半乳糖联合脂多糖诱导Balb/C小鼠急性肝功能衰竭,对照组腹腔注射0.9％氯化钠溶液1 mL.模型组给药后0、3、5和7h分别处死小鼠各8只,采集血清及肝组织,观察小鼠给药后肝功能生物化学指标及肝组织病理学变化.抽提血清及肝组织miRNA,取0、5和7h肝组织进行锁核酸(LNA)-miRNA微阵列分析,并用实时定量反转录PCR检测miRNA.组间均数比较用单因素方差分析,相关性分析采用Pearson和Spearman相关分析.结果 随着小鼠急性肝功能衰竭的发生,肝组织miRNA的表达发生显著变化,共有21个miRNA明显上调,27个miRNA明显下调,其中miRNA-122和miRNA-1187表达下调,miRNA-146a、miRNA-155表达上调.经PCR验证发现小鼠肝组织miRNA 122和miRNA-1187表达逐渐下调,血清miRNA-122和miRNA-1187的表达则逐渐上调;炎性相关的miRNA 146a和miRNA-155在肝组织和血清中表达均明显增加.小鼠miRNA-122和miRNA-1187在组织与血清中的表达呈负相关(r值分别=-0.477和-0.420,P值分别=0.0089和0.0231),而miRNA-155在组织与血清中表达呈正相关(r=0.678,P=0.0001).小鼠血清miRNA 122(r值分别=0.571和0.554)、miRNA-1187(r值分别=0.471和0.542)的相对表达量与ALT和AST水平均呈正相关(均P＜0.05).血清miRNA 122和miRNA-1187在给药5h上升显著,早于血清转氨酶的变化.结论急性肝功能衰竭小鼠肝组织和血清miRNA-122和miRNA-1187的表达呈负相关,血清中miRNA-122、miRNA-1187的变化早于血清转氨酶的变化,有可能成为早期预测肝损伤的血清标志物.     

e抗原阳性慢性乙型肝炎患者外周血树突状细胞干扰素β的表达

目的探讨慢性乙型肝炎患者树突状细胞干扰素β（IFN—β）表达与乙型肝炎病毒（HBV）感染后宿主免疫清除障碍的关系。方法选择e抗原阳性慢性乙型肝炎患者52例,健康对照48例,用免疫磁珠细胞分选乙型肝炎e抗原（HBeAg）法从外周血获得纯化的CD14^＋单核细胞,并用hOMCSF、hIL-4诱导单核细胞成为未成熟的髓样树突状细胞（mDC）,加入polyI：C（25ug／ml）刺激后获得成熟的mDC,在刺激后0h、12h、24h、48h用流式细胞仪检测细胞表面分化抗原CD86、HLA-DR、CD1a,real—time PCR检测IFN8的表达变化。用ELISA方法检测mDC细胞上清液中IFN-β、IL-12、IL-10的浓度变化。结果两组mDC上0h IFN-β mRNA表达水平及细胞上清液中IFN—β浓度差异无统计学意义（P〉0．05）。健康对照组mDC在12hIFN—β mRNA表达水平及IFN-β浓度与0h相比显著升高（P〈0．05）,较患者组0h、12h、24h、48h IFN—β表达显著升高（P〈0．05）。而患者组mDC刺激后12h、24h和48hIFN—β mRNA及IFN-β表达水平与0h相比无显著变化。与0h比较,健康对照组12h、24h、48hCD86表达水平较患者组显著上升（P〈0．05）。两组之间CD1a、HLA—DR表达差异无统计学意义。二组IL-10及IL-120h表达水平差异无统计学意义（P〉0．（15）,患者组IL-10表达24h及48h与0h相比明显上升（P〈0．05）。而对照组12h、24h、48hIL-10表达水平没有明显上升。与之相反,患者组12h、24h、48hIL-12表达与0h相比表达水平没有明显上升,对照组在12hIL-12表达水平与0h相比差异有统计学意义（P〈0．05）,24h、48hIL-12表达水平继续升高（P〈0．05）。结论慢性HBV感染者mDC受polyI：C刺激后IFN-β表达异常,协同刺激因子CD86表达低下,可能造成宿主对HBV感染的免疫清除障碍,导致疾病慢性化。     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).