PGA指数在诊断慢性乙型肝炎肝纤维化中的价值

肝组织病理检查是确诊肝纤维化的重要方法 ,但难以推广与重复。近十余年来 ,已有不少血清学指标用于临床辅助诊断肝纤维化 ,如透明质酸 (ＨＡ)、层黏连蛋白 (ＬＮ )、Ⅲ型前胶原肽 (ＰⅢＰ)与Ⅳ型胶原 (Ｃ Ⅳ )等 ,与病理检查结果有很好的相关性[1 3 ] 。但存在不能自动化检测、难以每日常规测定、需放射免疫检测设备、检测价格较高等问题 ,后人们发现由凝血酶原时间 (ＰＴ)、谷氨酰转肽酶 (ＧＧＴ)与载脂蛋白Ａ1(ＡｐｏＡ1)组成的ＰＧＡ指数是诊断酒精性肝纤维化的敏感指标[4] 。我们的临床病理对照研究证明 ,ＰＧＡ指数也是诊断慢性乙型肝…     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的探讨FIB-4（fibrosis index based on the 4 factor）指数对慢性乙型肝炎患者肝纤维化诊断价值。方法检测86例慢性乙肝患者血清ALT（谷丙转氨酶）、AST（谷草转氨酶）、PLT（血小板）等指标,根据病理肝纤维化分期设定两个判定点,分别为显著纤维化（≥S2级）和肝硬化（S4级）,采用FIB-4指数加以评分,以肝组织病理学检查作对比,根据受试者工作特征曲线（AUROCs）评价FIB-4对于肝纤维化的诊断价值。结果FIB-4指数采用AUROCs加以评价,显示FIB-4≥S2级（显著纤维化）AUC曲线下面积为0．813,以1．56分值为界值,诊断显著肝纤维化敏感性、特异性、PPV和NPV分别达到86．21％、71．43％、86．2％和71．4％。S4级（肝硬化）AUC曲线下面积为0．802,以2．2分值为界值,诊断肝硬化敏感性、特异性、PPV和NPV分别达到87．5％、67．14％、37．8％和95．9％。结论FIB-4指数是一种简单易行、预测结果可靠的非侵入诊断方法,在一定程度上可替代肝活检。     

氧化苦参碱治疗慢性乙肝肝纤维化的临床研究

目的：探讨氧化苦参碱对慢性乙肝肝纤维化的临床疗效。方法：经肝组织病理检查筛选98例慢性乙肝肝纤维化病人，用氧化苦参碱100mL静滴，6月后观察其HBV－DNA定量，血清HA、LN、PCⅢ及肝组织病理变化。并设54例对照组进行比较。结果：与对照组比较，治疗组病人HBV－DNA阴转率高于对照组，其HA、LN、PCⅢ均较对照组明显降低，肝组织病理检查，肝纤维化程度明显减轻，减轻程度明显高于对照组。结论：氧化苦参碱通过其抗病毒，稳定肝细胞膜，抑制贮脂细胞增生，减少细胞外基质（ECM）的形成，而起到有效的抗纤维化作用。     

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。     

AST/PLT和GGT/PLT比值对肝纤维化的诊断价值

目的探讨AST/PLT和GGT/PLT比值对肝纤维化的诊断价值。方法比较慢乙肝组和正常对照组,不同炎症分级(G)和纤维化程度分期(S)的慢乙肝病例组间血常规、肝功能和血清肝纤维化常规四项指标(HA、CⅣ、PCⅢ和LN)的差异。结果不同程度的S1~4和G1~4的AST/PLT、GGT/PLT、HA、CⅣ、PCⅢ和LN 6项指标与正常人比较,差异均非常显著(P<0.001)。AST/PLT和GGT/PLT比值的阳性率在不同程度的S和G之间均无显著性差异。肝纤维化常规四项指标中阳性率以HA为佳,与前两比值之间无显著差异。结论AST/PLT和GGT/PLT对肝纤维化的诊断有一定价值,但需排除其他原因引起AST、GGT增高和PLT(血小板计数)减少。     

瞬时弹性成像在慢性乙型肝炎肝纤维化诊断中的应用

目的：探讨瞬时弹性成像（ FS）在慢性乙型肝炎（乙肝）肝纤维化诊断中的应用价值。方法选取慢性乙肝患者165例,其中轻度肝纤维化者77例,中度肝纤维化者47例,重度肝纤维化及肝硬化者41例;另选同期健康体检者50例。采用FS扫描仪检测所有受试者肝脏硬度值;采用常规及临床生化检查检测血小板、AST、谷氨酰转肽酶及胆固醇,计算APRI指数、Forns指数。采用受试者工作特征（ ROC）曲线分析FS、APRI、Forns单独及联合诊断慢性乙肝肝纤维化的准确性。结果在诊断中度肝纤维化时,FS、Forns、APRI的ROC曲线下面积（ AUC）值分别为0．807、0．786、0．767,诊断界值分别为8．5 kPa及8．1、11．7,敏感度分别为83．3％、60．0％、73．3％,特异度分别为81．6％、92．1％、76．3％;在诊断重度肝纤维化及肝硬化时,FS、Forns、APRI的AUC值分别为0．896、0．886、0．829,诊断界值分别为16．3 kPa及8．4、9．3,敏感度分别为73．3％、80．0％、73．3％,特异度分别为90．6％、83．0％、88．7％。在诊断中度肝纤维化时,FS＋APRI ＋Frons、FS＋Frons、FS＋APRI、FS 的AUC 值分别为0．851、0．832、0．826、0．807,敏感度分别为66．7％、76．7％、70．0％、83．3％,特异度分别为97．4％、81．6％、89．5％、81．6％;在诊断重度肝纤维化及肝硬化时,FS＋APRI＋Frons、FS＋Frons、FS＋APRI、FS的AUC值分别为0．922、0．904、0．907、0．896,敏感度分别为86．7％、86．7％、80．0％、73．3％,特异度分别为88．7％、83．0％、88．7％、90．6％。结论 FS对慢性乙肝肝纤维化诊断准确性高,联合血清学检测诊断效能增高,具有良好的临床应用价值。     

慢性乙肝患者脯氨酸肽酶与肝纤维化的关系分析

目的了解血清脯氨酸肽酶（prolidase,PLD）与乙型病毒性肝炎肝纤维化程度的关系。方法测定191例乙型肝炎患者血清中PLD水平,利用ROC曲线分析ALT、AST、AST/ALT和PLD的面积,判断PLD的最优截断点并计算不同标准的灵敏度、特异度、阳性预测值（PPV）、阴性预测值（NPV）、Youden指数。结果慢性乙型肝炎患者PLD值随着肝纤维化严重程度升高,S2-4期（明显肝纤维化）明显高于S0-1期（无明显肝纤维化）（P〈0.01）。ALT、AST、AST/ALT和PLD的ROC曲线下面积分别为0.614、0.648、0.655和0.807。PLD的最优截断点约为1 250 U/L,灵敏度和特异度分别为75.6%和75.2%。结论血清PLD测定对于慢性乙型肝炎患者肝纤维化程度判定有一定的临床价值。     

肝组织HBcAg表达与慢性乙肝肝纤维化的相关性探讨

目的探讨肝组织HBcAg表达与肝纤维化的关系。方法采用免疫组化法检测86例慢性乙型肝炎（乙肝）患者肝组织中HBcAg表达,分析HBcAg表达与肝纤维化的关系。结果HBcAg阳性者54例,其肝纤维化分期为S2～S4期36例（67％）;HBcAg阴性者32例,其中肝纤维化分期为S2～S4期6例（18％）;P〈0．05。HBcAg表达为胞膜型、胞质型及胞核型者肝纤维化分期为S2-S4。期分别占88％、57％、33％,胞膜型者明显高于其他两型,P〈0．05。结论肝组织HBcAg表达与肝纤维化程度有关;HBcAg阳性者及HBcAg表达为胞膜型者肝纤维化程度重。     

IFN-α对慢性乙肝肝纤维化阻断作用的研究

探讨IFN -α对慢性乙肝肝纤维化的阻断作用。 6 5例慢性乙肝患者随机分为对照组和IFN组 ,动态观察治疗前后血清HA、PCⅢ、Ⅳ -C水平及IFN疗效与治疗前肝组织纤维化程度关系。IFN -α治疗后血清HA、PCⅢ、Ⅳ -C水平较治疗前及对照组明显降低 (P <0 0 5 ,P <0 0 1) ;IFN无应答组患者治疗前血清HA、PCⅢ水平明显高于应答组 (P <0 0 5 )。IFN -α疗效与治疗前肝组织纤维化分期呈负相关 (r=- 0 6 773,P <0 0 5 )。IFNα对慢性乙肝有明显的抗肝纤维化作用 ,其抗病毒疗效受治疗前肝纤维化程度的影响     

Genotype/subgenotype distribution of hepatitis B virus among hemodialysis patients with chronical hepatitis B

Introduction. Hepatitis B virus (HBV) infection in hemodialysis (HD) patients is a major concern, but limited information exists on the HBV genotyping in patients on maintenance HD in Turkey.Aim. To investigate the genotype and subgenotype distribution of HBV in Turkish HD patients with chronic hepatitis B.Material and methods. A total of 248 HBsAg positive patients undergoing long-term HD from all regions of Turkey were included in this study. HBV genotypes were determined by phylogenetic analysis and by genotyping tools.Results. HBV DNA was detected in 94/248 (38%) of the patients. Among the study patients, genotype D of HBV was predominant (99%) and one patient (1%) was infected with genotype G. The majority (82%) of HBV genotype D branched into subgenotype D1, and also in ayw2 HBsAg subtype clusters in the phylogenetic tree. However, 10% and 8% of the strains branched into subgenotype D2 (also in ayw3 HBsAg subtype cluster) and subgenotype D3 clusters, respectively.Conclusion. In conclusion, HBV genotyping should be routinely applied to HD patients to establish a baseline. Determination of genotypes/subgenotypes of HBV may provide robust epidemiological data related to their circulation as well as their transmissibility.     

Helicobacter pylori seroprevalence in cirrhotic patients with hepatitis B virus infection

Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. The burden of cirrhotic patients on the National Health System is extremely high due to the frequent need for medical care. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over one-third of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we wished to ascertain the prevalence of H. pylori infection in cirrhotic patients. In a case-control study we looked for this infection in 45 consecutive male patients suffering from hepatitis B virus (HBV)-related cirrhosis and 310 sex and age matched blood donors resident in the same area. Antibodies against H. pylori were present in 40/45 (89%) patients and 183/310 (59%) blood donors (P<0.001). This very high prevalence of H. pylori may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients. (See Editorial p. 203)     

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

AIM To investigate the value of the gamma-glutamyltraspeptidase(GGT)-to-platelet(PLT) ratio(GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B(CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase(AST)-to-PLT ratio index(APRI), and fibrosis-4(FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin(TBil), alanine aminotransferase(ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic(ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated withCHB patients' age, gender, or disease duration(P 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count(P 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis(P 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI(F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series.CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.     

Hepatocellular carcinoma in cirrhotic patients: role of hepatitis B virus

Four hundred and fifty seven Italian patients with liver cirrhosis--140 with hepatocellular carcinoma (HCC) and 317 without HCC (CP)--were studied in order to assess the risk factors of HCC in cirrhotic patients in Italy and, particularly, the role of HBV infection, that seems to be important in high and not in low incidence areas of HBV infection. All HCC were histologically confirmed and all cirrhotic patients were followed-up for one year or more without evidence of HCC. The statistical analysis was carried out by means of Stepwise Logistic Regression. Increasing age, male sex and HBV infection were found to be significant risk factors of HCC in CP, in a medium-incidence area of HCC and HBV as in Italy. There is, therefore, a striking correlation between HBV and the geographical incidence of HCC. In general, the higher the incidence of HBV, the greater its importance as a risk factor of HCC.     

拉米夫定对慢性乙型肝炎肝硬化患者的疗效观察

我们用随机对照临床试验研究拉米夫定对乙型肝炎肝硬化的疗效现报道如下。1.资料与方法:89例慢性乙型肝炎肝硬化失代偿患者,诊断符合2000年病毒性肝炎诊断标准[1]。血清定量PCR法测定HBV DNA均阳性,年龄16-65岁,Child-pugh分级在A、B级。排除标准:肝性脑病、原发性肝癌、血清胆红素>85 μmol/L、Ⅲ型腹水和肾功能不全者、血清丙型肝炎病毒或丁型肝炎病毒阳性、血小板计数<80 ×109/L或粒细胞计数<1.5 ×109/L酗酒者和不稳定糖尿病患者。随机分为两组,拉米夫定治疗组49例,其中HBeAg阳性29例,阴性20例;Child A级13例,B级36例。对照组40     

瞬时弹性成像在诊断HBeAg阴性慢性乙型肝炎肝纤维化中的价值

目的探讨肝脏瞬时弹性成像(FibroScan,FS)在HBeAg阴性慢性乙型肝炎(CHB)患者肝纤维化中的应用价值。方法选择2011年6月-2013年5月在湖北省中医院诊治的HBeAg阴性CHB患者104例,运用FS进行肝脏硬度(Stiffness值)测量,所有患者均行肝穿刺活组织检查。以肝活组织检查病理结果为标准,Stiffness值与之对比;同时绘制FS工作特征曲线,计算受试者工作特征曲线下面积(AUC)。组间比较采用Kruskal-Wallis H检验,两组比较采用Mann-Whitney U检验。双变量相关性分析采用Pearson相关和Spearman等级相关法。结果随肝纤维化程度的提高,Stiffness值逐渐增高,差异有统计学意义(P0.01或P0.05)。Stiffness值与肝纤维化分期呈正相关(r=0.810,P0.01)。FS检测肝硬化AUC为0.956,其中以13.1 kPa作为肝硬化的诊断界值,敏感度为92.7%,特异度为80%。结论 FS在HBeAg阴性CHB患者肝纤维化程度的评估中具有较好的应用价值,尤其诊断肝硬化的准确性较高,直接、间接标志物和FS的联合应用有助于肝纤维化患者的鉴别诊断及疗效评估。     

乙型肝炎肝硬变患者外周血和肝组织中HBV cccDNA的定量检测

目的:研究乙型肝炎肝硬变患者HBV共价闭合环状DNA(cccDNA)在肝组织和外周血中的分布及临床应用.方法:选取60例乙型肝炎肝硬变患者肝组织和外周血样本,外周血样本以不降解质粒的ATP依赖的DNA酶(PSAD)进行酶切,肝组织样本以限制性内切酶Mlu联合PSAD酶切.而后进行荧光定量PCR检测.结果:60例乙型肝炎肝硬变患者外周血HBVcccDNA均阴性,肝组织HBV cccDNA阳性24例(40.00%),在HBeAg( )组、HBeAg(-)HBeAb(-)组、HBeAb( )组分布分别为66.67%、52.94%和26.47%,定量结果在3组呈递减趋势,且HBeAg( )组与HBeAb( )组差异存在统计学意义(P＜0.05).肝组织HBV cccDNA占总HBVDNA 0%-7.77%.肝组织HBV cccDNA与肝组织总HBV DNA存在相关性(r=0.53,P＜0.01),与外周血总HBV DNA无相关性(r=0.18,P=0.18),与ALT、TBIL均无相关性(r=0.15,P=0.25;r=0.01.P=0.94).结论:乙型肝炎肝硬变患者外周血检测不到HBV cccDNA.肝组织HBV cccDNA占总HBVDNA比例较低,HBeAg( )患者病毒复制最为活跃.     

慢性乙型肝炎肝硬化患者发生肝细胞癌的危险因素分析

目的 探讨乙型肝炎肝硬化患者发生肝细胞癌(HCC)的危险因素. 方法 收集2009年1月至2014年9月在复旦大学附属中山医院就诊的来自上海及周边地区的汉族乙型肝炎肝硬化患者资料,将其分为肝硬化组和HCC组.收集患者病史、血清学、影像学及病理检查资料,比较两组间的一般情况及临床检测数据,用SPSS 19.0统计软件进行包括采用x2检验的单因素分析和logistic多因素回归分析的统计学分析.结果 共收集715例患者资料,其中肝硬化组281例,HCC组434例.单因素分析结果显示男性、年龄≥50岁,有肝癌家族史、饮酒史、脂肪肝、可检出HBV DNA、未得到有效的抗病毒治疗与乙型肝炎肝硬化患者发生HCC显著相关.多因素回归分析结果显示年龄≥50岁(P=0.005,OR=1.766)、饮酒史(P=0.002,OR=2.570)、肝癌家族史(P=0.014,OR=2.268)、脂肪肝(P=0.023,OR=3.390)、未得到有效的抗病毒治疗(P＜ 0.001,OR=5.389)是乙型肝炎肝硬化患者发生HCC的危险因素.达到持续病毒学抑制(SVS)的乙型肝炎肝硬化患者仍可能发生HCC,HBV感染家族史(P=0.014,OR=2.537)、肝癌家族史(P=0.037,OR=3.339)和脂肪肝(P=0.018,OR=11.646)与达到SVS的乙型肝炎肝硬化患者发生HCC显著相关.结论 乙型肝炎肝硬化患者并发HCC的独立危险因素包括年龄≥50岁、饮酒史、肝癌家族史、脂肪肝和未得到有效的抗病毒治疗.HBV感染家族史、肝癌家族史和脂肪肝是达到SVS的乙型肝炎肝硬化患者发生HCC的危险因素.     

肝组织学检查在慢性乙型肝炎患者病情评估中的价值

目的 进一步研究肝组织学检查在慢性乙型肝炎(CHB)患者病情评估中的价值.方法 对176例入院诊断为CHB的患者进行肝组织活检,同时进行实验室及影像学检查,对临床及病理诊断进行对比分析,以组织学炎症活动度＜G2和≥G2、纤维化程度＜S2和≥S2分组,分别比较肝功能生物化学指标.单因素分析采用秩和检验和x2检验,多因素分析采用双变量Logistic回归分析方法.结果 176例患者临床诊断CHB 171例、肝硬化5例.171例CHB患者中,病理与临床诊断总体符合102例,占59.6%,临床诊断重于病理诊断60例,占35.1%,临床诊断轻于病理诊断9例,占5.3%.44例G2患者中,ALT≥2×正常值上限(ULN)的为41例,占93.2%.多因素Logistic回归分析显示,年龄、明显的症状、ALT、胆碱酯酶(CHE)、Alb、总胆汁酸(TBA)水平及肝脏彩色超声提示肝表面不光滑是肝纤维化分期≥S2相关的独立影响因素.结论 CHB程度分级的临床与病理诊断符合率不高.G2作为CHB中度、S2作为CHB重度的病理学界定标准似乎更符合临床实际.

Abstract：

Objective To explore the value of liver biopsy in diagnosis of the severity of chronic hepatitis B (CHB).Methods The liver biopsy, laboratory examination and imaging were performed in 176 CHB patients. The clinical and histological diagnoses were compared. Biochemical indexes of liver function were also compared between patients with histological inflammation activity ＜G2 and≥G2 or the patients with fibrosis score ＜S2 and ≥S2. Rank sum test and χ2 test were used in univariate analysis. Binary Logistic regression was used in multivariate analysis. Results Among 176patients, the clinical diagnosis of CHB and cirrhosis were established in 171 patients and five patients,respectively. Among 171 CHB patients, the clinical diagnosis was consistent with histological diagnosis in 102 (59.6%) patients. The clinical diagnosis was more severe than histological diagnosis in 60 (35.1%) patients and the clinical diagnosis was less severe than histological diagnosis in nine (5.3%) patients. Among 44 patients with histological grade G2, 41 (93.2 %) patients had alanine aminotransferase (ALT)≥2 × upper limits of normal (ULN). According multiple Logistic regression analysis, age, overt symptom, ALT level, cholinesterase (CHE), albumin (Alb), total bile acid (TBA) and ultrasonic appearance of non-smooth liver surface were independent risk factors for the diagnosis of fibrosis score ≥S2. Conclusions The CHB diagnosis based on clinical evidences doesn't show acceptable consistency with the diagnosis based on histological evidences. G2 and S2 may be more reliable criteria for diagnosing moderate and severe CHB.