肝纤维化血清标志物在肝病中的诊断价值

目的探讨肝纤维化血清标志物在肝病中的诊断价值。方法采用放射免疫分析法（RIA法）检测148例肝病患者的血清Ⅲ型前胶原、Ⅳ型胶原及层粘连蛋白的含量。结果慢活肝、肝硬化、肝癌组的血清Ⅲ型前胶原的含量均显著升高（P〈0．01）,而慢迁肝、急性肝炎组升高不明显（P〉0．05）：血清IV型胶原及层粘连蛋白含量在慢性肝炎、肝硬化及肝癌中均有不同程度的升高（P〈0．01）,尤以肝硬化组升高显著。结论Ⅲ型前胶原、Ⅳ型胶原及层粘连蛋白血清含量的联合检测可作为监测肝纤维化的发生与发展的较好指标。     

血清肝纤维化四项检测在慢性肝病诊断中的意义

<正>慢病肝病主要包括肝纤维化和肝硬化,其中肝纤维化是肝硬化的前题。肝纤维化会使肝脏结构发生改变,肝细胞的血液供应等受到影响,使肝脏功能逐渐丧失,并最终发展为肝硬化[1,2]。近年来,血清肝纤四项检查已被认为是理想的诊断慢性肝病患者病情发展状况和治疗效果,衡量炎症活动     

肝纤维化程度与血清标志物的相关性分析

目的 探讨血清透明质酸（HA），Ⅲ型前胶原（PC-Ⅲ），层粘蛋白（LN），Ⅳ型胶原（C-Ⅳ）与肝纤维化程度的相关性及在诊断中的价值。方法 121例慢性肝病患者的血清标本，采用放射免疫（RIA）检测HA，PC-Ⅲ，LN，C-Ⅳ并与病理检查结果比较分析评价其相关性。结果 HA、PC-Ⅲ、C-Ⅳ检测水平随炎症及纤维化的进展而逐渐升高；LN在不同炎症及纤维化期改变差异无显著性。结论 HA、PC-Ⅲ、C-Ⅳ与炎症及纤维化程度有较好的相关性，对观察慢性肝病的纤维化和炎症性改变及其进展具有较高的价值。     

血清肝纤维化指标在慢性肝病中的临床分析

目的：探讨联合测定血清透明质酸（HA）、层黏蛋白（LN）、Ⅲ型前胶原（PCⅢ）及Ⅳ型胶原（Ⅳ-C）对慢性肝炎肝纤维化的诊断意义。方法：采用放射免疫分析法检测143例肝病患者的HA、LN、PCⅢ、Ⅳ-C,并与30例健康体检者对比。结果：各组肝病四项纤维化指标较对照组有明显升高。结论：联合测定HA、LN、PCⅢ及Ⅳ-C对肝纤维化的诊断有较高的临床价值,并适合于动态观察肝病的进展,对肝病的预后有一定的指导意义。     

肝纤维化血清学指标在肝病中的临床意义

目的:探讨血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、IV型胶原(CIV)及层粘连蛋白(LN)的测定值在诊断肝纤维化中的临床意义。方法用放射免疫计数法检测128例慢性肝病,18例急性乙型肝炎及22例健康人血清HA、PCⅢ、CIV、LN4项指标定量并进行了统计学分析。结果慢性乙型肝炎中、重度,慢性重型肝炎及活动性肝硬化4项指标定量结果均高于对照组、急性乙型肝炎及慢性乙型肝炎轻度(P<0.01),但静止性肝硬化该4项指标定量反而降低甚至正常。结论联合检测血清HA、PCⅢ、CIV、LN水平对诊断肝纤维化有较大意义,其中HA的敏感性最高,动态监测其变化情况很重要。     

血清肝纤维项对肝纤维化诊断价值及相关性研究

目的 评价血清透明质酸（HA）、层粘连蛋白（LN）、Ⅳ型胶原（Ⅳ—C）、Ⅲ型前胶原（PC—Ⅲ）水平与肝纤维化病变程度的相关性。方法应用放射免疫法对90例健康者，90例慢性肝病患者进行血清HA、LN、Ⅳ—C、PC-Ⅲ含量的测定，并进行对比分析，同时做肝组织活检，进行纤维化分期，对比不同分期四种指标的含量。结果 ①慢性肝病组4项指标均高于对照组，差异具有统计学意义（P〈0．05）；②随着肝脏损伤程度的严重程度，4项指标均逐渐增加，其中HA在早期即开始升高，Ⅳ-C在S0～S1期开始升高，S3～S4水平最高。结论 HA、LN、Ⅳ—C、PCⅢ联合检测，对肝纤维化的诊断具有重要意义，其水平变化与肝脏损伤程度密切相关，其中HA和Ⅳ-C在肝纤维化的早期诊断可能具有重要意义。     

血清透明质酸Ⅲ型前胶原Ⅳ型胶原层粘连蛋白水平与肝纤维化相关性的观察

目的:研究肝纤维化灵敏可靠的血清学诊断指标。方法:检测113例慢性肝炎病人血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(IV-C)、层粘连蛋白(LN):并与20例健康者对照观察。结果:慢性乙型肝炎(中度及重度)及肝硬变患者血清HA、PCⅢ、Ⅳ-C、LN水平与正常对照组相比明显增高;其中慢性肝炎重度及肝硬变为最高,均有显著性差异(p<0.05)。而慢性肝炎重度与肝硬变组患者没有显著性差异。结论:四项血清学指标检测可作为慢性乙型肝炎肝组织损伤程度,肝纤维化与肝硬变的关系的诊断指标,为阻止和延缓肝硬变有临床意义。     

4种血清学指标对肝病患者肝纤维化的诊断意义

肝纤维化是慢性肝炎向肝硬化发展的可逆阶段。因此,做好肝纤维化的防治工作,是减少肝硬化发生的关键。目前,反映肝纤维化的方法主要有影像学检测和血清学检测,其中,血清学检测对患者无放射性损伤且操作简便,因此,肝纤维化的血清学检测是近年来发展较快并对肝纤维化具有一定诊断价值的非创伤性诊断方法。     

慢性肝病患者血清HA、PCⅢ、C-Ⅳ、LN和TNF水平变化分析

目的：探讨肝纤维化标志物Ⅲ型前胶原（PCⅢ）、透明质酸（HA）、Ⅳ型胶原（C-Ⅳ）、层粘连蛋白（LN）和肿瘤坏死因子（TNF）在慢性肝病纤维化诊断和疗效观察中的临床意义。方法：采用RIA对80名健康对照者，60例慢性肝病患者经保肝及抗纤维化治疗后血清中的HA、PCⅢ、C-Ⅳ、LN和，TNF进行检测，同时与对照组和治疗后进行对比分析。结果：60例慢性肝病治疗后血清HA、PCⅢ、C-Ⅳ、LN和TNF都有不同程度的下降，与治疗前比较有差异显著性（P〈0．05）。结论：血清HA、PCⅢ、C-Ⅳ、LN和，TNF的测定对慢性肝病纤维化的诊断及疗效观察具有重要的临床意义。     

Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C

Aliment Pharmacol Ther 2011; 33: 138–148

Summary

Background Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C. Aim To validate and compare the diagnostic performance of non‐invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment. Methods The performances of Forns’ score, AST to platelet ratio index (APRI), FIB‐4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients. Results Forns’ score, APRI, FIB‐4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB‐4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non‐1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR. Conclusions Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.     

肝脏纤维化血清标志物与肝脏病理的对照研究

目的:探讨慢性肝病患者纤维化血清透明质酸(HA)、层粘蛋白(LN)、IV型胶原(IVC)、Ⅲ型前胶原(PⅢP)与肝组织病理检查即炎症活动程度和纤维化程度之间的关系。方法:对80例慢性肝病患者及30例正常对照者采用放射免疫法检测血清肝纤维化四项指标;对80例慢性肝病患者行肝组织穿刺作肝脏病理炎症分级和纤维化分期;然后将两者进行比较分析。结果:血清纤维化四项指标由G1~G4、S0~S4依次升高,但在各级及各期间升幅不完全一致;在反映肝脏炎症活动程度方面以HA上升最早,级间升幅较大;在反映肝组织纤维化程度方面PⅢP在S2期就明显升高;血清HA、LN、IVC、PⅢP水平与肝病分期及分级呈正相关。结论:透明质酸(HA)在反映肝脏炎症程度方面较敏感,Ⅲ型前胶原(PⅢP)在反映肝脏纤维化程度方面较敏感。肝纤维化血清学四项指标对了解肝脏炎症及纤维化程度有较高的临床价值。     

肺癌患者69例血清肿瘤标记物测定分析

目的探讨肿瘤标记物在肺癌诊断中的意义。方法收集各型肺癌患者的血清标本69例，正常对照组30例，对这些血清标本进行CEA、CA125、CA199、CA242、NSE五项指标的测定。结果肺癌各组的CEA、CA125均值均高于正常参考值，肺腺癌组与正常组比较有显著差异。正常组及肺癌各组CA199 CA242的检测值均在正常范围内。正常组及肺腺癌、肺鳞癌的NSE在正常参考值内，只有小细胞肺癌的NSE明显高于正常参考值，与正常组比较，有显著差异。各项标记物的特异度均较高，但灵敏度不同。肺腺癌的CEA、CA125、CA242的灵敏度较高，小细胞肺癌的CEA、CA125、NSE的灵敏度较高。选择二项阳性作为诊断指标，则肺癌、肺腺癌、小细胞肺癌的阳性率均有50％以上，与正常组比较均有显著差异。结论CEA、CA125、CA242可作为肺腺癌；NSE、CA125、CEA可作为小细胞肺癌较好的肿瘤标记物。联合检测中二项阳性率对肺癌诊断最有价值。     

慢性病毒性乙型肝炎患者血清肝纤维化指标检测的临床意义

目的 探讨慢性病毒性乙型肝炎(乙肝)患者血清肝纤维化指标水平与临床的关系.方法 应用放射免疫法及化学发光法检测146例慢性病毒性乙型肝炎患者及40例健康人(对照组)血清肝纤维化指标血清透明质酸(HA)、Ⅳ型胶原(Ⅳ-C)、层粘连蛋白(LN)及Ⅲ型前胶原(PCⅢ)水平,并就上述指标与临床肝功能指标关系进行分析.结果 慢性乙肝患者血清HA、Ⅳ-C、LN、PCⅢ水平均不同程度高于对照组(P＜0.05或P＜0.01),在不同病程之间差异有统计学意义(P＜0.05或P＜0.01);慢性乙肝患者血清Ⅳ-C、PCⅢ水平与血浆PT呈正相关,HA、Ⅳ-C、LN水平与Alb呈负相关,HA水平与TBil呈正相关,PCⅢ水平与ALT呈正相关,LN水平与CHE呈负相关.结论 检测慢性病毒性乙型肝炎患者血清HA、Ⅳ-C、LN、PCⅢ水平,可反映肝纤维化进展情况和肝功能损害程度.     

肝纤维化血清学指标水平与肝癌的相关性研究

Objective To investigate the significance of serum fibrosis markers in liver fibrosis in liver neoplasms. Methods Radioimmunoassay was used to measure the level of serum procollagen (PC) Ⅲ, collagen type Ⅳ(Ⅳ-C), laminin LN and hyaluronic acid(HA) in 120 patients with liver neoplasms and 100 healthy people.Results Before therapy, the level of Ⅳ-C in the hepatocellular carcinoma group showed significant difference compared with those in control group (P＜0. 01 ). The levels of PCⅢ and LN in the hepatocellular carcinoma group were higher than those in control group ( P ＜ 0.05 ). Before therapy the levels of HA in metastatic cancer of liver group and extrahepatic malignant tumor group were higher than those in control group ( P ＜ 0. 05 ). Before and after the therapy the levels of hepatocellular carcinoma group serum PC Ⅲ, Ⅳ-C, LN and HA were significantly higher than those in the metastatic cancer of liver group ( P ＜ 0. 05). Before and after the therapy the levels of hepatocellula carcinoma group serum PC Ⅲ, Ⅳ-C, LN and HA were significantly difference ( P ＜ 0.05 ). Conclusions The levels of serum PC Ⅲ, Ⅳ-C, LN and HA are significantly related with the hepatocellular carcinoma. These markers can reflect the fibrosis degree of chronic hepatocellular carcinoma and will be an indicator of prognosis.     

肝纤维化血清学指标水平与肝癌的相关性研究

目的 研究血清Ⅲ型前胶原、Ⅳ型胶原、层粘连蛋白和透明质酸在肝癌诊断中的价值.方法 采用放射免疫法测定52例原发性肝癌、34例转移性肝癌、34例肝外恶性肿瘤患者及100例健康体检人员血清Ⅲ型前胶原、Ⅳ型胶原、层粘连蛋白和透明质酸水平,并进行分析比较.结果 治疗前和治疗1、3个月后,原发性肝癌组Ⅲ型前胶原、Ⅳ型胶原、层粘连蛋白、血清透明质酸水平(计量单位为μg/L)分别为(176±43)、(166±38)、(129±38);(139±34)、(108±31)、(85±32);(123±23)、(100±23)、(93±18);(347±136)、(299±120)、(266±113)μg/L,转移性肝癌组分别为(97±25)、(93±22)、(79±16);(96±31)、(80±28)、(77±19);(93±24)、(80±21)、(62±15);(254±108)、(199±98)、(132±93)μg/L.原发性肝癌组血清透明质酸和Ⅳ型胶原水平在治疗前与对照组[(67±11)、(55±15)μg/L]比较差异均有统计学意义(均P＜0.01),Ⅲ型前胶原和层粘连蛋白水平明显高于对照组[(55±11)、(54±13)μg/L,P＜0.05)].转移性肝癌组及肝外恶性肿瘤组治疗前透明质酸[(149±68)μg/L]与对照组比较,差异均有统计学意义(均P＜0.05).原发性肝癌组治疗前后血清Ⅲ型前胶原、Ⅳ型胶原、层粘连蛋白和透明质酸水平均明显高于同一时间转移性肝癌组的水平(均P＜0.05).原发性肝癌组各项指标治疗前和治疗1、3个月后之间相比均差异有统计学意义(均P＜0.05).结论 血清Ⅲ型前胶原、Ⅳ型胶原、层粘连蛋白和透明质酸水平与原发性肝癌具有相关性,可作为反映原发性肝癌严重程度和预后的指标.

Abstract：

Objective To investigate the significance of serum fibrosis markers in liver fibrosis in liver neoplasms. Methods Radioimmunoassay was used to measure the level of serum procollagen (PC) Ⅲ, collagen type Ⅳ(Ⅳ-C), laminin LN and hyaluronic acid(HA) in 120 patients with liver neoplasms and 100 healthy people.Results Before therapy, the level of Ⅳ-C in the hepatocellular carcinoma group showed significant difference compared with those in control group (P＜0. 01 ). The levels of PCⅢ and LN in the hepatocellular carcinoma group were higher than those in control group ( P ＜ 0.05 ). Before therapy the levels of HA in metastatic cancer of liver group and extrahepatic malignant tumor group were higher than those in control group ( P ＜ 0. 05 ). Before and after the therapy the levels of hepatocellular carcinoma group serum PC Ⅲ, Ⅳ-C, LN and HA were significantly higher than those in the metastatic cancer of liver group ( P ＜ 0. 05). Before and after the therapy the levels of hepatocellula carcinoma group serum PC Ⅲ, Ⅳ-C, LN and HA were significantly difference ( P ＜ 0.05 ). Conclusions The levels of serum PC Ⅲ, Ⅳ-C, LN and HA are significantly related with the hepatocellular carcinoma. These markers can reflect the fibrosis degree of chronic hepatocellular carcinoma and will be an indicator of prognosis.     

肝纤维化血清学指标水平与肝癌的相关性研究

Objective To investigate the significance of serum fibrosis markers in liver fibrosis in liver neoplasms. Methods Radioimmunoassay was used to measure the level of serum procollagen (PC) Ⅲ, collagen type Ⅳ(Ⅳ-C), laminin LN and hyaluronic acid(HA) in 120 patients with liver neoplasms and 100 healthy people.Results Before therapy, the level of Ⅳ-C in the hepatocellular carcinoma group showed significant difference compared with those in control group (P＜0. 01 ). The levels of PCⅢ and LN in the hepatocellular carcinoma group were higher than those in control group ( P ＜ 0.05 ). Before therapy the levels of HA in metastatic cancer of liver group and extrahepatic malignant tumor group were higher than those in control group ( P ＜ 0. 05 ). Before and after the therapy the levels of hepatocellular carcinoma group serum PC Ⅲ, Ⅳ-C, LN and HA were significantly higher than those in the metastatic cancer of liver group ( P ＜ 0. 05). Before and after the therapy the levels of hepatocellula carcinoma group serum PC Ⅲ, Ⅳ-C, LN and HA were significantly difference ( P ＜ 0.05 ). Conclusions The levels of serum PC Ⅲ, Ⅳ-C, LN and HA are significantly related with the hepatocellular carcinoma. These markers can reflect the fibrosis degree of chronic hepatocellular carcinoma and will be an indicator of prognosis.     

慢性肝炎肝纤维化血清学指标与肝组织病理变化的关系探讨

目的探讨肝纤维化血清学指标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324例慢性肝炎患者经肝脏活检行常规病理检查，同时肝活检前一周内采血检测血清纤维化指标[Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、透明质酸(HA)、层粘蛋白(LN)]，探讨它们与肝脏病理的关系。结果血清．PCⅢ、HA、IV—C水平与肝组织病理分期有相关性，PCⅢ、HA水平随纤维化分期(S1-S4)依次升高，各期中差异有显著性；PCⅢ水平在SO期已有明显升高。Ⅳ-C水平在肝组织病理纤维化分期各期中无差异。LN水平与肝纤维化分期无相关性。血清PCⅢ、HA、Ⅳ-C水平与肝组织病理分级有相关性，PCⅢ、HA水平随着组织病理分级而升高，各级中差异有显著性。Ⅳ-C水平在肝组织病理分级中有差异，但其水平不随分级而升高。结论血清PCⅢ、HA水平与肝组织病理的分级和分期的相关性较好，是反映肝纤维化程度的良好指标，有较高的诊断价值；Ⅳ-C、LN水平对肝纤维化的诊断价值有待进一步研究。PCⅢ可能对肝纤维化的早期诊断有意义。     

Diagnostic value of serum protein profiling by SELDI-TOF ProteinChip compared with a biochemical marker, FibroTest, for the diagnosis of advanced fibrosis in patients with chronic hepatitis C

BACKGROUND: FibroTest has been validated for the diagnosis of liver fibrosis in patients with chronic hepatitis C. AIM: To compare FibroTest with a new proteome-based model for the prediction of advanced liver fibrosis. METHODS: Sera from 191 consecutive patients with simultaneous liver biopsy and FibroTest on fresh sera were used for retrospective mass spectrometry analysis. A new fibrosis index was constructed combining proteomic peaks, selected on differential expression according to fibrosis stages in logistic regression analyses. The main end point was the diagnosis of advanced fibrosis on liver biopsy. RESULTS: Eight out of 1000 peaks were selected for the construction of the proteomic index. The area under the receiver operating curve (AUROC) of the proteomic index was 0.88 (95% CI: 0.82-0.92), significantly greater than the FibroTest AUROC of 0.81 (95% CI: 0.74-0.86; P = 0.04); the AUROC of the proteomic and FibroTest combination was 0.88 (95% CI: 0.83-0.92). Seven of the eight selected peaks were highly associated with the FibroTest score, with different patterns of association with the five components of FibroTest. CONCLUSIONS: A proteomic index combining eight peaks had an excellent accuracy value for the diagnosis of advanced fibrosis in patients with chronic hepatitis C. However, despite a statistical significance, the small improvement delivered by proteomics impairs clinical applications because of its cost and its variability compared with the well validated FibroTest.