Usefulness of six non-proprietary indirect markers of liver fibrosis in patients with chronic hepatitis C.

BACKGROUND: The aim of the study was to perform a comprehensive diagnostic evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in a cohort of patients with chronic hepatitis C representing the full spectrum of disease severity. METHODS: A total of 167 consecutive, hepatitis C virus RNA positive, untreated patients with chronic hepatitis C were studied. Liver biopsy with histological evaluation and age/platelet index, aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and FibroIndex were assessed in all patients. RESULTS: The area under the receiver operating characteristic curves of the six tests was always greater when performed to discriminate patients with METAVIR score F4 than when assessed to discriminate patients with METAVIR score > or =F2. At step-wise discriminant analysis the only indirect marker of fibrosis entered was FibroIndex, with the following correct classification of the patients: total=52.1, patients with scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score F4=68.4. CONCLUSIONS: The ability to correctly classify patients using a panel of non-proprietary indirect markers of liver fibrosis is far from being ideal. Among them, FibroIndex appears to possess the best discriminating capacity. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.     

慢性肝病患者血清TIMP-1和TIMP-2的变化及其临床意义

目的探讨慢性乙型肝炎(CHB)和乙型肝炎后肝硬化(LC)患者血清中的基质金属蛋白酶-1组织抑制因子(TIMP-1)、基质金属蛋白酶-2组织抑制因子(TIMP-2)的变化及其临床意义。方法用酶联免疫吸附试验(ELISA)检测75例CHB患者和41例乙型肝炎后LC患者血清TIMP-1、TIMP-2含量,并与30名健康献血员比较。结果CHB轻度、中度、重度和LC A级、B级、C级患者血清TIMP-1均明显高于正常对照组(P均<0.01),与透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)呈正相关(r=0.935、0.836、0.910,P均<0.01);CHB重度和LC A级、B级、C级患者血清TIMP-2均明显高于正常对照组(P均<0.01),与HA、LN、CⅣ呈正相关(r=0.765、0.623、0.716,P均<0.01)。结论血清TIMP-1、TIMP-2在慢性肝病患者肝纤维化过程中明显升高,并与肝纤维化指标呈正显著性相关,可作为判断肝纤维化程度的指标。     

Biological markers of liver fibrosis and activity as non-invasive alternatives to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis

OBJECTIVE AND METHODS: We assessed the reliability of non-invasive biological scoring indexes (Fibrotest-Actitest [FT-AT], Forns, APRI, age-platelet, platelet, hyaluronic acid) as non-invasive alternatives to liver biopsy (LB) in 138 HCV-infected patients. RESULTS: Thirty-six of 138 (26%) patients had systemic vasculitis, 27% significant serum inflammation, 47% fibrosis (F2F3F4) on LB. The diagnostic value of FT (F2F3F4 vs. F0F1) was assessed by an AUC of 0.83, without difference regarding to systemic vasculitis or serum inflammation. A discordance between FT-AT and the Metavir scoring indexes, present in 29% of patients, was associated with serum hemolysis and male but not with systemic vasculitis or serum inflammation. The other non-invasive biological tests were not influenced by serum inflammation or systemic vasculitis but were less reliable than FT (P 相似文献   

慢性肝病患者血清TIMP-1和TIMP-2的变化及其临床意义

目的探讨慢性乙型肝炎（CHB）和乙型肝炎后肝硬化（LC）患者血清中的基质金属蛋白酶-1组织抑制因子（TIMP-1）、基质金属蛋白酶-2组织抑制因子（TIMP-2）的变化及其临床意义。方法用酶联免疫吸附试验（ELISA）检测75例CHB患者和41例乙型肝炎后LC患者血清TIMP-1、TIMP-2含量,并与30名健康献血员比较。结果CHB轻度、中度、重度和LCA级、B级、C级患者血清TIMP-1均明显高于正常对照组（P均〈0．01）,与透明质酸（HA）、层黏连蛋白（LN）、Ⅳ型胶原（CⅣ）呈正相关（r=0．935、0．836、0．910,P均〈0．01）;CHB重度和LC级、B级、C级患者血清TIMP-2均明显高于正常对照组（P均〈0．01）,与HA、LN、CⅣ呈正相关（r=0．765、0．623、0．716,P均〈0．01）。结论血清TIMP-1、TIMP-2在慢性肝病患者肝纤维化过程中明显升高,并与肝纤维化指标呈正显著性相关,可作为判断肝纤维化程度的指标。     

Advanced liver fibrosis and care continuum in emergency department patients with chronic hepatitis C

Background

FIB-4, a non-invasive serum fibrosis index (which includes age, ALT, AST, and platelet count), is frequently available during ED visits. Our objective was to define 1-year HCV-related care outcomes of ED patients with known HCV, for the overall group, and both those with and without advanced fibrosis.

病毒性肝炎患者血清中肝纤维化标志物的联合测定

目的 联合测定病毒性肝炎患者血清中肝纤维化标志物以全面分析肝纤维化情况.方法 放射免疫法检测血清肝纤维化标志物HA、PCⅢ、LN.结果 病毒性肝炎患者血清HA含量从轻度慢肝到肝硬化各组变化显著,与正常对照及前一组比较差异均有显著性(P＜0.01),尤其在肝硬化时升高明显.但血清PCⅢ、LN含量在各检测组和对照组间差异显著 (P＜0.01),中度与轻度慢肝组间差异显著(P＜0.01),而重度与中度、肝硬化与重度慢肝组间差异均无显著性(P＞0.05).肝硬化组血清LN平均水平明显高于慢性肝炎组水平,但差异无统计学意义(P＞0.05).肝硬化组血清PCⅢ平均水平明显低于重度慢肝组(P＜0.05).结论 慢性病毒性肝炎病人血清HA、PCIII、LN水平能综合反映肝纤维化的程度.     

Cytokines as predictors for sustained response and as markers for immunomodulation in patients with chronic hepatitis C.

OBJECTIVES: (i) To characterize serum cytokine levels of tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL 6), IL 8 and IL 12 in non-cirrhotic patients with chronic hepatitis C, (ii) to correlate the levels of these cytokines with the degree of the disease at the basal level, (iii) to correlate these levels with the response to therapy, (iv) to compare profiles of cytokines in monotherapy (MT) versus combination therapy (CT), and (v) to compare the immunomodulatory effects of MT versus CT. DESIGN AND METHODS: 47 patients were enrolled in the study. The controls were 120 volunteers (recruited from students and staff) that did not present HCV RNA positive and were not known to suffer any other metabolic disease. Thirty patients formed the other group of controls, with alcoholic liver disease (ALD). Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The sustained responders (SRs) have basal values much lower than relapsed responders (RRs) and non-responders (NRs) regardless of the therapy. CONCLUSIONS: Cytokines can be used as non-invasive markers for sustained response and as monitors for the outcome of therapy.     

化学发光法检测慢性乙型肝炎肝纤维化四项标志结果分析

目的探讨应用化学发光法定量检测肝纤维化指标透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原氮端肽(PⅢNP)、Ⅳ型胶原(CⅣ)对肝纤维化的诊断价值。方法应用化学发光法检测了196例乙型肝炎病毒感染者血清样本的肝纤维化指标。其中乙型肝炎病毒携带者50例,慢性乙型肝炎患者48例,慢性重肝36例,乙型肝炎肝硬化患者62例,正常对照40例,并对结果进行统计学分析。结果肝纤维化四项指标(HA、LN、PⅢNP、CⅣ)在乙型肝炎携带者、慢性乙型肝炎、慢性重肝、乙型肝炎肝硬化测定值之间差异有统计学意义(P<0.05)。测定值升高的幅度为:慢性重肝>乙型肝炎肝硬化>慢性乙型肝炎>乙型肝炎携带者。结论应用化学发光法动态检测肝纤维化四项指标是指导临床判断肝纤维化程度的非损伤性的良好检测方法。     

Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients

BACKGROUND: Determining the stage of fibrosis by liver biopsy is important in managing patients with hepatitis C virus infection. We investigated the predictive value of the proprietary FibroTest score to accurately identify significant fibrosis in Australian hepatitis C patients. METHODS: Serum obtained from 125 confirmed hepatitis C patients before antiviral therapy was analyzed for haptoglobin, alpha(2)-macroglobulin, apolipoprotein A1, bilirubin, and gamma-glutamyltransferase activity, and the FibroTest score was computed. Liver fibrosis pathology was staged according to a defined system on a scale of F0 to F4. We used predictive values and a ROC curve to assess the accuracy of FibroTest scores. RESULTS: The prevalence of significant fibrosis defined by liver biopsy was 0.38. The most useful single test for predicting significant fibrosis was serum alpha(2)-macroglobulin (cutoff value, 2.52 g/L; sensitivity, 75%; specificity, 67%). The negative predictive value of a FibroTest score <0.1 was 85%, and the positive predictive value of a score >0.6 was 78%. Although 33 of the 125 patients had FibroTest scores <0.1 and were therefore deemed unlikely to have fibrosis, 6 (18%) had significant fibrosis. Conversely, of the 24 patients with scores >0.6 who were likely to have significant fibrosis, 5 (21%) had mild fibrosis. Of the 125 patients in the cohort, 57 (46%) could have avoided liver biopsy, but discrepant results were recorded in 11 of those 57 (19%). CONCLUSION: The FibroTest score could not accurately predict the presence or absence of significant liver fibrosis.     

Diagnostic values of MMP-7, MMP-9, MMP-11, TIMP-1, TIMP-2, CEA,and CA19-9 in patients with colorectal cancer

ObjectiveColorectal cancer (CRC) is one of the most common and lethal malignancies. The identification of precise and noninvasive biomarkers is urgently needed to aid the early diagnosis and clinical management of CRC.MethodsA total of 112 patients with CRC and 115 healthy control subjects were included in this study. Serum levels of matrix metalloproteinase (MMP)-7, MMP-9, MMP-11, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by enzyme-linked immunosorbent assay, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 levels were measured using an automatic immunoassay analyzer.ResultsMMP-7, MMP-9, MMP-11, TIMP-1, TIMP-2, CEA, and CA19-9 levels were all significantly higher in CRC patients compared with healthy controls. MMP-7, TIMP-1, and CEA levels were also closely related to clinicopathologic features in patients with CRC. The combination of serum CEA, MMP-7, and TIMP-1 significantly improved the diagnostic value compared with any single marker (area under the curve 0.858–0.890). Furthermore, a combined detection model including MMP-7, TIMP-1, and CEA improved both the specificity and sensitivity for detecting CRC.ConclusionsThe results showed that combined detection of CEA, MMP-7, and TIMP-1 in serum could provide a specific and sensitive biomarker for the diagnosis of CRC.     

Antiretroviral therapy based on protease inhibitors as a protective factor against liver fibrosis progression in patients with chronic hepatitis C

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.     

慢性乙肝患者肝纤指标与肝损关系研究

目的研究慢性乙型肝炎（CHB）患者肝纤维化指标透明质酸（HA）、Ⅲ型前胶原（PⅢP）、层黏连蛋白（LN）、IV型胶原（IVC）与肝功能损害的关系。方法以65例正常体检人员为对照,比较CHB中度组（89例）、CHB重度组（72例）及肝硬化组（34例）HA、PⅢP、LN、IVC变化特点,及相应肝功能情况。结果 HA、PⅢP、LN、IVC在CHB中度、重度组及肝硬化组中均有不同程度的升高,丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）在CHB中度、重度组升高,在肝硬化组中降低并出现倒置。结论在CHB患者中肝纤维化指标HA、PⅢP、LN、IVC结合传统肝功能监测指标ALT、AST更能准确反映肝脏纤维化及肝功能受损程度。     

Expression of apoptotic markers BCL-2 and bax in chronic hepatitis C virus patients

ObjectivesHepatitis C viral infection(HCV) influence the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection.Design and methodsGroup 1: chronic HCV patients with liver cirrhosis and ascites. Group 2: chronic HCV patients without liver cirrhosis and group 3: healthy subjects as control group. Bcl-2 and Bax expression were evaluated by flowcytometry.ResultsHCV patients (with cirrhosis and ascites) had a statistically significantly low Bcl-2 expression, a significantly high Bax expression and a significantly decreased Bcl-2/Bax ratio compared with controls. While, the results are inverted in the other HCV group. Both groups of HCV, Bcl-2/Bax ratio showed a significant positive correlation with Bcl-2 and a significantly negative correlation with Bax.ConclusionsChronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.     

慢性乙型肝炎患者E-选择素A561C多态性在肝纤维化中的作用

目的探讨中国河北汉族人群E-选择素A561C基因多态性与慢性乙型肝炎(CHB)的相关性,以及对肝脏纤维化的影响.方法采用PCR-RFLP技术,检测91例CHB患者和85例健康对照者的E-选择素基因多态性,同时采用RIA法检测CHB患者HA、PCⅢ水平.结果中国河北汉族人群中E-选择素A561C多态性存在AA、AC和CC三种基因型,E-选择素A561C多态性在CHB组和对照组间的分布差异显著(x2=5.96,P＜0.05).AC CC基因型患CHB的风险是AA基因型的2.89倍,等位基因频率在两组间也存在着显著性差异(P＜0.05).CHB患者两组基因型间肝功能指标、肝纤维化指标间无差异(P＞0.05).结论中国河北汉族人群中存在E-选择素A561C位点单核苷酸多态性,C等位基因可能是中国河北地区CHB发病的易感因素之一,但该位点多态性对肝功能损伤、肝纤维化程度、病情进展可能不起直接的作用.     

慢性丙型肝炎患者血清HCV-RNA水平与抗-HCV抗体和肝纤指标水平相关性分析

目的探讨丙型肝炎患者RNA水平与抗-HCV抗体和肝纤指标水平的关系。方法收集96例慢性丙型肝炎患者的血清,实时荧光定量PCR测定HCV-RNA和ELISA法检测抗-HCV抗体。化学发光法检测LN、PCⅢ、CⅣ及放免法检测HA。并对抗-HCV抗体、HCV-RNA水平与血清肝纤指标之间的关系进行分析。结果本研究的96例抗-HCV抗体阳性的慢性丙型肝炎患者中,HCV-RNA阳性52例,阳性率为54.2%。随着抗-HCV抗体的S/CO值升高,HCV-RNA检出率也在增高,分别为9.5%、37.1%和92.5%。高病毒载量组与低病毒载量组比较,血清HA、LN、PCⅢ及CⅣ水平的差异无统计学意义(P0.05)。结论慢性丙肝患者HCV-RNA阳性检出率与抗-HCV抗体的S/CO值有关,S/CO值越高,HCV-RNA阳性率越高。而RNA水平与肝纤指标水平没有相关性。     

苦参素对慢性乙型肝炎患者血清肝纤维化指标及细胞因子的影响

目的 观察苦参素对慢性乙型肝炎患者肝纤维化指标及细胞因子的影响.方法 68例慢性乙型肝炎患者随机分为治疗组(一般保肝治疗+苦参素)和对照组(一般保肝治疗),治疗前后检测肝功能,用放射免疫法检测血清肝纤维化指标、透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(CⅣ),应用ELISA法检测血清TGF-β1、PAF、sICAM-1.结果 治疗组治疗前后HA、LN、PC-Ⅲ、CⅣ、TGF-β1及PAF水平较治疗前及对照组治疗后均显著降低(P＜0.05或P＜0.01).结论 苦参素通过影响慢性乙型肝炎患者血清细胞因子TGF-β1、PAF发挥抗肝纤维化作用.     

Significant liver damage in patients with bleeding disorders and chronic hepatitis C: non-invasive assessment of liver fibrosis using transient elastography

Summary.  Background: Many patients with bleeding disorders have been infected with the hepatitis C virus (HCV), mainly with genotype 1. Antiviral treatment is only effective in 50% of these patients and is often accompanied by serious side effects. Consequently, careful selection of patients for treatment is warranted. Liver biopsies are generally not performed in these patients because of increased bleeding risk and high costs. We therefore assessed liver fibrosis and cirrhosis non-invasively using liver stiffness measurement (LSM). Methods: We enrolled 124 patients with bleeding disorders and chronic hepatitis C. Liver fibrosis was assessed by LSM using Fibroscan^®. In order to assess the validity of LSM in our hands, a separate group of 63 patients without bleeding disorders infected with HCV were evaluated with both LSM and biopsy. Results: In the validation study, liver elasticity was highly correlated with histological fibrosis stage (correlations coefficient 0.73, P  < 0.001). Based on LSM, 18% of patients with bleeding disorders and chronic hepatitis C had severe fibrosis, and 17% had cirrhosis after 34 years of infection (range 14–40). However, the prevalence of cirrhosis based on laboratory and ultrasonographic findings was only 7%. Independent risk factors for an increase in LSM were older age at infection, higher body mass index, presence of viral co-infection, and male gender. Fifteen out of 59 patients (25%) with an apparent indication for treatment (significant fibrosis by LSM) agreed to start antiviral therapy within 3 months. Conclusions: We found an unexpected high number of patients with significant fibrosis and cirrhosis in patients with bleeding disorders and hepatitis C detected by LSM, with considerable impact on the management of the disease.     

益肝康治疗慢性乙型肝炎肝纤维化365例疗效观察

目的探讨中药益肝康对慢性乙型肝炎、肝纤维化的疗效。方法将365例慢性乙型肝炎患者随机分为两组,治疗组（305例）给予益肝康袋装浓缩煎剂1袋,每日2次,对照组（60例）给予葡醛内酯（肝太乐）0．2g,每日3次,水飞蓟宾140mg,每日3次,治疗6个月。分别于治疗前后记述症状,观察肝、脾变化,检测肝功能、血清肝纤维化指标,肝组织病理,进行疗效评价。结果治疗组和对照组血浆透明质酸、层黏连蛋白和Ⅲ型前胶原水平间差别有统计学意义,（185．13±10．84）μg／L vs（121．43±10．91）μg／L,（175．03±7．14）pg／L vs （142．86±14．66）μg／L,（153．37±20．96）μg／L vs （128．00±18．52）μg／L（P〈0．01）;同时,治疗组患者症状改善,肝、脾回缩,肝功能明显好转,白蛋白水平升高。结论益肝康是治疗慢性肝病、肝纤维化的有效药物。     

Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C.

The hepatitis C virus is a positive stranded hepatotropic RNA virus. We describe a method of detecting positive and negative strands of hepatitis C viral RNA using the polymerase chain reaction. We tested serum and liver tissue from nine patients with chronic hepatitis C. The positive RNA strand of HCV was detected in the sera and livers of all nine, the negative strand was detected in the livers of eight (89%), and in the sera of five (55%). Titers of both strands of HCV RNA were determined by serial endpoint dilutions. The amount of the negative strand in the serum and liver was usually 10-100 times less than the positive strand. Predigestion of serum with ribonucleases did not alter the detection of the negative strand. This suggests that the negative strand found in the serum may be protected from digestion by being associated with virions.