Mean platelet volume as a fibrosis marker in patients with chronic hepatitis B

Introduction: Many noninvasive tests have been studied for the diagnosis and determining the liver fibrosis score (LFS). In this study, we aimed to research the correlation of mean platelet volume (MPV) and stage of liver fibrosis in patients with chronic hepatitis B (CHB). Patients and Methods: Fifty‐nine patients with CHB were enrolled retrospectively into the study. Age–sex matched 25 healthy subjects were used as control group. The following data were obtained from computerized patient registry database: HBV‐DNA level, hepatitis B e‐antigen seropositivity, liver enzymes and function tests, white blood cell count, platelet count, hemoglobin, histological activity index, LFS, and MPV. Patients were divided into two groups: patients without significant fibrosis (F0, F1, or F2) (Group 1) and patients with advanced fibrosis (F3, F4) (Group 2). Results: A statistically significant increase in MPV was seen in patients with CHB compared with healthy controls (8.49±0.84 fl vs.7.65±0.42 fl, P<0.001). Receiver operating characteristic curve analysis suggested that the optimum MPV level cut‐off points for CHB was 8.0 fl, with sensitivity, specificity, PPV, and NPV of 68, 76, 86, and 50%, respectively. MPV levels were significantly higher in Group 2 (8.91±0.94 fl, P: 0.009) compared with Group 1 (8.32±0.74 fl). ROC curve analysis suggested that the optimum MPV level cut‐off points for Group 2 was 8.45 fl, with sensitivity, specificity, positive and negative predictive value of 77, 59, 45, and 85%, respectively. Multivariable logistic regression model, which consisted of HAI, ALT, HBV‐DNA, platelet count, and MPV, was performed. We showed that MPV was independently associated with advanced fibrosis (P: 0.031). Conclusion: We suggest that MPV might help in the assessment of fibrosis in CHB. It should not be considered a stand‐alone test for this use owing to nonspecificity with other diseases. J. Clin. Lab. Anal. 25:162–165, 2011. © 2011 Wiley‐Liss, Inc.     

脂联素与慢性乙型肝炎病毒感染肝纤维化的关系研究

目的研究脂联素在慢性乙型肝炎病毒感染患者中的表达,并对部分患者抗病毒治疗前后的结果进行对比,探讨脂联素与慢性乙型肝炎肝纤维化的相关性。方法采用酶联免疫法（ELISA）定量检测血清脂联素水平,免疫组织化学法检测肝活检组织脂联素的表达,同时检测患者肝功能以及HBV DNA变化,并对患者进行抗病毒治疗前后的纤维化程度进行比较。结果血清脂联素在肝纤维化的各个阶段均有表达且与肝纤维化的分级呈正相关（r=0.976,P〈0.01）,与转氨酶水平及HBV DNA浓度无相关性（P〉0.05）;血清脂联素与肝硬化呈独立相关（P=0.02,相对危险度为1.07,95%可信区间为1.00～1.14）。在抗病毒治疗后,肝纤维化程度改善以及获得持续病毒学应答的患者血清脂联素水平降低。结论血清脂联素在慢性乙型肝炎肝纤维化的进展过程中发挥了作用,血清脂联素水平在抗病毒治疗后显著下降,并与肝纤维化改善有关。     

Serum proteomic MRM identify peptide ions of transferrin as new fibrosis markers in chronic hepatitis B

Background and aim

Because of the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are needed. The aim of this study was to identify such markers by the use of serum proteomics in chronic hepatitis B (CHB).

Methods

Two-dimensional gel electrophoresis (2-DE) was used to identify differentially expressed protein spots in sera from 40 CHB patients [20 with mild fibrosis (S0–S1) and 20 with severe fibrosis (S3–S4)]. Mass spectrometry (MS) based multiple reaction monitoring (MRM) was used to quantify peptide ions of differential protein spots in another set of sera from 86 CHB patients with different liver fibrosis (S0–S4).

Results

Seven differentially expressed protein spots were found by 2-DE. Fourteen peptide ions of seven target protein spots were quantified by MS-based MRM. Summed peak areas ratio (SPAR) values of peptide ions from protein spot 1, 4 and 8, identified as apo serum transferrin, complement component C3c and transferrin, were significantly different from non-fibrosis (S0) to fibrosis stage 4. AUROCs of models established by peptide ions (protein spot 1, 4, 8) and model consisting of a combination of all ions were 0.848∼0.966 (S2–S4 versus S0–S1) and 0.785∼0.875 (S3–S4 versus S0–S2). Only the peptide ions model of transferrin had better sensitivity and specificity for predicting fibrosis stages than did aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forn's index.

Conclusions

Serum peptide ions of transferrin, detected by proteomic MRM, are new and promising biomarkers for staging liver fibrosis in CHB patients.     

兰州地区慢性乙型肝炎患者病毒复制与肝纤维化指标的相关性研究

目的：探讨兰州地区慢性乙型肝炎（CHB）患者肝纤维化四项指标：层粘连蛋白（LN）、透明质酸（HA）、Ⅳ型胶原（CⅣ）、Ⅲ型前胶原 N 端肽（PⅢNP）与乙型肝炎病毒（HBV）DNA 复制的相关性。方法分别采用化学发光法和实时荧光定量 PCR （RT-PCR）法检测肝纤维化指标和 HBV-DNA,以不同临床分型和自然史分期为背景,对兰州地区724例 HBV 感染者的肝纤维化指标和病毒复制作量化检测研究。结果在所有临床类型中,肝纤维化指标和 HBV-DNA 数值均高于正常,且最高为乙型肝炎肝硬化组;CⅣ、PⅢNP 均以 HBeAg（＋）CHB 组最高。按乙型肝炎自然史分期,P ⅢNP、CⅣ在免疫清除期最高且 CⅣ在HBeAg 及 HBV-DNA（＋）组中均值都高于 HBeAg 及 HBV-DNA（-）组。四项指标均为 HBeAg（＋）CHB 组高于 HBeAg（-） CHB 组,但仅有 HA 有统计学差异（P ＜0．01）。结论 CⅣ与 HBV-DNA 以及 HBV-M 具有一定相关性,提示其可以间接反映肝损害程度以及病毒复制水平。     

Prediction on liver fibrosis using different APRI thresholds when patient age is a categorical marker in patients with chronic hepatitis B

BackgroundPatient age as a predictive variable plays an important role in some indices and models. It was hypothesized that patient age might be a categorical marker.MethodsWe collected the data of 623 CHB patients with liver biopsies. Two-hundred fifty-two patients could provide the duration of HBsAg-positive.ResultsThe positive correlation between duration of HBsAg-positive and patient age was statistically significant (r = 0.487, P < 0.001). When the cutoff value of patient age was 33.5 y, the best accuracy for liver fibrosis could be obtained. If we could use APRI threshold value of 0.11 for patients with age ≤ 35 and 0.18 for those > 35 y, we could correctly identify 110 CHB patients with insignificant fibrosis which were free of liver biopsy. For all CHB patients based on the APRI threshold of 0.11, 75 patients could be safely predicted as insignificant fibrosis.ConclusionsMany more CHB patients with insignificant fibrosis could be free of liver biopsy when we used different APRI threshold values based on patient age, especially in patients with > 35 y. The study indicated that more attention should be paid to the influence of patient age on fibrosis.     

天冬氨酸转氨酶与血小板比值在预测慢性乙型肝炎肝纤维化中的作用

目的:评价天冬氨酸转氨酶(AST)与血小板(PLT)比值在预测慢性乙型肝炎(CHB)肝纤维化中的作用。方法:对161例CHB患者肝组织纤维化程度进行Ishak分期,同时检测AST和PLT,计算AST与PLT比值指数(APRI)。比较不同肝纤维化分期与APRI间的关系,通过APRI的受试者工作特征(ROC)曲线下面积,分析其预测显著肝纤维化和肝硬化的准确率,并对CHB患者抗病毒治疗前、后肝组织纤维化分期和APRI的变化进行对比研究。结果:AST、PLT和APRI是反映CHB进展为显著肝纤维化的重要指标。APRI随着肝纤维化程度的增高而升高(P<0.001),其预测CHB患者发生显著肝纤维化及肝硬化的ROC曲线下面积分别为0.786和0.703(P值均1.5和2分别为显著肝纤维化和肝硬化的截断点,其阳性预测值分别为97%和76%,阴性预测值分别为45%和75%。CHB患者经抗病毒药物治疗后,肝组织学检查结果证实其纤维化程度比治疗前明显减轻,而APRI也明显降低。结论:APRI可作为预测CHB患者发生显著肝纤维化及肝硬化的指标之一。     

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.     

Autotaxin as a novel serum marker of liver fibrosis

BackgroundThe clinical significance of autotaxin (ATX), a key enzyme for the production of the bioactive lysophospholipid lysophosphatidic acid remains unknown. Serum ATX enzymatic activity reportedly increases in parallel with liver fibrosis and exhibits a gender difference.MethodsSerum ATX antigen level, measured easier than the activity, was evaluated as a marker of liver fibrosis in 2 cohorts of chronic liver disease caused by hepatitis C virus.ResultsIn the first cohort, serum ATX level correlated significantly with liver fibrosis stage and was the best parameter for prediction of cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.756 in male and 0.760 in female, when compared with serum hyaluronic acid and aminotransferase-to-platelet ratio index, an established marker of liver fibrosis. In another cohort, serum ATX level correlated significantly with liver stiffness, a novel reliable marker of liver fibrosis, being the second-best parameter in male (AUROC, 0.799) and in female (AUROC, 0.876) for prediction of significant fibrosis, and the best parameter in male (AUROC, 0.863) and the third-best parameter in female (AUROC, 0.872) for prediction of cirrhosis, both of which were judged by liver stiffness.ConclusionsSerum ATX level may be a novel marker of liver fibrosis.     

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。     

超声组织定征对慢性乙型肝炎肝纤维化的研究

目的探讨超声组织定征对慢性乙型肝炎不同程度肝纤维化进行灰阶测量的作用。方法用超声组织定征视频法测量慢性乙型肝炎患者二维声图像的灰阶值,并与其肝穿刺病理组织学纤维化分级对比。结果超声组织定征视频法测出的肝声像图的灰阶值在慢性乙型肝炎肝纤维化病理组织学分级中的差异有显著性意义(F=34.3,P<0.001),肝纤维化S0、S1、S2和S3各组间灰阶值的差异均有显著性意义(P<0.05)。结论超声组织定征视频法可对慢性乙型肝炎肝纤维化的程度进行声像图灰阶测量。     

慢性乙型肝炎合并肝脂肪变的相关因素及对肝脏炎症和纤维化的影响

目的探讨慢性乙型肝炎合并肝脂肪变的相关因素及发生脂肪变对肝脏炎症和纤维化的影响。方法病例选自2008年7月至2009年12月有肝活组织检查的慢性乙型肝炎患者306例,肝组织中脂肪变肝细胞<5%小叶内肝细胞者为慢性乙型肝炎组,共有165例。脂肪变肝细胞>5%小叶内肝细胞者为慢性乙型肝炎合并脂肪肝组,共有141例。用t检验比较两组患者血糖、血脂和体重指数的差异,对肝脂肪变可能相关因素如性别、年龄、体重指数、血脂、血糖等进行Logistic多因素回归分析,用χ2检验分析不同程度的肝脂肪变对肝脏炎症、纤维化的影响。结果高体重指数和男性是慢性乙型肝炎患者合并肝细胞脂肪变的危险因素,脂肪变的程度与肝脏炎症和纤维化分级无相关性(χ2=6.374,P=0.605和χ2=8.428,P=0.393),差异无统计学意义。结论慢性乙型肝炎合并肝脂肪变主要与高体重指数及男性相关,肝脏脂肪变并不加重肝组织的炎症及纤维化。     

苦参素对慢性乙型肝炎患者血清肝纤维化指标影响的研究

目的 观察苦参素对慢性乙型肝炎患者肝纤维化指标的影响.方法 60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)、层黏蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)和Ⅳ型胶原(CⅣ).结果 治疗组治疗后HA、LN、PC-Ⅲ和CⅣ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 苦参素是能降低肝纤维化指标,有一定的抗肝纤维化作用.     

肝细胞再生衰竭与慢性重型乙型肝炎的相关性

目的了解慢性重型乙型肝炎患者肝细胞再生衰竭的相关指标及其临床意义。方法检测慢性重型乙型肝炎患者的肝功能及相关生化指标,观察其临床转归,并比较慢性重型乙型肝炎肝衰竭患者中死亡者与存活者之间有关检查结果的差异,探寻其与肝细胞再生衰竭的关系。结果死亡组谷氨酰转肽酶（γ-GT）、血清白蛋白（ALB）随着病情加重呈进行性下降,而血清总胆红素（TBIL）进行性上升;好转组γ—GT、ALB随时间延迟趋于平行或有所回升,血清胆红素在发病第2周上升至最高,以后呈进行性下降;两组之间TBIL、γ—GT、ALB差异有统计学意义（P〈0．05）。结论临床观察上述指标有助于了解慢性重型乙型肝炎患者肝细胞坏死程度及肝干细胞新生肝细胞的能力,判断肝细胞再生衰竭,有助于为人工肝支持治疗及肝移植提供理论依据。     

FibroTouch检测肝脏硬度评价慢性乙型肝炎肝纤维化程度的影响因素分析

目的：探讨影响FibroTouch检测肝脏硬度(LSM值)评价慢性乙型肝炎肝纤维化程度的相关因素。方法：收集2015年1月至11月就诊经肝组织穿刺活检确诊的慢性乙型肝炎病毒感染者144例,应用FibroTouch技术检测肝脏LSM值,同时收集患者一般临床信息及常规血液检测指标。将筛选出的自变量进行多元线性回归分析,建立回归方程,并对回归模型进行评估。结果：经多元线性回归筛选出6个独立预测因子,分别为：脾脏肋间厚度(脾厚),体质指数(BMI),血清白蛋白(ALB)、总胆红素(TBiL)、凝血酶原时间(PT)、IV型胶原(CIV),以此建立回归方程。该回归模型决定系数R方=0.648,调整R方=0.609,具有良好的拟合度。结论：在进行FibroTouch 检测LSM时,脾厚、CIV、ALB、TBiL 、PT和BMI值,可能会对检测结果产生影响,对于影响因素的探讨仍有待进一步的大样本多中心研究。     

瞬时弹性扫描仪测定中国人慢性乙型肝炎患者肝脏硬度的影响因素分析

目的观察瞬时弹性扫描仪测定中国慢性乙型肝炎病人硬度值的影响因素。方法对110例中国慢性乙型肝炎患者应用瞬时弹性扫描仪进行检测,根据ALT情况分为3组,观察肝弹性值及各个血清学指标有无明显差异。结果经统计学检查,三组患者在年龄、性别方面无显著差异;A、B、C三组在肝弹性值、ALT、AST、TBIL水平上均有明显差异,A、B两组与C在ALP指标上均有明显差异,而三组在GGT及PLT水平检测未见明显差异。三组分别进行前后两次成组比较,发现A组在所关注的指标中均无差异。B组在肝弹性值、ALT、AST指标有所差异。C组在肝弹性值、ALT、AST、TBIL指标有所差异。B、C两组LSM与ALT呈显著相关性。随ALT下降此2组LSM绝大部分逐渐降至肝硬化界值17KPa以下。结论当患者ALT升高程度在2倍以上时肝弹性值会受到影响,在10倍以上升高时影响更为明显。当ALT明显升高时,动态观察LSM会更准确的判定肝纤维化的程度。