慢性乙型肝炎肝纤维化辨证分型与肝纤维化病理及血清学指标的相关性研究

目的:探讨慢性乙型肝炎(CHB)肝纤维化证型分布与血清肝纤维化指标及肝纤维化病理分期的相关性.方法:对确诊的171例CHB肝纤维化患者进行辨证分型,并观察肝纤维化病理分期、肝纤维化4项与辨证分型的关系.结果:肝郁脾虚型主要见于在肝纤维化早期(S1),瘀血阻络型主要见于肝纤维化中晚期(S3～S4),两者比较,各病理期的分布有显著性差异(P＜0.01);脾肾阳虚型、瘀血阻络型HA含量显著高于肝郁脾虚型,差异有显著性意义(P＜0.05或P＜0.01);瘀血阻络型HA含量高于肝肾阴虚型和湿热中阻型,差异有显著性意义(P＜0.05);瘀血阻络组LN和Ⅳ-C含量明显高于肝郁脾虚型,差异有显著性意义(P＜0.05);各证型患者血清PCⅢ含量差异无显著性意义(P＞0.05).结论:CHB肝纤维化不同病理阶段,证型分布发生相应变化,并与肝纤维化指标具有显著相关性.     

慢性肝炎临床诊断与病理分级分期诊断的对比分析

１９１例慢性肝炎患者进行了肝活检，病理切片按Ｓｃｈｅｕｅｒ推荐标准进行了分级分期诊断，并与肝功能、肝脾Ｂ型超声检查对照，提示慢性肝炎随着炎症活动的严重和反复，肝内纤维化程度亦愈明显。慢性小叶性肝炎诊断必须依赖于病理诊断。肝硬化临床诊断与病理诊断符合率为３３％，故病理诊断分级分期是目前慢性肝炎，尤其是肝纤维化者的必要检查手段。     

基于肝组织病理动态变化情况探讨血清学指标在肝纤维化诊断中的意义

目的基于药物干预前后的肝组织病理动态变化情况，探讨肝功能、肝纤维化血清学指标在慢性乙型肝炎肝纤维化诊断和预后判断中的价值。方法根据扶正化瘀胶囊抗慢性乙型肝炎肝纤维化多中心，随机、双盲，对照临床试验中93例（包括试验组和对照组）治疗6个月前后2次肝活体组织病理学检查的资料，并依据肝组织纤维化程度减轻和未减轻（或继续加重）的情况将病例分为两组（减轻组36例，未减轻组57例），分析该两组肝组织炎症、肝功能、肝纤维化血清学指标及相应的血常规变化规律。结果纤维化减轻组伴有肝组织炎症程度的显著减轻。药物干预后，纤维化减轻组的血清透明质酸和Ⅲ型前胶原肽含量明显下降（t=3．34与t=3．17，P值均〈0．01），并显著低于未减轻组；但层黏连蛋白和Ⅳ型胶原含量差异均无统计学意义。纤维化减轻组伴有血清白蛋白升高（t=3．24，P〈0．01）及γ-谷氨酰转肽酶，天冬氨酸氨基转移酶活性和凝血酶原时间的下降，而未减轻组无类似变化。结论慢性乙型肝炎肝纤维化患者血清γ-谷氨酰转肽酶，天冬氨酸氨基转移酶活性，凝血酶原时间，白蛋白、血清透明质酸和Ⅲ型前胶原肽含量的变化有助于肝纤维化减轻与否的判断和药物疗效评价，而血清层黏连蛋白和Ⅳ型胶原含量在肝纤维化诊断中的价值有待商榷。     

彩色超声与慢性肝炎肝纤维化分期的相关性分析

目的探讨超声诊断慢性乙型肝炎(CHB)患者代偿期肝硬化的价值。方法 2010年1月至2015年1月行肝活组织检查的CHB患者226例,收集患者B型超声资料,利用Logistic回归分析与代偿期肝硬化程度相关的指标,采用受试者工作特征曲线下面积(AUROC)评价B型超声诊断代偿期肝硬化的价值。结果超声指标中SWV、门静脉主干内径、胆囊壁厚度、脾脏长径、脾脏厚度、脾脏面积、脾静脉内径、门静脉最大流速共8项指标与肝脏炎症分级和纤维化分期均相关。其中,SWV、门静脉主干内径、脾脏长径、门静脉最大流速、脾静脉内径与组织学代偿期肝硬化独立相关,AUC均0.7。结论超声的部分影像学指标对预测组织学代偿期肝硬化有潜在的价值。     

超声综合评估系统诊断慢性乙型肝炎肝纤维化

目的探讨超声定量及半定量评估系统对慢性乙型肝炎肝纤维化的诊断价值。方法110例接受肝穿刺活组织检查的慢性乙型肝炎患者同时行彩色多普勒超声检查,记录、分析19项超声量化指标、12项超声形态学指标与肝纤维化病理分期的相关性,并以7项综合超声指标为基础建立判别肝纤维化程度的超声半定量积分系统,以3项定量超声指标为基础建立判别肝纤维化程度的Fisher判别函数,同时分析二者联合诊断的效果。结果超声半定量积分系统诊断不同程度肝纤维化的曲线下面积（AUC）分别为≥S2：0．946,≥S3：0．914,S4：0．915。超声总积分与肝纤维化程度显著正相关（r=0．824,P＜0．01）,且在肝纤维化各分期间差异有统计学意义（P＜0．01）。由肝包膜厚度、脾面积、肝静脉内径为基础建立的判别函数,对各研究终点的诊断准确率分别为76．5%、78．2%和67．3%。将其与超声积分系统联合起来判别肝纤维化分期的特异性为85%～90%,准确性为77%～84%。结论以超声形态学指标为主构建的超声半定量积分系统对诊断肝纤维化程度具有较高价值,将其与由超声定量指标建立的判别函数结合起来,可明显提高超声诊断肝纤维化的准确性。     

肝纤维化的病理

肝脏的纤维化或硬化是肝内过多或异常胶原纤维沉积所导致的病理状态及其相关改变。病因不同,肝纤维化的部位、发展过程、相关细胞种类及病理形态各异。一般认为,活化肝星状细胞、纤维母细胞与胆管细胞、肝细胞是重要的纤     

慢性肝炎血清肝纤维化指标与中医虚、实证及与肝脏病理分级分期的关系

目的:探讨慢性肝炎血清肝纤维化指标与中医虚、实证及肝脏病理的关系.方法:将75例慢性肝炎患者(其中偏实证组30例,偏虚证组45例)用放射免疫法测定血清肝纤维化指标:透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)和Ⅳ型胶原(Ⅳ-C),以同期健康体检正常者15例作对照.并对其中20例患者行肝组织活检.结果:①慢性肝炎患者血清肝纤维化指标(HA、LN、PCⅢ、Ⅳ-C)偏实证组较偏虚证组明显升高,两组差异有统计学意义.②慢性肝炎患者肝脏病理分级分期与血清肝纤维化指标存在相关性.结论:①血清肝纤维化指标可作为慢性肝炎中医虚、实证微观辨证指标之一.②湿热中阻和瘀血阻络是肝纤维化的活跃期,抗肝纤维化治疗的重点是清除湿热邪毒,活血化瘀、祛瘀通络.     

探讨慢性肝炎患者血清肝纤维化指标的临床价值

探讨慢性肝炎患者血清肝纤维化指标（ＨＡ、ＰＣⅢ、Ⅴ－Ｃ、ＬＮ）的临床实用价值。对２５００例慢性肝炎患者,用放射免疫法进行血清ＨＡ、ＰＣⅢ、Ⅳ－Ｃ、ＬＮ指标均有是面肝纤维化指标水平与乙肝口才的肝脏炎症活动度分级、肝发给化程度分期与病理组织学分主工均存在显著相关。血清肝纤维化指标对判断慢性肝炎的肝纤维化和肝硬化倾向具有临床实用意义。     

血清肝纤维化指标与临床及病理的关系

目的 了解血清肝纤维化指标与临床及病理的关系。方法 对１９０例各种肝炎患者血清进行透明质酸酶,板层素,ＩＮ型胶原（ＩＶ－Ｃ）,Ⅲ型前胶原（ＰＣⅢ）测定,部分病例进行肝活检。结果 血清ＨＡ,ＬＮ,ＩＶ－Ｃ,ＰＣⅢ水平随着肝炎疾病程度的加重而升高。ＨＡ,ＬＮ,ＩＶ－Ｃ,ＰＣⅢ在病理不同阶段变化不同。结论 肝纤维化指标可用于慢性肝炎病情严重程度的判断,且ＨＡ,ＬＮ较早反映炎症活动度,而ＰＣⅢ则较反映纤维     

慢性肝炎肝纤维化

慢性肝炎 (ＣＨ )时肝脏由于反复炎症坏死后发生纤维增生 ,虽然临床可根据血液生化指标的检测 ,例如Ⅲ型前胶原氨基端肽 (ＰⅢＰ)来判断肝脏胶原合成情况 ,但肝穿刺活检对于诊断肝炎肝纤维化有着不可取代的作用。一份供病理诊断肝穿刺标本的长度应超过 1ｃｍ (即镜下超过 6个肝     

Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B

Infection with hepatitis B virus is an important healthproblem worldwide:it affects more than 350 millionpeople and is a leading cause of liver-related morbidity,accounting for 1 million deaths annually.Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver.An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease.Liver biopsy has been considered the gold standard for diagnosing disease,grading necroinflammatory activity,and staging fibrosis.However,liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications,including death.Several noninvasive evaluations have been introduced for the assessment of liver fibrosis:serum biomarkers,combined indices or scores,and imaging techniques including transient elastography,acoustic radiation force impulse,real-time tissue elastography,and magnetic resonance elastography.Here,we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B.Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C,and later in those with chronic hepatitis B.The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease.     

Non-invasive assessment of liver fibrosis in patients with chronic hepatitis B

In patients with chronic hepatitis B (CHB), liver fibrosis assessment is essential not only for determining prognosis but also for identifying patients who should receive treatment. Liver biopsy is limited by its invasiveness and sampling error. To explore effective non-invasive methods for liver fibrosis assessment, we reviewed international literature published over the past decade that focused on patients with CHB. Biomarker panels such as API, FIB-4, Forns Index, HepaScore, FibroMeter, FibroTest, Zeng Index and Hui Index detect advanced fibrosis and cirrhosis with fairly satisfactory accuracy with area under the receiver-operating characteristics curve higher than 0.85. However, most panels and the suggested cutoffs have not been independently validated. Transient elastography is accurate in detecting advanced fibrosis and cirrhosis, and the relative cutoffs have been defined. False-positive results may, however, occur in cases of active necroinflammation and cholestasis. Other promising imaging methods such as acoustic radiation force impulse and magnetic resonance elastography still require further validating studies. We conclude that transient elastography, FibroTest and API are the most widely validated. Transient elastography has been validated as the most useful non-invasive method for liver fibrosis assessment. To improve non-invasive performance of detecting liver fibrosis, a combined application of transient elastography and biomarkers may be the preferred course of action.     

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role, clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus (HBV) infection. During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility, poor acceptance by patients. Elastographic techniques conceived to assess liver stiffness, in particular transient elastography, and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis. Recent evidence highlights that both liver stiffness and some bio-chemical markers correlate with survival and major clinical end-points such as liver decompensation, development of hepatocellular carcinoma and portal hypertension. Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis. Given their prognostic value, transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes. Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.     

Non-invasive assessment of liver fibrosis in chronic hepatitis C

Quantification of hepatic fibrosis is of critical importance in chronic hepatitis C not only for prognosis, but also for antiviral treatment indication. Two end points are clinically relevant: detection of significant fibrosis (indication for antiviral treatment) and detection of cirrhosis (screening for eosphageal varices and hepatocellular carcinoma). Until recently, liver biopsy was considered the reference method for the evaluation of liver fibrosis. Limitations of liver biopsy (invasiveness, sampling error, and inter-observer variability) have led to the development of non-invasive methods. Currently available methods rely on two different approaches: a “biological” approach based on the dosage of serum fibrosis biomarkers; and a “physical” approach based on the measurement of liver stiffness, using transient elastography (TE). This review is aimed at discussing the advantages and limits of non-invasive methods and liver biopsy and the perspectives for their rational use in clinical practice in the management of patients with chronic hepatitis C.     

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.     

Noninvasive assessment of liver fibrosis in chronic hepatitis C infection

Hepatic fibrogenesis is a dynamic process that reflects a balance between matrix synthesis and degradation. An accurate determination of hepatic fibrosis is important in determining prognosis, requirement for therapy, and disease progression in chronic hepatitis C infection. Histologic assessment relies on a liver biopsy, an invasive procedure associated with sampling error and inaccurate staging that provides only a semiquantitative and static measure of fibrosis and inflammatory activity. Several noninvasive tools initially developed and validated in chronic hepatitis C patients are now being applied to other chronic liver disease states. These noninvasive approaches include simple and complex serum biochemical marker algorithms, radiologic methods such as elastography, and emerging genomics and proteomics technologies. In the future, the combination of these diagnostic modalities likely will provide a more accurate and reliable measure of disease severity in chronic liver disease patients.     

Quantitative assessment of fibrosis in liver biopsies from patients with chronic hepatitis B.

BACKGROUND/AIM: Accurate histological assessment of liver fibrosis is essential in the management of chronic hepatitis B (CHB). Although semi-quantitative scoring systems describe well the pathological patterns of hepatic structure, they produce fibrosis evaluation that is not very precise. Image analysis or morphometry has the theoretical advantage of providing truly quantitative data. PATIENTS AND METHODS: The present study aimed at validating a new image analysis system, Bioquant Nova Prime, in estimating collagen content in liver biopsy samples from patients with CHB. The biopsies were stained with picrosirius red and the areas of collagen were measured. The results were correlated with laboratory parameters and Ishak modified histological scores. Discriminative reliability of morphometry was determined using receiver operating characteristics (ROC) analysis. RESULTS: There was excellent interobserver agreement (r=0.84-0.94, P<0.01) in the morphometric analysis. Significant correlations between the quantitative morphometric data and the semi-quantitative score (Spearman's r=0.68-0.78, P<0.001) were also demonstrated. Excellent discriminative power of morphometry in differentiating mild from advanced fibrosis and cirrhosis from absence of cirrhosis was shown by the ROC analysis. CONCLUSIONS: Our results validated the use of Bioquant Nova Prime in estimating collagen content in liver biopsies. We showed that morphometry is a sensitive method of liver fibrosis quantification in CHB and complements semi-quantitative histological scoring system. This tool, with its reliable intraassay variability, could be of special value in assessing histological response to treatment after anti-viral or anti-fibrotic therapy.     

Comparison of non-invasive assessment to diagnose liver fibrosis in chronic hepatitis B and C patients

Abstract

Objective. Chronic viral hepatitis B and C cause liver fibrosis, leading to cirrhosis. Fibrosis assessment is essential to establish prognosis and treatment indication. We compared seven non-invasive tests, separately and in combination, in chronic hepatitis patients to detect early stages of fibrosis according to the Metavir score in liver biopsy. Material and methods. Galactose and methacetin breath tests (GBT and MBT), biomarkers (hyaluronic acid (HA), aspartate aminotransferase platelet ratio index (APRI), FibroTest, and Fib-4) and transient elastography (TE) were evaluated in 89 patients. Additionally, 31 healthy controls were included for evaluation of breath tests and biomarkers. Results. Serum markers (HA, APRI, FibroTest, and Fib-4) and elastography significantly distinguished non-cirrhotic (F0123) from cirrhotic (F4) patients (p < 0.001, p = 0.015, p < 0.001, p = 0.005, p = 0.006, respectively). GBT, HA, APRI, FibroTest, Fib-4, and TE detected F01 from F234 (p = 0.04, p = 0.011, p = 0.009, p < 0.001, p < 0.001, and p < 0.001, respectively). A combination of different tests (TE, HA, and FibroTest) improved the performance statistically, area under the curve (AUC) = 0.87 for F234, 0.92 for F34, and 0.90 for F4. Conclusion. HA, APRI, FibroTest, Fib-4, and TE reliably distinguish non-cirrhotic and cirrhotic patients. Except for MBT, all tests discriminate between mild and moderate fibrosis. As single tests: FibroTest, Fib-4, and TE were the most accurate for detecting early fibrosis; combining different non-invasive tests increased the accuracy for detection of liver fibrosis to such an extent and thus might be acceptable to replace liver biopsy.