Fibroscan在慢性乙型肝炎肝纤维化诊断中的作用及影响因素

目的探讨肝脏瞬时弹性超声成像(Fibroscan,FS)在评估慢性乙型肝炎肝纤维化中的作用及影响因素。方法选择上海瑞金医院感染科2009年1月至2011年12月慢性乙型肝炎(CHB)患者410例,运用FS检测肝脏硬度值(Stiffness值)。所有患者同期行经皮肝穿刺活组织检查,同时检测肝功能、血小板、凝血等指标。以肝活检结果为标准绘制FS工作特征曲线,计算受试者工作特征曲线下面积(AUROC),Stiffness值与Ishak评分比对,运用统计学方法进行分析。结果无肝纤维化(S0期)、轻度肝纤维化(S1～S2期)、中度肝纤维化(S3～S4期)和重度肝纤维化及肝硬化(S5期～S6期)患者Stiffness值(kPa)分别为5.45±1.44、7.01±2.42、9.23±3.00、16.87±6.77,对Stiffness值进行组间比较,差异有统计学意义(P<0.01)。Stiffness值与肝纤维化分期呈显著正相关(r=0.67812,P<0.01)。Fibroscan检测显著肝纤维化和肝硬化的AUROC分别为0.840和0.938,其中以Stiffness值8.050kPa作为显著肝纤维化的诊断界值,敏感度为60.3%,特异度为93.7%,阳性预测值为94.71%,阴性预测值为55.83%;以12.150kPa作为重度肝纤维化和肝硬化的诊断界值点,敏感度和特异度分别为75.9%和92.0%,阳性预测值和阴性预测值分别为61.11%和95.86%。逐步回归统计分析,Alb、PLT、AST、年龄、体质量对Stiffness值有影响。结论 Fibroscan评估CHB患者肝纤维化程度尤其是显著肝纤维化和肝硬化准确性高,在诊断与疗效评估中具有较好的应用价值。     

肝脏瞬时弹性值评估慢性乙型肝炎肝纤维化程度及肝脏储备功能的临床研究

目的探讨慢性乙型肝炎(CHB)患者FibroScan与肝组织纤维化面积之间的相关性,以评价FS值对肝纤维化程度测定的意义,分析乙型肝炎后肝硬化患者的FS值变化与肝脏储备功能评价系统CTP分级的关系。方法前瞻性研究正常对照组30例、肝病组113例(CHB患者62例及其所致肝硬化患者51例)FS值,对研究对象行腹部B超检查后,应用肝脏瞬时弹性超声进行FS值测定,收集肝硬化患者入院24 h内的临床资料,计算CTP分值,根据评分分为A、B、C 3级,同时采用计算机辅助数字图像分析法检测肝组织标本的纤维化程度,分析肝病组FS值与肝纤维化面积之间的相关性以及肝硬化患者FS值变化与CTP分级的关系。结果 (1)CHB患者组的FS值与正常对照组比较,肝硬化患者的FS值与CHB组比较,差异均有统计学意义(P<0.05);(2)在肝硬化组中FS值随着CTP分级升高而升高,ChildA、B、C 3组之间FS值差异均有统计学意义(P<0.05);肝病组的FS值与肝纤维化面积有显著的线性正相关性,且相关系数较高(r=0.804,P<0.01)。结论 FS弹性值与肝纤维化面积有很好的相关性,肝硬化患者的FS值随着CTP分级的上升而增加,FS值可以评估CHB肝纤维化程度,在一定程度上可以评估肝硬化患者的肝脏储备功能。     

肝纤维化和肝硬化逆转的组织学评价

肝纤维化的诊断为慢性肝病的治疗决策和预后评价等提供了重要依据。随着治疗学的飞速进步,各类新的临床问题纷纷涌现,对肝纤维化诊断技术的需求也不断更新。目前多数情况下,组织学评价仍是慢性肝病肝纤维化和肝硬化明确诊断的最可靠方式。基于主要临床文献数据,分析和讨论了组织学评价在当前慢性肝病管理和临床研究中诊断肝纤维化/肝硬化及其逆转的应用价值及研发方向。     

瞬时弹性成像对慢性肝病肝纤维化的诊断价值

目的评价瞬时弹性成像(TE)对慢性肝病肝纤维化的诊断价值。方法分析100例本科就诊的慢性肝病肝纤维化患者,肝组织病理活检确定肝纤维化分期,同时100例患者均行实时组织弹性成像(RTE)与TE检测,比较两者与慢性肝病肝纤维化分期的相关性以及诊断肝纤维化与肝硬化的受试者工作特征曲线(ROC)曲线下面积。结果 TE与肝纤维化病理分期高度相关(r=0.763),RTE与肝纤维化病理分期中度相关(r=0.476),前者相关性显著高于后者(P=0.001);诊断肝纤维化的ROC曲线比较,TE的ROC曲线下面积(0.901)显著高于RTE的曲线下面积(0.738)(P=0.004);诊断肝硬化的ROC曲线比较,TE的曲线下面积(0.923)显著高于RTE的曲线下面积(0.791)(P=0.001)。结论TE较RTE对慢性肝病肝纤维化的诊断效能更高,但由于TE实际操作较RTE要求更高,推广程度低于RTE。     

重视肝纤维化的诊治

肝纤维化是各种病因引起慢性反复肝损伤后的疤痕修复反应,是肝硬化发生的早期、可逆阶段。概述了肝纤维化与肝硬化的区别和慢性肝病的分期方法,重点论述了肝纤维化早期诊治的重要性,介绍了目前早期诊断评估方法以及肝纤维化的药物开发与治疗进展。强调肝纤维化患者的诊断及治疗对防止肝病进展为失代偿期肝硬化具有重要意义。     

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。     

水飞蓟素在抗肝纤维化中的应用

肝纤维化是各种病因引起慢性肝损伤,激活肝星状细胞(HSC),导致细胞外基质(ECM)合成大于降解进而在肝脏异常沉积的结果,进一步发展,则引起肝小叶结构改建,假小叶形成,称为肝硬化.肝纤维化是慢性肝病重要的病理特征,也是肝硬化发生的前奏和必经中间环节.近年来有关肝纤维化的研究取得了长足进展,水飞蓟素(silymarin)在世界各国治疗肝病已有数千年的历史,其在抗肝纤维化中的作用值得人们关注.     

瞬时弹性扫描仪在肝纤维化诊断中的应用价值

瞬时弹性扫描仪(Fibroscan,FS)是一种新型的、无创性的通过测定肝脏硬度值来评估慢性肝脏疾病患者肝纤维化程度的仪器.他具有操作简单、快速、重复性好等优点.目前,FS不仅用于慢性丙型肝炎患者肝纤维化的测定,也可用于其他原因引起的肝脏疾病的肝纤维化测定.FS对测定早期肝硬化及合并肝硬化并发症患者的肝脏硬度值有较大的价值.由于FS能被患者普遍接受及可以重复测定,因此可用于监测肝脏纤维化的进展或逆转,指导临床治疗.但FS在临床应用中也存在一些影响因素和一定局限性.本文就FS在肝纤维化诊断方面的应用价值作一综述.     

高尔基体蛋白73的生物学特征及在肝纤维化 和肝硬化中的诊断价值

肝纤维化是慢性肝病发展至肝硬化的必经阶段,肝硬化是各种慢性肝病的终末期改变,其早期诊断对及时治疗和预后非常重要。目前,肝纤维化和肝硬化的诊断方法主要包括肝活组织检查、超声、CT和MRI等。肝活组织检查是诊断肝纤维化及肝硬化程度的金标准,但由于其侵袭性及样本误差,临床应用受到限制。常规的非侵入性措施不能满足肝纤维及肝硬化的诊断要求。因此,寻找一种新的肝纤维化及肝硬化血清学标志物已成为研究热点。相关研究表明,血清高尔基体蛋白73是一种可用于肝纤维化及肝硬化诊断的血清标志物,有较大的临床应用价值。对目前临床上常用的肝纤维化和肝硬化诊断方法进行了陈述,并阐述了高尔基体蛋白73的生物学特征及其在肝纤维化及肝硬化诊断中的价值。     

瞬时弹性成像技术与APRI指数判定慢性肝病肝纤维化程度的临床研究

目的评估肝脏瞬时弹性成像技术(Fibro Scan,FS)的应用价值,为肝纤维化的准确诊断提供安全、可靠的检测方法。方法选择2014年3月至2015年5月就诊于漯河市中心医院和郑州大学第一附属医院并经肝组织活检确定为慢性肝病患者168例,运用FS检测肝脏硬度(LSM);测定丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBIL);检测血小板计数,并计算AST/PLT比值(APRI)。以肝活组织检查病理结果为依据,分析LSM、APRI与肝纤维化程度的相关性。应用SPSS 17.1统计软件进行统计分析。绘制受试者工作特征曲线分析二者诊断慢性肝病肝纤维化的准确性,Spearman相关分析影响肝硬度值的相关因素。结果 168例慢性肝病患者LSM值中位数为10.8 k Pa;APRI中位数为0.71;LSM值与肝纤维化成正相关(r=0.832,P=0.000),LSM诊断肝组织病理学纤维化分期S≥2,S≥3及S=4的ROC曲线下面积分别为0.894,0.923和0.951,明显高于APRI(0.691,0.715及0.736)诊断的ROC曲线下面积。Spearman相关分析显示,LSM与年龄、ALT≥2倍正常上限值、AST、TBIL及肝组织炎症呈正相关,相关系数r分别为0.486、0.570、0.617、0.481及0.549(P0.05),与PLT呈负相关(r=-0.527,P0.05)。结论FS是一种简便、可靠的慢性肝病肝纤维化诊断方法,其灵敏度及特异度均优于APRI。年龄、高水平的ALT、AST和TBIL≥2×ULN是其独立的影响因素。     

慢性肝病患者肝纤维化血清学指标与肝组织纤维化分期的量化关系

目的研究肝纤维化血清学指标与慢性肝病患者肝穿刺活体组织学检查纤维化分期的量化关系。方法用放射免疫法检测118例肝病患者血清层黏连蛋白（LN）、透明质酸（HA），Ⅲ型前胶原蛋白（PCⅢ）、Ⅳ型胶原蛋白（CⅣ）的水平，并与患者的肝组织病理学检查作对比。通过SPSS11．0软件包分析LN、HA、PCⅢ、CⅣ与肝组织纤维化分期及炎症分级的量化关系。结果LN、HA、PCⅢ、CⅣ与肝组织学炎症分级有相关性（r分别为0．394．0．449、0．443、0．35l，P值均〈0．01）；与肝组织纤维化分期也有相关性（r值分别为0．456、0．564、0．476、0．42l，P值均〈0．01）。LN．HA、PCⅢ、CⅣ对S2以上肝纤维化诊断界值分别为110、110、100、70ng／ml，其诊断灵敏度分别为70％、79％、79％、74％，特异度分别为68％，72％、64％、73％。对S4（早期肝硬化）的诊断界值分别为130、140、120．70ng／ml，其诊断灵敏度分别为79％、93％，79％，86％，特异度分别为66％、82％．72％、61％。受试者工作特征曲线分析显示：在这些患者中判断有无肝硬化存在，HA比其它指标更有价值；HA测定值大于l90ng／ml时，其诊断早期肝硬化的准确度为93％。结论慢性肝病患者，血清HA、LN、PCⅢ、CⅣ水平与肝纤维化分期有一定量化关系，其中HA诊断早期肝硬化有重要意义。     

评估肝纤维化进展相关的血清标志物研究现状

肝纤维化是各种慢性肝病重要的病理特征,也是进一步向肝硬化发展的必经阶段,早期诊断和治疗对阻止肝纤维化发展为肝硬化具有重要意义。肝活检仍是诊断肝纤维化的金标准,但具有创性,不易动态观察,临床应用受到限制,因此需寻求理想的无创诊断方法。在过去的十年中,肝纤维化进展相关的血清标志物研究取得了很大的进展,为肝纤维化的无创诊断带来了新希望。     

Advances in noninvasive methods for diagnosing nonalcoholic fatty liver disease

The prevalence of nonalcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide, has been increasing. In terms of pathological changes, NAFLD can be divided into simple steatosis, nonalcoholic steatohepatitis (NASH) and liver cirrhosis. Hepatocyte damage and inflammatory activity are the main characteristics for evaluating the progress of liver disease. Early and effective diagnosis of the disease is quite important. Pathological findings based on liver biopsy or resected specimens are considered the gold standard for diagnosing and staging steatosis, fibrosis and cirrhosis; however, it is invasive and may lead to related complications. Non‐imaging methods such as clinical features and biochemical tests, and imaging methods such as ultrasonography, FibroScan, computed tomography and magnetic resonance imaging are the commonly used noninvasive alternatives, being relatively novel, safe and reliable. In this review, we summarized the benefits and shortcomings of these non‐invasive methods for the evaluation of NAFLD.     

Transient elastography for liver fibrosis diagnosis

Liver biopsy is considered the “golden standard” for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems.Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate fibrosis. Most of the studies have been conducted on patients with chronic hepatitis but a few studies have also covered fibrosis and cirrhosis due to other etiologies, and they also demonstrate the high sensitivity and specificity. Transient elastography for assessment of fibrosis may turn out to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases.     

Non-invasive prediction of forthcoming cirrhosis-related complications

In patients with chronic liver diseases,identification of significant liver fibrosis and cirrhosis is essential for determining treatment strategies,assessing therapeutic response,and stratifying long-term prognosis.Although liver biopsy remains the reference standard for evaluating the extent of liver fibrosis in patients with chronic liver diseases,several non-invasive methods have been developed as alternatives to liver biopsies.Some of these non-invasive methods have demonstrated clinical accuracy for diagnosing significant fibrosis or cirrhosis in many cross-sectional studies with the histological fibrosis stage as a reference standard.However,non-invasive methods cannot be fully validated through cross-sectional studies since liver biopsy is not a perfect surrogate endpoint marker.Accordingly,recent studies have focused on assessing the performance of non-invasive methods through longterm,longitudinal,follow-up studies with solid clinical endpoints related to advanced stages of liver fibrosis and cirrhosis.As a result,current view is that these alternative methods can independently predict future cirrhosis-related complications,such as hepatic decompensation,liver failure,hepatocellular carcinoma,or liver-related death.The clinical role of non-invasive models seems to be shifting from a simple tool for predicting the extent of fibrosis to a surveillance tool for predicting future liver-related events.In this article,we will summarize recent longitudinal studies of non-invasive methods for predicting forthcoming complications related to liver cirrhosis and discuss the clinical value of currently available non-invasive methods based on evidence from the literature.     

Liver fibrosis markers of nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH.     

Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

There are approximately 240 million patients with chronic hepatitis B virus (HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the “gold standard” for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBV-infected patients, owing to its high applicability, inter-laboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBV-infected patients for clinicians.     

Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage

Transient elastography [FibroScan (FS)] is a rapid, noninvasive, and reproducible method for measuring liver stiffness, which correlates with the degree of liver fibrosis in patients with chronic hepatitis. Whether FS is useful in the detection of preexisting liver fibrosis/cirrhosis in patients presenting with acute liver damage is unclear. Patients with acute liver damage of different etiologies were analyzed. Liver stiffness was measured during the acute phase of the liver damage and followed up to the end of the acute phase. A total of 20 patients were included in the study. In 15 of the 20 patients, initial liver stiffness values measured by FS during the acute phase of the liver damage were suggestive of liver cirrhosis. However, none of these 15 patients showed any signs of liver cirrhosis in the physical examination, ultrasound examination, or liver histology [performed in 11 of 15 (73%) patients]. A significant difference was observed in the initial bilirubin levels (5.8 +/- 6.5 mg/dL versus 15.7 +/- 11.8 mg/dL; P = 0.042) and age (32.4 +/- 17.5 years versus 49.7 +/- 15.8 years; P = 0.042) between patients with liver stiffness below or above 12.5 kPa. Six patients with initially high liver stiffness were followed up to abatement of the acute hepatitic phase; in all of them, liver stiffness values decreased to values below the cutoff value for liver cirrhosis. CONCLUSION: Transient elastography frequently yields pathologically high values in patients with acute liver damage and is unsuitable for detecting cirrhosis/fibrosis in these patients.