声触诊弹性成像检测肝脾硬度诊断慢性乙型肝炎患者肝纤维化效能分析

目的 探讨应用声触诊弹性成像(APE)行肝脏硬度检测(LSM)和脾脏硬度检测(SSM)诊断慢性乙型肝炎(CHB)患者肝纤维化的效能.方法 2020年1月～2021年10月我院诊治的CHB患者392例,行肝穿刺组织病理学检查,将≤F1期为非显著性肝纤维化,≥F2期为显著性肝纤维化,F4期为早期肝硬化.使用超声APE计数获...     

Non‐invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B

Background: The need for new non‐invasive tools to assess liver fibrosis in chronic liver diseases has been largely advocated. Liver stiffness measurement (LSM) using transient elastography (FibroScan^®, Echosens^?) has been shown to be correlated to liver fibrosis in various chronic liver diseases. This study aims to assess its diagnosis accuracy in patients with chronic hepatitis B. Patients and methods: We prospectively enrolled 202 patients with chronic hepatitis B in a multicentre study. Patients underwent liver biopsy (LB) and LSM. METAVIR and Ishak liver fibrosis stages were assessed by two pathologists. Results: LSM or LB was considered unreliable in 29 patients. Statistical analysis was conducted in 173 patients. LSM was significantly (P<0.001) correlated with METAVIR (r=0.65) and Ishak fibrosis stage (0.65). The area under receiver‐operating characteristic curves were 0.81 (95% confidence intervals, 0.73–0.86) for F≥2, 0.93 (0.88–0.96) for F≥3 and 0.93 (0.82–0.98) for F=4. Optimal LSM cut‐off values were 7.2 and 11.0 kPa for F≥2 and F=4, respectively, by maximizing the sum D of sensitivity and specificity, and 7.2 and 18.2 kPa by maximizing the diagnosis accuracy. Conclusion: In conclusion, LSM appears to be reliable for detection of significant fibrosis or cirrhosis in HBV patients and cut‐off values are only slightly different from those observed in HCV patients.     

Acoustic radiation force impulse imaging for non‐invasive assessment of liver fibrosis in chronic hepatitis B

Acoustic radiation force impulse (ARFI) imaging is a novel ultrasound‐based elastography method that is integrated in a conventional ultrasound machine. It might provide an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. While previous studies have shown comparable diagnostic accuracy of ARFI to transient elastography in chronic hepatitis C, the aim of the present prospective multicenter study was to evaluate ARFI for the assessment of liver fibrosis in chronic hepatitis B. ARFI imaging involves the mechanical excitation of tissue using short‐duration acoustic pulses to generate localized displacements in tissue. The displacements result in shear‐wave propagation which is tracked using ultrasonic, correlation‐based methods and recorded in m/s. In the present international prospective study, patients infected with chronic hepatitis B received ARFI imaging, blood tests and if available transient elastography. The results were compared to liver biopsy as reference method analysed by a central pathologist. In 92 of 114 patients, a comparison of ARFI with transient elastography was possible. ARFI imaging and transient elastography correlated significantly with histological fibrosis stage. The diagnostic accuracy expressed as areas under ROC curves for ARFI imaging and transient elastography was 0.75 and 0.83 for the diagnosis of significant fibrosis (F ≥ 2), 0.93 and 0.94 for the diagnosis of severe fibrosis (F ≥ 3), and 0.97 and 0.93 for the diagnosis of liver cirrhosis, respectively. No significant difference was found between ARFI and transient elastography. ARFI imaging is a reliable ultrasound‐based method for the assessment of advanced stages of liver fibrosis in chronic hepatitis B.     

声脉冲辐射力成像技术评价慢性乙型肝炎肝纤维化程度的研究

目的分析声脉冲辐射力成像技术在肝纤维化诊断中的应用价值。方法利用声辐射力脉冲成像技术对52例慢性乙型肝炎患者和31例健康人肝脏右叶进行检查,测得感兴趣区肝脏组织声触诊组织量化(VTQ)值,并与肝活检组织病理学检查结果相比较。结果慢性乙型肝炎患者肝脏VTQ值显著高于健康人(P=0.012),VTQ值与肝纤维化程度呈正相关(Spearman r=0.737,P<0.01);将肝组织病理学检查结果≤G2S2合并为轻度肝纤维化组,≥G3S3合并为中/重度肝纤维化组,结果 VTQ诊断中/重度肝纤维化的VTQ值的cut-off值为1.6m/s,其诊断中/重度肝纤维化的敏感度为93.8%,特异度为73.7%,准确性为85.1%。结论声脉冲辐射力成像技术在慢性乙型肝炎患者对评估肝纤维化程度有重要的价值。     

Effects of patient factors on noninvasive liver stiffness measurement using acoustic radiation force impulse elastography in patients with chronic hepatitis C

ABSTRACT: BACKGROUND: Previous research has shown variation in the effects of patient factors, including hepatic necroinflammatory activity, on liver stiffness measurement (LSM). This prospective study attempts to identify explanatory factors for LSM in patients with chronic hepatitis C (CHC) using acoustic radiation force impulse (ARFI) technology. METHODS: A cohort of 127 Taiwanese patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy. This study compares the concurrent diagnostic performances of LSM and FibroTest using receiver operating characteristic (ROC) curves. Three multiple linear regression models were used to evaluate the significance of concurrent patient factors in explaining LSM. RESULTS: To classify METAVIR fibrosis (F) stages, the areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI), 0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95% CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and biological covariates, biochemical and histological necroinflammatory factors consistently explained LSM. Factors included serum alanine aminotransferase (ALT)/upper limit of normal (ULN) categories (model R2 = 0.661, adjusted R2 = 0.629), ActiTest A scores (R2 = 0.662, adjusted R2 = 0.636), and METAVIR activity (A) grades (R2 = 0.651, adjusted R2 = 0.620). METAVIR F stages, body mass index, and platelet count were also independently associated with LSM. Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A grades, explained the false positivity of liver fibrosis staging using ARFI LSM. CONCLUSIONS: The degree of hepatic necroinflammatory activity independently and significantly exaggerated liver fibrosis evaluation using ARFI LSM. However, comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising alternative, or adjunctive single indicator, for liver fibrosis evaluation in patients with CHC.     

A diagnostic algorithm for assessment of liver fibrosis by liver stiffness measurement in patients with chronic hepatitis B

Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)‐infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV‐infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut‐offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut‐off for severe steatosis (≥30%) was 287 dB/m. Among patients with low‐grade fibrosis (S0‐S2/S0‐S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low‐grade fibrosis, a higher rate of false‐positive rate was observed in patients with severe steatosis than those in patients without (F0‐F2: 28.2% vs 9.7%; F0‐F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0‐F2: 23.7% vs 9.2%; F0‐F3: 14.1% vs 4.8%). Low‐grade fibrosis was accurately identified by γ‐glutamyl transpeptidase‐to‐platelet ratio (GPR) with a cut‐off value of 0.17. In patients with GPR<0.17, similar results were observed. The presence of steatosis may lead to overestimation of fibrosis assessed by liver stiffness measurement in patient with chronic hepatitis B. A diagnostic algorithm for assessing fibrosis using liver stiffness was developed by combining both controlled attenuation parameter and GPR values.     

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C

Liver fibrosis is the main predictor of the progression of chronic hepatitis C, and its assessment by liver biopsy (LB) can help determine therapy. However, biopsy is an invasive procedure with several limitations. A new, noninvasive medical device based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with chronic hepatitis C. We prospectively enrolled 327 patients with chronic hepatitis C in a multicenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists. LSM was performed by transient elastography. Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver-operating characteristics (ROC) curve analysis and cross-validated by the jack-knife method. LSM was well correlated with fibrosis stage (Kendall correlation coefficient: 0.55; P < .0001). The areas under ROC curves were 0.79 (95% CI, 0.73-0.84) for F > or =2, 0.91 (0.87-0.96) for F > or =3, and 0.97 (0.93-1) for F=4; for larger biopsies, these values were, respectively, 0.81, 0.95, and 0.99. Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F > or =2 and F=4, respectively. In conclusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis C.     

Factors correlating with acoustic radiation force impulse elastography in chronic hepatitis C

AIM: To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse(ARFI) elastograpy in chronic hepatitis C. METHODS: ARFI elastograpy was performed in 108 consecutive patients with chronic hepatitis C who underwent a liver biopsy. The proportion of fibrosis area in the biopsy specimens was measured by computerassisted morphometric image analysis. RESULTS: ARFI correlated significantly with fibrosis stage(β = 0.1865, P < 0.0001) and hyaluronic acid levels(β = 0.0008, P = 0.0039) in all patients by multiple regression analysis. Fibrosis area correlated significantly with ARFI by Spearman’s rank correlation test but not by multiple regression analysis. ARFI correlated significantly with body mass index(BMI)(β =-0.0334, P = 0.0001) in F 0 or F 1, with γ-glutamyltranspeptidase levels(β = 0.0048, P = 0.0012) in F 2, and with fibrosis stage(β = 0.2921, P = 0.0044) and hyaluronic acid levels(β = 0.0012, P = 0.0025) in F 3 or F 4. The ARFI cutoff value was 1.28 m/s for F ≥ 2, 1.44 m/s for F ≥ 3, and 1.73 m/s for F 4. CONCLUSION: ARFI correlated with fibrosis stage and hyaluronic acid but not with inflammation. ARFI was affected by BMI, γ-glutamyltranspeptidase, and hyaluronic acid in each fibrosis stage.     

慢性乙型肝炎患者肝脏硬度值下降趋势与肝纤维化逆转结局的关系

目的 分析抗病毒治疗中慢性乙型肝炎患者肝脏硬度值变化趋势与肝纤维化逆转结局的相关性。方法 基于恩替卡韦初治慢性乙型肝炎患者临床随访队列(2013年7月-2015年9月),检测基线和治疗中每半年HBV DNA水平、肝功能、肝脏硬度值。根据更为严格的标准将治疗前后Ishak评分变化分为3组:确定逆转组,Ishak评分下降≥2;不确定组,Ishak评分下降0~1;进展组,Ishak评分升高>1。多组间比较采用单因素方差分析。采用分段线性混合模型拟合不同肝纤维化逆转结局的慢性乙型肝炎患者肝脏硬度值下降趋势,斜率的显著性及不同组间斜率的比较采用t检验。结果 共纳入239例慢性乙型肝炎患者,恩替卡韦治疗1.5年后,18例患者(7.5%)达到肝纤维化组织学确定逆转、196例(82.0%)为不确定、25例(10.5%)为进展。开始抗病毒治疗半年内肝脏硬度值下降率:确定逆转组为-36.3%[95%可信区间(95%CI):-52.8%^-19.7%],不确定组为-23.7%(95%CI:-29.7%^-17.8%),进展组为-12.6%(95%CI:-31.0%~5.9%)。在确定逆转组与不确定组,肝脏硬度值在治疗后的前6个月比治疗6个月后的下降速度更快(P值均<0.05)。结论 抗病毒治疗半年内肝脏硬度值的下降速度与肝纤维化逆转结局相关性较强,治疗半年时肝脏硬度值下降超过30%者发生肝纤维化确定逆转的可能性更大。     

声辐射力脉冲成像技术定量评价慢性丙型肝炎肝纤维化的临床研究

目的 探讨声脉冲辐射力成像技术(ARFI)在评价慢性丙型肝炎肝纤维化程度上的临床价值. 方法 对108例慢性丙型肝炎患者应用ARFI技术对肝脏的实时超声弹性进行测量,患者均进行肝活组织检查,以病理检查结果与肝脏的实时超声弹性测值进行比较,计算ARFI技术诊断肝纤维化的灵敏度,特异度,取敏感度和特异度之和最大时为最佳界限值.应用SPSS10.0统计学软件进行统计学处理,多组间比较根据数据是否正态分布及方差齐性来选择采用参数或非参数检验分析,相关性分析采用spearman相关分析. 结果 慢性丙型肝炎患者肝纤维化分期S1 ～ S4期的ARFI平均值分别为(1.26±0.27) m/s(n=36)、(1.45±0.51) m/s(n=31)、(2.01±0.54)m/s(n=27)和(2.28±0.82) m/s(n=14),组间比较,秩和检验KW=42.307,P＜0.01.肝脏ARFI测值与肝纤维化分期相关,相关系数为0.61,P＜0.01.ARFI技术诊断慢性丙型肝炎肝纤维化S≥2,S≥3和S=4的受试者工作特征曲线下面积分别为0.779,0.863和0.880.结论 ARFI可较准确的定量评价慢性丙型肝炎肝纤维化程度,具有良好的临床应用前景.     

Simpler score of routine laboratory tests predicts liver fibrosis in patients with chronic hepatitis B

Background and Aim: In recent years, a great interest has been dedicated to the development of noninvasive predictive models to substitute liver biopsy for fibrosis assessment and follow‐up. Our aim was to provide a simpler model consisting of routine laboratory markers for predicting liver fibrosis in patients chronically infected with hepatitis B virus (HBV) in order to optimize their clinical management. Methods: Liver fibrosis was staged in 386 chronic HBV carriers who underwent liver biopsy and routine laboratory testing. Correlations between routine laboratory markers and fibrosis stage were statistically assessed. After logistic regression analysis, a novel predictive model was constructed. This S index was validated in an independent cohort of 146 chronic HBV carriers in comparison to the SLFG model, Fibrometer, Hepascore, Hui model, Forns score and APRI using receiver operating characteristic (ROC) curves. Results: The diagnostic values of each marker panels were better than single routine laboratory markers. The S index consisting of γ‐glutamyltransferase (GGT), platelets (PLT) and albumin (ALB) (S‐index: 1000 × GGT/(PLT × ALB²)) had a higher diagnostic accuracy in predicting degree of fibrosis than any other mathematical model tested. The areas under the ROC curves (AUROC) were 0.812 and 0.890 for predicting significant fibrosis and cirrhosis in the validation cohort, respectively. Conclusions: The S index, a simpler mathematical model consisting of routine laboratory markers predicts significant fibrosis and cirrhosis in patients with chronic HBV infection with a high degree of accuracy, potentially decreasing the need for liver biopsy.     

Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: a pilot study

Background: Acoustic radiation force impulse (ARFI) is a new technology integrated into conventional B‐mode ultrasonography. ARFI is used to evaluate tissue stiffness in several organs, but this method has not been applied for liver fibrosis. Aim: The aim of this study was to determine whether ARFI elastography is useful for the evaluation of liver fibrosis. Methods: This study enrolled 55 consecutive patients with chronic liver disease who underwent a liver biopsy for histological assessment of liver fibrosis by the Metavir scoring system. Liver stiffness of the 55 patients and 25 healthy volunteers was evaluated by ARFI elastography and was expressed as the shear wave velocity. Cut‐off values were determined using receiver‐operating characteristic (ROC) curves. Results: Histological liver fibrosis was evaluated by Metavir scoring; F0: six cases, F1: 14 cases, F2: nine cases, F3: nine cases and F4: 17 cases. Liver stiffness determined by ARFI elastography was correlated with histological liver fibrosis (P<0.0001). The areas under the ROC curves were 0.94 (95% confidence intervals, 0.87–0.99) for F2–F4, 0.94 (0.88–0.99) for F3–F4 and 0.96 (0.91–1.01) for F4. The cut‐off values of the shear wave velocity were as follows: >1.34 m/s for F2–F4 (sensitivity 91.4%, specificity 80%); >1.44 m/s for F3–F4 (sensitivity 96.2%, specificity 79.3%); and >1.80 m/s for F4 (sensitivity 94.1%, specificity 86.8%). Conclusions: Ultrasonic ARFI elastography is a novel, non‐invasive and reliable method for the assessment of liver fibrosis in patients with chronic liver disease.     

Noninvasive assessment of liver steatosis, fibrosis and inflammation in chronic hepatitis C virus infection.

BACKGROUND: Duplex-Doppler ultrasound is a noninvasive method for the assessment of hepatic hemodynamics beyond conventional gray-scale imaging. The clinical value of the method for the grading and staging of chronic hepatitis C virus (HCV) infection and the prediction of hepatic steatosis still has to be determined. This study aimed to compare Duplex-Doppler and ultrasound with the histologic staging and the estimation of hepatic steatosis in chronic HCV infection. PATIENTS AND METHODS: One hundred and nineteen consecutive patients with chronic HCV infection underwent both liver biopsy and ultrasound with Duplex-Doppler. Maximum portal venous blood flow velocity, portal venous flow undulation, hepatic venous flow pattern and spleen size were assessed and compared with histologic findings. Histologic grading and staging was performed according to the modified HAI and hepatic steatosis was estimated. RESULTS: Doppler ultrasound was unable to discriminate between different degrees of fibrosis. Sensitivity/specificity of portal venous flow and undulations for the diagnosis of hepatic cirrhosis was 74.5%/53% and 76.5%/100%. The PPV and NPV of reduced undulations was 100% and 96.2%. Mono- or biphasic hepatic venous flow indicated advanced hepatic steatosis (sensitivity 88.2%, specificity 74.5%, PPV 36.6%, NPV 97.5%). Spleen size was significantly enlarged both in patients with cirrhosis and steatosis. CONCLUSIONS: Although Duplex-Doppler of the portal and hepatic veins is not a substitute for histologic grading and staging, portal vein undulations can predict liver cirrhosis with considerable accuracy. Moreover, triphasic patterns of hepatic venous flow virtually exclude significant fatty liver disease. Additional studies should perform intraindividual follow-up investigations to further define the role of Duplex-Doppler ultrasound in chronic HCV infection.     

慢性乙型肝炎肝纤维化无创性诊断模型的建立

目的建立由临床及血清指标组成的综合诊断模型，以无创性的评估慢性乙型肝炎肝纤维化。方法慢性乙型肝炎患者270例，随机分成模型组（195例）和验证组（75例），均行肝活组织检查及病理分期，并按纤维化程度设定不同判别终点（≥S2，≥S3，S4），同时检测、记录26项临床和实验室常用指标，包括年龄、性别、血常规、生化、凝血酶原时间、病毒载量及血清纤维化四项标志物等参数。在模型组，对指标依次行单因素分析和多因素Logistic回归分析，筛选出与研究终点相关的独立预测因子，在此基础上构建诊断肝纤维化的指数模型，最后在独立的验证组中检验模型的诊断效率。结果在模型组，建立了一个由年龄、血小板计数、γ-谷氨酰转肽酶和透明质酸四项指标构成的判别肝纤维化程度的指数模型（FibroIndex）。受试者工作特征曲线（ROC）分析显示，FibroIndex判别≥s3的ROC曲线下面积（AUC）为0．889，以积分3．0为界值，诊断的敏感性90．2％，特异性76．1％，准确性82．0％，且其积分与肝纤维化分期呈良好的正向线性相关（r=0．731，p〈0．01）I该指数判别≥s2和s4的界值分别为2．2、5．4，诊断的AUC分别为0．873．0．872，敏感性、特异性分别为79％、82％和83％、75％。将FibroIndex以同样标准应用于验证组，其与模型组AUC比较差异无统计学意义，两组的诊断效率总体上相近。结论运用无创诊断模型评价慢性肝炎肝纤维化严重程度具有敏感、准确和可重复性，并有望在一定程度上替代肝活组织检查来监测慢性乙型肝炎肝纤维化的动态变化。