Quantitative Assessment of Hepatic Fibrosis by Contrast-enhanced Ultrasonography

Objective To explore the contrast-enhanced ultrasonographic features for quantitative assessment of hepatic fibrosis. Methods 86 patients with chronic viral hepatitis B were enrolled in this study from March 2007 to August 2009. The patients were classified into 5 groups (S0-S4) according to fibrosis stage evaluated with ultrasound guided liver biopsy. New contrast-enhanced ultrasonography (CEUS) features including area under the time-intensity curve (TIC) of portal venous phase/hepatic arterial phase (Qp/Qa) and intensity of portal venous phase/hepatic arterial phase (Ip/Ia) were used to detect the blood supply ratio (portal vein/hepatic artery) in each group. Arrival time of portal vein trunk (Tp) and decreasing rate of TIC (β ) were also analyzed. Results Qp/Qa and Ip/Ia decreased from S0 to S4, while Tp and β increased. These 4 features were significantly correlated with the degree of fibrosis (P<0.001) and were significantly different among the five groups (P<0.001). Sensitivity and specificity of Ip/Ia were 80% and 86% for groups ≥S1, 75% and 86% for groups ≥ S2, 71% and 84% for groups ≥ S3, and 76% and 80% for group S4, respectively. Sensitivity and specificity of Qp/Qa were 70% and 88% for groups ≥ S1, 80% and 76% for groups ≥ S2, 74% and 70% for groups ≥ S3, and 81% and 95% for group S4, respectively. Conclusion Ip/Ia and Qp/Qa could be adopted as reliable, non-invasive features for quantitative assessment of hepatic fibrosis.

Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis

AIM: To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound(CEUS) in a canine model.METHODS: Liver fibrosis was established in adult canines(Beagles; n = 14) by subcutaneous injection of carbon tetrachloride(CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases(Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures(FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Q p/Q a and I p/I a.RESULTS: Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0(n = 3), F1(n = 12), F2(n = 14), F3(n = 11), and F4(n = 2). There were significant differences in the measurements of Qp/Qa(19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia(1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively(all P < 0.001). There were statistically significant negative correlations between FPP and Q p/Q a(r =-0.707, P < 0.001), and between FPP and Ip/Ia(r =-0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Q p/Q a and I p/I a was highly sensitive, as assessed by the area under the receiveroperating curve(0.866 and 0.895, respectively).CONCLUSION: C E U S i s a p o t e n t i a l m e t h o d t o accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

Analysis of B-ultrasound and contrast-enhanced ultrasound characteristics of different hepatic neuroendocrine neoplasm

BACKGROUND Hepatic neuroendocrine neoplasm(hNEN) is a highly heterogeneous tumor. The exact identification of the source and malignant degree of hNEN is important.However, there is a lack of information regarding diagnosis of hNEN with imaging. In addition, no studies have compared the imaging between hNEN and hepatocellular carcinoma(HCC) and among different sources and malignant degrees of hNEN.AIM To compare the ultrasound characteristics between hNEN and HCC and among different sources and malignant degrees of hNEN.METHODS A total of 55 patients with hNEN were recruited and defined as the hNEN group.Among them, 35 cases of hNET were defined as the hNET group. Twenty cases of hepatic neuroendocrine carcinoma(hNEC) were defined as the hNEC group.Among the 55 lesions, 29 were transferred from the pancreas, 20 were from the gastrointestinal tract, and six were from other sites. In total, 55 patients with HCC were recruited and defined as the HCC group. The characteristic differences of Bmode ultrasound and contrast-enhanced ultrasound(CEUS) between hNEN and HCC and among different sources and malignant degrees of hNEN were compared.RESULTS In the hNEN group, the proportions of multiple liver lesions, unclear borders,and high echo lesions were higher than those in the HCC group. The proportions of non-uniform echo and peripheral acoustic halo were lower than those in the HCC group(P < 0.05). The washout to iso-enhancement time and washout to hypo-enhancement time were lower than those in the HCC group(P < 0.05). The characteristics of B-ultrasound and CEUS among different sources of hNEN were similar, and the differences were not statistically significant(P > 0.05). B-mode ultrasound characteristics of hNET and hNEC were similar. The proportions of low enhancement at portal venous phase, non-uniform enhancement forms, and combined tumor vasculature in the hNEC group were larger than those in the hNEN group(P < 0.05).CONCLUSION Compared with HCC, hNEN showed multiple intrahepatic lesions, uniform high echo, uniform high enhancement at arterial phase, and rapid washout. Low enhancement at portal venous phase, overall non-uniform enhancement form,and the proportion of combined tumor vasculature in hNEC were larger than those in hNET.

Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.

Assessing significant fibrosis using imaging-based elastography in chronic hepatitis B patients: Pilot study

BACKGROUND Accurate detection of significant fibrosis(fibrosis stage 2 or higher on the METAVIR scale)is important especially for chronic hepatitis B(CHB)patients with high viral loads but with normal or mildly elevated alanine aminotransferase(ALT)levels because the presence of significant fibrosis is accepted as the indication for antiviral treatment.Liver biopsy is the reference standard for diagnosing significant fibrosis,but it is an invasive procedure.Consequently,noninvasive imaging-based measurements,such as magnetic resonance elastography(MRE)or two-dimensional shear-wave elastography(2DSWE),have been proposed for the quantitative assessment of liver fibrosis.AIM To explore MRE and 2D-SWE to identify fibrosis stage,and to compare their performance with that of serum-based indices.METHODS The study enrolled 63 treatment-na?ve CHB patients with high viral loads but with normal or mildly elevated ALT levels who underwent liver biopsy before a decision was made to initiate antiviral therapy.MRE and 2D-SWE were performed,and serum-based indices,such as FIB-4 and aspartate transaminase to platelet ratio index(APRI),were calculated.The diagnostic performances of MRE,2D-SWE,FIB-4,and APRI for assessing significant fibrosis(≥F2)and cirrhosis(F4)were evaluated with liver histology as the reference standard,using receiver operating characteristic analyses.RESULTS The liver fibrosis stage was F0/F1 in 19,F2 in 14,F3 in 14,and F4 in 16 patients,respectively.MRE significantly discriminated F2 from F0/1(P=0.022),whereas 2D-SWE showed a broad overlap in distinguishing those stages.MRE showed a higher correlation coefficient value with fibrosis stage than 2D-SWE with fibrosis stage(0.869 vs 0.649,Spearman test;P<0.001).Multivariate linear regression analyses showed that fibrosis stage was the only factor affecting the values of MRE(P<0.001),whereas body mass index(P=0.042)and fibrosis stage(P<0.001)were independent factors affecting 2D-SWE values.MRE performance for diagnosing significant fibrosis was better[area under the curve(AUC)=0.906,positive predictive value(PPV)97.3%,negative predictive value(NPV)69.2%]than that of FIB-4(AUC=0.697,P=0.002)and APRI(AUC=0.717,P=0.010),whereas the performance of 2D-SWE(AUC=0.843,PPV 86%,NPV 65%)was not significantly different from that of FIB-4 or APRI.CONCLUSION Compared to SWE,MRE might be more precise non-invasive assessment for depicting significant fibrosis and for making-decision to initiate antiviral-therapy in treatment-na?ve CHB patients with normal or mildly-elevated ALT levels.

Clinical diagnosis and treatment of alpha-fetoprotein-negative small hepatic lesions

Objective： We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha- fetoprotein （AFP）-negative small hepatic lesions. Background： Small hepatic lesions （less than 2 cm in diameter） usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result. Methods： A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography （DSA）, dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）, contrast-enhanced ultrasound （CEUS）, or positron emission tomography-computed tomography （PET-CT） based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. Results： Hepatocellular carcinoma （HCC） diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively. Conclusions： DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

Ultrasound findings in autoimmune hepatitis

Ultrasound findings in autoimmune hepatitis(AIH) have not been reported systematically so far. The use of reliable and accurate noninvasive methods for determining fibrosis stage is important in evaluation of treatment efficacy and fibrosis regression in AIH. Imaging plays an important role in detection of complications and ruling out other possible causes of chronic liver diseases. Ultrasound elastography cutoff values in AIH patients are not the same as those in patients with chronic viral hepatitis or non-alcoholic fatty liver disease. AIH is characterized by wide fluctuations in inflammatory activity. Here we report on current knowledge of ultrasound findings in AIH.

Insulin-like growth factor binding protein related protein 1 knockdown attenuates hepatic ?brosis via the regulation of MMPs/TIMPs in mice

Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.

瞬时弹性成像技术对乙肝及自身免疫性肝病诊断效能对比分析

目的 探讨瞬时弹性成像技术(fibrotouch,FT)对乙型肝炎及自身免疫性肝病诊断效能对比价值。方法 选取我院收治的乙型肝炎患者59例(A组)、原发性胆汁性胆管炎患者31例(B组),两组均接受肝组织穿刺病理检查,获取患者病理纤维化程度分期;分别对两组进行FT检查,获得两组患者的肝硬度值(LSM),尝试分析患者LSM与病理纤维化分期的关联及差异。结果 两组患者的肝细胞炎症程度、肝组织纤维化变化基本趋于一致,Pearson分析结果显示,炎症、纤维化程度呈正相关(P<0.05);两组无纤维化、轻中度、重度纤维化患者的肝硬度值呈上升趋势,病理分期越严重,LSM越大,且不同病理分期LSM差异有统计学意义(t=234.599,321.819;均P<0.001);两组患者LSM:A组无纤维化、中轻度及重度纤维化患者LSM均低于B组,其中S0分期差异无统计学意义(t=1.780;P=0.079);S1~S2、S3~S4分期差异具有统计学意义(t=8.352,6.392;P<0.001)。结论 FT为无创、定量评估肝病患者肝脏纤维化程度的有效方式,为临床诊治提供科学依据;肝纤维化程度越高则FT检查提示LSM越高;同一病理分期下,乙型肝炎、原发性胆汁性胆管炎患者LSM存在差异;后续可尝试构建不同类型肝炎患者FT检查肝脏损伤程度参考标准。

超声造影在器官纤维化评价中的应用研究进展

许多器官的慢性疾病发展至严重并发症阶段的共同病理特征为组织纤维化。在慢性疾病的早期阶段,纤维化具有可逆性,早期评价纤维化程度对器官慢性疾病的诊断、治疗和预后具有十分重要的意义。超声造影及近来快速发展的超声分子成像新技术在评估一些器官纤维化程度方面取得了一定的研究进展,从而为无创性超声检查技术提供了广阔的发展和临床应用前景。本文就超声造影在肝、肾、心等器官纤维化中的应用进行综述。

实时二维超声剪切波弹性成像在慢性乙型肝炎肝纤维化分期中的临床应用

目的探讨实时二维超声剪切波弹性(2D shear wave elasticity,2D-SWE)成像检测杨氏模量在慢性乙型肝炎(chronic hepatitis b,CHB)肝纤维化分期中的应用价值。方法选取我院2019年1月至2022年12月诊治为CHB肝纤维化分期患者117例,分别行二维超声检查及2D-SWE检查,二维超声以M0、M1为阴性,以M2、M3、M4为阳性组,SWE以E1级为阴性组,以E2、E3、E4级为阳性组,进行对比研究,并观察SWE杨氏模量值与病理分期的相关性。结果2D-SWE与二维超声评估CHB肝纤维化相比,诊断效能明显提高,ROC曲线下面积分别为:0.915、0.752,P值均<0.05,具有统计学意义;SWE弹性模量与病理分期成正相关,r值0.903。结论2D-SWE在评价慢性乙型肝炎肝纤维化中,与临床病理分期具有高度相关性,且比二维超声具有更可靠的诊断价值。

超声弹性成像结合血清指标评估慢性乙型肝炎患者乙肝纤维化的应用研究

目的探讨超声弹性成像结合血清指标评估慢性乙型肝炎患者肝纤维化的应用效果。方法选取2022年4月—2023年4月在扬州市第三人民医院肝病科确诊为显著性肝纤维化的66例慢性乙型肝炎患者为试验组,同期临床确诊为非显著性肝纤维化的66例慢性乙型肝炎患者为对照组。2组患者均行肝脏超声弹性成像检测,同时检测血清相关指标。比较2组杨氏模量值等超声弹性成像检查结果和相关血清学指标。结果肝脏超声弹性成像检测结果显示,试验组杨氏模量值(9.26±1.43)kPa、肝纤维化指数肝纤维指数(liver fibrosis index,LF Index)(2.85±1.23)水平显著高于对照组[(5.56±1.35)kPa、(2.14±0.43)],差异有统计学意义(P<0.001)。试验组肝功能指标血清透明质酸(hyaluronic acid,HA)、层粘连蛋白(laminin,LN)、Ⅳ型胶原(typeⅣcollagen,Ⅳ-C)、Ⅲ型前胶原氨基端肽水平(level of amino terminal peptide of typeⅢprocollagen,PⅢP)[(86.36±12.24)μg/L、(64.38±8.96)μg/L、(72.03±11.12)μg/L、(13.42±4.02)μg/L]水平高于对照组[(45.41±10.35)μg/L、(51.12±10.23)μg/L、(48.25±13.02)μg/L、(8.02±1.39)μg/L],差异有统计学意义(P<0.001)。试验组谷草转氨酶(glutamic oxaloacetic transaminase,AST)、谷丙转氨酶(glutamic-pyruvic transaminase,ALT),γ-谷氨酞转肽酶(γ-glutathione transdermal enzyme,GGT)、碱性磷酸酶(alkaline phosphatase,ALP)[(25.62±4.22)U/L、(33.56±3.43)U/L、(22.76±3.06)U/L、(73.92±8.63)U/L]高于对照组[(18.36±4.96)U/L、(20.36±4.23)U/L、(18.38±2.64)U/L、(52.31±10.25)U/L],差异有统计学意义(P<0.001)。试验组三酰甘油(triacylglycerol,TG)、胆固醇(cholesterol,CHOL)水平[(1.03±0.31)mmol/L、(4.33±0.52)mmol/L]低于对照组[(1.83±0.29)mmol/L、(5.02±0.38)mmol/L],差异有统计学意义(P<0.001)。结论慢性乙型肝炎患者肝纤维化存在超声弹性成像结果改变,且伴有血清指标异常变化,两者联合诊断可为肝纤维化评估与预测提供参考依据。

多模态影像技术对大鼠肝纤维化评估的实验研究

目的:探讨多模态影像技术对大鼠肝纤维化(HF)的评估价值。方法:选取健康雄性(SD)大鼠48只,采用随机数表法将其均分为对照组、M1模型组、M2模型组和M3模型组,共4组,每组12只。M1、M2和M3模型组采用四氯化碳(CCl4)加乙醇复合法进行诱导,制备肝纤维化模型。分别在造模第4、6和8周时,M1模型组进行超声检测,M2模型组进行动态增强磁共振影像(DCE-MRI)检测,M3模型组采用常规超声、超声弹性成像联合DCE-MRI技术检测。对照组大鼠随机分为3组,每组4只,分别与M1、M2、M3组大鼠进行对照。影像检查结束后取肝组织行HE染色,观察模型组大鼠肝脏纤维化的程度。采用常规超声观察大鼠肝脏形态,测量门静脉主干内径。彩色多普勒测量门静脉血流速度。超声弹性观察肝实质硬度颜色分布、测量肝脏实质的弹性值。采用受试者工作特征(ROC)初始曲线下面积(iAUC)分析DCE-MRI检查中血流动力参数容量转运常数(Ktrans)、速率常数(Kep)和血管外细胞外间隙体积百分数(Ve)的诊断效能。结果:常规超声显示,对照组大鼠肝脏无异常变化,M1组大鼠肝脏形态发生改变。超声弹性成像显示:M1组大鼠肝脏弹性值(33.16kPa)随着纤维化程度的加重而呈上升趋势,且高于对照组(13.11kPa)。M2组常规MRI显示:对照组大鼠肝脏形态正常,M2组中,造模6与8周大鼠较4周大鼠肝脏形态改变更明显。DCE-MRI结果中的ROC曲线分析显示,Ktrans与Ve对肝纤维化具有较高的诊断效能,其iAUC均>0.9。M1模型组、M2模型组、M3模型组大鼠进行组间比较,多模态影像技术对大鼠早期肝纤维化诊断的灵敏度、准确率、阳性预测值、阴性预测值均高于单独的检查手段,差异有统计学意义(χ^(2)=0.634、0.644、0.621、0.543,P<0.05)。HE染色结果显示,模型组大鼠肝组织出现不同程度的纤维增生。结论:多模态影像技术可以作为评价肝脏纤维化的有效检测方法。

超声弹性成像联合血清Mac-2结合蛋白糖基化异构体、NADPH氧化酶2对慢性乙型肝炎患者肝纤维化的诊断价值

目的探讨超声弹性成像联合血清Mac-2结合蛋白糖基化异构体(Mac-2 binds protein glycosylated isomers,M2BPGi)、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NADPH oxidase 2,NOX2)对慢性乙型肝炎(chronic hepatitis B,CHB)患者肝纤维化的诊断价值。为肝纤维化的诊断提供参考依据。方法选取宜昌市第三人民医院于2021年1月—2023年3月期间收治的175例CHB患者为研究对象,并根据肝纤维化程度分为非显著性肝纤维化组(n=67)和显著性肝纤维化组(n=108)。多因素Logistic回归分析法分析发生显著性肝纤维化的影响因素;超声弹性成像联合血清M2BPGi、NOX2水平对显著性肝纤维化的诊断价值采用受试者工作特征(receiver operating characteristic,ROC)曲线分析。结果非显著性肝纤维化组和显著性肝纤维化组丙氨酸氨基转移酶(alanine transaminase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、白蛋白(albumin,ALB)和血小板计数(platelet count,PLT)比较差异均具有统计学意义(P均<0.05);与非显著性肝纤维化组比较,显著性肝纤维化组患者应变均值(mean strain value,MEAN)和峰度明显较低(P<0.05),偏度、复杂度(complexity,COMP)、对比度、标准差、蓝色区域面积比(ratio of blue area,AREA)和血清M2BPGi和NOX2水平均明显较高(P<0.05)。血清M2BPGi、NOX2、ALT、COMP、AREA是影响CHB患者发生显著性肝纤维化的独立危险因素,而PLT和MEAN是其保护因素(P<0.05)。ROC分析结果显示,M2BPGi、NOX2、MEAN、COMP和AREA联合诊断显著性肝纤维化的AUC为0.933,显著大于各指标单独诊断的AUC(P<0.05)。结论M2BPGi和NOX2在发生显著性肝纤维化的CHB患者血清中的水平较高,2者联合超声弹性成像对显著性肝纤维化具有较高的诊断价值。

Performance of liver stiffness measurements by transient elastography in chronic hepatitis

AIM:To compare results of liver stiffness measurements by transient elastography(TE) obtained in our patients population with that used in a recently published meta-analysis.METHODS:This was a single center cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy at the outpatient ward of our Infectious Diseases Department were enrolled.TE was carried out by using FibroScan(Echosens,Paris,France).Liver biopsy was performed on the same day as TE,as day case procedure.Fibrosis was staged according to the Metavir scoring system.The diagnostic performance of TE was assessed by using receiver operating characteristic(ROC) curves and the area under the ROC curve analysis.RESULTS:Two hundred and fifty-two patients met the inclusion criteria.Six(2%) patients were excluded due to unreliable TE measurements.Thus,246(171 men and 75 women) patients were analyzed.One hundred and ninety-five(79.3%) patients had chronic hepatitis C,41(16.7%) had chronic hepatitis B,and 10(4.0%) were coinfected with human immunodeficiency virus.ROC curve analysis identified optimal cut-off value of TE as high as 6.9 kPa forF ≥ 2;7.9 kPa forF ≥ 3;9.6 kPa for F = 4 in all patients(n = 246),and as high as 6.9 kPa for F ≥ 2;7.3 kPa for F ≥ 3;9.3 kPa for F = 4 in patients with hepatitis C(n = 195).Cut-off values of TE obtained by maximizing only the specificity were as high as 6.9 kPa for F ≥ 2;9.6 kPa for F ≥ 3;12.2 kPa for F = 4 in all patients(n = 246),and as high as 7.0 kPa forF ≥ 2;9.3 kPa forF ≥ 3;12.3 kPa forF = 4 in patients with hepatitis C(n = 195).CONCLUSION:The cut-off values of TE obtained in this single center study are comparable to that obtained in a recently published meta-analysis that included up to 40 studies.

CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.METHODS: This prospective study included 15 patients with NAFLD, 17 patients with NASH and 16 healthy controls.In each patient, real-time ultrasound was used to locate the portal vein (PV) and the right liver lobe, and 5 mL of SonoVue? was then injected intravenous in a peripheral vein of the left arm over a 4-s span. Digital recording was performed for 3 min thereafter. The recording was subsequently retrieved to identify an area of interest in the PV area and in the right liver parenchyma(LP) to assess the blood flow by processing the data using dedicated software (Qontrast?, Bracco, Italy).The following parameters were evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP, s), regional blood volume (RBV, cm3), regional blood flow (RBF, cm3/s) and mean transit time (MTT, s).At 24-48 h post-injection, liver stiffness was evaluated using Fibroscan and measured in kPa. The statistical evaluation was performed using Student’s t test.RESULTS: In the PV, the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patientscompared with the controls (Peak%: NAFLD 26.3 ± 6.6,NASH 28.1 ± 7.3 vs controls 55.8 ± 9.9, P < 0.001;RBV: NAFLD 4202.3 ± 3519.7, NASH 3929.8 ± 1941.3vs controls 7473 ± 3281, P < 0.01; RBF: NAFLD 32.5± 10.8, NASH 32.7 ± 12.1 vs controls 73.1 ± 13.9, P< 0.001). The TTP in the PV was longer in both patient groups but reached statistical significance only in the NASH patients compared with the controls (NASH 79.5± 37.8 vs controls 43.2 ± 30, P < 0.01). In the LP,the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patients compared with the controls (Peak%: NAFLD 43.2 ± 7.3, NASH 41.7 ± 7.7 vs controls 56.6 ± 6.3, P < 0.001; RBV: NAFLD 4851.5± 2009, NASH 5069.4 ± 2292.5 vs controls 6922.9 ±2461.5, P < 0.05; RBF: NAFLD 55.7 ± 10.1, NASH 54.5 ± 12.1 vs controls 75.9 ± 10.5, P < 0.001). The TTP was longer in both patient groups but did not reach statistical significance. The MTT in both the PV and LP in the NAFLD and NASH patients was not different from that in the controls. Liver stiffness was significantly increased relative to the controls only in the NASH patients(NASH: 6.4 ± 2.2 vs controls 4.6 ± 1.5, P < 0.05).CONCLUSION: Blood flow derangement within the liver present not only in NASH but also in NAFLD suggests that a vascular flow alteration precedes liver fibrosis development.

Liver ultrasound elastography: More than staging the disease

Ultrasound elastography is perhaps the most important breakthrough in the evolution of ultrasonography in the last 15 years. Since transient elastography was introduced, many other methods have been developed and became more and more widely available. The value of ultrasound elastography in staging a chronic liver disease has been established by numerous studies. There have been many studies that have shown that using liver elastography it is possible to predict thepresence of the complications of cirrhosis: portal hypertension, presence of esophageal varices(and even their risk of bleeding) and hepatocellular carcinoma. It has been shown that liver elastography can predict the progression of liver fibrosis and also the survival(hepatic events- free) of the patients with chronic liver diseases. These are the real quests of the clinicians, this is the ultimate scope of any medical investigation-to predict the outcome of a patient and to help making therapeutic decisions. I brought together only a small amount of the data that has already been written on this subject to support my affirmation that liver ultrasound elastography is more than a tool for staging the liver disease, but it is also comparable to a crystal ball which in the hands of a skilled clinician can reveal the future of the patient and can help to improve this future.

Assessment of liver disease in patients with chronic hepatitis C and unhealthy alcohol use

Hepatitis C virus(HCV)infection and unhealthy alcohol use are major drivers of the burden of liver disease worldwide and commonly co-occur.Assessment of underlying liver damage is a cornerstone of the clinical care of patients with chronic HCV infection and/or unhealthy alcohol use because many of them are diagnosed at advanced stages of disease.Early diagnosis of liver disease before decompensated liver cirrhosis becomes established is essential for treatment with direct acting antivirals and/or abstinence from alcohol consumption,which are the main therapeutic approaches for clinical management.In this review,we discuss current knowledge around the use of non-invasive methods to assess liver disease,such as abdominal ultrasound,controlled attenuation parameter,transient elastography,magnetic resonance imaging,and indices based on serum markers of liver injury.

超声弹性成像评估自身免疫性肝炎患者肝纤维化分期价值分析

目的 探讨采用超声弹性成像(UE)检测评估自身免疫性肝炎(AIH)患者肝纤维化分期的价值。方法 2017年3月~2022年3月我院诊治的AIH患者58例,均接受肝穿刺组织病理学检查,采用METAVIR标准评估肝纤维化分期。使用超声诊断仪进行肝脏硬度检查,获得病灶处剪切波速度(SWV)。常规检测血清和血液学指标,计算天冬氨酸氨基转移酶与血小板计数比值指数(APRI)。应用受试者工作特征曲线下面积(AUC)评估各指标诊断肝纤维化的效能。结果 经肝组织病理学检查,在AIH患者中发现F0期肝纤维化7例(12.1%)、F1期15例(25.9%),即无显著性肝纤维化22例(37.9%),F2期17例(29.3%)、F3期13例(22.4%)和F4期6例(10.3%),即显著性纤维化36例(62.1%);显著性肝纤维化组外周血血小板(PLT)计数为(119.7±26.4)×10^(9)/L,显著低于无肝纤维化组【(180.9±31.2)×10^(9)/L,P<0.05】,APRI为(3.6±1.1),显著高于无肝纤维化组【(2.7±0.8),P<0.05】,SWV为(1.7±0.3)m/s,显著高于无肝纤维化组【(1.2±0.2)m/s,P<0.05】;分别以PLT计数<120.0×10^(9)/L、APRI≥3.0和SWV≥1.6 m/s为截断点,诊断AIH患者显著性肝纤维化的AUC分别为0.74、0.75和0.95,敏感度分别为66.7%、75.0%和91.7%,特异度分别为77.3%、68.2%和86.4%,其中以SWV的诊断效能最高(P<0.05)。结论 采用UE检测SWV评估AIH患者肝纤维化分期有一定的应用价值,有望成为无创性定量诊断肝纤维化程度的重要指标,值得进一步研究。

瞬时弹性成像联合APRI诊断自身免疫性肝炎患者肝纤维化效能研究

目的探讨应用天冬氨酸氨基转移酶/血小板计数比值(APRI)联合瞬时弹性成像行肝硬度检测(LSM)诊断自身免疫性肝炎(AIH)患者肝纤维化的效能。方法2019年8月~2022年8月我院诊治的AIH患者67例和同期健康体检者54例。AIH患者接受肝活检,所有受试者接受FibroScan肝脏弹性成像和血液检测,获得LSM和APRI。绘制受试者工作特征曲线(ROC),计算曲线下面积(AUC),评估参数诊断显著性肝纤维化的效能。结果AIH组血清AST水平为(104.3±21.9)U/L,显著高于对照组【(30.5±5.1)U/L,P<0.05】,APRI和LSM分别为(1.4±0.1)和(8.1±1.2)kPa,显著大于对照组【分别为(0.4±0.1)和(4.3±0.7)kPa,P<0.05】,而外周血PLT计数为(157.8±23.1)×10^(9)/L,显著低于对照组【(208.5±20.7)×10^(9)/L,P<0.05】;肝组织病理学检查显示,67例AIH患者存在肝纤维化S0期10例、S1期17例、S2期19例、S3期13例和S4期8例;S4期患者APRI和LSM分别为(2.1±0.3)和(13.9±2.8)kPa,S3期分别为(1.8±0.2)和(11.2±2.1)kPa,S2期分别为(1.5±0.2)和(7.6±1.5)kPa,均显著高于S1期【分别为(1.1±0.2)和(6.1±1.2)kPa,P<0.05】或S0期【分别为(0.8±0.1)和(4.0±0.5)kPa,P<0.05】;经ROC分析显示,分别以APRI=1.5和LSM=7.5 kPa为截断点,两者联合诊断显著性肝纤维化的AUC为0.950,其敏感度和特异度分别为95.0%和85.2%,显著优于APRI(其敏感度和特异度分别为90.0%和81.5%)或LSM(其敏感度和特异度分别为75.0%和96.3%)诊断。结论应用LSM联合APRI诊断AIH患者显著性肝纤维化具有较高的临床应用价值,或可用于初筛检查。