瞬时弹性扫描诊断肝纤维化准确性研究

目的验证瞬时弹性扫描（FibroScan）诊断肝纤维化的准确性。方法选取141例慢性肝病患者,每例均进行肝脏活体组织检查,并应用瞬时弹性扫描仪测量肝脏硬度,以病理检查结果为金标准,验证FibroScan诊断肝纤维化的准确性。结果肝脏硬度与肝纤维化程度密切相关,Kendall相关系数为0．74（P=0．001）。FibroScan诊断肝纤维化F1～F4、F2～F4、F3～F4、F4期的受试者工作特征曲线下面积分别为0．97、O．96、0．99、0．97。结论FibroScan诊断肝纤维化有较好的准确性。     

The combination of a blood test and Fibroscan improves the non‐invasive diagnosis of liver fibrosis

Background and aims: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm. Methods: Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included. Five blood fibrosis tests were evaluated: APRI, FIB‐4, Hepascore, Fibrotest and FibroMeter. The reference was fibrosis Metavir staging. Results: Diagnosis of significant fibrosis (Metavir F≥2). The most accurate synchronous combination was FibroMeter+LSE, which provided a significantly higher area under the receiver operating characteristic curve (0.892) than LSE alone (0.867, P=0.011) or Fibrometer (0.834, P<10^?3). An algorithm using the FibroMeter+LSE combination and then a liver biopsy in indeterminate cases had 91.9% diagnostic accuracy and required significantly fewer biopsies (20.2%) than previously published Bordeaux algorithm (28.6%, P=0.02) or sequential algorithm for fibrosis evaluation (SAFE) (55.7%, P<10^?3). The Angers algorithm performance was not significantly different between viral hepatitis and other causes. Diagnosis of cirrhosis. The most accurate synchronous combination was LSE+FibroMeter, which provided ≥90% predictive values for cirrhosis in 90.6% of patients vs 87.4% for LSE (P=0.02) and 57.9% for FibroMeter (P<10^?3). An algorithm including the LSE+FibroMeter combination, and then a liver biopsy in indeterminate cases, had a significantly higher diagnostic accuracy than the SAFE algorithm (91.0 vs 79.8%, P<10^?3), and required significantly fewer biopsies than the Bordeaux algorithm (9.3 vs 25.3%, P<10^?3). Conclusion: The synchronous combination of a blood test plus LSE improves the accuracy of the non‐invasive diagnosis of liver fibrosis and, consequently, markedly decreases the biopsy requirement in the diagnostic algorithm, notably to <10% in cirrhosis diagnosis.     

Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients

Failure of liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) and unreliable results occur in ≈ 5% and 15% of patients, respectively, mainly due to obesity. In this multicenter study, we evaluated the feasibility and performance of the novel FibroScan XL probe in 276 patients with chronic liver disease (42% viral hepatitis, 46% nonalcoholic fatty liver disease [NAFLD]) and a body mass index (BMI) ≥ 28 kg/m(2) . Patients underwent liver biopsy and TE with the standard M and XL probes. TE failure was defined as no valid LSMs and unreliable examinations as <10 valid LSMs or an interquartile range (IQR)/LSM >30% or success rate <60%. Probe performance for diagnosing ≥ F2 fibrosis and cirrhosis (F4) versus biopsy were examined using areas under receiver operating characteristic curves (AUROC). FibroScan failure was less frequent with the XL probe than the M probe (1.1% versus 16%) and the XL probe was more often reliable (73% versus 50%; both P < 0.00005). Reliable results with the XL probe were obtained in 61% of patients in whom the M probe was unreliable. Among 178 patients with ≥ 10 valid LSMs using both probes, liver stiffness was highly correlated between probes (ρ = 0.86; P < 0.0005); however, median liver stiffness was lower using the XL probe (6.8 versus 7.8 kPa; P < 0.00005). The AUROC of the XL and M probes were similar for ≥ F2 fibrosis (0.83 versus 0.86; P = 0.19) and cirrhosis (0.94 versus 0.91; P = 0.28). CONCLUSION: Compared with the M probe, the FibroScan XL probe reduces TE failure and facilitates reliable LSM in obese patients. Although the probes have comparable accuracy, lower liver stiffness cutoffs will be necessary when the XL probe is used to noninvasively assess liver fibrosis.     

A noninvasive diagnosis of hepatic fibrosis by BioFibroScore® in chronic hepatitis C patients

Background and Aims

The diagnostic accuracy of a novel serological panel (BioFibroScore®) to predict hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection is unknown.

Methods

Three markers of BioFibroScore, including urokinase plasminogen activator, matrix metalloproteinase‐9, and beta‐2 microglobulin, were retrospectively evaluated in 635 HCV‐infected patients who received percutaneous liver biopsy and FibroScan®. The formula of BioFibroScore to predict the severity of hepatic fibrosis was developed by adaptive boosting algorithm. The diagnostic accuracy of hepatic fibrosis was assessed both for BioFibroScore and FibroScan, taking METAVIR fibrosis score as the reference standard.

Results

Urokinase plasminogen activator and beta‐2 microglobulin were positively and matrix metalloproteinase‐9 was negatively associated with the severity of hepatic fibrosis. Thirty‐five (5.5%) patients had failed FibroScan assessment. By adaptive boosting model for BioFibroScore and the established reference ranges for FibroScan, 85.7% and 89.0% of the patients had an identical result for F0‐1, F2, F3, and F4, as compared with liver biopsy. The concordance rate between BioFibroScore and FibroScan was 80.7%. BioFibroScore overestimated and underestimated the stage of hepatic fibrosis in 8.3% and 6.0% patients, and most patients had one stage error. Among patients with failed FibroScan assessment, 82.9% of them were correctly diagnosed by BioFibroScore. Bootstrap analysis for BioFibroScore showed the diagnostic accuracy was 80.9–88.4%.

Conclusions

BioFibroScore is accurate to assess the stage of hepatic fibrosis in HCV‐infected patients. Applying this noninvasive test can substantially reduce the need for invasive liver biopsy and can play a role for fibrosis evaluation when FibroScan assessment was unavailable or unreliable.     

FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy

BACKGROUND: The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment decisions. Due to the limitations of biopsy, noninvasive alternatives including FibroTest and FibroScan have been developed. Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis. METHODS: Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression. RESULTS: Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively. Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not calculable) and 0.95 (0.87-0.99), respectively. CONCLUSIONS: FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy.     

丙氨酸转氨酶对FibroScan诊断慢性乙型肝炎肝纤维化分期的影响

目的 探讨慢性乙型肝炎(CHB)患者中,不同水平的ALT对FibroScan诊断不同肝纤维化分期准确性的影响.方法 回顾性分析213例慢性乙型肝炎患者,根据血清ALT水平分为ALT＜1×正常值上限(ULN)、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组,分析3组采用FibroScan诊断不同肝纤维化分期的ROC曲线下面积,判断其诊断准确性.根据不同资料采用t检验、x2检验、受试者工作曲线或其曲线下面积(AUROC)进行统计学分析.结果在213例CHB患者中,FibroScan值与不同肝纤维化分期在3组患者中均有明显的相关性(rs值分别为0.773、0.889和0.412,P值均＜0.05).FibroScan诊断2级以上肝纤维化(F≥2,F0～1对比F2～4)和肝硬化(F=4,F0～3对比F4)的AUROC分别为0.916和0.971;其截断值分别为7.0kPa和13.0kPa;准确度分别为84.0%和93.4%.其诊断F≥2的AUROC和准确度均低于肝硬化.ALT＜1×ULN、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组在诊断明显肝纤维化的AUROC分别为0.939、0.967和0.687,其敏感度分别为90.0%、89.7%和47.8%;准确度为90.5%、93.9%和68.4%.ALT≥2×ULN组的AUROC、敏感度和准确度明显低于另两组;而ALT＜2×ULN两组的AUROC和准确度相近.ALT＜1×ULN、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组在诊断肝硬化的AUROC分别为0.970、0.985和0.952,其敏感度分别为93.8%、100%和100%;准确度分别为:88.9%、95.9%和92.1%.3组的AUROC、敏感度和准确度均较高,未随ALT升高而出现明显变化.结论 FibroScan是诊断2级以上肝纤维化,尤其是肝硬化可靠的检测方法; FibroScan诊断慢性乙型肝炎所致肝硬化的准确性可能受ALT升高的影响不明显;诊断2级以上肝纤维化的准确性对于ALT＜2×ULN的慢性乙型肝炎患者无明显影响,但是对ALT≥2×ULN的患者,其诊断的准确性降低.

Abstract：

Objective To analyze whether or not the accuracy of liver stiffness measurement (LSM)with transient elastography (FibroScan) for the diagnosis of liver fibrosis influenced by serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis B. Methods 213 consecutive CHB patients who underwent liver biopsy and LSM were enrolled and divided into three groups by the criteria of ALT＜1×ULN, 1×ULN≤ALT＜2×ULN and ALT≥2×ULN. The areas under the receiver operating curve (AUC) were analyzed and the accuracy of FibroScan for the diagnosis of liver fibrosis were detected in the three groups. Results Significant correlation existed between the stages of liver fibrosis and LSM (rs=0.773,0.889 and 0.412, P＜0.05). AUCs of LSM in all patients for significant fibrosis (F≥2, F0-1 vs F2-4)and cirrhosis (F=4, F0-3 vs F4) were 0.916 and 0.971 respectively.The accuracy of diagnosis for significant fibrosis and cirrhosis were 84.0% and 93.4% respectively.AUCs of LSM in ALT＜1×ULN,1×ULN≤ALT＜2×ULN and ALT≥2×ULN groups for significant fibrosis were 0.939, 0.967 and 0.687 respectively.The sensitivity of the three groups was 90.0%, 89.7% and 47.8% respectively. The accuracies of the three groups was 90.5%, 93.9% and 68.4% respectively. The AUC, sensitivity and accuracy of ALT≥2×ULN group for significant fibrosis were significantly lower than the other two groups. AUCs of LSM in three groups for cirrhosis were 0.970, 0.985 and 0.952 respectively. The sensitivities of the three groups were 93.8%,100% and 100% respectively. The accuracies of the three groups were 88.9%, 95.9% and 92.1% respectively.The AUCs, sensitivity and accuracy for cirrhosis of the three groups didn't change with elevated ALT. Conclusion Transient elastography (FibroScan) is a reasonable noninvasive tool to diagnose significant fibrosis,especially liver cirrhosis in CHB patients. The accuracy of FibroScan for diagnosis of liver cirrhosis may not be influenced by elevated ALT. While in ALT≥2 ×ULN group, the accuracy of FibroScan for diagnosis of significant fibrosis was significantly lower as compared to the ALT≤2×ULN groups.     

FibroScan对原发性胆汁性肝硬化患者肝纤维化的诊断价值

目的探讨FibroScan对于原发性胆汁性肝硬化（primary biliary cirrhosis,PBC）肝纤维化诊断的准确性。方法选择2009年10月—2013年12月经肝脏穿刺病理诊断的PBC患者56例,进行FibroScan检测得到肝脏硬度测量（liver stiffness measurement,LSM）值。以肝脏活组织检查结果作为＂金标准＂,计算受试者工作特征曲线下面积（AUROC）,评价FibroScan对PBC肝纤维化的诊断价值。结果 LSM值平均为（13.714±7.475）kPa,与肝脏病理分期呈正相关,Kendall相关系数为0.897,P〈0.01。FibroScan诊断PBC肝纤维化≥S2期、≥S3期、S4期的AUROC分别为0.897、0.959、0.989。纤维化分期为≥F2、≥F3、F4时对应的最佳截断值分别为12.9、16.1和19.7 kPa。肝硬度、血清透明质酸、AST/PLT（APRI）均为肝脏病理分期独立相关因素。结论 FibroScan是一项方便、准确的用于诊断PBC肝纤维化程度的方法。     

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.Liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan.Patients with liver inflammation activity≥2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage,whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity<2(all P<0.05).A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan,and the AUC was 0.701.CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage.A combination of other related noninvasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.     

FibroTouch、FibroScan及ARFI在原发性胆汁性胆管炎相关肝纤维化中的诊断价值

目的评估FibroTouch与FibroScan、声辐射力脉冲成像(ARFI)对原发性胆汁性胆管炎(PBC)患者肝纤维化程度的诊断效能。方法回顾性纳入2014年9月—2018年10月在首都医科大学附属北京友谊医院行肝穿刺活检明确诊断为PBC的患者。采用METAVIR评分系统评估肝纤维化和炎症程度。在肝活检1周内分别应用瞬时弹性成像(FibroTouch和FibroScan)和ARFI技术检测肝脏硬度值(LS);以病理结果作为金标准,采用受试者工作特征曲线下面积(AUC)比较3种超声弹性成像技术对PBC肝纤维化的诊断价值,并分析其影响因素;采用Youden指数计算不同程度肝纤维化的诊断界值。多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Bonferroni法校正P值。采用Spearman进行相关性分析,采用多重线性回归模型进行多因素分析。结果研究共纳入68例PBC患者,其中肝纤维化F0、F1、F2、F3和F4分别为13、15、18、12和10例。FibroTouch获得的LS(FT-LS)、FibroScan获得的LS(FS-LS)和ARFI获得的LS(ARFI-LS)与肝纤维化程度均呈强正相关(r值分别为0.798、0.782和0.742,P值均<0.001)。FT-LS诊断F≥2、F≥3、F=4 AUC分别为0.922、0.881、0.926,对应的cut-off值分别为10.5、15.8和17.5 kPa;FS-LS诊断F≥2、F≥3、F=4 AUC分别为0.918、0.878、0.939,对应的cut-off值分别为10.1、12.9和18.2 kPa;ARFI-LS诊断F≥2、F≥3、F=4 AUC分别为0.904、0.869、0.928,对应的cut-off值分别为1.45、1.83和2.08 m/s。3种超声成像技术对各期纤维化程度的诊断差异无统计学意义(P>0.05)。多因素分析结果显示,FT-LS的影响因素有肝纤维化程度(β=0.399,P<0.001)、TBil水平(β=0.466,P<0.001)和PTA(β=-0.195,P=0.020);FS-LS的影响因素有肝纤维化程度(β=0.370,P<0.001)、AST(β=0.450,P<0.001)、PTA(β=-0.303,P=0.001)和ALP(β=-0.187,P=0.042);而ARFI-LS的影响因素有肝纤维化程度(β=0.489,P<0.001)、AST(β=0.467,P<0.001)和PLT(β=-0.188,P=0.028)。结论FibroTouch与FibroScan和ARFI在诊断PBC肝纤维化程度的效能相似,特别是对显著纤维化(F≥2)和肝硬化(F=4)具有较高的诊断效能,可作为诊断PBC患者肝纤维化程度的可靠手段。     

FibroScan与FibroTouch对肝纤维化程度诊断价值的比较分析

目的比较FibroScan与FibroTouch对肝纤维化程度的诊断价值。方法收集2013年9月-2014年3月就诊于吉林大学第一医院肝胆胰内科的患者962例,同时行FibroScan和FibroTouch检测。其中33例有肝穿刺病理分期,66例可计算天冬氨酸转氨酶与血小板比值指数(APRI)(53例慢性乙型肝炎,13例慢性丙型肝炎)。2种检测值之间的相关性采用Spearman秩相关检验。利用受试者工作特征曲线(ROC)分析2种检测方法对肝纤维化程度的诊断价值,并进行比较。结果对所有患者FibroScan与FibroTouch的测量值进行分析,FibroScan与FibroTouch的相关系数为0.866(P0.05,n=962),与APRI的相关系数分别为0.58、0.63(P0.05,n=66),与肝穿刺病理分期的相关系数分别为0.67、0.74(P0.05,n=33)。对于慢性乙型肝炎患者,FibroScan与FibroTouch诊断APRI分期≥2的ROC曲线下面积(AUC)分别为0.761和0.728,两者差异无统计学意义(P=0.61);对于慢性丙型肝炎患者,两者诊断APRI分期≥1的AUC分别为0.810和0.893,两者差异亦无统计学意义(P=0.38)。FibroScan与FibroTouch诊断肝脏病理分期≥S1、≥S2、≥S3、≥S4的AUC分别为0.830 vs 0.889(P=0.15)、0.841 vs 0.835(P=0.90)、0.888 vs0.920(P=0.43)和0.964 vs 0.979(P=0.45)。结论 FibroScan与FibroTouch检测对肝纤维化程度的诊断价值相似,但本研究肝穿刺病例数较少,有待扩大样本进一步研究。     

Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients

Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3-6 were classified as having advanced fibrosis (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of > or = 2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80.     

Transient elastography for patients with chronic hepatitis B and C virus infection: Non-invasive, quantitative assessment of liver fibrosis

Aim/Methods: The aim of the present study was to compare the diagnostic performance of transient elastography (FibroScan) with that of serum fibrosis markers and stages of hepatic fibrosis by biopsy in 68 patients with chronic hepatitis B virus (HBV) and in 161 patients with hepatitis C virus (HCV) infection. Results: The serum levels of hyaluronic acid (r = 0.601) and type IV collagen (r = 0.663) significantly positively associated with the FibroScan values (all P < 0.05). Classified by fibrosis stages, the median values of FibroScan were 3.5 kPa for F0, 6.4 kPa for F1, 9.5 kPa for F2, 11.4 kPa for F3, and 15.4 kPa forF4 in patients with chronic HBV infection, and were 6.3 kPa for F0, 6.7 kPa for F1, 9.1 kPa for F2, 13.7 kPa for F3, and 26.4 kPa for F4 in those with chronic HCV infection. The values were significantly correlated with fibrosis stage for both (HBV, r = 0.559, P = 0.0093, and HCV, r = 0.686, P < 0.0001). Conclusion: These results suggest that FibroScan is an efficient and simple method for evaluating liver fibrosis in patients with chronic infection, both for HBV and HCV.     

Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infection

OBJECTIVE: The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut‐off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage. METHODS: In 44 patients with HCV infection, liver stiffness was evaluated by FibroScan, serum fibrosis markers and a liver biopsy. Associations between these indices were also analyzed. RESULTS: FibroScan values showed a good correlation with serum levels of type IV collagen, hyaluronic acid and procollagen‐III‐peptide, and with the platelet count. Compared with liver histology, the FibroScan values increased proportionally with the progression of the histological fibrosis stage. Advanced fibrosis (F3 or F4) could be efficiently predicted by a FibroScan cut‐off value of 15 kPa. The FibroScan sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100%, 73.9%, 77.8%, 100%, and 86.4%, respectively. CONCLUSION: FibroScan values gave a good correlation with various markers of fibrosis and increased proportionally with the progression of the hepatic fibrosis stage. A FibroScan value of 15 kPa was found to be a significant separation limit for differentiating advanced fibrosis stages (F3 and F4) from the milder stages (F0–F2). FibroScan values are clinically useful for predicting the fibrosis stages and helpful in managing interferon therapy in patients with chronic hepatitis C.     

Comparison of FibroTouch and FibroScan for staging fibrosis in chronic liver disease: Single-center prospective study

BackgroundThe aim of this study was to compare the diagnostic accuracy of the FibroTouch and FibroScan in patients with chronic liver disease (CLD) for staging fibrosis.MethodsA prospective study was conducted in 435 CLD patients between 2014 and 2017. Index tests (FibroTouch, FibroScan, APRI, and FIB-4 score) and a reference standard (liver biopsy) were performed within one week.ResultsThe area under the receiver operating curve (AUROC) of the FibroTouch was similar with that of the FibroScan for the diagnosis of significant fibrosis, severe fibrosis, or cirrhosis; however, the AUROC of the FibroTouch was higher than that of APRI or FIB‐4 (p < 0.001). There was a significant correlation (rho = 0.85, p < 0.001) between the FibroTouch and FibroScan for liver stiffness. The overall diagnostic accuracy of FibroTouch for significant fibrosis, severe fibrosis, or cirrhosis was 73.3%, 83.2%, or 84.1%, respectively. No significant differences between the FibroTouch and FibroScan were detected regarding the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. The optimal cut-off values for each stage of fibrosis were similar between the FibroTouch and FibroScan.ConclusionThe FibroTouch is a valuable diagnostic tool for diagnosing liver fibrosis with good diagnostic accuracy which was comparable with that of the FibroScan, but superior to that of the APRI and FIB-4.     

Liver biopsy versus noninvasive testing in chronic hepatitis C: Where do we stand in 2008?

The liver biopsy has historically been the diagnostic gold standard, albeit imperfect, for establishing the degree of inflammation and fibrosis in patients with chronic hepatitis C (CHC). However, this procedure is associated with the risk of complications, sampling variability, intra-and interobserver interpretation variability, and high cost. Recently, there has been significant interest in developing noninvasive modalities to accurately assess disease severity in CHC. Numerous scoring models have been proposed and validated, each with variable results depending on the study population assessed, the degree of significant fibrosis, and the type of liver biopsy scoring system and fibrosis markers used, making interpretation of the literature potentially confusing. Individual scoring algorithms have been shown to accurately distinguish F0–F1 versus F2–F4 fibrosis in about 50% of cases, with the rate improving somewhat for distinguishing more advanced fibrosis. Combination testing may further enhance the diagnostic accuracy of the tests. Imaging studies such as FibroScan (Echosens, Paris, France) and magnetic resonance elastography hold significant promise, but caution should be used when considering this modality in the setting of obesity, nonalcoholic fatty liver disease, ascites, or acute hepatitis.     

Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C

BACKGROUND/AIMS: In chronic hepatitis C, biopsy is the gold standard for assessment of liver fibrosis. Non-invasive markers have been proposed but their use is limited by diagnostic accuracy. Our aim was to increase the diagnostic performance of non-invasive markers of liver fibrosis by combining them in sequential algorithms. METHODS: One hundred and ninety patients with chronic hepatitis C were evaluated for AST to platelets ratio (APRI), Forns' index and Fibrotest at the time of liver biopsy and stepwise combination algorithms were developed and validated prospectively in 100 additional patients. RESULTS: Three algorithms were developed: (1) significant fibrosis (F>or=2 by METAVIR) was identified with high diagnostic performance (>94% accuracy) using APRI as screening test, followed by Fibrotest in APRI non-classified cases and restricting liver biopsy to patients classified F0-F1 by non-invasive tests. (2) A slightly modified algorithm had similar performance when applied to hepatitis C carriers with normal ALT. (3) Identification of cirrhosis (95% accuracy) was achieved using a dedicated algorithm with different cut-off, reducing by 60-70% the liver biopsies needed. CONCLUSIONS: Stepwise combination of non-invasive markers of liver fibrosis improves the diagnostic performance in chronic hepatitis C. Need for liver biopsy is reduced by 50-70% but cannot be completely avoided.     

Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis

Acoustic Radiation Force Impulse (ARFI) imaging is a novel ultrasound-based elastography method that is integrated in a conventional ultrasound machine enabling the exact localization of measurement site. It might present an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. At present, studies with small patient population have shown promising results. A systematic review and meta-analysis of pooled patient data were performed to evaluate the overall performance of ARFI for the staging of liver fibrosis. Literature databases were searched up to 10/2010. The authors of the original publication were contacted, and the original patient data were requested. A meta-analysis was performed using a random effect meta-analytic method for diagnostic tests. In addition, available data comparing ARFI with FibroScan with the DeLong test were evaluated. Literature search yielded nine full-paper publications evaluating ARFI while using liver biopsy as reference method. Original patient data were available from eight studies including 518 patients. The mean diagnostic accuracy of ARFI expressed as areas under ROC curves (AUROC) was 0.87 for the diagnosis of significant fibrosis (F ≥ 2), 0.91 for the diagnosis of severe fibrosis (F ≥ 3), and 0.93 for the diagnosis of cirrhosis. ARFI can be performed with good diagnostic accuracy for the noninvasive staging of liver fibrosis.     

FibroTest联合FibroScan对慢性乙型肝炎纤维化的诊断价值

目的：探讨FibroTest联合FibroScan对慢性乙型肝炎肝纤维化的诊断价值。方法留取2011年8月至2013年7月天津市第二人民医院的99例行肝活组织检查的慢性乙型肝炎患者的血清,检测α2-巨球蛋白（α2-MG）、结合珠蛋白（HP）和载脂蛋白A1（apoAⅠ）,记录TBil和GGT的数值,并根据其结果结合患者的年龄和性别计算出FibroTest的数值。并对99例慢性乙型肝炎患者用FibroScan测定肝脏硬度值。根据Scheuer肝纤维化分期标准设定2个判定点,分别为显著肝纤维化（S2～S4期）,严重肝纤维化（S3～S4期）。以肝活组织检查病理结果为金标准绘制出FibroTest及FibroScan的受试者工作特征曲线下面积（AUROC）。评价两者对慢性乙型肝炎肝纤维化的诊断价值,并应用 Logistic 逐步回归分析方法探讨联合诊断价值。结果 FibroTest 与 Fi-broScan对S2～S4期的AUROC分别0．805（95％CI：0．713～0．897,P＜0．001）,0．896（95％CI：0.833～0．959,P＜0．001）,对S3～S4期的AUROC值分别为0．834（95％CI：0．741～0．928,P＜0．001）,0．945（95％CI：0．891～0．999,P＜0．001）。两者联合后对显著纤维化（S2～S4期）的AUROC值为0．911（95％CI：0．854～0．967,P＜0．001）。结论 FibroTest联合FibroScan可以更准确地估计慢性乙型肝炎患者肝脏有无显著纤维化,提高诊断特异度,并保证较高的诊断准确率,对于慢性乙型肝炎预后评估及治疗决策有指导意义。     

Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis B patients treated with nucleoside analog

Aim: To evaluate the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of long‐term nucleoside analog (NA) treatment for patients with chronic hepatitis B. Methods: Study 1: Forty‐four chronic HBV patients had liver stiffness measured by FibroScan and underwent liver biopsy. Study 2: Group A: 22 patients started NA treatment at entry and FibroScan was done annually for 3 years. Group B: 23 patients started NA treatment prior to pretreatment FibroScan measurement, and FibroScan was done for from 3 to 5 years after the start of NA treatment. Results: Study 1: The FibroScan values were significantly correlated with fibrosis stage (r = 0.672, P < 0.0001). Optimal cutoff of FibroScan values were 6.1 kPa for ≥ F1, 6.3 kPa for ≥ F2, 8.9 kPa for ≥ F3 and 12.0 kPa for F4. Study 2: For Group A, the baseline median FibroScan value was 8.2 kPa. FibroScan values significantly decreased annually for 3 years after the start of NA treatment (6.4 kPa, 5.8 kPa and 5.3 kPa at years 1, 2 and 3, respectively). For Group B, the FibroScan values did not significantly improve over the 3 years after the start of NA treatment. Conclusions: Liver stiffness, measured by transient elastography, of chronic hepatitis B patients treated with NA showed a rapid decline in the first 3 years followed by a more steady transition for from 3 to 5 years irrespective of long term virological effect.     

FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎合并非酒精性脂肪性肝病进展期肝纤维化的诊断价值比较

目的评价FibroScan、GPR、APRI、NFS、FIB-4单独应用及FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者进展期肝纤维化的诊断价值。方法选取2014年11月-2018年8月在四川省人民医院行肝穿刺病理检查并确诊为CHB合并NAFLD的患者92例。根据肝穿刺病理SAF分级诊断标准,分为轻中度肝纤维化(F1+F2)组(n=69)和进展期肝纤维化(F3)组(n=23)。同时应用FibroScan测得肝脏硬度值,根据临床指标分别计算GPR、APRI、NFS、FIB-4。计量资料两组间比较采用Mann-Whitney U检验;相关性分析采用Spearman秩相关;多因素二元logistic回归构建联合预测因子(向前逐步回归法),绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),并采用Delong方法进行比较,评价各种无创诊断方法单独及联合应用对CHB合并NAFLD进展期肝纤维化的诊断价值。结果轻中度肝纤维化组的FibroScan、GPR、APRI、NFS及FIB-4水平明显低于进展期肝纤维化组(Z值分别为-4.910、-3.425、-3.837、-3.873、-3.990,P值均<0.05)。相关性分析结果显示,FibroScan、GPR、APRI、NFS、FIB-4与肝纤维化病理分期均呈正相关(r值分别为0.518、0.361、0.405、0.407、0.418,P值均<0.001)。FibroScan、GPR、APRI、NFS及FIB-4单独应用对诊断进展期肝纤维化均有一定价值(AUC分别为0.844、0.740、0.770、0.771、0.779,P值均<0.001),但FibroScan诊断价值并不优于GPR、APRI、NFS、FIB-4(P值均>0.05)。将FibroScan分别与GPR、APRI、NFS、FIB-4联合,诊断进展期肝纤维化的AUC均较单独应用时明显提高(Z值分别为1.977、2.076、2.361、2.206,P值均<0.05);将FibroScan与GPR+APRI+NFS+FIB-4同时联合诊断进展期肝纤维化的AUC及95%可信区间为0.896(0.813~0.950)。结论FibroScan、GPR、APRI、NFS及FIB-4诊断进展期肝纤维化均有一定的临床价值,FibroScan分别与GPR、APRI、NFS、FIB-4联合诊断进展期肝纤维化的效能优于单项血清学模型,其中FibroScan联合NFS或FIB-4的临床价值可能最佳。