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.     

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。     

Transient elastography for measurement of liver stiffness measurement can detect early significant hepatic fibrosis in Japanese patients with viral and nonviral liver diseases

BACKGROUND: Many studies have reported the efficiency of transient elastography, a noninvasive, reproducible, and reliable method for predicting liver fibrosis, in patients with chronic hepatitis C (CHC) and B (CHB), but there are few reports about nonviral chronic liver disease (CLD) such as primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NAFLD), and autoimmune hepatitis (AIH). We therefore compared the efficiency of transient elastography between CHC and nonviral CLD. METHODS: We assessed the accuracy of liver stiffness measurement (LSM) using Fibroscan, and compared these values with those of hyaluronic acid, type 4 collagen, platelet count, prothrombin index, and AST/platelet ratio index (APRI) as indices for the diagnosis of liver fibrosis in 114 patients with a variety of chronic liver diseases: CHC (n = 51), CHB (n = 11), NAFLD (n = 17), PBC (n = 20), and AIH (n = 15). The histology was assessed according to the METAVIR score by two pathologists. RESULTS: The number of fibrosis stage (F0/1/2/3/4) with CHC was 9/15/12/6/10, and that with nonviral CLD was 10/21/11/4/6, respectively. The ability, assessed by area under receiver operating characteristic (AUROC) curve, to predict liver fibrosis F >or= 2 for LSM, HA, type 4 collagen, platelet count, prothrombin index, and APRI, was 0.92, 0.81, 0.87, 0.85, 0.85, and 0.92 in CHC patients, respectively; and 0.88, 0.72, 0.81, 0.67, 0.81, and 0.77 in nonviral CLD patients, respectively. CONCLUSIONS: In patients with nonviral CLD, LSM was most helpful in predicting significant fibrosis (F >or= 2). Transient elastography is a reliable method for predicting significant liver fibrosis, not only in CHC patients but also in nonviral CLD patients.     

Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV‐coinfected patients

Summary. Transient elastography (TE) is a noninvasive technique to evaluate liver fibrosis. We compared the performance of TE with liver biopsy (LB) in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Patients prospectively underwent TE and LB. The diagnosis accuracy of TE was calculated using receiver operating characteristic (ROC) curves for different stages of fibrosis, and optimal cut‐off values were defined. A sequential algorithm combining TE with biochemical score (Fibrotest®) is proposed. Fifty‐seven patients had both TE and LB (median time: 3 days) and two with proven cirrhosis, only TE. Forty‐six (78%) were under antiretroviral therapy with anti‐HBV drugs in 98%, and 19 (32%) had elevated alanine aminotransferase (ALT). A significant correlation was observed between liver stiffness measurement (LSM) and METAVIR fibrosis stages (P < 0.0001). Patients with elevated ALT tended to have higher LSM than those with normal ALT. The areas under the ROC curves were 0.85 for significant fibrosis (≥F2), 0.92 for advanced fibrosis (≥F3) and 0.96 for cirrhosis. Using a cut‐off of 5.9 kPa for F≥2 and 7.6 kPa for F ≥ 3, the diagnosis accuracy was 83% and 86%, respectively. With an algorithm combining TE and Fibrotest®, 97% of patients were well classified for significant fibrosis. Using this algorithm, the need for LB can be reduced by 67%. In HIV/HBV‐coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease.     

Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis

The development of liver fibrosis markers in primary biliary cirrhosis (PBC) is needed to facilitate the assessment of its progression and the effectiveness of new therapies. Here, we investigated the potential usefulness of transient elastography (TE) in the noninvasive evaluation of liver fibrosis stage and disease progression in PBC. We performed, first, a prospective performance analysis of TE for the diagnosis of METAVIR fibrosis stages in a diagnostic cohort of 103 patients and, second, a retrospective longitudinal analysis of repeated examinations in a monitoring cohort of 150 patients followed-up for up to 5 years. All patients were treated with ursodeoxycholic acid. Diagnostic thresholds of liver stiffness in discriminating fibrosis stages ≥ F1, ≥ F2, ≥ F3, and =F4 were 7.1, 8.8, 10.7, and 16.9 kPa, respectively. TE showed high performance and was significantly superior to biochemical markers (e.g., aspartate aminotransferase [AST]/platelet ratio, FIB-4, hyaluronic acid, AST/alanine aminotransferase ratio, and Mayo score) in diagnosing significant fibrosis, severe fibrosis, or cirrhosis. Analysis of the monitoring cohort data set using generalized linear models showed the following: (1) an overall progression rate of 0.48 ± 0.21 kPa/year (P = 0.02) and (2) no significant progression in patients with F0-F1, F2, or F3 stages, but a significant increase (4.06 ± 0.72 kPa/year; P < 0.0001) in cirrhotic patients. A cut-off value of 2.1 kPa/year was associated with an 8.4-fold increased risk of liver decompensations, liver transplantations, or deaths (P < 0.0001, Cox regression analysis). CONCLUSION: TE is one of the best current surrogate markers of liver fibrosis in PBC. Over a 5-year period, on-treatment liver stiffness appears stable in most noncirrhotic PBC patients, whereas it significantly increases in patients with cirrhosis. Progression of liver stiffness in PBC is predictive of poor outcome.     

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

Summary.  The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.     

瞬时弹性成像技术、APRI及FIB-4对胆道闭锁患儿肝纤维化程度的诊断价值

目的探讨肝脏瞬时弹性成像技术检测肝脏硬度(LSM)、AST-PLT比值指数(APRI)、基于4因子的肝纤维化指数(FIB-4)对胆道闭锁患儿肝纤维化程度的诊断价值。方法选取2016年1月1日-2018年12月31日于湖南省儿童医院新生儿外科行Kasai术的胆道闭锁患儿110例。收集患儿术中肝脏病理活检标本及术前1周内血常规、肝功能、瞬时弹性成像检查结果。计数资料组间比较采用χ2检验,非正态分布的计量资料多组间比较采用Kruskal-Wallis H秩和检验。采用MedCalc软件绘制受试者工作特征曲线(ROC曲线),通过ROC曲线评估瞬时弹性成像技术、APRI和FIB-4对胆道闭锁患儿肝纤维化程度的诊断效能。采用Spearman相关法进行相关性分析。结果ROC曲线分析显示,LSM、APRI、FIB-4用于判断胆道闭锁明显肝纤维化(F≥2)的临界值分别为9.250 kPa、0.680、0.047,ROC曲线下面积(AUC)分别为0.874[95%可信区间(95%CI):0.778~0.970]、0.636(95%CI:0.362~0.911)、0.622(95%CI:0.363~0.880);LSM、APRI、FIB-4用于判断胆道闭锁进展性肝纤维化(F≥3)的临界值分别为10.75 kPa、0.70、0.05,AUC分别为0.781(95%CI:0.689~0.873)、0.519(95%CI:0.401~0.636)、0.506(95%CI:0.389~0.623);LSM、APRI、FIB-4用于判断胆道闭锁肝硬化(F≥4)的临界值分别为11.85 kPa、0.82、0.09,AUC分别为0.855(95%CI:0.769~0.942)、0.701(95%CI:0.599~0.803)、0.717(95%CI:0.609~0.825)。相关性分析结果显示,LSM值与AST水平呈正相关(r=0.258,P=0.007),与PLT水平呈负相关(r=-0.248,P=0.009)。结论瞬时弹性成像技术对于胆道闭锁患儿肝纤维化分级具有较高的准确性,其诊断肝纤维化程度的临床价值高于APRI、FIB-4。     

The usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis

Introduction

Liver stiffness measurement (LSM) is used for the assessment of liver fibrosis. However, there is limited data in Indian patients.

Aims and Objective

The aim of this study was to find the correlation of LSM, aspartate transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver biopsy (LB), and predictors of discordance between LB and LSM.

Methods

One hundred and eighty-five consecutive patients who underwent liver biopsy and transient elastography (TE) were enrolled. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) was used to evaluate the accuracy of transient elastography and APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4).

Results

Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was unsuccessful in ten patients (5 %) because of small intercostal space (n?=?3) and obesity (n?=?7). Fibrosis is significantly correlated with LSM (r?=?0.901, p?=?0.001) and APRI (r?=?0.736, p?=?0.001). There was a significant difference in median LSM value in patients with no fibrosis (F0) in comparison to patients having mild fibrosis [mild portal fibrosis (F1)?+?fibrosis with few septa (F2)] (4.5 vs. 7.5 kPa, p?=?0.001) and advanced fibrosis [bridging fibrosis that is spreading and connecting to other areas that contain fibrosis (F3)?+?cirrhosis or advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p?=?0.001). Similarly, there was a significant difference in mean APRI value in patients with F0 in comparison to patients having mild fibrosis (F1?+?F2) (0.55?±?0.31 vs. 1.09?±?0.81, p?=?0.001) and advanced fibrosis (F3?+?F4) (2.3?±?1.3, p?=?0.001). AUROC for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI) 0.963–0.999) for TE and 0.865 (95 % CI 0.810–0.920) for APRI. Optimal TE value was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively. On multivariate analysis, total bilirubin and histological activity index (HAI) were identified as an independent predictor of TE inaccuracy.

Conclusion

LSM is a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of discordance between LB and LSM.     

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.     

Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study

BACKGROUND

Liver stiffness measurement (LSM) using transient elastography (TE) is a promising tool for the noninvasive assessment of hepatic fibrosis.

OBJECTIVES

To determine the feasibility and performance of TE in a North American cohort of patients with chronic liver disease.

METHODS

LSMs were obtained using TE in 260 patients with chronic hepatitis B or C, or nonalcoholic fatty liver disease from four Canadian hepatology centres. The accuracy of TE compared with liver biopsy for the prediction of significant fibrosis (Metavir fibrosis score of F2 or greater), bridging fibrosis (Metavir fibrosis score of F3 or greater) and cirrhosis (Metavir fibrosis score of F4 ) was assessed using area under ROC curves (AUROCs), and compared with the aspartate aminotransferase-to-platelet ratio index. The influence of alanine aminotransferase (ALT) levels and other factors on liver stiffness was determined using linear regression analyses.

RESULTS

Failure of TE occurred in 2.7% of patients, while liver biopsies were inadequate for staging in 0.8%. Among the remaining 251 patients, the AUROCs of TE for Metavir fibrosis scores of F2 and F3 or greater, and F4 were 0.74 (95% CI 0.68 to 0.80), 0.89 (95% CI 0.84 to 0.94), and 0.94 (95% CI 0.90 to 0.97), respectively. LSM was more accurate than the aminotransferase-to-platelet ratio index for bridging fibrosis (AUROC 0.78) and cirrhosis (AUROC 0.88), but not significant fibrosis (AUROC 0.76). At a cut-off of 11.1 kPa, the sensitivity, specificity, and positive and negative predictive values for cirrhosis (prevalence 11%) were 96%, 81%, 39% and 99%, respectively. For significant fibrosis (prevalence 53%), a cut-off of 7.7 kPa was 68% sensitive and 69% specific, and had a positive predictive value of 70% and a negative predictive value of 65%. Liver stiffness was independently associated with ALT, body mass index and steatosis. The optimal LSM cut-offs for cirrhosis were 11.1 kPa and 11.5 kPa in patients with ALT levels lower than 100 U/L and 100 U/L or greater, respectively. For fibrosis scores of F2 or greater, these figures were 7.0 kPa and 8.6 kPa, respectively.

CONCLUSIONS

The major role of TE is the exclusion of bridging fibrosis and cirrhosis. However, TE cannot replace biopsy for the diagnosis of significant fibrosis. Because liver stiffness may be influenced by significant ALT elevation, body mass index and/or steatosis, tailored liver stiffness cut-offs may be necessary to account for these factors.     

Acoustic Radiation Force Impulse (ARFI) Elastography in Autoimmune and Cholestatic Liver Diseases

Introduction.Acoustic Radiation Force Impulse (ARFI) elastography evaluates hepatic fibrosis non-invasively and has been mainly validated in viral hepatitis. Data on rare liver diseases such as autoimmune hepatitis (AIH), overlap syndrome, primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) are sparse.Material and methods. 85 patients (including 31 AIH, 26 PBC, 16 PSC and 3 PSC-and 9 PBC-AIH-overlap syndromes) were retrospectively analysed pointing at ARFI elastography of the liver and the correlation with histologic Ishak fibrosis score (F0-6). Results of shear wave velocities (m/s) were expressed as mean ± standard deviation.Results. The mean shear wave velocity of all 85 patients showed 1.80 ± 0.84 m/s (0.74-3.98). The ARFI elastography values correlated with the degree of fibrosis in all patients overall and in patients with AIH, overlap syndrome and PSC, respectively. The subgroup of 26 patients with PBC (only with Ishak F > 3) revealed no correlation between ARFI and these early fibrosis stages (r = 0.019, p = 0.927). ARFI elastography correlated with bilirubin, AST, but not with patient age, body mass index or measurement depth. The cut-off of 2.04 m/s for detecting cirrhosis (Ishak F > 5) leads to a sensitivity of 90.0% and specificity of 74.7% (AUROC 87.2%).Conclusion. ARFI elastography can evaluate fibrosis in AIH, PSC and PSC-/PBC-AIH-overlap syndrome with good accuracy for the detection of hepatic cirrhosis. Shear wave velocities in PBC should be interpreted with caution in early stages of fibrosis.     

Comparison of liver biopsy and transient elastography based on clinical relevance

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography has recently been validated for the evaluation of liver fibrosis in chronic liver diseases. The present study focused on cases in which liver biopsy and LSM were discordant. METHODS: Three hundred eighty-six patients with chronic hepatitis C who underwent a liver biopsy between December 2004 and April 2007 were studied. First, the optimal cut-off value of LSM was selected for the determination of cirrhosis based on the receiver operating characteristic curve. Then, the cases in which liver histology and evaluation by LSM were discordant were selected. Laboratory test results such as serum total bilirubin concentration, prothrombin activity, albumin concentration, platelet count and the aspartate aminotransferase to platelet ratio index, together with the presence of esophageal varices, were analyzed. RESULTS: The optimal cut-off value was chosen to be 15.9 kPa for cirrhosis (fibrosis stage [F] 4) determination to maximize the sum of sensitivity (78.9%) and specificity (81.0%). There were 78 discordant cases: 51 patients showed an LSM of 15.9 kPa or higher and a fibrosis stage of F1 to F3 (high LSM group), and 27 patients had an LSM lower than 15.9 kPa and a fibrosis stage of F4 (low LSM group). Esophageal varices were seen in 11 patients in the high LSM group (n=51) and in no patients in the low LSM group (n=27) (P=0.0012). The aspartate aminotransferase to platelet ratio index was significantly higher in the high LSM group (1.49 versus 0.89, P=0.019). Other parameters did not differ significantly. However, platelet count, prothrombin activity and albumin concentration tended to be lower in the high LSM group. CONCLUSIONS: Patients with a high LSM need proper attention for cirrhosis, even if liver biopsy does not reveal cirrhosis.     

Outreach screening of drug users for cirrhosis with transient elastography

Aims Transient elastography (TE) is a non‐invasive sensitive tool for diagnosing cirrhosis in hospital‐based cohorts. This study aimed to evaluate TE as a screening tool for cirrhosis among drug users. Design Cross‐sectional study. Setting All treatment centres in the county of Funen, Denmark. Participants Drug users attending treatment centres during the presence of the study team. Measurements Liver stiffness measurements (LSM) by transient elastography using the Fibroscan device; blood tests for viral hepatitis, HIV infection and hyaluronic acid (HA) levels; and routine liver tests. Individuals with LSM ≥ 8 kPa were referred to the hospital for treatment evaluation. Individuals with LSM ≥ 12 kPa were recommended a liver biopsy. Findings Among 175 drug users negative for hepatitis C, 13% had LSM = 8–11.9 kPa and 4% had LSM ≥ 12 kPa; elevated LSM was associated with a body mass index (BMI) > 30. Among 128 drug users with chronic hepatitis C, 19.5% had LSM = 8–11.9 kPa and 21.1% had LSM ≥ 12 kPa (P < 0.001). Repeat LSM at liver biopsy performed a median 3 months after screening showed a significant decrease (<12 kPa) among 30% (six of 20), and this was independent of alcohol consumption, BMI, age and gender. In 29 patients where liver biopsy was performed a LSM ≥ 16 kPa predicted cirrhosis with 88.9% sensitivity and 90% specificity. Conclusions Transient elastography is a feasible screening tool for cirrhosis among drug users. Transient elastography identifies severe liver fibrosis in a significant proportion of drug users with hepatitis C infections but management should not be based on a single elevated liver stiffness measurement.     

How efficient is acoustic radiation force impulse elastography for the evaluation of liver stiffness?

Background

In chronic liver diseases, a correct estimation of the severity of liver fibrosis is important for recommendations regarding the treatment. Nowadays, evaluation of fibrosis is done by noninvasive methods such as biochemical scores and transient elastography instead of liver biopsy. The lack of sensitivity to detect fibrosis, because of its heterogeneity is a drawback of liver biopsy (LB).

Objectives

To compare transient elastography (TE) and acoustic radiation force impulse (ARFI) for the evaluation of liver stiffness (LS), against percutaneous LB.

Patients and Methods

Our study comprised of 223 subjects; 52 without fibrosis (38 volunteers and 14 patients with F0 on LB), 36 with F1, 40 with F2, 26 with F3 and 69 with liver cirrhosis (46 with LB and 23 with signs of cirrhosis). For each patient we performed in the same session 10 TE and 5 ARFI measurements. The median values were calculated.

Results

A strong linear correlation (Spearman rho = 0.870) was found between TE and fibrosis (P < 0.0001); there was also a weaker correlation between ARFI and fibrosis (Spearman rho = 0.646; P < 0.0001). TE measurements were also correlated with ARFI measurements (Spearman rho = 0.733, P < 0.0001). The best test for predicting significant fibrosis (F ≥ 2) was TE with a cut-off value of 7.1 kPa (AUROC 0.953). For ARFI, the cut-off value was 1.27 m/s-area under ROC curve (AUROC): 0.890, sensitivity (Se) of 88.7%, specificity (Sp) of 67.5%, positive predictive value (PPV) of 64.5%, and negative predictive value (NPV) of 90% (P = 0.0044). For predicting cirrhosis (F = 4), the optimum cut-off values were 14.4 kPa for TE (AUROC: 0.985, Se: 95.6%, Sp: 94.7%, PPV: 89.2%, NPV: 98%) and 1.7 m/s for ARFI (AUROC: 0.931, Se: 93%, Sp: 86.7%, PPV: 73.6%, NPV: 96.9%) (P = 0.0102).

Conclusions

LS evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. ARFI is an accurate test for the diagnosis of cirrhosis.     

Serum levels of soluble dipeptidyl peptidase-4 in type 2 diabetes are associated with severity of liver fibrosis evaluated by transient elastography (FibroScan) and the FAST (FibroScan-AST) score,a novel index of non-alcoholic steatohepatitis with significant fibrosis

AimTo investigate the relationship in people with type 2 diabetes between serum soluble dipeptidyl peptidase-4 (sDDP-4) and degree of liver fibrosis assessed as the liver stiffness measurement (LSM) and FAST (FibroScan-AST) score, both of which were measured by transient elastography (FibroScan).Subjects and methodsIn this cross-sectional study, we examined 115 patients with type 2 diabetes. With transient elastography (FibroScan), we assessed the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) as measures of hepatic steatosis and liver fibrosis, respectively. We calculated the FAST score, which identifies progressive non-alcoholic steatohepatitis (NASH), from CAP, LSM, and the serum aspartate aminotransferase level. Significant hepatic steatosis was defined as CAP ≥280 dB/m; and significant liver fibrosis, as LSM ≥ 8.0 kPa. LSM was divided into 3 severity levels: significant fibrosis (8.0 to <9.7 kPa); advanced fibrosis, (9.7 to <13.0 kPa); and liver cirrhosis (≥ 13.0 kPa).ResultsSerum sDPP-4 correlated positively with liver enzymes, CAP, LSM, and FAST score. Multivariate analysis showed that LSM remained to be an independent factor for serum sDDP-4. Serum sDPP-4 was significantly higher in patients with LSM ≥ 8.0 kPa than in those with LSM <8.0 kPa and was significantly elevated in patients who are at risk for non-alcoholic steatohepatitis (NASH) with fibrosis (FAST score ≥ 035 or 0.67). Patients with both hepatic steatosis and liver fibrosis had the highest serum sDPP-4.ConclusionSerum sDPP-4 was strongly associated with severity of liver fibrosis evaluated by LSM and the FAST score and was markedly elevated in diabetic patients with LSM ≥ 13.0 kPa indicating probable cirrhosis.     

Assessment of liver fibrosis by Fibroscan as compared to liver biopsy in biliary atresia

AIM: To evaluate liver stiffness measurement(LSM)using non-invasive transient elastography(Fibroscan)in comparison with liver biopsy for assessment of liver fibrosis in children with biliary atresia(BA).METHODS: Thirty-one children with BA admitted to the Department of Pediatric Surgery of Beijing Children's Hospital from March 2012 to February 2013 were included in this study. Their preoperative LSM, liver biopsy findings, and laboratory results were studied retrospectively.RESULTS: The grade of liver fibrosis in all 31 patients was evaluated according to the METAVIR scoring system, which showed that 4 cases were in group F2, 20 in group F3 and 7 in group F4. There were 24non-cirrhosis cases(F2-F3) and 7 cirrhosis cases(F4).In groups F2, F3 and F4, the mean LSM was 9.10 ±3.30 kPa, 11.02 ± 3.31 kPa and 22.86 ± 12.43 kPa,respectively. LSM was statistically different between groups F2 and F4(P = 0.002), and between groups F3 and F4(P = 0.000), however, there was no statistical difference between groups F2 and F3(P = 0.593). The area under the receiver operating characteristic curve of LSM for ≥ F4 was 0.866. The cut-off value of LSM was 15.15 kPa for ≥ F4, with a sensitivity, specificity,positive predictive value and negative predictive value of 0.857, 0.917, 0.750 and 0.957, respectively.CONCLUSION: Fibroscan can be used as a noninvasive technique to assess liver fibrosis in children with BA. The cut-off value of LSM(15.15 kPa) can distinguish cirrhotic patients from non-cirrhotic patients.     

Assessment of liver stiffness in patients after living donor liver transplantation by transient elastography

Objective. Recurrence of hepatitis and progression of fibrosis are major problems in liver transplantation (LT) for patients with hepatitis C. Liver stiffness measurement (LSM) by transient elastography correlates well with histologic liver fibrosis stages in chronic liver diseases. The aim of this study was to evaluate the usefulness of transient elastography for the assessment of fibrosis in patients after living donor LT. Material and methods. Seventy-nine patients who visited our institution, and in whom LSM was successfully evaluated, were enrolled in the study. The patients were divided into three groups according to positivity for hepatitis C antibody and hepatitis B surface antigen as the hepatitis C virus (HCV) group (n=37), the hepatitis B virus (HBV) group (n=10), and the NBNC (negative for both hepatitis B and C) group (n=32). The correlation between LSM and histologic fibrosis stage was assessed in 36 patients. LSM was also compared with regard to the effect of interferon therapy in HCV patients. Results. The median value for liver stiffness was 6.8 kPa and the median time from LT was 3.1 years. In patients who underwent liver biopsy, stiffness was significantly correlated with the stages of fibrosis (p<0.001, rho = 0.848). In patients who received interferon therapy after LT, the LSM decreased over time in those with a sustained virological response, whereas LSM increased in patients without a response. Conclusion. Transient elastography may be an appropriate non-invasive procedure to sequentially assess the progression of liver fibrosis in patients after LT.     

Increased liver stiffness measurement by transient elastography in severe acute exacerbation of chronic hepatitis B

Background and Aims:  The proposed cut-off values for the degree of fibrosis as assessed by liver stiffness measurement (LSM) might not be applicable in severe acute exacerbation of chronic hepatitis B (CHB). We aimed to assess the effect of necroinflammatory activity on LSM in this condition.
Methods:  We prospectively recruited consecutive patients with severe acute exacerbation of CHB (alanine aminotransferase or ALT > 10× upper limit of normal). The relationship of ALT levels and LSM were serially assessed and liver biopsy was carried out after ALT normalization.
Results:  Eleven patients (10 male, median age 43 years) were followed up for 25 weeks; nine patients received antiviral therapy. Overall, LSM was positively correlated with ALT levels ( r  = 0.67, P  < 0.001). At initial presentation, the median serum ALT and LSM was 1136 (581–2210) IU/L and 26.3 (11.1–33.3) kPa. A progressive reduction in LSM was observed during subsequent visits in parallel with the reduction of ALT levels. At the last visit, the median ALT was 27 (11–52) IU/L and LSM was 7.7 (4.7–10.8) kPa. Among the five patients who had liver biopsy carried out at week 25, four patients had F2 fibrosis (LSM 5.7–8.1 kPa) and one patient had F3 fibrosis (LSM 8.6 kPa).
Conclusions:  LSM using transient elastography with the current proposed cut-off values might misdiagnose liver cirrhosis in patients suffering from severe acute exacerbation of CHB. LSM should be assessed after normalization of ALT levels in order to accurately assess the degree of fibrosis.     

Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C

BACKGROUND AND AIMS: Transient elastography (FibroScan; Echosens, Paris, France) is a novel, noninvasive, and rapid bedside method to assess liver fibrosis by measuring liver stiffness. We prospectively assessed the performance of FibroScan in patients with chronic hepatitis C, in comparison with and combined with currently available biochemical markers (Fibrotest; Biopredictive; and the aspartate transaminase to platelets ratio index [APRI]); a liver biopsy examination performed the same day served as the reference. METHODS: We studied 183 consecutive patients with chronic hepatitis C (METAVIR fibrosis stage F1, n = 47; F2, n = 53; F3, n = 37; F4, n = 46). RESULTS: FibroScan values ranged from 2.4 to 75.4 kilopascals (median, 7.4 kilopascals). Cut-off values were 7.1 kPa for F > or = 2, 9.5 kPa for F > or = 3, and 12.5 kPa for F = 4. The areas under the receiver operating characteristic (ROC) curve of FibroScan, FibroTest, and APRI values were of the same order (.83, .85, and .78, respectively, for F > or = 2; .90, .90, and .84, respectively, for F > or = 3; and .95, .87, and .83, respectively, for F = 4). The best performance was obtained by combining the FibroScan and FibroTest, with areas under the ROC curve of .88 for F > or = 2, .95 for F > or = 3, and .95 for F = 4. When the FibroScan and FibroTest results agreed, liver biopsy examination confirmed them in 84% of cases for F > or = 2, in 95% for F > or = 3, and in 94% for F = 4. CONCLUSIONS: FibroScan is a simple and effective method for assessing liver fibrosis, with similar performance to FibroTest and APRI. The combined use of FibroScan and FibroTest to evaluate liver fibrosis could avoid a biopsy procedure in most patients with chronic hepatitis C.     

血清IL-34联合超声弹性成像诊断慢性乙型肝炎患者肝纤维化的效能分析

目的 研究应用血清IL-34和肝脏硬度检测(LSM)诊断慢性乙型肝炎(CHB)患者肝纤维化的效能.方法 2018年6月～2019年6月我院接受经皮肝穿刺活检的CHB患者100例,采用ELISA法检测血清IL-34和血清HBsAg水平,采用实时荧光定量PCR法检测血清HBV DNA,使用雅培公司生产的全自动生物化学分析仪...