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Background and Aims: In non-alcoholic fatty liver disease (NAFLD), fibrosis is the strongest prognostic factor and can be assessed by non-invasive methods. We evaluated the ability of liver stiffness measurement (LSM) to predict overall survival and liver, cardiovascular and oncologic complications., Methods: We prospectively collected data on 2251 consecutive NAFLD patients (mean age 59 years, male 53%, mean body mass index 28 kg/m 2 ) in two centres. At inclusion, all patients had LSM, clinical and biological evaluation. During follow-up, we recorded cardiovascular events, cancers, liver complications, liver transplantation and death. The primary endpoint was overall survival. Survival curves according to LSM were first performed using Kaplan-Meier method for the primary endpoint, and Aalen-Johansen method for secondary outcomes to take into account competitive risks. In a second step, a Cox proportional hazard model analysis was done to identify independent predictors of overall survival., Results: Median follow-up was 27 months [IQR: 25-38]. Fifty-five patients died and three patients had liver transplantation. Overall survival significantly decreased as baseline LSM increased. Twenty-one patients (0.9%) had a liver event, 142 (6.3%) developed cancer (excluding HCC) and 151 (6.7%) had a cardiovascular event during follow-up. By multivariable analysis, independent predictors of overall survival were as follows: baseline LSM (adjusted HR (aHR) = 2.85 [1.65-4.92], P = .0002), age (aHR = 1.11 [1.08-1.13], P < .0001) and male sex (aHR = 2.05 [1.17-3.57], P = .012). Patients with elevated LSM were also more likely to develop cardiovascular, and liver events but not other cancers., Conclusion: LSM can be used to predict survival, cardiovascular and liver complications in NAFLD patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients' body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis., Design: We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy., Results: 391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75-0.88 for F2-4, 0.83-0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m 2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m 2 , respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe., Conclusion: High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI., Competing Interests: Competing interests: VW-SW, GL-HW, HL-YC and VdL have served as speakers for Echosens., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease (NAFLD) as it defines the subgroup of patients with impaired prognosis. The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone (representing indeterminate diagnosis) of fibrosis tests. Here, we aimed to determine the best combination of non-invasive tests for the diagnosis of advanced fibrosis in NAFLD., Methods: A total of 938 patients with biopsy-proven NAFLD were randomized 2:1 into derivation and validation sets. All patients underwent liver stiffness measurement with vibration controlled transient elastography (VCTE) and blood fibrosis tests (NAFLD fibrosis score, Fibrosis-4 [FIB4], Fibrotest, Hepascore, FibroMeter). FibroMeter VCTE , which combines VCTE results and FibroMeter markers in a single test, was also calculated in all patients., Results: For the diagnosis of advanced fibrosis, VCTE was significantly more accurate than the blood tests (area under the receiver operating characteristic curve [AUROC]: 0.840 ± 0.013, p ≤0.005). FibroMeter was the most accurate blood test (AUROC: 0.793 ± 0.015, p ≤0.017). The combinatory test FibroMeter VCTE outperformed VCTE and blood tests (AUROC: 0.866 ± 0.012, p ≤0.005). The sequential combination of FIB4 then FibroMeter VCTE (FIB4-FM VCTE algorithm) or VCTE then FibroMeter VCTE (VCTE-FM VCTE algorithm) provided an excellent diagnostic accuracy of 90% for advanced fibrosis, with liver biopsy only required to confirm the diagnosis in 20% of cases. The FIB4-FM VCTE and VCTE-FM VCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed., Conclusion: The sequential combination of fibrosis tests in the FIB4-FM VCTE and VCTE-FM VCTE algorithms provides a highly accurate solution for the diagnosis of advanced fibrosis in NAFLD. These algorithms should now be validated for the diagnosis of advanced liver fibrosis in diabetology or primary care settings., Lay Summary: The evaluation of liver fibrosis is mandatory in non-alcoholic fatty liver disease (NAFLD), as advanced fibrosis identifies the subgroup of patients with impaired prognosis. FibroMeter VCTE is a new fibrosis test combining blood markers and the result of vibration controlled transient elastography (VCTE) into a single diagnostic test. Our results show that FibroMeter VCTE outperforms other blood fibrosis tests and VCTE alone for the diagnosis of advanced fibrosis in a large multi-centric cohort of 938 patients with biopsy-proven NAFLD. Sequential algorithms using a simple blood test or VCTE as a first-line procedure, then FibroMeter VCTE as a second-line test accurately classified 90% of patients., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: FibroScan's M and XL probes give significantly different results, which could lead to misevaluation of liver fibrosis if the correct probe is not chosen. According to the manufacturer, the M probe should be used when the skin-liver capsule distance (SCD) is <25 mm, and the XL probe should be used when SCD is ≥25 mm. We aimed at validating this recommendation and defining the conditions of use for FibroScan probes in clinical practice., Methods: Four hundred thirty-nine patients with biopsy-proven chronic liver disease were included. Of them, 382 had successful examinations with both M and XL probes. Advanced fibrosis was defined as Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) F ≥3 or Metavir F ≥2., Results: In a same patient, XL probe results were significantly lower than M probe results: 7.9 (5.6-11.7) vs 9.5 (6.7-14.6) kPa, respectively (P < 0.001). After matching for age, sex, liver fibrosis, and serum transaminases, M probe results in patients with SCD <25 mm and XL probe results in those with SCD ≥25 mm did not significantly differ: 8.8 (6.0-12.0) vs 9.1 (6.7-12.8) kPa, respectively (P = 0.175). Of note, 81.4% of patients with body mass index (BMI) <32 kg/m had SCD <25 mm, and 77.7% of patients with BMI ≥32 kg/m had SCD ≥25 mm. A practical algorithm using BMI first and then the FibroScan Automatic Probe Selection tool was proposed to help physicians accurately choose which probe to use in clinical practice., Conclusions: There is no significant difference in results between M and XL probes when they are used in the right conditions. In clinical practice, the probe should be selected according to the BMI and the Automatic Probe Selection tool.

Background and Aim: Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in non-alcoholic fatty liver disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters., Methods: All CAP examinations performed in NAFLD patients with a liver biopsy performed within 1 week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activity score, and steatosis graded as follows: S0, steatosis < 5%; S1, 5-33%; S2, 34-66%; S3, >66%., Results: Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis < 5%. The area under the receiver-operating characteristics curve of CAP for steatosis ≥S2 and S3 was 0.80 and 0.66, respectively. At a cut-off value of 310 dB/m, the sensitivity, specificity, and positive and negative predictive values for ≥S2 steatosis were 79%, 71%, 86%, and 71%, respectively. Discordance of at least one grade between CAP and steatosis was observed in 81 patients. By multivariate analysis, only steatosis S2S3 was associated with no discordance. By multivariate analysis, only BMI ≥ 30 kg/m(2) was significantly associated with CAP > 310 dB/m., Conclusion: The association of CAP with steatosis, especially in patients with non-alcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: Transient elastography (TE; Fibroscan, Echosens, France) is a non-invasive and reproducible approach to assess liver stiffness (LS). LS has been reported to be associated with fibrosis but central venous pressure (CVP) can also influence LS values. We sought to evaluate the correlation between LS and CVP in a large cohort of children and adults with congenital heart disease., Methods: All patients referred in our institution between 2012 and 2013 for diagnostic or interventional right heart catheterisation (RHC) were prospectively enrolled excluding patients with acute heart failure, chronic alcohol abuse, chronic liver disease, severe obesity and ascites. Patients underwent LS measurement and CVP measurement by RHC under general anaesthesia within the same or subsequent day., Results: Sixty children (7.4±5.5 years) and 36 adults (38±16 years) were included. Median CVP was 6 mm Hg (range 3-15), median LS was 5 kPa (range 2.8-47.2). LS significantly correlated with CVP (r=0.75, p<10(-4)). In the two subgroups (ie, children and adults), correlation was r=0.68 and r=0.84 (p<10(-4)), respectively. In the overall population, the area under the curve of LS for identification of CVP >10 mm Hg was 0.972 (95% CI 0.855 to 1; p<0.05). Optimal cut-off value of LS for detection of CVP >10 mm Hg was 8.8 kPa (sensitivity=91.67%, specificity=96.25%)., Conclusions: LS measurement using TE is a rapid and reliable method to evaluate CVP in patients with congenital heart disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Elastography is a promising non-invasive approach for assessing liver fibrosis. We assessed diagnostic performances of liver and spleen stiffness using supersonic shear imaging for diagnosing cirrhosis severity and oesophageal varices., Methods: 401 consecutive cirrhotic patients were prospectively enrolled from November 2012 to March 2014. All patients underwent liver and spleen stiffness measurement with supersonic shear imaging and Fibroscan., Results: Failures of measurement were 6.2% and 29.2% for liver and spleen stiffness (supersonic shear imaging), and 18.4% for liver stiffness (Fibroscan). Liver and spleen stiffness were correlated with severity of cirrhosis, with values increasing according to Child-Pugh subclasses and presence of complications. With a negative predictive value ≥90%, liver stiffness cut-offs for high-risk oesophageal varices, history of ascites, Child-Pugh B/C, variceal bleeding and clinical decompensation were 12.8, 19, 21.4, 30.5, and 39.4 kPa, respectively. Areas under the curve of spleen and liver stiffness (supersonic shear imaging), and liver stiffness (Fibroscan) were 0.80, 0.77 and 0.73 respectively for detection of oesophageal varices., Conclusion: Liver stiffness using supersonic shear imaging is a relevant diagnostic tool for assessing cirrhosis severity and its complications. Spleen stiffness shows promising results for the detection of oesophageal varices but is not yet sufficiently robust for clinical practice owing to high failure rates., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Liver stiffness measurement (LSM) by transient elastography is a popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize patients and do not clearly indicate the confidence of diagnosis., Aim: We derived and validated probability functions of fibrosis and cirrhosis based on LSM and determined the effect of alanine aminotransferase (ALT) on the scores., Methods: Consecutive chronic hepatitis B patients who underwent liver function tests, LSM, and liver biopsies at six European and Asian centers (2/3 in the training cohort and 1/3 in the validation cohort) were recruited. Binary logistic regression was performed to predict the probabilities of different fibrosis stages based on LSM and/or ALT., Results: A total of 1,051 patients were included in the final analysis (53 % with ALT ≥ 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The probability functions (LiFA-HBV score) with and without ALT adjustment closely mirrored the proportion with different fibrosis stages in both the training and validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear relationship with LSM for each fibrosis stage (r (2) = 0.018-0.13). Based on relative integrated discrimination improvement, the addition of ALT to the LiFA-HBV score increased the correct reclassification of F3-4 and F4 by 5 and 17 %, respectively., Conclusions: ALT increases LSM in a linear fashion in chronic hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately predicts the probability of fibrosis. ALT adjustment increases the rate of reclassification modestly and is not essential.

Background & Aims: Non-invasive assessment of liver fibrosis by elastography is a rapidly developing field with frequent technological innovations. The aim of this study was to assess the diagnostic performances of Supersonic Shear Imaging (SSI) for the diagnosis of liver fibrosis in chronic liver disease., Methods: A total of 349 consecutive patients with chronic liver diseases who underwent liver biopsy from November 2011 to October 2013 were prospectively enrolled. For each patient, liver stiffness was assessed by SSI, ARFI, FibroScan® (M probe for patients with BMI <30 kg/m(2), and XL probe for patients with BMI ⩾30 kg/m(2)), performed within two weeks of liver biopsy. Areas under the receiver operating curves (AUROCs) were performed and compared for each degree of liver fibrosis., Results: SSI, FibroScan®, and ARFI correlated significantly with histological fibrosis score (r=0.79, p<0.00001; r=0.70, p<0.00001; r=0.64, p<0.00001, respectively). AUROCs of SSI, FibroScan®, and ARFI were 0.89, 0.86, and 0.84 for the diagnosis of mild fibrosis; 0.88, 0.84, and 0.81 for the diagnosis of significant fibrosis; 0.93, 0.87, and 0.89, for the diagnosis of severe fibrosis; 0.93, 0.90, and 0.90 for the diagnosis of cirrhosis, respectively. SSI had a higher accuracy than FibroScan® for the diagnosis of severe fibrosis (⩾F3) (p=0.0016), and a higher accuracy than ARFI for the diagnosis of significant fibrosis (⩾F2) (p=0.0003). No significant difference was observed for the diagnosis of mild fibrosis and cirrhosis., Conclusions: SSI is an efficient method for the assessment of liver fibrosis in chronic liver diseases, comparing favourably to FibroScan® and ARFI., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan®) is a recent method for non-invasive assessment of steatosis. Its usefulness in clinical practice is unknown. We prospectively investigated the determinants of CAP failure and the relationships between CAP and clinical or biological parameters in a large cohort of consecutive patients., Methods: All CAP examinations performed in adult patients with suspected chronic liver disease were included. CAP failure was defined as zero valid shot. The following factors were analyzed for their influence on CAP value and the relationships between CAP and clinico-biological parameters: age, gender, body mass index, waist circumference, hypertension, diabetes, metabolic syndrome, alcohol use, liver stiffness measurement, indication, and different biological parameters., Results: CAP failure occurred in 7.7% of 5323 examinations. By multivariate analysis, factors independently associated with CAP measurement failure were female gender, BMI, and metabolic syndrome. By multivariate analysis, factors significantly associated with elevated CAP were BMI [25-30]kg/m(2), BMI >30kg/m(2), metabolic syndrome, alcohol >14 drink/week and liver stiffness >6kPa. CAP increased with the number of parameters of metabolic syndrome, BMI, waist circumference, the presence of diabetes or hypertension, and the cause of the disease. In the 440 patients with liver biopsy, for the diagnosis of steatosis >10%, steatosis >33%, and steatosis >66%, AUROCs of CAP were 0.79 (95% CI 0.74-0.84, p<0.001), 0.84 (95% CI 0.80-0.88, p<0.001), 0.84 (95% CI 0.80-0.88, p<0.001), respectively., Conclusions: CAP provides an immediate assessment of steatosis simultaneously with liver stiffness measurement. The strong association of CAP with the metabolic syndrome and alcohol use could be of interest for the follow-up of NAFLD or alcoholic patients., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of critical steps defined by occurrence of cirrhosis without complications (F4.1), esophageal varices (F4.2), and severe complications (F4.3): primary liver cancer, variceal bleeding, or decompensation (ascites, encephalopathy, or jaundice)., Methods: The updated individual data of 3927 patients (1046 cirrhotics) without complications at baseline were pooled from three prospective cohorts called "EPIC", "Paris", and "Bordeaux" cohorts., Results: At 5 years, among 501 patients without varices at baseline (F4.1) varices occurred in 19 patients [F4.2 incidence of 4.0% (95% CI 2.2-5.8)]. The predictive performance (AUROC) of FT was 0.77 (0.66-0.84; p<0.001). At 10 years severe complications occurred in 203 patients, [F4.3 incidence of 13.4% (9.6-17.1)], including primary liver cancer in 84 patients [6.4% (3.5-9.3)]. FT was predictive (Cox adjusted on treatment) of severe complications [AUROC 0.79 (76-82); p<0.0001], including primary liver cancer [AUROC 0.84 (80-87); p<0.0001]. Similarly TE was predictive of severe complications [AUROC 0.77 (72-81); p<0.0001], including primary liver cancer [AUROC 0.86 (81-90); p<0.0001]., Conclusions: FibroTest™ and TE increase were associated with the occurrence of all severe complications including hepatocellular carcinoma, hepatic insufficiency, and variceal bleeding. FibroTest™ increase was also associated with the occurrence of esophageal varices., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: To compare the diagnostic performance of acoustic radiation force impulse (ARFI) elastography with that of FibroScan M and XL probes and FibroTest in the staging of fibrosis in patients with chronic liver disease., Materials and Methods: This study received ethics approval, and all participants provided written informed consent. A total of 321 consecutive patients with chronic liver disease who underwent liver biopsy were prospectively enrolled from April 2010 to May 2012. Liver disease was caused by viral hepatitis (n = 136), alcoholic or nonalcoholic steatohepatitis disorders (n = 113), or some other disease (n = 72). In each patient, liver stiffness was evaluated with ARFI elastography, M and XL probes, and FibroTest within 1 month before liver biopsy. Histologic staging of liver fibrosis served as the reference standard., Results: Liver stiffness measurement failure rates were 11.2% with the M probe (36 of 321 patients), 2.3% with the XL probe (six of 260 patients), and 0% with ARFI elastography (0 of 321 patients). Unreliable results with ARFI elastography were more frequent in obese patients (those with a body mass index of 30 kg/m(2) or more) (42 of 86 patients [48.8%] vs 34 of 235 patients [14.5%], P < .0001). No significant difference was found between ARFI elastography and the M probe in the diagnosis of cirrhosis (area under under the receiver operating characteristic curve [Az], 0.88 vs 0.91; P = .12) or severe fibrosis (Az, 0.85 vs 0.89; P = .15); however, the M probe demonstrated better results in the diagnosis of moderate fibrosis (Az, 0.81 vs 0.88; P = .008). No significant difference was found between ARFI elastography and the XL probe in the diagnosis of moderate fibrosis, severe fibrosis, or cirrhosis. The diagnostic performance of ARFI elastography improved when it was applied in nonobese patients (Az of ARFI for cirrhosis and severe fibrosis = 0.92 and 0.91, respectively, in nonobese patients [P = .0002] and 0.63 and 0.63, respectively, in obese patients [P < .0001])., Conclusion: ARFI elastography is reliable in the assessment of liver fibrosis in patients with chronic liver disease, especially nonobese patients., (© RSNA, 2013.)

Unlabelled: BACKGROUND AND RATIONALE FOR THE STUDY: Limited studies have aimed to define the cut-offs of XL probe (XL cut-offs) for different stages of liver fibrosis, whereas those of M probe (M cut-offs) may not be applicable to XL probe. We aimed to derive appropriate XL cut-offs in overweight patients. Patients with liver stiffness measurement (LSM) by both probes were recruited. XL cut-offs probe for corresponding M cut-offs were derived from an exploratory cohort, and subsequently validated in a subgroup patients also underwent liver biopsy. The diagnostic accuracy of XL cut-offs to diagnose advanced fibrosis was evaluated., Results: Total 517 patients (63% male, mean age 58) who had reliable LSM by both probes were included in the exploratory cohort. There was a strong correlation between the LSM by M probe (LSM-M) and LSM by XL probe (LSM-XL) (r² = 0.89, p < 0.001). A decision tree using LSM-XL was learnt to predict the 3 categories of LSM-M (< 6.0kPa, 6.0-11.9kPa and ≥ 12.0kPa), and XL cut-offs at 4.8kPa and 10.7kPa were identified. These cut-offs were subsequently validated in a cohort of 147 patients who underwent liver biopsy. The overall accuracy was 89% among 62 patients whose LSM-XL < 4.8kPa or ≥ 10.7kPa. These cut-offs would have avoided under-staging of fibrosis among patients with body mass index (BMI) > 25-30 kg/m2 but not > 30 kg/m2., Conclusions: XL cut-offs at 4.8kPa and 10.7kPa were the best estimates of 6.0kPa and 12.0kPa of M probe for patients with BMI > 25-30 kg/m2. Patients with BMI > 30 kg/m² might use M probe cut-offs for XL probe.

Objectives: Liver stiffness measurement (LSM) by transient elastography is a noninvasive test of liver fibrosis, but cannot be performed in a significant proportion of obese patients. The aim of this study was to evaluate the performance of the new XL probe in patients with nonalcoholic fatty liver disease (NAFLD)., Methods: Liver biopsy and paired LSM by both the original M probe and XL probe were performed on 193 consecutive NAFLD patients in France and Hong Kong., Results: Compared with M probe, XL probe was more likely to achieve 10 valid measurements (95% vs. 81%; P<0.001) and a success rate of over 60% (90% vs. 74%; P<0.001). The areas under receiver operating characteristics curves of XL probe for F2, F3, and F4 disease were 0.80, 0.85, and 0.91, respectively. XL probe tended to generate lower LSM than M probe in the same patient. At a cutoff of 7.2 kPa, the sensitivity, specificity, positive, and negative predictive values for F3 or greater disease were 78%, 78%, 60%, and 89%, respectively. Discordance of at least two stages between XL probe and histology was observed in 16 (9%) patients. Body mass index (BMI) over 35 kg/m(2) was independently associated with discordance (adjusted odds ratio 9.09; 95% confidence interval 1.10-75.43). Reliable measurements by XL probe were obtained in 75% of the overall population and 65% of patients with BMI over 30 kg/m(2)., Conclusions: LSM by XL probe can be performed successfully in most NAFLD patients, but obesity is associated with less accurate and reliable measurements.

Introduction: Recently, a study showed that Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could efficiently separate steatosis grades. The aim of this study was to prospectively evaluate the performance of CAP for the diagnosis of steatosis in patients with chronic liver disease., Patients and Methods: Consecutive patients with chronic liver disease had steatosis diagnosis using CAP, blood sample and liver biopsy. Steatosis was graded as the percentage of hepatocytes with fat: S0 ≤ 10%, S1: 11 ~ 33%, S2: 34 ~ 66%, S3 ≥ 67%., Results: Characteristics of the 112 patients included were as follows: age 54 years, BMI 26 kg m(-) ², HCV 36%, NAFLD 25%. Steatosis repartition was: S0 52%, S1 19%, S2 14%, S3 15%. CAP was significantly correlated with SteatoTest, Fatty Liver Index (FLI), percentage of steatosis on liver biopsy, steatosis grade and slightly with liver stiffness, but not with fibrosis and activity grade on liver biopsy. Using CAP vs SteatoTest vs FLI score, Area Under the Receiver-Operating Characteristics (ROC) curves (AUROC)s were 0.84 vs 0.72 vs 0.72 for the diagnosis of steatosis ≥ S1, 0.86 vs 0.73 vs 0.71 for the diagnosis of steatosis ≥ S2, and 0.93 vs 0.73 vs 0.75 for the diagnosis of steatosis S3 respectively. For a sensitivity ≥ 90%, cut-offs of CAP were 215 dB m(-1) for S ≥ 1, 252 dB m(-1) for S ≥ 2, and 296 dB m(-1) for S3., Conclusion: CAP is very efficient to detect even low grade steatosis. CAP being implemented on FibroScan(®) (Echosens, Paris, France), both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of non-invasive techniques for the management of chronic liver diseases., (© 2012 John Wiley & Sons A/S.)

Background & Aims: Unreliable results of liver stiffness measurement are obtained in 16% of cases and are independently associated with body mass index (BMI) greater than 30 kg/m(2). A new FibroScan® probe (XL probe) was designed specifically for obese patients. The aim of this study was to evaluate the accuracy of liver stiffness measurement using M and XL probes of Fibroscan® for the diagnosis of fibrosis and cirrhosis in a large cohort of patients., Methods: Consecutive patients undergoing liver biopsies for chronic liver disease were prospectively recruited. Liver stiffness measurement was performed within 1 week before liver biopsy using both M and XL probes of FibroScan®., Results: A total of 286 patients were evaluated. A reliable liver stiffness measurement using M probe was obtained in 79.7% of cases. In the other 21.3%, liver stiffness measurement using XL probe was obtained in 56.9% of patients. A strong correlation was found between M and XL values, regardless of BMI. In all groups, median liver stiffness measurement using the XL probe was significantly lower than liver stiffness measurement using the M probe. By multivariate analysis, unsuccessful liver stiffness examination with M probe was independently associated with age >50 years and BMI >30 kg/m(2). By univariate analysis, only BMI >30 kg/m(2) was associated with unsuccessful liver stiffness measurement with XL probe. No significant difference was observed between the M and XL probes for the diagnosis of liver fibrosis., Conclusions: Liver stiffness measurement with either M or XL probe is possible in 91.2% of patients with comparable diagnostic accuracy. In clinical practice, the M probe could be used as first step for liver stiffness measurement. In case of no valid shot or unreliable measurement, the XL probe could be used. This result could be useful for the assessment of liver fibrosis in NAFLD and/or obese patients., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: Precise evaluation of the level of liver fibrosis is recommended in patients with chronic hepatitis C (CHC). Blood fibrosis tests and Fibroscan are now widely used for the non-invasive diagnosis of liver fibrosis. Detailed fibrosis stage classifications have been developed to provide an estimation of the liver fibrosis stage from the results of these non-invasive tests. Our aim was to develop a new and more accurate fibrosis stage classification by using new scores combining non-invasive fibrosis tests., Methods: In all, 729 patients with CHC (exploratory set: 349; validation set: 380) had liver biopsy for Metavir fibrosis (F) staging, and 6 fibrosis tests: Fibroscan, Fibrotest, FibroMeter, Hepascore, FIB-4, APRI., Results: Exploratory set: Fibroscan and FibroMeter were the independent predictors of different diagnostic targets of liver fibrosis. New fibrosis indexes combining FibroMeter and Fibroscan were thus developed for the diagnosis of clinically significant fibrosis (CSF-index) or severe fibrosis (SF-index). The association of CSF- and SF-indexes provided a new fibrosis stage classification (CSF/SF classification): F0/1, F1/2, F2 ± 1, F2/3, F3 ± 1, F4. Validation set: CSF/SF classification had a high diagnostic accuracy (85.8% well-classified patients), significantly higher than the diagnostic accuracies of FibroMeter (69.7%, P<0.001), Fibroscan (63.3%, P<0.001), or Fibrotest (43.9%, P<0.001) classifications., Conclusions: The association of new fibrosis indexes combining FibroMeter and Fibroscan provides a new fibrosis stage classification. This classification is significantly more accurate than Fibrotest, FibroMeter, or Fibroscan classifications, and improves the accuracy of the non-invasive diagnosis of liver fibrosis stages to 86% without any liver biopsy.

Background & Aims: Liver stiffness can be measured noninvasively to assess liver fibrosis in patients with chronic hepatitis C. In patients with chronic liver diseases, level of fibrosis predicts liver-related complications and survival. We evaluated the abilities of liver stiffness, results from noninvasive tests for fibrosis, and liver biopsy analyses to predict overall survival or survival without liver-related death with a 5-year period., Methods: In a consecutive cohort of 1457 patients with chronic hepatitis C, we assessed fibrosis and, on the same day, liver stiffness, performed noninvasive tests of fibrosis (FibroTest, the aspartate aminotransferase to platelet ratio index, FIB-4), and analyzed liver biopsy samples. We analyzed data on death, liver-related death, and liver transplantation collected during a 5-year follow-up period., Results: At 5 years, 77 patients had died (39 liver-related deaths) and 16 patients had undergone liver transplantation. Overall survival was 91.7% and survival without liver-related death was 94.4%. Survival was significantly decreased among patients diagnosed with severe fibrosis, regardless of the noninvasive method of analysis. All methods were able to predict shorter survival times in this large population; liver stiffness and results of FibroTest had higher predictive values. Patient outcomes worsened as liver stiffness and FibroTest values increased. Prognostic values of stiffness (P<.0001) and FibroTest results (P<.0001) remained after they were adjusted for treatment response, patient age, and estimates of necroinflammatory grade., Conclusions: Noninvasive tests for liver fibrosis (measurement of liver stiffness or FibroTest) can predict 5-year survival of patients with chronic hepatitis C. These tools might help physicians determine prognosis at earlier stages and discuss specific treatments, such as liver transplantation., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Liver stiffness measurement (LSM) failure when using transient elastography occurs in 2-10% of patients, and is generally related to obesity. The aim of this prospective study was to assess the feasibility of LSM when using a new XL probe on patients with a body mass index (BMI) > or =30 kg/m(2)., Methods: For each patient, LSM was performed using both M probe (currently available and dedicated to patients with standard morphology) and XL probe (dedicated to overweighed patients). A blood sample was taken to assess usual biological variables and simple readily available fibrosis blood tests., Results: Ninety-nine patients were included (27 men, mean age 52 years, mean BMI 40.5 kg/m(2)). LSM was successful (10 valid measurements) in 45% of the cases with the M probe, vs 76% of the cases with the XL probe (P<0.001). Fifty-nine percent of those who could not be measured (<10 valid measurements) using the M probe could successfully be measured using the XL probe. In the 44 patients successfully measured with both probes, LSM was correlated with the platelet count, prothrombin time, gamma-glutamyltransferase, aspartate aminotransferase, fasting glucose, AST platelet ratio index, Forns score and FIB-4., Conclusion: The new XL probe allows providing a higher rate of LSM than the M probe in patients with an increased BMI and shows promising results for the evaluation of liver fibrosis.

Background: The only way to diagnose nodular regenerative hyperplasia (NRH) is liver biopsy., Aim: To evaluate in a prospective study the performance of noninvasive liver investigations in patients with NRH., Methods: All consecutive patients with NRH who were being followed up in our unit from 2004 to 2007 were included. All biopsy specimens were reanalysed independently to confirm the diagnosis of NRH (classified as certain or probable) and to assess portal or sinusoidal associated fibrosis. All patients had liver stiffness (using FibroScan) and FibroTest measurements. Magnetic resonance imaging (MRI) was performed using two contrast agents (gadolinium-chelate and ferucarbotran)., Results: Thirty patients were included (mean age: 53 years). Median liver stiffness value was 7.9 kPa (range: 3.5-16.8), with 63% of the patients having more than 7.1 kPa. No relationship was found between NRH with or without portal hypertension and liver stiffness or Fibrotest. No correlation was found between liver stiffness and portal and/or sinusoidal fibrosis. In patients studied with MRI, 55% had portal hypertension and 9% a diffuse fine-nodular loss of iron uptake after ferucarbotran injection., Conclusion: Liver stiffness and FibroTest values may be increased in NRH patients, with no correlation with portal hypertension or portal and sinusoidal fibrosis. Contrast-enhanced MRI is disappointing in NRH.

Unlabelled: Liver stiffness measurement (LSM) based on transient elastography (TE, FibroScan) is gaining in popularity for noninvasive assessment of liver fibrosis. However, LSM has limitations, which have not yet been thoroughly evaluated. We prospectively investigated the frequency and determinants of LSM failure and unreliable results over a 5-year period, based on 13,369 examinations (134,239 shots). LSM failure was defined as zero valid shots, and unreliable examinations were defined as fewer than 10 valid shots, an interquartile range (IQR)/LSM greater than 30%, or a success rate less than 60%. LSM failure occurred in 3.1% of all examinations (4% at first examination [n = 7261]) and was independently associated at first examination with body mass index (BMI) greater than 30 kg/m(2) (odds ratio [OR], 7.5; 95% confidence interval [CI], 5.6-10.2; P = 0.0001), operator experience fewer than 500 examinations (OR 2.5 [1.6-4.0]; P = 0.0001); age greater than 52 years (OR 2.3 [1.6-3.2]; P = 0.0001), and type 2 diabetes (OR 1.6 [1.1-2.2]; P = 0.009). Unreliable results were obtained in a further 15.8% of cases (17% at first examination) and were independently associated at first examination with BMI greater than 30 kg/m(2) (OR 3.3 [2.8-4.0]; P = 0.0001), operator experience fewer than 500 examinations (OR 3.1 [2.4-3.9]; P = 0.0001), age greater than 52 years (OR 1.8 [1.6-2.1]; P = 0.0001), female sex (OR 1.4 [1.2-1.6], P = 0.0001), hypertension (OR 1.3 [1.1-1.5]; P = 0.003), and type 2 diabetes (OR 1.2 [1.0-1.5]; P = 0.05). When metabolic syndrome and waist circumference were taken into account in a subgroup of 2835 patients, waist circumference was the most important determinant of LSM failure and unreliable results., Conclusion: In our experience, liver stiffness measurements are uninterpretable in nearly one in five cases. The principal reasons are obesity, particularly increased waist circumference, and limited operator experience. These results emphasize the need for adequate operator training and for technological improvements in specific patient subpopulations.

Unlabelled: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty-six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver-operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase-to-alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81, P < 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0-2 disease were associated with discordance., Conclusion: Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa.

Unlabelled: The purpose of this study was to assess the influence of success rate and interquartile range on the accuracy of transient elastography for the diagnostic of fibrosis in hepatitis C virus infection. Two-hundred fifty-four consecutive patients had liver stiffness measurements and liver biopsy of at least 15 mm. Discordances of at least two stages between transient elastography and histological assessment were observed in 28 cases (11%). Factors of discordance were assessed by comparing the 28 misclassified cases with the 226 others. In multivariate analysis, fibrosis stage (F0-F2 versus F3-F4) and the ratio interquartile range/median value of liver stiffness measurement (IQR/M) were associated with discordances (P or= 0.21, discordances of at least two stages of fibrosis were respectively observed in 10 of 135 cases (7.4%) versus 18 of 119 cases (15.1%) (P or= 0.21 versus IQR/M < 0.21, for the diagnosis of liver fibrosis F >or= 2, F >or= 3, F = 4, areas under the receiver operating characteristic curve (AUROCs) were 0.80 (95% confidence interval [CI], 0.73-0.89) versus 0.81 (95% CI, 0.70-0.90), (P = NS); 0.80 (95% CI, 0.72-0.88) versus 0.89 (95% CI, 0.83-0.95) (P = 0.04); and 0.86 (95% CI, 0.77-0.94) versus 0.95 (95% CI, 0.92-0.99) (P = NS). No association was found between success rate and discordance., Conclusion: IQR/M is a factor of overestimation of liver fibrosis, and the most discriminant cutoff value is 0.21. Success rate is not a factor of accuracy for the diagnosis of hepatic fibrosis.

Background/aims: To assess prospectively the accuracy of transient elastography (TE, FibroScan) for the detection of cirrhosis and oesophageal varices (OV) in chronic hepatitis C (CHC), as compared with currently available non-invasive methods (AST/ALT ratio (AAR), APRI, prothrombin index (PI), platelet count (PC), FibroTest (FT) and Lok index)., Methods: All tests were performed the day of liver biopsy (LB), taken as reference, in 298 consecutive CHC patients (cirrhosis: 70; Child-Pugh A: 70; OV: 25)., Results: TE had the best diagnostic accuracy for detection of cirrhosis (AUROCs: TE 0.96 vs. FT 0.82, Lok and APRI 0.80, PC 0.79, PI 0.73, AAR 0.61, respectively; p < 0.0001). Overall, the percentage of saved LB was: TE (cut-off: 12.5 kPa) 90%, PC 82%, FT 79%, PI 77%, AAR 76%, APRI 70%, and Lok 45%, respectively. At a cut-off of 21.5 kPa, TE predicted the presence of OV with 76% sensitivity and 78% specificity and correctly classified 73% of patients vs. AAR 81%, Lok 77%, FT, PI 70%, PC 69%, and APRI 66%, respectively., Conclusions: TE is currently the most accurate non-invasive method for early detection of cirrhosis in CHC (cut-off: 12.5 kPa), as compared with other available methods, but cannot replace endoscopy for OV screening.

Objective: Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness in adult patients. The usefulness of FibroScan in children with chronic liver diseases is unknown. The aim of this prospective study was to evaluate the feasibility of liver stiffness measurement and to compare FibroScan, Fibrotest, and aspartate transaminase to platelets ratio index (APRI) with liver biopsy for the diagnosis of cirrhosis in children with chronic liver diseases., Patients and Methods: Between February 2004 and October 2005, 116 consecutive children with chronic liver diseases were prospectively included. All except 1 child (58 boys, mean age 10.7 years) could have noninvasive tests for fibrosis: FibroScan, Fibrotest, and APRI, and, when necessary, a liver biopsy (n = 33)., Results: FibroScan, Fibrotest, and APRI were correlated with clinical or biological parameters of chronic liver diseases, but the FibroScan marker correlated most with all parameters. By histology, the METAVIR fibrosis category score was F1 in 7 cases, F2 in 8 cases, F3 in 6 cases, and F4 in 12 cases. FibroScan, Fibrotest, and APRI were significantly correlated with the METAVIR fibrosis score. For the diagnosis of cirrhosis, the area under the receiver operating characteristic curve was 0.88, 0.73, and 0.73 for FibroScan, Fibrotest, and APRI, respectively., Conclusions: These results indicate that liver stiffness measurement is feasible in children and is related to liver fibrosis. A specific probe dedicated to children and slender patients has thus been developed and is currently under evaluation. The FibroScan equipped with this specific probe could become a useful tool for the management of chronic liver diseases in children.