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Inter-platform variation in liver stiffness evaluation (LSE) could hinder dissemination and clinical implementation of new ultrasound methods. We aimed to determine whether measurements of liver stiffness by bi-dimensional shear wave elastography (2D-SWE) with a Supersonic Imagine apparatus are comparable to those made by vibration-controlled transient elastography (VCTE).We collected data from 1219 consecutive patients with chronic liver disease who underwent LSE by VCTE and 2D-SWE (performed by blinded operators), on the same day, at a single center in France from September 2011 through June 2019. We assessed the ability of liver stiffness value distributions and 2D-SWE performances to identify patients with compensated advanced chronic liver disease (cACLD) according to the Baveno VI criteria, based on VCTE cut-off values.VCTE and 2D-SWE values correlated (Pearson's correlation coefficient, 0.882; P.0001; Lin concordance coefficient, 0.846; P.0001). The median stiffness values were 6.7 kPa with VCTE (interquartile range, 4.8-11.6 kPa) and 7.1 kPa with 2D-SWE (interquartile range, 5.4-11.1 kPa) (P = .736). 2D-SWE values were slightly higher in the low percentiles and lower in the high percentiles; the best match with VCTE values were at approximately 7-9 kPa. The area under the curve of 2D-SWE for identifying of VCTE values below 10 was 0.964 (95% CI, 0.952-0.976) and for VCTE values above 15 kPa was 0.976 (95% CI, 0.963-0.988), with Youden index-associated cut-off values of 9.5 and 13kPa and best accuracy cut-off values of 10 kPa and 14 kPa, respectively. A 2D-SWE cut-off value of 10 kPa detected VCTE values below 10k Pa with 92% sensitivity, 87% specificity, and 91% accuracy.Measurement of liver stiffness by VCTE or 2D-SWE produces comparable results. 2D-SWE accurately identifies patients with cACLD according to the Baveno VI criteria based on VCTE cut-off values. A 10 kPa 2D-SWE cut-off value can be used to rule out cACLD.

BACKGROUND One of the unmet needs in patients with metabolic risks is the prediction of metabolic liver disease (MLD) by noninvasive tests (NITs). OBJECTIVE The primary aim of this study was to construct a new quantitative test for the diagnosis of nonalcoholic steatohepatitis (NASH) using a simplified histological definition. PATIENTS AND METHODS As a reference, we used a simplified histological definition of NASH derived from the FLIP-CRN-definition that does not require the presence of steatosis and the presence of both lobular inflammation and ballooning. We analyzed 1081 patients from two prospective cohorts at risk of MLD who had biopsies and contemporaneous blood samples. These patients were divided randomly into a training group (n=541) and a control group (n=540) for internal validation. The new test was compared with standard tests, and applied in two large populations at risk of MLD. RESULTS Out of 1081 patients with biopsy, 39 (3.6%) cases with significant inflammatory activity or fibrosis (A2orF2) were missed by the current histological definitions. The combination of 11 parameters permitted to construct a test (NIT-NASHs) predicting NASH with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% confidence interval: 0.730-0.810), confirmed in the control group 0.814 (0.774-0.847). The AUROCs of NIT-NASHs were higher (all P

SummaryBackground The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. Aim To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. Methods We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. Results LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (

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/m2 ) 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

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). FibroMeterVCTE, 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 FibroMeterVCTE outperformed VCTE and blood tests (AUROC: 0.866 ± 0.012, p ≤0.005). The sequential combination of FIB4 then FibroMeterVCTE (FIB4-FMVCTE algorithm) or VCTE then FibroMeterVCTE (VCTE-FMVCTE 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-FMVCTE and VCTE-FMVCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed. Conclusion The sequential combination of fibrosis tests in the FIB4-FMVCTE and VCTE-FMVCTE 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. FibroMeterVCTE 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 FibroMeterVCTE 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 FibroMeterVCTE as a second-line test accurately classified 90% of patients.

International audience; Because only a minority of patients with nonalcoholic fatty liver disease (NAFLD) have advanced fibrosis and would eventually develop liver-related complications, current guidelines recommend initial assessment with noninvasive tests of fibrosis.1-3 Most previous studies focused on overweight and obese patients. Despite a strong association between obesity and NAFLD, 3%-30% of people with relatively normal body mass index (BMI) may still have NAFLD.4,5 Hence, this study aims to evaluate the performance of the common noninvasive tests in non-obese (BMI

Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels.METHODS:We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured.RESULTS:LSM was better than both FIB-4 and NFS for staging F3-F4 fibrosis area under the receiver operating characteristic curve test (AUC) 0.863, 0.777, and 0.765, respectively; P < 0.001 for both), showing higher accuracy and higher negative predictive value (NPV), but lower positive predictive value (PPV). LSM worked less well in high ALT (>100 IU) (AUC 0.811 vs 0.877, P = 0.04; PPV 57.5% vs 62.4%; NPV 90.7% vs 94%) or obese patients (AUC 0.786 vs 0.902, P < 0.001; PPV 58.7% vs 64.8%; NPV 88.3% vs 95.2%), the latter not being affected by the M or XL probe. Consistently, LSM worked better in terms of AUC and accuracy compared with both FIB-4 and NFS only in nonobese or high ALT patients, even with always keeping a slightly lower PPV. A serial combination of FIB-4 or NFS with LSM as the second test in patients in the gray area of the first test retained - in most scenarios - similar PPV and NPV compared with LSM alone. These strategies also increased the diagnostic accuracy of about 20% in all groups of patients, even if with a lower overall accuracy in obese patients (71.3% and 67.1% for FIB-4 and NFS as the first test, respectively) compared to nonobese patients (81.9% and 82.4% for FIB-4 and NFS as the first test, respectively).CONCLUSIONS:All tested noninvasive tools have overall better NPV than PPV. LSM has a better diagnostic accuracy for advanced fibrosis than both FIB-4 and NFS only in nonobese and/or low ALT patients. Serial combination strategies are better than a single tool strategy, regardless of obesity and ALT levels, although the accuracy is lower in obese patients.

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 66%. Results Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis 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.

ObjectiveThe 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.DesignWe 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.Results391 (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 (p2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI 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.ConclusionHigh 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.

Background & Aims Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. Methods CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n = 340; validation cohort, n = 414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52 ± 14; body mass index 27.2 ± 5.3 kg/m2). The primary outcome was the diagnosis of fatty liver, defined as steatosis involving ≥5% of hepatocytes. Results The area under the receiver-operating characteristics curve (AUROC) for CAP diagnosis of fatty liver was 0.85 (95% CI 0.82–0.88). The interquartile range (IQR) of CAP had a negative correlation with CAP (r = −0.32, p

Background and aims: Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis In Nonalcoholic Fatty Liver Disease (NAFLD). Controlled Attenuation Parameter (CAP) is a new parameter provided by the same machine used for LSM, and associated with both steatosis and BMI, the two factors mostly affecting LSM peformance in NAFLD. We aimed to determine wheter prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Methods: Patients (n=324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower from 132 to 298, middle from 299 to 338, higher form 339 to 400 dB/m). Results: Among patients with F0-F2 fibrosis, mean LSM values- expressed in kPa- increased according to CAP tertiles (6.8 vs. 8.6 vs. 9.4; p=0.001), and along this line the AUC of LSM for the diagnosis of F3-F4 fibrosis was progressively reduced from lower to middle and further to higher CAP tertiles (0.915, 0.848-0.982; 0.830, 0.753-0.908; 0.806, 0.723-0.890). As a consequence, in subjects with F0-F2 fibrosis, the rates of false-positive LSM results for F3-F4 fibrosis increased according to CAP tertiles (7.2% in lower vs. 16.6% in middle vs. 18.1% in higher). Consistent with this, a decisional flow-chart for prediciting fibrosis was suggested by combining both LSM and CAP values. Conclusions: In patients with NAFLD, CAP values should always be taken into account in order to avoid overestimations of liver fibrosis assessed by TE. This article is protected by copyright. All rights reserved.

Background & Aims The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response. Methods The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts. Results Of the 1312 patients without a history of complications, varices had occurred after 10years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6–2.8]), and severe complications in 25 (F4.3 3.7% [1.8–5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5–5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71–0.90]; p p Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p =0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p =0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2–9.1]) including 19 HCC (5.8% [2.6–9.0]) and 10 with varices (2.6% [0.8–4.4]). Of the 138 responders with advanced fibrosis, only 31% (15–47%) had fibrosis regression. Conclusions FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.

International audience; UNLABELLED: No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM 0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis.CONCLUSION: Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome.

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).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.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; p0.001). 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); p0.0001], including primary liver cancer [AUROC 0.84 (80-87); p0.0001]. Similarly TE was predictive of severe complications [AUROC 0.77 (72-81); p0.0001], including primary liver cancer [AUROC 0.86 (81-90); p0.0001].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.

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).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.Compared with M probe, XL probe was more likely to achieve 10 valid measurements (95% vs. 81%; P0.001) and a success rate of over 60% (90% vs. 74%; P0.001). 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).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.

Summary Background Non invasive methods for fibrosis evaluation remain to be validated longitudinally in hepatitis B. Aim To evaluate longitudinally transient elastography (TE) and biomarkers for liver fibrosis assessment and follow-up of hepatitis B virus (HBV) inactive carriers. Methods Three hundred and twenty-nine consecutive HBeAg-negative HBV patients (201 inactive carriers) who underwent TE, Fibrotest and aspartate to platelet ratio index (APRI) the same day were studied. Results TE (median 4.8 vs. 6.8 kPa, P 7.2 kPa) confirmed during follow-up in two with significant fibrosis (F2 and F3) on liver biopsy. Conclusion Non-invasive tools, particularly TE, could be useful, in addition to HBV DNA and transaminase levels, for follow-up of HBV inactive carriers as well as better selection of patients who require a liver biopsy.

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)≥30 kg/m2. 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/m2). 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

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. (HEPATOLOGY 2010;51:454–462.)

Summary Background The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated. Aim To evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin. Patients and methods Patients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment. Results At week 4, a strong correlation was found between HCV-RNA and Cmin of ribavirin plasma level (r = −0.376, P = 0.002) and AUC012h of ribavirin plasma level (r = −0.277, P = 0.018). At week 12, a strong correlation was found between HCV-RNA and Cmin of ribavirin plasma level (r = −0.384, P

The recent advent of non-invasive methods for assessment of fibrosis allows serial assessments in all patients with hepatitis C. The aim of this prospective study was to evaluate changes in liver fibrosis, as measured with non-invasive methods, in a large cohort of HCV-infected patients with and without treatment. From May 2003 through March 2006, all previously untreated HCV-infected patients were enrolled in this study. Liver fibrosis was staged with FibroScan and Fibrotest at inclusion, then every year in untreated patients, and at the end of treatment and 6 months later in treated patients. The study population consisted of 416 patients, of whom 112 started treatment after enrolment. In the treatment group, FibroScan and Fibrotest values were significantly higher before and after treatment than in untreated patients at baseline and after 1 year. However, there was no significant difference between treated and untreated patients at the end of follow-up. FibroScan and Fibrotest values fell in all treated patients, whatever their virological response. In multivariate analysis, treatment was the only factor independently associated with a fall in the FibroScan value. In conclusion, whatever the virological response, treatment for HCV infection is associated with an improvement of FibroScan and Fibrotest values. Further studies are needed to compare these non-invasive methods with liver biopsy. These non-invasive methods, and especially FibroScan, should be useful for assessing treatment efficacy in clinical trials of new drugs.

Summary Background The role of hepatic iron overload in the development of hepatic fibrosis in patients with hemochromatosis is well-established. Transient elastography (FibroScan) is a new noninvasive, rapid, reproducible bedside method, allowing assessment of liver fibrosis by measuring liver rigidity. Objectives The aim of this prospective study was to evaluate liver fibrosis with FibroScan and other noninvasive biochemical methods in patients with hemochromatosis (C282Y homozygosity) compared with control patients. Patients and methods From January 2004 through October 2006, all consecutive patients with hemochromatosis were evaluated for liver fibrosis using noninvasive methods (FibroScan and biochemical markers). These patients were compared with patients who had chronic cytolysis and no fibrosis on liver biopsy. Results One hundred and three consecutive patients (57 cases and 46 controls) were fully investigated. Median FibroScan values were similar in both groups, 5.20 kPa versus 4.9 kPa, respectively. No differences were observed between cases and controls for all biochemical markers. A strong correlation was observed between FibroScan and many biochemical markers, although ferritin levels did not correlate with FibroScan values. The prevalence of patients with FibroScan values greater than 7.1 kPa (cut-off level for significant fibrosis) was 22.8% in patients with hemochromatosis and 0% in the controls ( P Conclusion FibroScan and biochemical markers could be reliable noninvasive methods for detecting liver fibrosis in patients with hemochromatosis. Such patients have high FibroScan values more often than do control patients. Further longitudinal and prospective studies are necessary to confirm these preliminary data.

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.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%.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.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.

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.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.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), BMI30kg/m(2), metabolic syndrome, alcohol14 drink/week and liver stiffness6kPa. 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 steatosis10%, steatosis33%, and steatosis66%, AUROCs of CAP were 0.79 (95% CI 0.74-0.84, p0.001), 0.84 (95% CI 0.80-0.88, p0.001), 0.84 (95% CI 0.80-0.88, p0.001), respectively.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.

Background Telaprevir (TVR) is a protease inhibitor (PI) used in chronic hepatitis C treatment with pegylated interferon plus ribavirin. We analysed the prevalence and kinetic development of TVR resistance upon treatment. Methods A total of 24 cirrhotic patients (genotype 1a, n=8; genotype 1b, n=16) previously non-responders to standard therapy were treated with TVR-based therapy. The distribution of TVR-resistant variants was assessed at every HCV-RNA-positive time point by 454 ultra-deep pyrosequencing (UDPS) during a mean follow-up period of 9.4 months. Results A median of 6,837 reads/specimen was studied. Based on control UDPS, we considered mutations as real when present >0.4%. TVR-resistant variants were found at baseline in 8/24 patients (33.3%). Four of the 24 patients (16.7%), all genotype 1a, did not achieve HCV RNAConclusions TVR-resistant variants are widely present at baseline. The presence of TVR-resistant mutants at baseline, even in high abundance (>20%), did not always preclude TVR treatment success. The detection of R155K/T/Q at baseline may predict failure in genotype 1a patients. At failure, which occurred in genotype 1a patients, a significant enrichment in V36A/M and R155K/T/Q was observed.

Summary Background Liver stiffness and non-invasive tests predict overall survival in chronic hepatitis C. However, in patients chronically infected with hepatitis B virus (HBV), only the association between liver stiffness and the risk of hepatocellular carcinoma has been published. Aim To evaluate the 5-year prognostic value of liver stiffness, non-invasive tests of liver fibrosis, and liver biopsy, to predict overall survival in chronic hepatitis B. Methods In a consecutive cohort, we prospectively assessed fibrosis, with liver stiffness, FibroTest, APRI, FIB-4 and liver biopsy (if indicated). We examined death and liver transplantation during a 5-year follow-up, and factors associated with overall survival. Results A total of 600 patients (men 64%, mean age 42 years, inactive carriers 36%) with chronic hepatitis B were included. At 5 years, 25 patients were dead (13 liver-related deaths) and four patients had liver transplantation. Overall survival was 94.1% and survival without liver-related death 96.3%. No liver-related death was observed in inactive carriers. Survival was significantly decreased in patients diagnosed with severe fibrosis, whatever the non-invasive method used (P

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 30kg/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 1week 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 >50years and BMI >30kg/m 2 . By univariate analysis, only BMI >30kg/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.

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).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.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 (P0.001). 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.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.

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/m2 (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/m2 (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. (HEPATOLOGY 2010.)

Although hepatitis C virus (HCV) infection prevalence is high among drug users, they do not commonly receive regular care in academic centres. The aim of this prospective study was to assess the influence of FibroScan use on HCV screening and management in street-based outreach. From January 2006 to January 2007, all consecutive drug users were offered noninvasive evaluation of liver fibrosis with FibroScan. After FibroScan, parameters were recorded with a structured, face-to-face questionnaire by outreach workers. All 298 subjects accepted FibroScan evaluation drug use was--ever injected heroin (69%), ever snorted or injected cocaine (89%), current chronic alcohol abuse (44%). The median FibroScan score was 5.3 kPa. Before blood sampling, 34% of subjects reported HCV positivity. HCV positivity was found in 83 cases. All these subjects had positive HCV-RNA. Forty-five subjects agreed to meet a hepatologist. By multivariate analysis, never snorted cocaine, consumed alcohol21 drinks per week, duration of injected heroin7 years, and FibroScan7.1 kPa were significantly associated with HCV positivity. Thus in a street-based outreach service for drug users, the acceptance of FibroScan is excellent. FibroScan with a hospital-based physician may facilitate screening and management of drug users for HCV infection.

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).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).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; p0.0001). 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.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.

The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P0.0001), FIB-4 (r = 0.393, P0.0001) and Forns (r = 0.407, P0.0001)], regardless of the HIV status. In the multivariate analysis, age45 years, body mass index (BMI)25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.

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 ¼ 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. JPGN 45:443–450, 2007. Key Words: Cirrhosis—Cystic fibrosis—Fibrosis—Liver stiffness—Portal hypertension. # 2007 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

56 DYNAMICS OF HCV QUASISPECIES DURING TELAPREVIR TREATMENT DISSECTED USING ULTRA-DEEP PYROSEQUENCING: TREATMENT FAILURE IN 100% OF GENOTYPE 1A PATIENTS P. Pinson, P. Trimoulet, J. Papuchon, J. Foucher, J. Vergniol, F. Chermak, L. Wittkop, W. Merrouche, S. Reigadas, M. Kann, H. Fleury, V. de Ledinghen. Laboratoire de Virologie et UMR 5234 CNRS, Service d’Hepato-Gastroenterologie, Hopital du Haut Leveque, CHU Bordeaux et Universite Bordeaux Segalen, INSERM U897, Institut de Sante Publique, Epidemiologie et Developpement (ISPED), Universite Bordeaux Segalen, Laboratoire de Microbiologie Fondamentale et Pathogenicite UMR5234, CHU Bordeaux et Universite Bordeaux Segalen, Bordeaux, France E-mail: patricia.recordon-pinson@u-bordeaux2.fr

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.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.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.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.

most sensitive (p < 0.001 between % changes) of 5 blood tests for detecting fibrosis progression (0.25±0.29 at baseline vs 0.31±0.32 at 2 years, p = 0.003). CM was also reproducible (ric = 0.815). The % change in CM was significantly (p = 0.039) higher (median:32.3%) than that of area of fibrosis (median: 19.9%), which was the histological characteristic having the most significant change but poorly reproducible (ric = 0.439). Conclusion: For the diagnosis of cirrhosis, a specific test is more appropriate than a standard fibrosis test. A specific test offers the advantages of a high correct classification rate and excellent dynamic sensitivity and reproducibility. Its detailed classification (6 classes) also offers precise diagnostic probability. Thus, the CM test, with its specific classification, offers a more exact diagnostic method adapted to clinical practice.

accelerated in HCV patients with significant steatosis and/or insulin resistance (IR). There is little data regarding the impact of these factors on the accuracy of TE. Aim: To evaluate the influence of metabolic variables on the performance of TE for predicting fibrosis in HBV/HCV subjects. Methods: This study enrolled treatment-naive subjects with positive HBsAg or detectable HCVRNA ≥6 months, submitted to liver biopsy (LB) and TE on the same day. METAVIR score was used for histological analysis. Steatosis ≥30% was considered significant. TE cut-offs: 7.2 (F ≥ 2) and 8.1 (F ≥ 3) kPa for HBV; 7.1 (F ≥ 2) and 9.5 (F ≥ 3) kPa for HCV. IR was defined by HOMA-IR ≥3 and obesity by a BMI ≥30kg/m. Results: After excluding 48 cases (7.8%) with unreliable/unsuccessful TE measurement, 565 patients were analyzed (HBV = 202; HCV = 363). Mean age was 46.1±11.2 years, 67% male. Obesity and diabetes were identified in 6% and 5%, respectively. Significant steatosis was observed in 118 cases (21%) and 141 (25%) had IR. METAVIR F ≥2 was seen in 42% and 54% in HBV and HCV groups, respectively (P = 0.005). Higher TE values were observed in diabetics (P < 0.001), subjects with significant steatosis (P < 0.001), and in those with IR (P < 0.001). Obesity had no influence on TE values (P = 0.607). There was no correlation between TE and BMI (r = 0.108; P = 0.11) and positive but weak correlations were found between TE and HOMA-IR (r = 0.213; P = 0.001) and glucose (r = 0.217; P < 0.001). Discordant results between LB and TE were observed in 117/565 cases (21%). Discordant cases were comparable to concordant ones regarding age, etiology, gender, ALT, AST, GGT, A2/3 METAVIR grade, and all metabolic factors. TE overestimation of fibrosis was identified in 33/565 cases (6%). Among these, none had diabetes or obesity and no association was found between overestimation and metabolic factors. Conclusions: Higher TE values are observed in chronic viral hepatitis patients with metabolic disorders (IR, diabetes, significant steatosis). However, this seems not to exert a significant negative impact on the diagnostic performance of TE for predicting liver fibrosis.

Liver stiffness measurement (LSM) failure rate ranges between 2 and 10% when using FibroScan® and is generally due to obese patients. The aim of this prospective study was to evaluate a new probe for the FibroScan® designed to overcome this limitations in terms of feasibility compared to the M (standard) probe.100 patients with a BMI 30 kg/m2 were recruited (27 men, mean age 52 years, mean BMI 41 (30−64) kg/m2. LSM was attempted with the M (central US frequency: 5MHz, diameter: 7mm, measurement depths: 25−65mm below the skin surface) and XL (2.5MHz, 10mm, 35−75mm) probes using an ultrasound imaging system to optimize the measurement point.The feasibility of LSM with both probes is presented in Table 1 (Fisher’s exact test, Wilcoxon signed rank test). LSM was significantly (p< 0.05) correlated with platelets (Spearman: −0.24), phosphatase alkaline (0.25) and glycemia (0.45) but not to prothrombin time, total bilirubin, GGT or transaminases. It was significantly correlated with non invasive markers: FIB-4 (0.26), Forns (0.27) and Virahep-C (0.30). Due to the presence of non hepatic tissue in the volume explored with the M probe in overweighed patients, LSM was lower with XL probe than M Probe.

Objectif La sonde standard, sonde M, de FibroScan ne permet pas la mesure de l’elasticite hepatique dans 2 a 10 % des cas, generalement chez les malades obeses. En effet, la graisse thoracique attenue les ondes elastiques et ultrasonores rendant impossible la mesure de l’elasticite hepatique. Le but de cette etude prospective etait d’evaluer une nouvelle sonde de FibroScan, sonde XL, en termes de faisabilite de mesure d’elasticite hepatique et de performance technique et diagnostique. Patients et Methodes De janvier a septembre 2008, 84 malades consecutifs avec un index de masse corporelle (IMC) > 30 kg/m2 ont ete inclus (22 hommes, âge moyen 53 ans, IMC moyen 41 kg/m2, extremes 30-64 kg/m2). Pour chaque malade, l’elasticite hepatique a ete mesuree par la sonde M (frequence ultrasonore centrale 5 MHz, diametre 7 mm, profondeur de mesure 25-65 mm) et la sonde XL (2,5 MHz, 10 mm, 35-75 mm) par un operateur entraine en utilisant une sonde d’echographie pour reperer la zone de mesure. Un bilan sanguin a ete effectue pour tous les malades. Resultats La faisabilite de la mesure de l’elasticite hepatique est indiquee dans le tableau. Sur les 61 malades mesures avec la sonde XL (au moins 5 mesures valides), l’elasticite hepatique (valeur mediane 5,3 kPa, extremes 2,4-16,6 kPa) etait significativement correlee au taux de plaquettes (r = -0,33), des phosphatases alcalines (r = 0,26), de la GGT (r = 0,27), de l’ASAT (r = 0,27), de la glycemie (r = 0,46) mais pas de la prothrombine, de l’INR, de la bilirubine totale et de l’ALAT. La valeur d’elasticite hepatique etait significativement correlee aux marqueurs sanguins non-invasifs de fibrose : APRI (r = 0,34), GUCI (r = 0,29), score de Forns (r = 0,27), Virahep-C (r = 0,26). Conclusion Dans une population de malades avec IMC > 30 kg/m2, pres d’un malade sur deux qui n’etait pas evaluable avec la sonde M de FibroScan a ete evaluable avec la nouvelle sonde XL. L’elasticite hepatique mesuree avec cette nouvelle sonde etait significativement correlee aux marqueurs seriques de fibrose hepatique. L’etude de la performance de cette sonde XL pour le diagnostic de la fibrose significative et la cirrhose (estimees par ponction-biopsie hepatique) chez les malades obeses est en cours.