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Background: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder with not only motor symptoms but also extra-motor features including cognitive impairment. The most common cognitive profile observed in patients with ALS includes deficits in executive function, language, and social cognition. However, longitudinal studies on cognitive changes over time in ALS are sparse. We aimed to investigate the presence and nature of cognitive impairment at the time of ALS diagnosis and its association with survival as well as explore longitudinal cognitive change. Method: Patients (n = 216) were recruited at the Karolinska University Hospital in Stockholm, Sweden. Follow-up visits (n = 307 in total) were performed every 6 months. Cognitive impairment was assessed using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and/or Montreal Cognitive Assessment (MoCA). Results: Cognitive impairment was observed in 38% of the patients at the time of ALS diagnosis, and the majority of these patients had deficits in executive function and/or language. Patients with cognitive impairment at the time of diagnosis had a more rapid decline in ALSFRS-R at 12- and 18-months follow-up, and a shorter survival. Cognitive function was stable during the first 2 years after diagnosis, and did not follow the trajectories of decline in motor functions. Conclusion: Cognitive impairment in ALS was associated with a faster decline of motor functions, and shorter survival. However, cognitive function did not deteriorate over time. Cognitive assessment is essential for the patients and caregivers to understand the phenotypic expression of ALS. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is an ALS-specific multi-domain screening tool. Few studies have examined the relationship between ECAS scores and [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) findings. Objective: To assess the relationship between ECAS scores and glucose metabolism patterns on [18F]FDG -PET images in ALS. Methods: We collected [18F]FDG-PET images from 65 patients with ALS and 39 healthy controls. ECAS scores were collected on all patients and we calculated the correlation to [18F]FDG-PET in order to investigate the potential links between cognition and glucose metabolism. Results: We observed hypometabolism in the frontal cortex, insula, and limbic system, together with hypermetabolism in the cerebellum in patients with ALS compared to controls. A lower ECAS total score was associated with lower glucose metabolism in the right orbitofrontal gyrus and higher glucose metabolism in lateral occipital, medial occipital, and cerebellar regions, among patients with ALS. Similar results, although less widespread, were observed in the analyses of ECAS ALS-specific scores. Conclusions: The metabolic patterns in [18F]FDG -PET show that changes in the glucose metabolism of corresponding areas are related to cognitive dysfunction in ALS, and can be detected using the ECAS. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to outline the use of population and disease registries for clinical trial pre-screening. Materials and methods: The search was conducted in the time period of January 2014 to December 2022 in three databases: MEDLINE, Embase, and Web of Science Core Collection. References were screened using the Rayyan software, firstly based on titles and abstracts only, and secondly through full text review. Quality of the included studies was assessed using the List of Included Studies and quality Assurance in Review tool, enabling inclusion of publications of only moderate to high quality. Results: The search originally identified 1430 citations, but only 24 studies were included, reporting the use of population and/or disease registries for trial pre-screening. Nine disease domains were represented, with 54% of studies using registries based in the USA, and 62.5% of the studies using national registries. Half of the studies reported usage for drug trials, and over 478,679 patients were identified through registries in this review. Main advantages of the pre-screening methodology were reduced financial burden and time reduction. Discussion and conclusion: The use of registries for trial pre-screening increases reproducibility of the pre-screening process across trials and sites, allowing for implementation and improvement of a quality assurance process. Pre-screening strategies seem under-reported, and we encourage more trials to use and describe their pre-screening processes, as there is a need for standardized methodological guidelines. [ABSTRACT FROM AUTHOR]

Cognitive and behavioral impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a 5-domain screening tool customized for quick cognitive screening in patients with ALS. Although the ECAS is available in Swedish at the Karolinska University Hospital (SK-ECAS), it has not yet been validated in Sweden stressing the need to assess validity and reliability of the SK-ECAS Version A. The study included 176 patients with ALS or other motor neuron disease diagnosed between September 2017 and October 2021 at the Karolinska ALS Clinical Research Center in Stockholm, Sweden, and 35 age-matched healthy control subjects. SK-ECAS was validated against the Montreal Cognitive Assessment (MoCA) and optimal cutoffs, receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated. We identified an optimal cutoff of 108 for the SK-ECAS total score and 82 for the SK-ECAS ALS-specific score to detect cognitive impairment. The SK-ECAS showed good performance in indicating abnormal cognition with an AUC of 0.73 for SK-ECAS ALS-specific score and 0.77 for SK-ECAS total score. There was good internal consistency with a Cronbach's alpha of 0.79. This study demonstrates good validity and reliability indices for SK-ECAS Version A for the detection of cognitive impairment in newly diagnosed ALS patients. [ABSTRACT FROM AUTHOR]

The International Network for Amyotrophic Lateral Sclerosis (ALS) Research and Care (INARC) was founded in 2022. INARC's main goals are to offer a platform dedicated to staff members for ALS clinics and research teams who are not physicians. By nurturing experience and expertise exchanges to improve problem solving skills, the ultimate goal is to increase the standard ALS care and research. This brief report aims to describe the formation of INARC, the 2023 INARC meeting, as well as to report topics discussed, lessons learned and challenges raised by INARC members. [ABSTRACT FROM AUTHOR]

Background/Aims: Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results: 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the performances of quantitative ultrasound (QUS) for the detection and assessment of hepatic steatosis when implemented using an ultraportable ultrasound scanner. Seven established QUS parameters were investigated. Ultrasound signals were acquired using a new ultraportable ultrasound device, the Hepatoscope. The feasibility of QUS using the Hepatoscope was first assessed in vitro. Clinical reliability, accuracy and staging capabilities were evaluated in 60 patients referred to a hepatology consultation for known chronic liver disease and enrolled in a prospective clinical investigation using the controlled attenuation parameter (CAP) as ground truth. QUS parameters showed moderate (intra-class correlation coefficient [ICC] >0.50) to excellent (ICC >0.90) reliability. Two parameters, namely Lizzi-Feleppa mid-band fit and attenuation, were both reliable (ICC = 0.89 and 0.86, respectively) and correlated with the CAP (squared Pearson correlation coefficient of R2 = 0.65 and R2 = 0.6, respectively). For steatosis detection (S0 vs. ≥S1), the two parameters yielded an area under the receiving operating characteristic curve of 0.90 and 0.86, respectively (95% confidence interval: [0.81–0.99] and [0.76–0.96], respectively). QUS can be reliably and accurately implemented on ultraportable ultrasound scanners. The combination of ultraportability and quantitative assessment of liver fat is promising for large-scale screening and monitoring of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Background and purpose: RT001 is a deuterated synthetic homologue of linoleic acid, which makes membrane polyunsaturated fatty acids resistant to lipid peroxidation, a process involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Methods: We conducted a randomized, multicenter, placebo‐controlled clinical trial. Patients with ALS were randomly allocated to receive either RT001 or placebo for 24 weeks. After the double‐blind period, all patients received RT001 during an open‐label phase for 24 weeks. The primary outcome measures were safety and tolerability. Key efficacy outcomes included the ALS Functional Rating Scale (ALSFRS‐R), percent predicted slow vital capacity, and plasma neurofilament light chain concentration. Results: In total, 43 patients (RT001 = 21; placebo = 22) were randomized. RT001 was well tolerated; one patient required dose reduction due to adverse events (AEs). Numerically, there were more AEs in the RT001 group compared to the placebo group (71% versus 55%, p = 0.35), with gastrointestinal symptoms being the most common (43% in RT001, 27% in placebo, p = 0.35). Two patients in the RT001 group experienced a serious AE, though unrelated to treatment. The least‐squares mean difference in ALSFRS‐R total score at week 24 of treatment was 1.90 (95% confidence interval = −1.39 to 5.19) in favor of RT001 (p = 0.25). The directions of other efficacy outcomes favored RT001 compared to placebo, although no inferential statistics were performed. Conclusions: Initial data indicate that RT001 is safe and well tolerated. Given the exploratory nature of the study, a larger clinical trial is required to evaluate its efficacy. [ABSTRACT FROM AUTHOR]

Summary: Background: Non‐invasive assessment of fibrosis is predictive of the prognosis of non‐alcoholic and alcoholic fatty liver disease but this has not been demonstrated in metabolic (dysfunction)‐associated fatty liver disease (MAFLD). Aims: We assessed the prognosis of non‐invasive methods in patients with MAFLD. Methods: All consecutive patients with MAFLD, with liver stiffness measurements, FIB‐4 (Fibrosis‐4), and LIVERFASt were included in this cohort study. The primary endpoint was analysed by the Kaplan‐Meier method and secondary endpoints were estimated by Gray test or logistic regression. Factors independently associated with overall mortality and morbidity were identified by a multivariate Cox model. The prognostic performance of non‐invasive methods for prediction of mortality was evaluated by Harrell's C‐index and for morbidity by area under the receiver operating characteristics curve (AUC). Results: A total of 1239 patients with MAFLD were analysed (median age 56 years, male 56.5%, median body mass index 31 kg/m2 and obesity 59%). The median follow‐up was 62 months [42‐91 months] and 73 (5.8%) subjects died. Baseline results of non‐invasive methods were correlated with overall and liver‐related mortalities (P < 0.001), and with all‐cause and liver‐related outcomes (P < 0.001). A predictive model (composed of clinical parameters and liver stiffness measurement, FIB‐4 or LIVERFASt) was an excellent predictor of overall and liver‐related mortalities (C‐index 0.8‐0.9), and a good predictor of overall and liver‐related morbidities (AUC 0.72‐0.74). Conclusion: Baseline liver stiffness measurement, FIB‐4 and LIVERFASt can predict global and liver‐related mortality and morbidity in patients with MAFLD and could be prognosis endpoints in clinical trials. [ABSTRACT FROM AUTHOR]

Background & Aims: The boundary between non‐alcoholic (NAFLD) and alcohol‐related liver disease (ALD) is based on alcohol consumption. However, metabolic syndrome and alcohol use frequently co‐exist. The aim of this study was to determine prognostic factors of long‐term morbidity and mortality in patients with NAFLD or ALD. Methods: From 2003 to 2016, all consecutive NAFLD or ALD patients were prospectively included in this cohort study. We evaluated overall survival, specific cause of mortality and occurrence of any complication. The primary endpoint was analysed by the Kaplan Meier method, secondary endpoints were estimated by Gray test method or logistic regressions. Factors independently associated with overall mortality and morbidity were identified by a multivariate Cox model. Results: A total of 3365 patients (1667 with ALD and 1698 with NAFLD) were included. Median follow‐up was 54 months (range: 30‐86) and 563 subjects died. In the overall population, overall mortality was higher in patients with ALD (HR: 10.1 [7.57‐13.3]), and with weekly alcohol consumption >7 units (HR:1.66 [1.41‐1.96]). Liver‐related mortality was higher in patients with ALD (HR: 11 [7.27‐16.5]). In the NAFLD group, weekly alcohol consumption >1 unit was associated with higher overall mortality (HR: 1.9 [1.1‐3.4]), and weekly alcohol consumption >7 units was associated with higher overall morbidity (OR: 1.89 [1.61‐2.21]). In the ALD group, the presence of metabolic syndrome was associated with higher overall (HR:1.27 [1.02‐1.57]), and liver (HR: 1.47 [1.1‐1.96]) mortalities, and overall (OR: 1.46 [1.14‐1.88]), liver (OR: 1.46 [1.14‐1.88]) morbidities. Conclusion: In fatty liver diseases, light alcohol consumption and metabolic syndrome are prognosis cofactors. [ABSTRACT FROM AUTHOR]

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 Steato Test, 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 Steato Test 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. [ABSTRACT FROM AUTHOR]

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<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, γ-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. [ABSTRACT FROM AUTHOR]

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 <.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. [ABSTRACT FROM AUTHOR]

• Liver-related prognosis in non-alcoholic fatty liver disease (NAFLD) is impaired in patients with advanced fibrosis. • FibroMeterVCTE is a new test combining blood markers and elastography. • FibroMeterVCTE outperforms other fibrosis tests for the diagnosis of advanced fibrosis in NAFLD. • Algorithms using FibroMeterVCTE as a second-line test provide 90% diagnostic accuracy. 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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background & Aims Worldwide and, to a lesser extent, in France, a minority of individuals infected with hepatitis B (HBV) and C (HCV) is aware of its status. Given the current availability of highly effective anti-HBV and anti-HCV agents, the high rate of undiagnosed people, associated with individual and community prejudices (liver disease worsening, persistence of a hidden transmission reservoir and medicoeconomic burden of delayed care), is unacceptable. Methods On the occasion of the first French general report on viral hepatitis, new recommendations for HBV and HCV testing were issued. We aim to introduce the new French strategy for HBV and HCV screening, and to describe the underlying epidemiological data. Results These recommendations comprise various items. First, the screening of chronic viruses, namely HBV, HCV and HIV, should be quasi-systematically combined. Second, the targeted screening of groups at risk of viral exposure must be strengthened. Third, routine testing for each of these three viruses should be offered at least once to men of 18-60 years old who had never been tested. In parallel, in pregnant women, in addition to HIV-HBV screening, currently recommended HCV testing should be routinely performed during the first trimester of pregnancy. In order to best achieve the target populations, community initiatives that propose testing actions should be encouraged, particularly those including rapid point-of-care tests. Conclusions Overall, these recommendations aim to define a comprehensive testing strategy for chronic viral infections, emphasizing both targeted screening and mass screening and considering jointly HBV, HCV and HIV. [ABSTRACT FROM AUTHOR]

Background & Aims NAFLD is highly prevalent but only a small subset of patients develop advanced liver fibrosis with impaired liver-related prognosis. We aimed to compare blood fibrosis tests and liver stiffness measurement (LSM) by FibroScan for the diagnosis of liver fibrosis and the evaluation of prognosis in NAFLD. Methods Diagnostic accuracy was evaluated in a cross-sectional study including 452 NAFLD patients with liver biopsy (NASH-CRN fibrosis stage), LSM, and eight blood fibrosis tests (BARD, NAFLD fibrosis score, FibroMeter NAFLD , aspartate aminotransferase to platelet ratio index (APRI), FIB4, FibroTest, Hepascore, FibroMeter V2G ). Prognostic accuracy was evaluated in a longitudinal study including 360 NAFLD patients. Results LSM and FibroMeter V2G were the two best-performing tests in the cross-sectional study: AUROCs for advanced fibrosis (F3/4) were, respectively, 0.831 ± 0.019 and 0.817 ± 0.020 ( p ⩽0.041 vs. other tests); rates of patients with ⩾90% negative/positive predictive values for F3/4 were 56.4% and 46.7% ( p <0.001 vs. other tests); Obuchowski indexes were 0.834 ± 0.014 and 0.798 ± 0.016 ( p ⩽0.036 vs. other tests). Two fibrosis classifications were developed to precisely estimate the histological fibrosis stage from LSM or FibroMeter V2G results without liver biopsy (diagnostic accuracy, respectively: 80.8% vs. 77.4%, p = 0.190). Kaplan-Meier curves in the longitudinal study showed that both classifications categorised NAFLD patients into subgroups with significantly different prognoses ( p <0.001): the higher was the class of the fibrosis classification, the worse was the prognosis. Conclusions LSM and FibroMeter V2G were the most accurate of nine evaluated tests for the non-invasive diagnosis of liver fibrosis in NAFLD. LSM and FibroMeter V2G fibrosis classifications help physicians estimate both fibrosis stage and patient prognosis in clinical practice. Lay summary The amount of liver fibrosis is the main determinant of the liver-related prognosis in patients with non-alcoholic fatty liver disease (NAFLD). We evaluated eight blood tests and FibroScan in a cross-sectional diagnostic study and found that FibroScan and the blood test FibroMeter V2G were the two most accurate tests for the non-invasive evaluation of liver fibrosis in NAFLD. A longitudinal prognostic study showed these two tests initially developed for the diagnosis are also prognostic markers as they allow for the stratification of NAFLD patients in several subgroups with significantly different prognosis. [ABSTRACT FROM AUTHOR]

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/m2 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. [ABSTRACT FROM AUTHOR]

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±5.5years) and 36 adults (38±16years) were included. Median CVP was 6mmHg (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 >10mmHg was 0.972 (95% CI 0.855 to 1; p<0.05). Optimal cut-off value of LS for detection of CVP >10mmHg was 8.8kPa (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background MR relaxometry has been extensively studied in the field of cardiac diseases, but its contribution to liver imaging is unclear. We aimed to compare liver and spleen T1 mapping, T2 mapping, and diffusion-weighted MR imaging (DWI) for assessing the diagnosis and severity of cirrhosis. Methods We prospectively included 129 patients with normal ( n = 40) and cirrhotic livers ( n = 89) from May to September 2014. Non-enhanced liver T1 mapping, splenic T2 mapping, and liver and splenic DWI were measured and compared for assessing cirrhosis severity using Child-Pugh score, MELD score, and presence or not of large esophageal varices (EVs) and liver stiffness measurements using Fibroscan ® as reference. Results Liver T1 mapping was the only variable demonstrating significant differences between normal patients (500 ± 79 ms), Child-Pugh A patients (574 ± 84 ms) and Child-Pugh B/C patients (690 ± 147 ms; all p -values <0.00001). Liver T1 mapping had a significant correlation with Child-Pugh score (Pearson's correlation coefficient of 0.46), MEDL score (0.30), and liver stiffness measurement (0.52). Areas under the receiver operating characteristic curves of liver T1 mapping for the diagnosis of cirrhosis (O.85; 95% confidence intervals (CI), 0.77–0.91), Child-Pugh B/C cirrhosis (0.87; 95%CI, 0.76–0.93), and large EVs (0.75; 95%CI, 0.63–0.83) were greater than that of spleen T2 mapping, liver and spleen DWI (all p -values < 0.01). Conclusion Liver T1 mapping is a promising new diagnostic tool for assessing cirrhosis diagnosis and severity, showing higher diagnostic accuracy than liver and spleen DWI, while T2 mapping is not reliable. [ABSTRACT FROM AUTHOR]

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 = 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. [ABSTRACT FROM AUTHOR]

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 10 years 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 <0.0001) and (n = 8/844; AUROC = 0.82 [0.72–0.89]; p <0.0001) respectively. 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. [ABSTRACT FROM AUTHOR]

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 <30kg/m2, and XL probe for patients with BMI ⩾30kg/m2), 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. [ABSTRACT FROM AUTHOR]

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/m2, BMI >30kg/m2, 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 &y& Elsevier]

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 5years, 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 10years 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 &y& Elsevier]

Background and Aim Interferon-gamma-1b ( IFN-γ-1b) improves alpha interferon ( IFN-α) inhibition of hepatitis C virus ( HCV) replication in replicon system. We described virological response after addition of IFN-γ to a combination of ribavirin/peginterferon ( PEG-IFN)-α-2a or α-2b. Methods In this non-comparative, multicenter trial, patients chronically infected by HCV who were nonresponders to a previous treatment by PEG-IFN and ribavirin were restarted on a regimen of PEG-IFN-α-2a (180 μg/week) + ribavirin (1000-1200 mg/day) for 16 weeks. If HCV-RNA decreased less than 2 log10 copies/mL (nonresponders), and if PEG-IFN-α-2a and ribavirin dosages were unchanged while tolerance was good, IFNγ-1b (100 μg three times per week) was added for the last 32 weeks of treatment. Virological response was evaluated at week 28 (12 weeks after initiation of IFN-γ-1b). Results Among the 48 patients started on dual therapy, 23 patients (47%) were nonresponders at week 12 and received IFN-γ-1b from week 16 onward. Their mean HCV-RNA (log10 IU/mL) was 6.83 at baseline, 5.81 at week 12, and 5.63 at week 28. No patient reached undetectable HCV-RNA at week 28 (upper bound of 95% confidence interval: 14.8%); none had a decrease > 1 log10 IU/mL. One case of grade 4 neutropenia was reported. Conclusion Among the strictly selected nonresponders, IFN-γ-1b (at a dosage of 100 μg thrice a week) in combination with PEG-IFN-α-2a and ribavirin failed to show virological efficacy. [ABSTRACT FROM AUTHOR]

Is steatosis related to the spontaneous carbohydrate intake in patients with NAFLD? We performed dietary records for 24 patients with NAFLD, 3 months after their liver biopsy was performed and before the deliverance of a dietary advice. The food quotient, indicator of the proportion of calories from carbohydrates, was calculated as (1.00x% calories from carbohydrates/100) + (0.70x% calories from lipids/100) + (0.81x% calories from proteins/100).The associations between diet variables and steatosis% on the hepatic biopsies were tested by regression analysis, and diet variables were compared according to the presence of fibrosis. The subjects displayed a large range of steatosis, 50.5% ± 25.5 [10-90], correlated with their energy intake (1993 ± 597 kcal/d, r = 0.41, P < 0.05) and food quotient (0.85 ± 0.02, r = 0.42, P < 0.05), which remained significant with both variables by a multivariate regression analysis (r = 0.51,P < 0.05). For the 17/24 patients with a hepatic fibrosis, the energy intake was lower (fibrosis: 1863 ± 503 versus others: 2382 ± 733 kcal/d, P < 0.05), and their food quotients did not differ from patients without fibrosis. Hepatic steatosis was related to the energy and carbohydrate intakes in our patients; the role of dietary carbohydrates was detectable in the range of usual carbohydrate intake: 32% to 58% calories. [ABSTRACT FROM AUTHOR]

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/m2 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/m2.CONCLUSIONS:LSM by XL probe can be performed successfully in most NAFLD patients, but obesity is associated with less accurate and reliable measurements. [ABSTRACT FROM AUTHOR]

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/m2. 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/m2. By univariate analysis, only BMI >30kg/m2 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 &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921–1956], and the tMRCA of isolates from central France was dated to 1954 [1942–1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion. [Copyright &y& Elsevier]

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: 12.5kPa) 90%, PC 82%, FT 79%, PI 77%, AAR 76%, APRI 70%, and Lok 45%, respectively. At a cut-off of 21.5kPa, 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: 12.5kPa), as compared with other available methods, but cannot replace endoscopy for OV screening. [Copyright &y& Elsevier]

Background: The reliable diagnosis rate of diagnostic tests is provided by their intervals with acceptable accuracy (e.g. ≥90%) where a liver biopsy can be avoided. Aims: To evaluate the overall accuracy and improve the reliable diagnosis rates of blood tests for significant liver fibrosis. Methods: Five blood tests were compared with Metavir fibrosis (F) staging in 1056 patients with chronic hepatitis C. Results: Area under the receiver operating characteristics (F0-1 vs. F2-4) were: FibroMeter: 0.853, Fibrotest: 0.811, Fib-4: 0.799, aspartate aminotransferase to platelet ratio index (APRI): 0.786 and Hepascore: 0.784 ( P<10−3 between tests). The reliable diagnosis rates based on two traditional intervals defined by thresholds ≥90% of negative predictive values (NPV) and positive predictive values (PPV), diagnosing F0/1 and F2/3/4, respectively, were: FibroMeter: 43.5%, APRI: 19.6%, Fibrotest: 17.1%, Hepascore: 3.9%, Fib-4: 1.7% ( P<10−3). By dividing the indeterminate interval by the diagnostic cut-off, two new intervals could be diagnosed reliably: F1/2 and F1/2/3. Accordingly, the reliable diagnosis rate was increased, e.g. FibroMeter: 75.5% (accuracy: 89.5%) with three intervals (F0/1, F1/2, F2/3/4). It was possible to further increase this rate by using the more exportable 90% sensitivity/specificity thresholds, e.g. FibroMeter: 90.2% (accuracy: 86.4%). By using the four intervals, the reliable diagnosis rate was 100% (accuracy: 89.5% with predictive value (PV) and 87.5% with sensitivity/specificity). Conclusion: Reliable diagnosis is a diagnostic index devoted to clinical practice. Its rate can be increased by creating new intervals between diagnostic cut-off and 90% PVs or sensitivity/specificity thresholds. This increased the overall accuracy from 78.1 to 89.5% and reduced the need for a liver biopsy from 56.5 to 0% with the most accurate test. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to describe the natural history of a HCV infection outbreak in 196 patients who had sclerotherapy by a same physician and to confirm patient-to-patient transmission using phylogenetic analysis in a large series of patients. Methods: Demographic information included clinical and biological parameters. Fibrosis evaluation was performed using liver biopsy or transient elastography. Follow-up was maintained until death, or the end of the observation period. In order to determine if the virus had been transmitted between the HCV genotype 2 patients, sequence analysis was undertaken of a part of the NS5b region of the genomes in samples of patients. Results: The mean duration of follow-up was 23.1±6.7 years (4535 patient-years). In patients with fibrosis evaluation, 55.7% had no or mild fibrosis and 44.3% had significant fibrosis. No patient died from HCV-related disease. Nucleotide sequence analysis of a part of the NS5b region revealed that patients were all infected with the same HCV subtype (genotype 2d). The most evident feature of the tree is the clustering of all patients involved in the outbreak without any unrelated isolates. Conclusion: This study emphasizes the risk for nosocomial spread of HCV during intravenous therapy. [Copyright &y& Elsevier]

Background/Aims: Data on hepatitis C virus (HCV) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection. We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin.Methods: We randomly assigned 321 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b (3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks) and ribavirin (36 week treatment).Results: The rate of sustained virologic response (defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment) was higher in patients who received combination therapy with three times weekly interferon (51.7%) or daily interferon (46.1%) than in patients who received interferon alone (25%) (P=0.0001 and P=0.002, respectively). Independent predictive factors for sustained virologic response were combination therapy, weight, genotype and viral load. In conclusion, in patients with chronic hepatitis C, combination therapy with induction treatment (daily interferon for 12 weeks) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment.Conclusions: Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective. [Copyright &y& Elsevier]

Background: Screening T2DM for NASH fibrosis using specific markers is mandatory, as liver enzymes are often normal despite advanced fibrosis. LIVERFASt (LF), a serum marker with CPT code for assessing liver fibrosis (LF-Fib), activity and steatosis had high performance for identifying severe NASH in T2DM. Aim: To demonstrate that LF-Fib is an alternative to biopsy (LB) for the estimation of the transition rate to fibrosis [F1 stage or more (TRF1)], in T2DM NAFLD with better performances than transient elastography (TE) and FIB4. Methods: TRF1 was evaluated using Cox-Mantel HazardRatios [HR(95%CI), logrank comparison] with a modeling of hazard from birth to age of LB, in prospectively collected NAFLD pts with concomitant LB and LF, TE, FIB4. Results: N=583pts were included, 52% T2DM, 56%males, median (range) age 59.5% (18-85), HbA1c 6.6% (4.7-12), BMI 31.5 (20-54)kg/m2 (obesity 59%). The estimation of TRF1 [HR(95%CI)] using LF-Fib was similar to that of LB in both T2DM [0.67 (0.56-0.80) vs. 0.65(0.54-0.79)], and no-T2DM [1.50 (1.26-1.78) vs. 1.54 (1.27-1.86)], respectively, with earlier TRF1 in no-T2DM (logrank p<0.0001). The performance for estimating TRF1 was less fit to that of LB in both T2DM and no-T2DM groups for TE and FIB4 (Figure) Conclusion: Validated biomarkers such as LIVERFASt should allow a powerful analysis of fibrosis progression in T2DM similar to LB and better screening strategies for stratifying T2DM. Disclosure: V. Deledinghen: None. M. Munteanu: Consultant; Self; Fibronostics. I. Alam: Advisory Panel; Self; Fibronostics. A. Delamarre: None. B. Lebail: None. H. Marraud-des-grottes: None. M. Irlès-depé: None. M. Decraecker: None. J. Foucher: None. J. Hiriart: None. R. Quiambao: Employee; Self; Fibronostics. [ABSTRACT FROM AUTHOR]