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A better understanding of similarities and differences in the composition of the cellular immune system in non-human primates (NHPs) compared with human subjects will improve the interpretation of preclinical studies. It will also aid in addressing the usefulness of NHPs as subjects for studying chronic diseases, vaccine development and immune reconstitution. We employed high content colour flow cytometry and analysed simultaneously the expression of CD3, CD4, CD8alpha, CD8beta, CD16/CD56, CD45RA, CCR7, CD27, CD28, CD107a and the interleukin-7 receptor alpha-chain (IL-7Ralpha) in peripheral blood mononuclear cells (PBMCs) of 27 rhesus macaques and 16 healthy human subjects. Regulatory T cells (Tregs) were identified using anti-CD3, -CD4, -CD25, -FoxP3, and -IL-7Ralpha monoclonal antibodies. Responsiveness to IL-7 was gauged in a signal transducer and activation of transcription 5 (STAT-5) phosphorylation assay. Human and NHP PBMCs showed a similar T-cell composition pattern with some remarkable differences. Similarities: human and NHP CD4(+) and CD8(+) cells showed a similar STAT-5 phosphorylation pattern in response to IL-7. Multicolour flow cytometric analysis identified a CD4(+) CD8alphaalpha(+) CD8alphabeta(+) T-cell population in NHPs as well as in human subjects that expressed the degranulation marker CD107a and may represent a unique CD4(+) T-cell subset endowed with cytotoxic capacity. Differences: we identified in PBMCs from NHPs a higher proportion (5.16% in CD3(+) T cells) of CD8alphaalpha(+) T cells when compared with human donors (1.22% in CD3(+) T cells). NHP CD8alphaalpha(+) T cells produced tumour necrosis factor-alpha / interferon-gamma (TNF-alpha/IFN-gamma) or TNF-alpha, whereas human CD8alphaalpha(+) T cells produced simultaneously TNF-alpha/IFN-gamma and IL-2. A minor percentage of human CD8(+) T cells expressed CD25(bright) and FoxP3 (0.01%). In contrast, 0.07% of NHP CD8(+) T cells exhibited the CD25(bright) FoxP3(+) phenotype. PBMCs from NHPs showed less IL-7Ralpha-positive events in all T-cell subsets including CD4(+) Tregs (median 5%) as compared with human (median 12%). The data visualize commonalities and differences in immune cell subsets in humans and NHPs, most of them in long-lived memory cells and cells with suppressive functions. This provides a matrix to assess future efforts to study diseases and vaccines in NHPs.

The impact of interferon treatment in patients with hepatitis B virus (HBV) infection on fibrosis progression in comparison with its natural history has yet to be assessed in any large-scale randomized studies. The present report is a review of the evidence-based data published so far.Studies were included if they had at least two repeated estimates of liver fibrosis per patient treated with interferon-alpha (whether pegylated or not). Meta-analysis was performed using a random-effects model.Altogether, 13 studies were included in the review, involving a total of 707 HBV patients treated with interferon-alpha-2a or -2b for 12-83 months. Only one study included pegylated interferon as monotherapy. A total of 787 untreated patients were also followed. Only one study used a non-invasive biomarker. There was a significant reduction in the fibrosis progression rate, with a risk reduction of 0.49 (95% CI: -0.64--0.34; chi(2)=119; degrees of freedom [DF]=6; P0.0001), and significant heterogeneity (Cochran Q=81; P0.0001). This significant impact was similar for both randomized (reduction of risk: -0.45; 95% CI: -0.64--0.26; P0.0001) and not-randomized (controlled) studies (reduction of risk: -0.53; 95% CI: -0.79--0.28; P0.0001).According to these findings, the benefit of interferon treatment on fibrosis progression is clinically significant in patients with advanced fibrosis by the reduction of fibrosis progression to cirrhosis. Pegylated interferon now needs to be compared, in terms of benefit-risk factors, with the new generation of HBV treatments (such as entecavir and tenofovir), using non-invasive biomarkers.

The authors describe five children with nasolacrimal duct obstruction who developed anisometropic amblyopia in the same eye. Because three children had no indication of vision loss at their initial presentation, cycloplegic refraction and periodic visual acuity screenings for such patients is recommended.

SUMMARY The aim was to assess the utility of FibroTest-ActiTest (FT-AT) as noninvasive markers of histological changes in patients with chronic hepatitis. Patients with chronic hepatitis B (HBeAg+ and HBeAg-) randomized in two trials of adefovir (ADV) vs placebo, with available paired liver biopsies and FT-AT at baseline and after 48 weeks of treatment were included. The predictive value of FT-AT was assessed using the area under the receiver operating characteristics curves (AUROCs) for the diagnosis of bridging fibrosis, cirrhosis and moderate-severe necroinflammatory activity. The impact of treatment with ADV vs placebo was assessed on liver injury according to baseline stage and virological response at 48 weeks. The analysis of 924 estimates for the diagnosis of bridging fibrosis, cirrhosis and moderate or severe necroinflammatory activity yielded FT-AT AUROCs: 0.76 +/- 0.02 (standardized 0.81 +/- 0.02), 0.81 +/- 0.02 and 0.80 +/- 0.01, respectively. Similar impacts of ADV on liver fibrosis and activity were observed both with paired biopsy (fibrosis stage from 1.6 to 1.4, activity grade from 2.5 to 1.3) and paired biomarkers (FT from 0.44 to 0.40, AT from 0.62 to 0.25) (P < 0.0001). FibroTest-ActiTest provides a quantitative estimate of liver fibrosis and necroinflammatory activity in patients with chronic hepatitis B and may be an alternative to reduce the need for liver biopsy.

FibroTest has been validated as a biomarker of fibrosis in patients with chronic viral hepatitis, with a similar prognostic value as biopsy. The aim of the study was to compare the diagnostic and prognostic values of FibroTest versus the recently patented biomarkers, FibrometerA, and Hepascore. A total of 218 consecutive patients with ALD and available liver biopsy examination were included. Biomarkers were compared using univariate area under the ROC curves (AUROC) and multivariate analysis (logistic regression and Cox). The median follow-up was 8.2 years. Eighty-five patients died, including 42 deaths related to liver complications. The diagnostic values of FibrometerA and Hepascore did not differ from that of FibroTest for advanced fibrosis (all AUROC = 0.83 ± 0.03) and cirrhosis (FibroTest and FibrometerA = 0.94 ± 0.02, Hepascore = 0.92 ± 0.02), and were significantly greater than those of nonpatented biomarkers (APRI, Forns, FIB4; P < 0.01). In multivariate analysis the most significant was FibroTest (P = 0.001), without independent diagnostic value for FibrometerA (P = 0.19), and Hepascore (P = 0.40). The prognostic values of FibroTest (AUROC for survival or non liver disease-related death = 0.79 ± 0.04), FibrometerA (0.80 ± 0.04), Hepascore (0.78 ± 0.04), did not differ from that of biopsy fibrosis staging (0.77 ± 0.04). In multivariate analysis the most significant were FibroTest (P = 0.004) and biopsy (P = 0.03), without independent prognostic values for FibrometerA (P = 0.41) and Hepascore (P = 0.28). In patients with alcoholic liver disease, FibrometerA and Hepascore did not improve the diagnostic and prognostic values of FibroTest. (HEPATOLOGY 2009;49:97-105.)

Background: FibroTest, a noninvasive method of measuring biomarkers of liver fibrosis, is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus (HCV) infection. We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection.Methods: Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospective cohort of 537 patients. Disease classification at baseline was 157 patients with severe fibrosis (FibroTest >0.58), 137 with moderate fibrosis (FibroTest 0.32–0.58), and 243 with no or minimal fibrosis (FibroTest Results: In 64 untreated patients with severe fibrosis, survival without HCV complications was 73% [95% confidence interval (CI), 59%–086%; 13 complications], and survival without HCV-related death was 85% (95% CI, 73%–96%; 7 HCV deaths). Survival rates were higher in patients with moderate fibrosis, [99% (95% CI, 97%–100%; 1 complication; P Conclusion: The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy.

Background Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system. Results 310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 – all significantly higher than the standard markers: γ-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0–5%); 0.58 in grade 2 (6–32%); and 0.74 in grade 3–4 (33–100%). For the diagnosis of grade 2–4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively. Conclusion SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor.

P1038 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION P. Schwabl, S. Bota, P. Salzl, M. Mandorfer, B.-A. Payer, A. Ferlitsch, J. Stift, F. Wrba, M. Trauner, M. Peck-Radosavljevic, T. Reiberger, Vienna Hepatic Hemodynamic Lab. Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, Medical University Vienna, Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria E-mail: philipp.schwabl@meduniwien.ac.at Background and Aims: Recently, new quality criteria for transient elastography (TE) measurements have been proposed (Boursier et. al. Hepatology 2013): very reliable: IQR/M 0.3 if TE 0.3 if TE >7.1 kPa. We evaluated the diagnostic power and accuracy of TE measurements according to these new quality criteria (accurate = very reliable + reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal hypertension (HVPG). Methods: Patients undergoing TE, HVPG measurement and liver biopsy within 3 months at a tertiary care were retrospectively identified. Results: Among 278 patients (48.7±13.1 years, 74.7% male, 75.7% viral etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate LS measurements (23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional or new criteria were all significantly and similarly strong correlated with fibrosis stage (R =0.648 vs. R = 0.636) and HVPG (R=0.836 vs. R = 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% for traditional and new TE criteria, respectively. The positive (PPV) and negative (NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For predicting HVPG ≥10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and 89.8% using traditional or new criteria, respectively. Both criteria resulted in AUCs for diagnosis of HVPG ≥10mmHg of over 0.95 with a PPV and NPV of 76% and 97%, respectively. Conclusions: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.

There is controversy about the performance of noninvasive tests such as FibroTest in diagnosing intermediate stages of fibrosis. We investigated whether this controversy results from limitations of biopsy analysis for intermediate-stage fibrosis and inappropriate determination of the standard area under the receiver-operator characteristic curve (AUROC).To determine whether biopsy has a lower diagnostic performance for fibrosis stage F2 (few septa) vs F1 (fibrosis without septa), compared with its performance for F1 vs F0 or F4 vs F3, we determined the fibrotic areas of large surgical samples collected from 20 consecutive patients with chronic liver disease or normal liver tissue that surrounded tumors. We analyzed digitized images of 27,869 virtual biopsies of increasing length and also analyzed data from 6500 patients with interpretable FibroTest results who also underwent biopsy analysis.The overall performance of biopsy analysis (by Obuchowski measure) increased with biopsy length from 0.885 for 5-mm to 0.912 for 30-mm samples (P.0001). The performance of biopsy was lower for the diagnosis of F2 vs F1 samples (weighted AUROC [wAUROC] = 0.505) than for F1 vs F0 (wAUROC = 0.773; 53% difference; P.0001) or F4 vs F3 (wAUROC = 0.700; 39% difference; P.0001), even when 30-mm biopsy samples were used. The performance of FibroTest was also lower for the diagnosis of F2 vs F1 samples (wAUROC = 0.512) than for F1 vs F0 samples (wAUROC = 0.626; 22% difference; P.0001) or F4 vs F3 (wAUROC = 0.628; 23% difference; P.0001). However, the FibroTest had smaller percentage differences among wAUROC values than biopsy.Biopsy has a low level of diagnostic performance for fibrosis stages F2 and F1. The recommendation for biopsy analysis, instead of a validated biomarker panel such as FibroTest, for the diagnosis of intermediate stages of fibrosis is therefore misleading.

The aim of this study was to determine cancer morbidity amongst Swedish iron foundry workers with special reference to quartz exposure. In addition to respirable dust and quartz, phenol, formaldehyde, furfuryl alcohols, polycyclic aromatic hydrocarbons (PAHs), carbon black, isocyanates and asbestos are used or generated by foundry production techniques and exposure to any of these substances could have potentially carcinogenic effects.Cancer morbidity between 1958 and 2004 was evaluated in a cohort of 3,045 male foundry workers employed for1 year between 1913 and 2005. Standardised incidence ratios (SIRs) with 95 % confidence intervals (95 % CI) were determined by comparing observed numbers of incident cancers with frequencies in the Swedish cancer register. Exposure measures were assessed using information from the personal files of employees and modelling quartz measurement based on a database of 1,667 quartz measurements. Dose responses for lung cancer were determined for duration of employment and cumulative quartz exposure for latency periods20 years.Overall cancer morbidity was not increased amongst the foundry workers (SIR 1.00; 95 % CI, 0.90-1.11), but the incidence of lung cancer was significantly elevated (SIR 1.61; 95 % CI, 1.20-2.12). A non-significant negative dose response was determined using external comparison with a latency period of20 years (SIR 2.05, 1.72 1.26 for the low, medium and high exposure groups), supported by internal comparison data (hazard ratios 1, 1.01, 0.78) for the corresponding groups. For cancers at sites with at least five observed cases and a SIR 1.25, non-significant risks with SIRs 1.5 were determined for cancers of the liver, larynx, testis, connective muscle tissue, multiple myeloma plasmacytoma and lymphatic leukaemia.A significant overall risk of lung cancer was determined, but using external and internal comparison groups could not confirm any dose response at our cumulative quartz dose levels.

Background: It is well known for Hepatologists, but not for nonspecialists and patients, that advanced fibrosis can occur in patients with chronic liver disease despite normal serum ALT. Validated non-invasive biomarkers, such as FibroTest (FT) which does not include ALT in its combination, now permit estimate of liver fibrosis progression (LFP) on very large populations. Aim: To assess the risk of LFP among patients with normal ALT. Patients and Methods: Consecutive and interpretable FT and ALT, prospectively measured between 2002 and 2009 on fresh samples, were analyzed. LFP was estimated using hazard rate (H) from birth to first bridging fibrosis (F2F3F4) and to cirrhosis (F4) presumed by FT (0.48 and 0.74 threshold respectively), age being the time exposure as previously published for biopsy (J Hepatol 2003). Comparisons of LFP according to ALT values used hazard-ratio (HR), Log-rank test and proportional hazard regression analysis to take into account gender, residency continent and HIV-coinfection). Sensitivity analysis used shorter time exposure, and FT adjustments on age and gender to prevent co-linearity effects.

Methods: The study group included 471 patients (p): 83 subjects without liver fibrosis (82 healthy volunteers, considered F0 Metavir and 1 patient with F0 in liver biopsy-LB), 13 p with F1 in LB, 25p with F2, 28p with F3 and 322p with liver cirrhosis (15p with LB and 307p with clinical, ultrasonographic, endoscopic and/or laparoscopic signs of cirrhosis). We performed 10 measurements in each patient expressed in meters/second (m/s) and a median value was obtained. We considered good technical parameters IQR< 30% and SR≥60%, similar to Transient Elastography. For statistical analysis we used the Spearman rank correlation coefficient (r). Results: In 11p we did not obtained valid ARFI measurements (2.3%) and in 45p (9.7%) of 460p with valid measurements, the technical parameters were unsatisfactory. In the study group, there was a direct, strong correlation (r = 0.744) between ARFI values and liver fibrosis (p < 0.0001); depending on technical parameters the correlation was: for IQR < 30% and SR≥60%: r = 0.779, p < 0.0001 and for IQR≥30% and/or SR< 60%: r = 0.268, p = 0.07. Conclusion: The SR and IQR influence the values of LS measured by ARFI, thus, as in Transient Elastography, we should propose reliable only the measurements with IQR < 30% and SR≥60%.

413 INCREASED LIVER STIFFNESS IN ALCOHOLIC LIVER DISEASE: DISSECTING FIBROSIS FROM STEATOHEPATITIS S. Mueller, G. Millonig, S. Friedrich, F. Stickel, T. Longerich, P. Schirmacher, H.-K. Seitz. Center for Alcohol Research and Salem Medical Center, University of Heidelberg, Heidelberg, Germany; Clinical Pharmacology, University of Bern, Bern, Switzerland; Institute of Pathology, University of Heidelberg, Heidelberg, Germany E-mail: sebastian.mueller@urz.uni-heidelberg.de

Objectif Le FibroTest (FT) est un marqueur serique de fibrose hepatique valide avec une valeur pronostique au moins egale a elle de la biopsie du foie chez les patients (pts) atteints d’hepatite chronique C (VHC) [1] et d’hepatite chronique B (VHB) [2]. Le but etait l’evaluation pronostique a long terme du FT comme marqueur de gravite pour les complications severes et le deces, selon une classification identique et simple en trois classes : fibrose severe (FT > 0,58), moderee (FT = 0,58-0,32) et minime (FT Patients et Methodes 1 829 pts (537 VHC, 1074 VHB et 218 MAF) avec FT ont ete inclus prospectivement. La survie a ete calculee a partir de la date de FT jusqu’a la date d’apparition de la premiere complication (decompensation, hemorragie, carcinome hepatocellulaire) ou deces lie a la maladie ou transplantation ; la survie globale a ete comparee avec celle de la population generale et dans chaque groupe de severite de fibrose : severe, moderee et minime. Resultats Selon la severite de la fibrose au FT et etiologie (VHC, VHB, MAF) les pts avaient : fibrose severe : 157, 208 et 94 ; moderee : 137, 229, 43 et minime : 243, 637 et 81, respectivement ; 21 % des pts MAF etaient abstinents pendant le suivi. Chez les pts VHC le survie a 10 ans sans complications ou deces lie a la maladie etait 71,0 % (95 % CI : 63,0-79,1) dans le groupe FT > 0,58, significativement inferieure par rapport a 97,0 % (95 % CI : 93,5-100,0) dans le groupe FT = 0,32-0,58 et a 99,5 % (95 % CI : 98,6-100) dans le groupe FT 0,58 [62,6 % (95 %CI : 52,2-73,1)] vs celles des groupes avec fibrose moderee [87,5 (95 % CI : 75,5-99,5)] et fibrose minime [92,0 (95 % CI : 84,9-99,0)], respectivement, tous p vs 96,3 % a 10 ans), VHB (80,5 % vs 97,3 % a 4 ans) et MAF (42,4 % vs 96,4 % a 10 ans). Conclusion Independamment de l’etiologie, VHC, VHB ou MAF, le FibroTest permet d’estimer la severite de la maladie hepatique avec une classification pronostique simple en 3 classes.

Introduction Le FibroTest (FT) a ete valide comme biomarqueur de fibrose avancee (FA) chez les sujets exposes aux maladies hepatiques les plus frequentes : hepatite C (HCV), hepatite B (HBV), maladie alcoolique (MAF) et steatose non alcoolique (NAFLD) et dans le depistage de FA chez les diabetiques [1, 2]. Le but principal a ete d’estimer la prevalence des sujets avec FA dans une population generale sans antecedents hepatiques. Le but secondaire etait d’estimer et de comparer les valeurs predictives des strategies utilisant les facteurs metaboliques, les ALAT, les anticorps antiVHC, la consommation declaree d’alcool (CDA), la carbohydrate deficient transferrin (CDT) et l’elastometrie (LSM par Fibroscan). Patients et Methodes 7 554 sujets volontaires de 40 ans ou plus, consultants dans 2 centres d’examens de sante CPAM-Paris ont ete prospectivement pre-inclus. Les donnees epidemiologiques, cliniques, biologiques, FT, SteatoTest, NashTest, etaient recueillis et les sujets avec FA presumee tFT > 0,48) etaient reconvoques dans un centre de reference pour une consultation avec un hepatologue et une elastometrie et si besoin echographie, endoscopie ou biopsie hepatique. FT a ete combine a la serologie C chez 3 602, a la CDT chez 1 074, et a l’elastometrie chez 893 sujets consecutifs. Resultats Le FT etait interpretable chez 99,6 % des cas, et apres exclusion des sujets refusant le protocole, ou presentant un antecedent hepatique, 7 464 sujets ont ete analyses, 55 % hommes, mediane 58 ans, un facteur de risque metabolique 53 %, et une consommation declaree d’alcool a risque (> 10 g/j chez la femme > 20 g chez l’homme) 26 % des cas. FT predisait une FA chez 209 (2,8 %) sujets, dont la cirrhose dans 25 cas (0,3 %). 103 sujets ont accepte les re-investigations. La FA a ete confirmee chez 52 sujets, fortement suspectee dans 20 cas (LSM > 5 kPa et un facteur de risque), moderement suspectee dans 28 (LSM > 5 kPa ou un facteur de risque), et indeterminee dans 3 cas (faux positif du FT ou faux negatif de LSM). Les reinvestigues n’etaient pas differents des non reinvestigues. La cause de FA chez les reinvestigues etaient 39 (38 %) NAFLD, 10 (10 %) MAF, 39 (38 %) mixte NAFLD et MAF, 5 (5 %) HCV, 2 (2 %) HBV, une (1 %) auto-immune, et pas de cause identifiee dans 7 cas (7 %). Les groupes a risque significatifs de FA en regression logistique ( odds ratio [OR]) etaient l’âge > 60 ans (OR-5,8 ; P 7,1 kPa (OR = 4,1 ; P 1,6 % (OR = 2,1 P = 0,02) et la serologie VHC positive (OR = 2,1 ; P = 0,02). ALAT et CDA n’etaient pas associes a un risque plus important. ALAT et CDA etaient disponibles chez 7 464 sujets, serologie VHC chez 3 602, CDT chez 1 074 et LSM interpretable chez 893 sujets consecutifs (concordance 91 % avec FT). La CDT a permis de soupconner 2 fois plus souvent une sous-estimation de la consommation d’alcool chez les patients avec FA (42 %) que chez les sujets sans FA (21 %). Conclusion Le depistage de la fibrose hepatique utilisant le FibroTest en premiere ligne et le FibroScan en confirmation parait efficace et acceptable chez 50 % des assures sociaux. La prevalence etait de 2,8 % avec 5 facteurs de risque additifs : metaboliques, âge, sexe masculin, consommation d’alcool et VHC.

AIM: To investigate the liver stiffness measurement (LSM) applicability and variability with reference to three probe positions according to the region of liver biopsy. METHODS: The applicability for LSM was defined as at least 10 valid measurements with a success rate greater than 60% and an interquartile range/median LSM < 30%. The LSM variability compared the inter-position concordance and the concordance with FibroTest. RESULTS: Four hundred and forty two consecutive patients were included. The applicability of the anterior position (81%) was significantly higher than that of the reference (69%) and lower positions (68%), (both P = 0.0001). There was a significant difference (0.5 kPa, 95% CI 0.13-0.89; P < 0.0001) between mean LSM estimated at the reference position (9.3 kPa) vs the anterior position (8.8 kPa). Discordance between positions was associated with thoracic fold (P = 0.008). The discordance rate between the reference position result and FibroTest was higher when the 7.1 kPa cutoff was used to define advanced fibrosis instead of 8.8 kPa (33.6% vs 23.5%, P = 0.03). CONCLUSION: The anterior position of the probe should be the first choice for LSM using Fibroscan, as it has a higher applicability without higher variability compared to the usual liver biopsy position.

Objective To investigate the hypothesis that surgical confusions rarely occur but are unacceptable to the public; occur in predictable circumstances; involve a wrong lens implant more often than a wrong eye, procedure, or patient; and can be prevented using the Universal Protocol. Methods A retrospective series of 106 cases, including 42 from the Ophthalmic Mutual Insurance Company and 64 from the New York State Health Department. We investigated how the error occurred; when and by whom it was recognized; who was responsible; whether the patient was informed; what treatment was given; what the outcome and liability was; what policy changes or sanctions resulted; and whether the error was preventable using the Universal Protocol. Results The most common confusion was wrong lens implants, accounting for 67 cases (63%). Wrong-eye operations occurred in 15 cases, wrong-eye block in 14, wrong patient or procedure in 8, and wrong corneal transplant in 2. Use of the Universal Protocol would have prevented the confusion in 90 cases (85%). Conclusions Surgical confusions occur infrequently. Although they usually cause little or no permanent injury, consequences for the patient, the physician, and the profession may be serious. Measures to prevent such confusions deserve the acceptance, support, and active participation of ophthalmologists.