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Aliment Pharmacol Ther 2011; 34: 462–469 Summary Background Faecal calprotectin is a reliable tool for predicting Crohn’s disease (CD) relapse in patients with sustained remission. Prediction of relapse with faecal calprotectin has been less studied in patients with severe CD treated with anti-TNF. Aim To identify an association between faecal calprotectin concentration and CD clinical relapse in patients achieving remission with infliximab (IFX). Methods From February 2007 to October 2008, consecutive patients with refractory luminal CD were prospectively included when they received three IFX infusions (5 mg/kg at weeks 0, 2 and 6) followed by maintenance with an immunomodulator alone. Faecal calprotectin and C-reactive protein (CRP) were measured at entry and at week 14 (w14). Results Sixty-five patients (43W; median age: 30.4 years) were included, and 50 (77%) were in clinical remission off steroids at w14; twenty-three of fifty (46%) experienced CD clinical relapse during the first year of follow-up. Median faecal calprotectin level at w14 was similar in patients with and without CD clinical relapse (200 and 150 μg/g respectively). When considering two suggested faecal calprotectin cut-offs to predict CD relapse, sensitivities and specificities were 61% and 48% for 130 μg/g, respectively, and 43% and 57% for 250 μg/g. Neither faecal calprotectin nor CRP at baseline and at w14 could predict relapse even when CD location subgroup analysis was considered. Conclusion In patients responding to an infliximab induction regimen, faecal calprotectin measurement at w14 cannot predict Crohn’s disease clinical relapse at 1 year.

Summary Background In Crohn’s disease (CD) patients naive to immunomodulators primary responding to infliximab (IFX) induction, maintenance with scheduled IFX or with immunomodulators is possible. The benefit of additional IFX infusions after failure of maintenance with immunomodulators is not known. Aim To assess the efficacy and factors associated with efficacy of postponed IFX retreatment. Methods All CD primary responders to an IFX induction regimen in maintenance with immunomodulators were retrospectively included when they received at least one additional IFX infusion after week 14. Efficacy was defined as clinical response at week 4 and absence of intolerance leading to discontinuation. Results Sixty-one patients were retreated with IFX with a 38-week median time from induction. Efficacy was achieved in 80% patients. Twelve patients had no clinical benefit: seven acute hypersensitivity reactions and five loss of response. By multivariate analysis, the only factor associated with no efficacy was a median time >50 weeks from induction to retreatment (odds ratio = 7.38; 95%CI: 1.38–39.59; P = 0.02). Conclusion Postponed retreatment with IFX in CD primary responders should be administered within 50 weeks after induction, for better efficacy and tolerance.

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.

Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.

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.

Transient elastography (FibroScan) is a new, non-invasive, rapid, and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness. In cirrhotic patients, liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. The aim of this prospective study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease.A total of 711 patients with chronic liver disease were studied. Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection, alcohol, non-alcoholic steatohepatitis, other, or a combination of the above aetiologies. Liver fibrosis was evaluated according to the METAVIR score.Stiffness was significantly correlated with fibrosis stage (r=0.73, p0.0001). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.80 (0.75-0.84) for patients with significant fibrosis (F2), 0.90 (0.86-0.93) for patients with severe fibrosis (F3), and 0.96 (0.94-0.98) for patients with cirrhosis. Using a cut off value of 17.6 kPa, patients with cirrhosis were detected with a positive predictive value and a negative predictive value (NPV) of 90%. Liver stiffness was significantly correlated with clinical, biological, and morphological parameters of liver disease. With an NPV90%, the cut off values for the presence of oesophageal varices stage 2/3, cirrhosis Child-Pugh B or C, past history of ascites, hepatocellular carcinoma, and oesophageal bleeding were 27.5, 37.5, 49.1, 53.7, and 62.7 kPa, respectively.Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease. Its use for the follow up and management of these patients could be of great interest and should be evaluated further.

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

Introduction L’infliximab (IFX) est efficace en traitement d’induction (5 mg/kg aux semaines (S) 0,2 et 6) de la maladie de Crohn (MC) luminale et fistulisante. Chez les repondeurs primaires a S14, l’IFX est ensuite soit poursuivi en maintenance, soit interrompu et relaye par un traitement immunosuppresseur (IS) en entretien. Dans cette derniere situation, en cas de rechute de la MC, le benefice d’un retraitement (R) a distance par IFX est mal connu. But Determiner l’efficacite et les facteurs predictifs de reponse a un R par IFX apres S14 chez des repondeurs primaries a un traitement d’induction. Patients et Methodes Tous les malades suivis pour MC, ayant repondu a l’IFX en induction puis traites par IS en entretien entre janvier 2001 et aout 2008, ont ete inclus lorsqu’ils recevaient une nouvelle perfusion d’IFX apres S14. L’efficacite du R par IFX etait definie par (i) la reponse clinique a S4 du R (sur une baisse du score CDAI > 100 points et/ou une reduction d’au moins 50 % des ecoulements fistuleux) et (ii) l’absence de reaction d’intolerance conduisant a l’arret de l’IFX. Les facteurs predictifs suivants ont ete etudies : caracteristiques de la MC selon la classification de Montreal, indication de l’IFX au R, prise de corticoides ou d’IS lors du R, schema de R (re-induction a S0-2-6 ou IFX toute les 8 S), R apres S50, taux de CRP et d’Ac anti-noyau au R. Resultats Au 1 er aout 2008, 61 malades (42F ; âge moyen : 38 ans) ont ete retraites par IFX. L’indication du R etait MC luminale, MC fistulisante ou les 2 dans respectivement 69 %, 11 % et 20 % des cas. Le delai median de R par l’IFX a ete de 38 S (extremes : 15 - 212) et 80 % des malades ont ete repondeurs a S4 du R sans reaction d’intolerance. De plus, l’IFX etait inefficace chez 12 malades (20 %), en raison d’une intolerance (n = 7 ; tous pour reaction d’hypersensibilite immediate sans gravite, resolutive a l’arret de la perfusion) ou d’une perte de reponse (n = 5). En analyse univariee, seul le R apres S50 etait associe a l’arret de l’IFX (OR = 7,5 ; IC 95 % : 1,76 - 31,85 ; P Conclusion En cas de MC luminale et/ou ano-perineale, un R a distance par IFX apres reponse primaire a un traitement d’induction est efficace et bien tolere quand il est realize dans l’annee. Au-dela d’un an, le R par IFX expose a un risque modere de reaction d’intolerance a mettre en balance avec les benefices attendus.

Introduction En France, la strategie de depistage des polypes et du cancer colorectal (CCR) repose sur la combinaison de la recherche de sang dans les selles et de la coloscopie. La video-capsule specifique du colon (VCC), pourrait etre une alternative a cette strategie [1, 2]. Le but de cette etude prospective, multicentrique francaise etait de comparer les performances diagnostiques de la VCC a celles de la coloscopie dans une population a risque moyen ou eleve de CCR. (analyse intermediaire planifiee apres 105 inclusions/550 prevues). Patients et Methodes Les patients a risque moyen de CCR (50-74 ans) ou a risque eleve (antecedents personnels ou familiaux de neoplasie colique) ont ete inclus dans l’etude. Les criteres d’exclusion etaient une symptomatologie evocatrice de stenose intestinale, une diverticulose colique recemment compliquee et une insuffisance cardiaque et/ou renale evoluee. La VCC et la coloscopie ont ete realisees, chez le meme patient, a 24 heures d’intervalle, selon une methodologie publiee (1, 2). Les donnees ont ete interpretees (niveau de preparation, presence de lesion,…), en double insu, par l’endoscopiste ayant realise la coloscopie et le lecteur de la VCC. En cas de discordance entre les deux interpretations, un comite d’adjudication tranchait. Resultats 105 patients (39 femmes et 66 hommes), âges en moyenne de 60 ± 10 ans ont ete inclus de mai 2007 a fevrier 2008. Trente patients (29 %) etaient a risque moyen de CCR et 75 patients (71 %) a risque eleve. 90 % des VCC etaient excretees dans les 10 heures apres l’ingestion. La preparation du colon etait jugee bonne ou excellente dans 55 % des cas en VCC et 87 % des cas en coloscopie. La prevalence de polype significatif (≥ 6 mm) etait de 25 % pour la VCC et la coloscopie. Les performances de la VCC pour le diagnostic de polype ≥ 6 mm etaient : Sensibilite 55 %, Specificite 87 %, Valeur Predictive Positive 52 % et Valeur Predictive Negative 88 %. Chez les patients ayant une preparation bonne ou excellente, les performances etaient respectivement de 69 %, 84 %, 56 %, et 90 %. Apres adjudication des cas discordants, les performances etaient respectivement de 73 %, 93 %, 73 % et 93 %. Cinq evenements secondaires ont ete observes, en rapport avec la preparation (2 fois) ou la coloscopie (3 fois). La VCC a ete mieux appreciee que la coloscopie (echelle visuelle analogique : 8,80 vs 8,27 p Conclusion Ces resultats montrent l’excellente acceptabilite et tolerance de la VCC pour le depistage et le suivi de lesions neoplasiques colo-rectales. Cependant la preparation etait jugee insuffisante chez pres d’un malade sur deux et a conduit a modifier le protocole de preparation. De plus, les resultats apres adjudication confirment l’importance d’un apprentissage prealable a l’utilisation de cette technique. Malgre ces reserves, la combinaison d’une sensibilite de 73 % et d’une VPN de 93 % pour la detection de polypes de plus de 6 mm semble particulierement prometteuse.

Background: Treatment with infliximab (IFX) can result in immunogenicity through the formation of human anti-chimeric antibodies (HACAs). These antibodies are associated with a decreased duration of response, whereas therapeutic levels of IFX are associated with durable clinical response. We evaluated the clinical utility of measuring serum IFX and HACA levels. Methods: We retrospectively reviewed charts of patients with inflammatory bowel disease who had IFX drug and HACA levels measured over a three-year period from 2005-2008. The clinical utility of these tests was assessed by determining whether the result affected clinical management. The management and subsequent clinical response to therapeutic changes based on test results was evaluated. Fisher's exact test and log-rank test for discontinuation were used for statistical analysis. Results: One hundred and fifty-five patients underwent IFX level and HACA status testing. The median time to initial testing after IFX initiation was 50 weeks (IQR: 22.7-120). The main indications for testing were: loss of response to IFX (50.3%), partial response after initiation of IFX (22.6%) and possible autoimmune/delayed hypersensitivity reaction (14.8%). HACAs were identified in 35 patients (22.6%) and therapeutic IFX levels were found in 51 (32.9%). Of 177 total tests assessed, the results impacted treatment decisions in 73.4% (95% CI: 66-80%). In those with positive HACAs, change to another anti-TNF was associated with a complete or partial response in 91.6% of patients whereas increasing the dose had a response of 16.7% (p

This article compares two groups of Catholic males: (1) Hawks--those favoring the use of nuclear weapons, and (2) Doves--those finding use of such weapons morally unjustifiable.Employing factor analysis and related techniques, the groups were compared on a battery of 42 variables. An eight-factor profile was developed for each group. The goal was to focus maximum attention on the differences between Hawks and Doves.It is suggested that three of the dimensions were of primary importance in determining selection of the Dove position: (1) satisfaction with reality; (2) strong parental religious influence--especially maternal; and (3) a positive and active religious commitment and identification. On the other hand, becoming a Hawk was attributed to: (1) sociocultural dissatisfaction; (2) socioreligious rejection; and (3) adherence to an ideological substitute for religion--political conservatism.