Prevalence of and Factors Associated With Extraintestinal Manifestations and Their Remission in Inflammatory Bowel Disease: The EXTRA-Intestinal Manifestation Prospective Study From the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

INTRODUCTION: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are challenging clinical situation. No prospective study assessed remission risk factors of EIMs. The aim of this study was to prospectively investigate the epidemiology, risk factors of EIM occurrence, and EIM remission in a large IBD cohort. METHODS: We conducted a cross-sectional study in 30 French referral centers. Between May 2021 and June 2021, all consecutive patients attending to hospital appointment were systematically invited to fill out a questionnaire. RESULTS: A total of 1,971 consecutive patients with IBD were analyzed. There were 1,056 women (53.8%), and the median age of patients was 41 years (31-54). The median disease duration was 11 years (1-18). Overall, 544 (27.6%) had at least 1 EIM. In 20.2% of cases, patients had multiple EIMs. The most frequent EIMs were rheumatological (19%) and dermatological (10%) manifestations. Immunosuppressant treatment (odds ratio [OR] = 2.56; P < 0.001) was a risk factor of EIM, while the Montreal A3 classification (OR = 0.61, P = 0.023) and male gender (OR = 0.61, P < 0.001) were associated with a lower risk of EIM occurrence. IBD current clinical remission (OR = 2.42; P < 0.001) and smoking cessation (OR = 2.98; P < 0.001) were associated factors of EIM remission. Conversely, age at IBD diagnosis (OR = 0.98; P < 0.018) was associated with a lower risk of EIM remission. DISCUSSION: One quarter of patients had at least 1 EIM. Beyond factors associated with the presence of EIMs, patients with IBD current clinical remission and smoking cessation are more likely to achieve EIM remission, while increasing age at IBD diagnosis is associated with decreased chance of remission.

Adalimumab in Biologic-naïve Patients With Crohn's Disease After Resolution of an Intra-abdominal Abscess: A Prospective Study From the GETAID.

BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess. CLINICALTRIALS: gov, Number: NCT02856763.

How are patients' preferences for anti-TNF influenced by quality of life? A discrete choice experiment in Crohn's disease patients.

BACKGROUND AND OBJECTIVE: Anti-TNFs have been shown to significantly improve the health-related quality of life (HRQoL) in Crohn's disease (CD) patients. The purpose of this study was to investigate to what extend the patients' preferences for these intravenous (IV) and subcutaneous (SC) treatments differ based on respondents' quality of life. An online discrete choice experiment (DCE) was conducted to understand patient trade-offs in treatment choice. METHODS: Fifty-seven Crohn's disease anti-TNF naïve patients were asked to choose between two different scenarios, considering the following attributes: mode of administration (MODE), total availability for injection (TIME), speed of onset (DELAY), risk of anti-TNF administration despite a contraindication (RISK) and total monthly out-of-pocket expenses (COST). At the same time, patients completed the IBDQ-32 questionnaire. Conditional logit models without and with interaction terms were estimated to evaluate attribute weights. RESULTS: Patients preferred to self-administer SC anti-TNF rather than have a primary care nurse do it, whereas the preference for IV route was negative. After adding interaction terms however, the IV route became preferred for patients with impaired HRQoL, this preference having decreased as HRQoL increased. Surprisingly, patients with impaired HRQoL were less willing to spend more time on treatment, and this effect diminished as HRQoL (overall and in each dimension) became higher. CONCLUSIONS: HRQoL level changed patients' preferences for the anti-TNF treatment. The results suggest the need to optimise the management of IV infusions in the hospital and reinforce the importance of patient-reported outcome measures (PROMS) as a common practice to improve shared medical decision making.

Predictors of each quality of life dimension in Crohn's disease patients initiating an anti-TNF treatment: differentiated effects of patient-, disease-, and treatment-related characteristics.

BACKGROUND AND AIMS: In Crohn's disease (CD), a composite therapeutic target was recently recommended, including both objective measurement (endoscopic remission) and Patient-Reported Outcomes (resolution of abdominal pain and normalization of bowel function). All dimensions of health-related quality of life (HRQoL) are impacted: not only bowel symptoms but also systemic symptoms, emotional wellbeing and social function. Thus, understanding the predictors of each HRQoL dimension would improve patient management. However, analysis of these factors has only been found in a few publications, with some limitations. Therefore, this study aimed to explore the evolution of the HRQoL of CD patients during six months after initiation of anti-TNF and to identify its predictors. METHODS: We analyzed data of 56 patients included in a multicenter prospective cohort study (COQC-PIT). HRQoL measures (using IBDQ-32) and data related to patient, disease and treatment characteristics were collected every two months. Generalized estimating equations were used. RESULTS: Overall HRQoL was significantly improved 2 months after anti-TNF initiation, and then stagnated. Patient, disease, and treatment characteristics have differentiated impacts on the overall score and on each dimension of quality of life. Subcutaneous anti-TNF had no significant effect on overall HRQoL, improving only emotional function and bowel symptoms. Concomitant use of corticosteroids and/or immunomodulators impaired almost all dimensions. Having children or working altered bowel symptoms. Disease duration and active smoking negatively impact emotional function and systemic symptoms. CONCLUSIONS: Each HRQoL dimension, not only bowel symptoms, and their influencing factors should therefore be considered in medical decision-making, especially in months following the initiation of a new treatment such as anti-TNF.

A predictive score of inadequate bowel preparation based on a self-administered questionnaire: PREPA-CO.

INTRODUCTION: Inadequate bowel preparation before colonoscopy has a 20-30% rate and impedes on the quality of the procedure. The aim of this study was to develop a predictive score of inadequate bowel preparation, using a patient questionnaire on potential risk factors. METHODS: In this single center study, consecutive patients with colonoscopy indication were enrolled. The primary outcome was inadequate bowel preparation defined by Boston Bowel Preparation Scale (BBPS) score <7 or a score ≤1 in any of the 3 colonic segments. RESULTS: A total of 561 patients were included. Inadequate bowel preparation was seen in 25.0% of cases. Seven risk factors were selected into the prediction model of inadequate bowel preparation: diabetes or obesity, irregular physical activity, cirrhosis, use of antidepressants or neuroleptics, use of opiate medication, history of surgery and history of inadequate bowel preparation. The risk score, named PREPA-CO, had an AUROC of 0.621, adequately predicted bowel cleanliness in 68.3% of cases, with a specificity of 75.8% and a negative predictive value of 80.8%. CONCLUSION: We developed a predictive score named "Prepa-Co", allowing the identification of patients at high risk of inadequate bowel preparation. In clinical practice, this score could help tailor the prescription of the preparation to the patient.

Ustekinumab for Perianal Crohn's Disease: The BioLAP Multicenter Study From the GETAID.

INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

Long-term outcome of Crohn's disease patients with upper gastrointestinal stricture: A GETAID study.

BACKGROUND: There are few data concerning patients with Crohn's disease (CD) complicated by a stricture of the upper gastrointestinal tract (UGT). AIMS: We evaluated the outcome and management of CD patients complicated by a stricture of the UGT. METHODS: We performed a retrospective multicenter study including all CD patients with a non-passable symptomatic UGT stricture on endoscopy. Primary outcome measure was surgery-free survival from diagnosis of stricture. Efficacy of medical, endoscopic, and surgical treatments, and identification of predictors of surgery were also evaluated. RESULTS: 60 CD patients with an UGT stricture were included. 60% of the strictures were located in the duodenum. With a median follow-up of 5.5 (IQR: 3.0-12.0) years since stricture diagnosis, surgical-free survival was 75% and 64% at 1 and 5 years, respectively. At the end of the follow up, 27 (45%) patients underwent surgery. 77 endoscopic procedures were performed in 30 patients with an immediate success of 81% and a clinical benefit in 84% of the procedures. In multivariate analysis, anti-TNF treatment initiation was associated with a reduced risk of surgery. CONCLUSION: CD UGT strictures are mainly located in the duodenum. Medical and endoscopic treatments allow to avoid surgery in half of the patients.

VALIDation of the IBD-Disk Instrument for Assessing Disability in Inflammatory Bowel Diseases in a French Cohort: The VALIDate Study.

BACKGROUND AND AIMS: Inflammatory bowel diseases [IBD] are disabling disorders. The IBD-Disability Index [IBD-DI] was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk and to assess the clinical factors associated with a change in the score and its variability over time. METHODS: From May 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3-12 month intervals. Validation included concurrent validity, reproducibility, and internal consistency. Mean IBD-Disk scores were compared according to clinical factors. Variability was assessed by comparing scores between baseline and follow-up visits. RESULTS: A total of 447 patients [71% Crohn's disease, 28% ulcerative colitis] were included in the analysis at baseline and 265 at follow-up. There was a good correlation between IBD-Disk and IBD-DI [r = 0.75, p <0.001]. Reproducibility was excellent [intra-class correlation coefficient = 0.90], as well as internal consistency [Cronbach's α = 0.89]. The IBD-Disk was not influenced by IBD type but was associated with female gender and physician global assessment. Extra-intestinal manifestations, history of resection, elevated C-reactive protein and faecal calprotectin also tended to be associated with higher disability. The IBD-Disk score decreased in patients becoming inactive over time. CONCLUSIONS: This study validated the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability for both CD and UC.

Vedolizumab for perianal Crohn's disease: a multicentre cohort study in 151 patients.

BACKGROUND: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

Maintenance of Remission Among Patients With Inflammatory Bowel Disease After Vedolizumab Discontinuation: A Multicentre Cohort Study.

BACKGROUND AND AIM: It is unclear whether vedolizumab therapy can be discontinued in patients with inflammatory bowel disease [IBD] after achieving steroid-free clinical remission. The aim was to assess the risk of relapse after vedolizumab therapy was discontinued. METHODS: This was a retrospective observational study, collecting data from 21 tertiary centres affiliated with the GETAID from January 2017 to April 2019. Consecutive patients with IBD, who were in steroid-free clinical remission for at least 3 months and were treated with vedolizumab for at least 6 months, were included at the time of vedolizumab discontinuation. RESULTS: A total of 95 patients [58 with Crohn's disease] discontinued vedolizumab after a median duration of therapy of 17.5 [10.6-25.4] months. After a median follow-up period of 11.2 [5.8-17.7] months, 61 [64%] patients experienced disease relapse. The probabilities of relapse-free survival were 83%, 59%, and 36% at 6, 12, and 18 months, respectively. According to the multivariate analysis, a C-reactive protein level less than 5 mg/L at vedolizumab discontinuation (hazard ratio [HR] = 0.56, 95% confidence interval [CI] [0.33-0.95], p = 0.03) and discontinuation due to patients' elective choice (HR = 0.41, 95% CI [0.21-0.80], p = 0.009) were significantly associated with a lower risk of relapse. Re-treatment with vedolizumab was noted in 24 patients and provided steroid-free clinical remission in 71% and 62.5% at Week 14 and after a median follow-up of 11.0 [5.4-13.3] months, respectively, without any infusion reactions. CONCLUSIONS: In this retrospective study, two-thirds of patients with IBD treated with vedolizumab experienced relapse within the first year after vedolizumab discontinuation. Re-treatment with vedolizumab was effective in two-thirds of patients.

Real-world evidence of tofacitinib effectiveness and safety in patients with refractory ulcerative colitis.

BACKGROUND: Phase III trials demonstrated effectiveness of tofacitinib, an oral Janus kinase inhibitor, to induce and maintain remission in patients with moderate-to-severe active ulcerative colitis (UC). AIMS: We report the real-world effectiveness and safety of tofacitinib in patients with UC in France. METHODS: From February 2017 to December 2018, we performed a national French cohort study, which included all consecutive patients with an active UC refractory to anti-TNF and vedolizumab, who received tofacitinib. Outcomes were survival without colectomy, survival without tofacitinib discontinuation and steroid-free clinical remission at weeks 14, 24 and 48. RESULTS: Thirty-eight patients were included, with a median follow-up of 41.5 (18.5-56.8) weeks. Survival without colectomy was 77% [95% confidence interval (95%CI): 59.3-87.9] at week 24 and 70% (95%CI: 50.9-82.8) at week 48. Survival without treatment discontinuation was 70% (95%CI: 52.6-82.3) at week 24. Steroid-free clinical remission was observed in 13 (34%) patients at week 48. Adverse events occurred in 14 (37%) patients, including 6 severe adverse events and three herpes zoster infections. CONCLUSION: In a highly refractory UC population, one third of patients treated with tofacitinib achieved steroid-free clinical remission at week 14 and 70% of patients avoided colectomy at one year, with an acceptable safety profile. These data confirm tofacitinib effectiveness in UC, especially after multiple biologic failures.

Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C.

BACKGROUND: Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology. METHODS: 650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis. RESULTS: The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic. CONCLUSION: A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.

Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD.

BACKGROUND AND AIM: We carried out morphometric measurements of steatosis to evaluate relationships between steatosis degree and other liver lesions or metabolic syndrome components in nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: We developed an algorithm to measure steatosis area. Two hundred and fourteen patients with NAFLD were included in derivation (10) and validation (204) groups. Controls consisted of patients who were steatosis-free (12), patients with chronic hepatitis C (188), and patients with alcoholic chronic liver disease (94). RESULTS: Accuracy of steatosis area was considered as good or very good in at least 72% of cases by three pathologists. Steatosis areas were as follows: NAFLD = 10.3 ± 9.7%, virus = 2.4 ± 3.1%, alcohol = 7.8 ± 8.2% (P<0.0001). Steatosis area was closely related to steatosis grades in NAFLD (P<0.0001 for linear trend). Steatosis area increased from the fibrosis stage F0 to the fibrosis state F2, then decreased in the stages F3 and F4 (cirrhosis) (P<0.0001 for quadratic trend). Fibrosis was present in an average steatosis area of approximately 4% (defining significant steatosis) and in nonalcoholic steatohepatitis by approximately 8% (defining severe steatosis). Steatosis and fibrosis area increased symmetrically until approximately 10%, then steatosis area decreased to null as average fibrosis area reached 32%. Average fasting glycemia (approximately 92 mg/dl) or triglycerides and BMI plateaued before a steatosis area of approximately 4%, then increased thereafter. Significant steatosis was present in 61.3% of NAFLD versus 20.2% of viral hepatitis (P<0.0001) and in 58.7% of alcoholic liver diseases (P=0.674). CONCLUSIONS: The average threshold of steatosis area is 4% for the development of fibrosis or metabolic syndrome components and 8% for nonalcoholic steatohepatitis. Steatosis area may contribute to defining the normal range and clinical course of metabolic components.

A new combination of blood test and fibroscan for accurate non-invasive diagnosis of liver fibrosis stages in chronic hepatitis C.

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.

Optimization and robustness of blood tests for liver fibrosis and cirrhosis.

OBJECTIVES: To optimize the performance and feasibility of fibrosis blood tests and evaluate their robustness. DESIGN AND METHODS: The derivation population included 1056 HCV patients with liver biopsy and blood markers. Validation populations included 984 patients with various viral hepatitis causes, and Fibroscan and/or liver biopsy and/or blood markers. RESULTS: The bootstrap method validated the markers of the original FibroMeter(2G), but not those of Fibrotest and Hepascore, and provided a hyaluronate-free FibroMeter(3G). AUROCs for significant fibrosis were: FibroMeter(2G): 0.853 vs. FibroMeter(3G): 0.851, p=0.489. Compared to FibroMeter(2G), FibroMeter(3G) had a significantly higher patient rate with predictive values ≥90% for significant fibrosis. Accuracy for fibrosis stage classification was: Fibrotest: 37.9%, FibroMeter(2G): 74.9%, and FibroMeter(3G): 86.9% (p<10(-3)). CONCLUSION: The bootstrap method validated FibroMeter(2G) and provided a cheaper and more feasible hyaluronate-free FibroMeter(3G) with comparable performance. Compared to binary diagnosis, fibrosis stage classification increased discrimination, with an increased accuracy to 87% for FibroMeter(3G).

Acoustic radiation force impulse: a new ultrasonographic technology for the widespread noninvasive diagnosis of liver fibrosis.

BACKGROUND/AIMS: As a module of a standard ultrasound imaging device, acoustic radiation force impulse (ARFI) is a new technology for liver stiffness evaluation (LSE). We aimed to evaluate accuracy, feasibility, reproducibility, and training effect of ARFI for liver fibrosis evaluation. METHODS: One hundred and one patients with chronic liver disease had LSE by Fibroscan and ARFI. LSE by ARFI was performed in the two liver lobes by two operators: an expert and a novice. Correlation and agreement were evaluated by the Pearson (Rp) and intraclass (Ric) correlation coefficients. The independent reference for liver fibrosis was fibrosis blood tests. RESULTS: ARFI results, ranging from 0.7 to 4.6 m/s, were well correlated with Fibroscan results (Rp=0.76). Fibroscan had a significantly higher area under the receiver operating characteristic curve (AUROC) than ARFI for the perprotocol diagnosis of significant fibrosis: 0.890+/-0.034 versus 0.795+/-0.047 (P=0.04). However, LSE failure occurred in zero patients using ARFI versus six patients using Fibroscan (P=0.03). Thus, on an intention-to-diagnose basis, Fibroscan and ARFI AUROCs for the diagnosis of significant fibrosis were not different: 0.791+/-0.049 versus 0.793+/-0.046 (P=0.98). Interobserver agreement was very good (Ric=0.84) and excellent for ARFI interquartile range (IQR)< or =0.30 (Ric=0.91). Indeed, agreement was independently predicted only by ARFI IQR, but not by LSE result as earlier observed for Fibroscan. ARFI AUROC was 0.876+/-0.057 in patients with ARFI IQR ratio< or =0.30, and Fibroscan AUROC was 0.912+/-0.034 in patients with Fibroscan IQR ratio less than 0.21 (P=0.59). Intersite ARFI agreement between the two liver lobes was fair (Ric=0.60). There was no training effect for LSE by ARFI. CONCLUSION: ARFI is highly feasible and reproducible, and provides diagnostic accuracy similar to Fibroscan. This new device seems noteworthy for the widespread noninvasive diagnosis of liver fibrosis.

The combination of a blood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis.

BACKGROUND AND AIMS: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm. METHODS: Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included. Five blood fibrosis tests were evaluated: APRI, FIB-4, Hepascore, Fibrotest and FibroMeter. The reference was fibrosis Metavir staging. RESULTS: Diagnosis of significant fibrosis (Metavir F>or=2). The most accurate synchronous combination was FibroMeter+LSE, which provided a significantly higher area under the receiver operating characteristic curve (0.892) than LSE alone (0.867, P=0.011) or Fibrometer (0.834, P<10(-3)). An algorithm using the FibroMeter+LSE combination and then a liver biopsy in indeterminate cases had 91.9% diagnostic accuracy and required significantly fewer biopsies (20.2%) than previously published Bordeaux algorithm (28.6%, P=0.02) or sequential algorithm for fibrosis evaluation (SAFE) (55.7%, P<10(-3)). The Angers algorithm performance was not significantly different between viral hepatitis and other causes. Diagnosis of cirrhosis. The most accurate synchronous combination was LSE+FibroMeter, which provided >or=90% predictive values for cirrhosis in 90.6% of patients vs 87.4% for LSE (P=0.02) and 57.9% for FibroMeter (P<10(-3)). An algorithm including the LSE+FibroMeter combination, and then a liver biopsy in indeterminate cases, had a significantly higher diagnostic accuracy than the SAFE algorithm (91.0 vs 79.8%, P<10(-3)), and required significantly fewer biopsies than the Bordeaux algorithm (9.3 vs 25.3%, P<10(-3)). CONCLUSION: The synchronous combination of a blood test plus LSE improves the accuracy of the non-invasive diagnosis of liver fibrosis and, consequently, markedly decreases the biopsy requirement in the diagnostic algorithm, notably to <10% in cirrhosis diagnosis.

Reproducibility of liver stiffness measurement by ultrasonographic elastometry.

BACKGROUND & AIMS: Fibroscan is a noninvasive device that assesses liver fibrosis by liver stiffness evaluation (LSE) with ultrasonographic elastometry. We evaluated LSE reproducibility and its influencing factors. METHODS: LSE was performed by 4 experienced physicians (>100 LSEs) in 46 patients with chronic liver disease at 4 different anatomic sites. Additional LSEs were performed for ancillary aims, so that 534 LSEs were available. RESULTS: Overall interobserver agreement for LSE results was considered as excellent, with intraclass coefficient correlation (Ric) of 0.93. Low LSE level, nonrecommended sites, LSE interquartile range >25%, and body mass index > or =25 independently decreased agreement. Thus, agreement was fair (Ric = 0.53) for LSE <9 kilopascals and excellent (Ric = 0.90) beyond. The best measurement site for LSE reproducibility was the median axillary line on the first intercostal space under the liver dullness upper limit, with the patient lying in dorsal decubitus. When LSE results were categorized into fibrosis Metavir stages, interobserver discordance was noticed in about 25% of the cases and was the highest for F2 and F3 stages and the lowest for F4. Intraobserver (Ric = 0.94), intersite (Ric = 0.92-0.98), and interequipment (Ric = 0.92) agreements for LSE results were excellent. Preliminary standard ultrasonography or probe pressure changes did not improve interobserver agreement. CONCLUSIONS: The best measurement site for LSE is the one generally used for liver biopsy. Reproducibility of LSE is globally excellent but is fair in patient with low liver stiffness. The fibrosis diagnosis by ultrasonographic elastometry in low stages or categorized into fibrosis Metavir stages must be interpreted with caution.

Current management of the complications of portal hypertension: variceal bleeding and ascites.

Portal hypertension is one of the main consequences of cirrhosis. It results from a combination of increased intrahepatic vascular resistance and increased blood flow through the portal venous system. The condition leads to the formation of portosystemic collateral veins. Esophagogastric varices have the greatest clinical impact, with a risk of bleeding as high as 30% within 2 years of medium or large varices developing. Ascites, another important complication of advanced cirrhosis and severe portal hypertension, is sometimes refractory to treatment and is complicated by spontaneous bacterial peritonitis and hepatorenal syndrome. We describe the pathophysiology of portal hypertension and the current management of its complications, with emphasis on the prophylaxis and treatment of variceal bleeding and ascites.

[Diffuse colonic ganglioneuromatous polyposis]. / La polypose colique ganglioneuromateuse diffuse.

Ganglioneuromatous polyposis is a very rare intestinal disease which differs from isolated polypoid ganglioneuroma and from diffuse ganglioneuromatosis. Its clinical, endoscopic, microscopic and evolutive features are poorly known. We report three cases of colonic ganglioneuromatous polyposis that illustrated an uncommon diffusion pattern in two men and one woman aged 63-72 who presented with chronic diarrhea. Endoscopic features suggesting the diagnosis were diffuse polyposis predominating in the cecum and right colon, with hyperhemic flat lesions enhanced after indigocarmin instillation. Histological study of the biopsies, and of colectomy specimens, showed a diffuse mucosal ganglioneuromatous proliferation with a few adenomatous polyps. Search for multiple endocrine neoplasia (MEN) type 2b was negative. In conclusion, this polypoid type of diffuse ganglioneuromatosis can be suspected in patients with chronic diarrhea by the special endoscopic aspect of the colonic polyposis. Pathologists should be aware of the distinctive features; diagnosis requires search for adenomas and/or neoplasia by total colopsy in addition to search for MEN 2b.