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Multiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion.This study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators.The study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course.VX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

Background Endoscopic access to common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique as part of a standardized protocol in CBD access, after failure of standard cannulation and to compare successful CBD access rates, complication rates and length of hospital stay (LOS) in two groups. Method From January 2012 to December 2014, all consecutive patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with “difficult” access to CBD were included in a “studied group”. CBD access was “difficult” after either: 5 unsuccessful attempts, 5 unintentional insertions in the pancreatic duct or more than 10-minute-long unsuccessful attempts. This group was compared to a historical control group undergoing ERCP from January 2009 to December 2011. In the studied group, a sequential strategy including DGW technique was performed when the guidewire was unintentional passed into the pancreatic duct. In the control group, only precut technique was used. Results Among the 538 patients with naive papilla eligible for ERCP, 73 had difficult CBD access. Successful CBD access rate was higher in the studied group: 91%(50/55) vs 67%(12/18) p=0.0215. Complication rates were similar in both groups: 28% vs 20%, p=0.5207. LOS was shorter in the studied group (9.2±8.5 days vs. 14.4±7.4 days, p=0.0028). Post-ERCP cholangitis were lower in the study group: 2%(1/55) vs 22%(4/18), p = 0.0118. Conclusion After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications. This article is protected by copyright. All rights reserved.

Preemptive therapy in hematopoietic cell transplantation is initiated by a diagnostic technique at first detection of cytomegalovirus (CMV). The aim of this study was to use the viral dynamics of CMV DNA viral to start preemptive therapy, and to prospectively compare the CMV viral load kinetics to pp65 antigenemia. Two hundred sixty-three blood samples were collected prospectively from 93 patients. All clinical decisions regarding use of preemptive therapy were based on CMV antigenemia. Based on the positivity of the antigen assay and clinical CMV outcome in allotransplant patients, an optimal threshold of 3.05 log 10 (1,130 copies/ml) was found to discriminate patients who required preemptive therapy and those who did not (sensitivity, 71%; specificity, 65%). A DNAemia level increase of 2.24 log 10 (174 copies/ml) per day was the optimal threshold to discriminate between patients who required preemptive therapy and those who did not (sensitivity, 93%; specificity, 43%). Sensitivity of PCR assay was 92.4% compared with 39% for the antigen assay (P

A lack of antiviral response in patients with chronic hepatitis C treated with pegylated (PEG)-interferon (IFN)-α-2a + ribavirin (RIBA) may be explained by neutralizing antibodies to IFN-α-2a. The aim of this study was to assess neutralizing antibodies to IFN-α-2a and IFN levels in non-responder patients who were re-treated by PEG IFN-α-2a and RIBA for 12 weeks. Non-responders to a first-line treatment of PEG IFN-α-2a + RIBA were included for treatment with PEG IFN-α-2a (180 µg/week) + RIBA (1,000 mg/day if

Background and Aims: Syndecan 1 (CD 138) is a cell surface proteoglycan shed by cells in several pathological conditions, including wound healing. The aim of this study was to test whether CD138 could serve as a non-invasive marker for detection of liver fibrosis and thereby reduce the need for liver biopsy. Patients and Methods: An estimation set of 134 patients and a validation set of 67 patients with chronic hepatitis C were studied. There were 80 normal healthy volunteers. Patients were staged according to liver biopsies (Metavir fibrosis staging, stage F0, n=35; F1, n=40; F2, n=37, F3, n=39; F4, n=51). Serum CD138 levels were retrospectively measured by enzyme-linked immunoabsorbent assay the same day of the liver biopsy. The primary endpoints were the diagnostic values of CD138 for F2–F4, F3–F4 and F4. Results: Respective areas under receiver operating characteristic curve of CD138 for F2–F4, F3–F4 and F4 diagnosis were 0.82, 0.76 and 0.81. CD138 had a positive predictive value of 82% for F2–F4 diagnosis and a high negative predictive value (86%) and specificity (84%) for exclusion of F4. Conclusion: CD138 is a new simple non-invasive marker for predicting liver fibrosis in patients with chronic hepatitis C. The relevance of this marker in combination with other fibrosis markers should be explored.

Summary Background Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries. Aims To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E. Methods This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases. Results A decreasing South-to-North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig. Conclusions This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non-endemic countries.

Summary. Non-invasive biomarkers have gained popularity for estimating fibrosis stage. In our hepatitis C-infected haemophilia patients, Fibrotest (FT) correctly identified clinically advanced or minimal liver disease. More accurate tests, like the FibroMeters, have recently been validated. The aim of the study was to improve the estimation of liver fibrosis in hepatitis C-infected haemophiliacs using a combination of biomarkers and FibroMeters. One hundred and thirty-two hepatitis C-infected haemophilia patients (124 male, mean age: 39 ± 14 years) were evaluated. The following biomarkers were used: FT, AST-to-platelet ratio index (APRI), Forns index, hyaluronic acid and FibroMeter. We applied a published algorithm suggesting that if FT is in concordance with APRI and/or Forns score, then the FT concurs with liver biopsy for estimation of fibrosis. Concordance of three or more biomarkers was present in 43.2% (57/132) of the patients. This high discordance rate was mainly because of indeterminate scores. Significant fibrosis (F2‐F4) was estimated at 34.8% (46/132) and 37.9% (50/ 132) by the FT and FibroMeter respectively. The discordance rate between the FT and FibroMeter was 16.7% (22/132), (P < 0.01 vs. other biomarkers). Using the algorithm, liver histology could be confidently estimated in 69.7% (92/132) of the patients. Concordance between the FT and FibroMeter in those patients who met the terms of the algorithm was 90.2% (83/92). Discordance between biomarkers is significant, and is mainly because of biomarkers with indeterminate results. The concordance rate between FT and FibroMeter is higher compared with the other biomarkers. Practical combination of tests may potentially limit the need of liver biopsy in the majority of haemophilia patients.

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).

Liver biopsy remains the gold standard for the evaluation of fibrosis despite its risks and limitations, especially in haemophilia patients. Recently, non-invasive biomarkers have been used to assess histological features. The most thoroughly evaluated biomarker is the FibroTest (FT) (AUROC 0.80 for fibrosis stages F2F3F4 vs. F0F1). To estimate liver fibrosis in haemophilia patients infected with hepatitis C (HCV) using non-invasive biomarkers without liver biopsy. One hundred and thirty-two haemophilia patients (124 male, mean age 38 +/- 14 years) with anti-HCV antibodies were evaluated. These patients were stratified into several groups: patients with features of advanced liver disease - seven, persistently HCV RNA-negative - 21, persistently normal liver function tests (LFTs)- 24, HCV/HIV co-infected - 27. The following biomarkers of fibrosis were used: FT, AST-to-platelet ratio index (APRI), Forns index, age-platelet index and hyaluronic acid. The obtained scores were correlated with the clinical features of the patients. Estimated by the FT, the distribution of the stage of fibrosis in the 132 patients was F0F1 = 65% (86/132), F2 = 5% (7/132), F3 = 13% (17/132) and F4 = 17% (22/132). Using FT, all patients with clinical suspicion of advanced liver disease were classified as F3F4, whereas patients with persistently HCV RNA-negative were all classified as F0F1. Twenty-one per cent (5/24) of the patients with persistently normal LFTs had fibrosis stage F3F4. The proportion of F3F4 among HCV/HIV co-infected patients was significantly higher than among HCV mono-infected (52% vs. 33%; P = 0.05). Concordance of three or more biomarkers was present in 43% (57/132) of the patients. Liver biopsy could be avoided in 70% (92/132) using a practical assumption that if FT is in concordance with APRI and/or Forns, then we may confidently rely on the biomarker. Concordance rate for patients with presumably advanced or minimal liver disease was excellent (100% and 95% respectively). In our HCV-infected haemophilia patients, FT correctly identified clinically advanced or minimal liver disease. Discordance among the various biomarkers of fibrosis was considerate; nevertheless, practical combination of FT, APRI, and Forns may predict stage of fibrosis with accuracy, potentially avoiding liver biopsy in the majority of the patients.

SUMMARY. The clinical significance of hepatitis B virus (HBV) genotypes is still under debate. The aims of this study were to assess the distribution of HBV genotypes in France and to identify the associations between HBV genotypes and patient demographics, severity of liver disease and HBeAg status in patients referred to tertiary care centres. This was a French, multicentre, retrospective study on 262 patients with chronic HBV infection. HBV genotypes were determined using INNO-LiPA. Liver fibrosis damage was evaluated by histological analysis of biopsy samples. Patients were mainly male (74%), of Caucasian (65%), Asian (17%) or African (18%) ethnicity and 36% were HBeAg positive. All A‐G genotypes were found, the most frequent being genotypes D (27%) and A (24%), followed by E (13%) and C (12%), and B (7%). Mixed genotypes were detected in 16% of the cases. Genotype A was associated with sexual contact (P < 0.001) and genotype D with transfusion (P < 0.001) and HBe antibody positivity (P ¼ 0.03).The distribution of HBV genotypes differed with regard to the ethnicity, and may reflect migration patterns. Genotypes A and D were the most frequent in France. Genotype A was associated with HBeAg positivity and genotype D with HBe antibody positivity. In our European patients, we find no clear association between a given HBV genotype and liver disease severity.

WHO International Standards for nucleic acid tests are used widely to compare the different assays used in HCV RNA quantitation. The aim of the study was to assess the impact of the international unit standard for measuring HCV RNA in the management of patients with chronic hepatitis C virus (HCV) infection. Twenty-seven naive patients infected chronically by HCV were treated with ribavirin plus PEG-interferon-alfa-2b for 48 weeks. SVR was obtained for 16 patients (the other were non-responders). For HCV RNA quantitation, four assays were undertaken: Versant HCV RNA 3.0 (Bayer), Real time PCR (TaqMan, Roche), LCx HCV RNA (Abbott), and Cobas Amplicor-Monitor v2 (Roche). Considering a 2-log decline at Week 12 after the beginning of therapy, discordant results were found with the four HCV RNA methods in predicting SVR or non-response. At Week 4 and Week 12, significant differences were observed between Versant HCV RNA 3.0 versus PCR HCV Taqman, Versant HCV RNA 3.0 versus LCx HCV RNA, Cobas Monitor Amplicor HCV 2.0 versus LCx HCV RNA, and Cobas Monitor Amplicor HCV 2.0 versus PCR HCV Taqman (P < 0.001). The HCV RNA cutoff, given a 100% negative predictive value at Week 4 and Week 12, differed with the assays used to quantify HCV RNA, despite the use of the IU/ml units. Eighty-nine percent of serum values for HCV RNA were concordant by the IU standard. All assays, however, failed to detect HCV RNA in some cases. Despite the use of the IU standard HCV-infected patients might be monitored with only one assay.