We report the results of the analyses of the cosmic ray data collected with a 4 tonne (3×1×1 m3) active mass (volume) Liquid Argon Time-Projection Chamber (TPC) operated in a dual-phase mode. We present a detailed study of the TPC's response, its main detector parameters and performance. The results are important for the understanding and further developments of the dual-phase technology, thanks to the verification of key aspects, such as the extraction of electrons from liquid to gas and their amplification through the entire one square metre readout plain, gain stability, purity and charge sharing between readout views.

The 3×1×1 m 3 demonstrator is a dual phase liquid argon time projection chamber that has recorded cosmic rays events in 2017 at CERN. The light signal in these detectors is crucial to provide precise timing capabilities. The performance of the photon detection system, composed of five PMTs, are discussed. The collected scintillation and electroluminescence light created by passing particles has been studied in various detector conditions. In particular, the scintillation light production and propagation processes have been analyzed and compared to simulations, improving the understanding of some liquid argon properties.

A 10 kilo-tonne dual-phase liquid argon TPC is one of the detector options considered for the Deep Underground Neutrino Experiment (DUNE). The detector technology relies on amplification of the ionisation charge in ultra-pure argon vapour and offers several advantages compared to the traditional single-phase liquid argon TPCs. A 4.2 tonne dual-phase liquid argon TPC prototype, the largest of its kind, with an active volume of \three has been constructed and operated at CERN. In this paper we describe in detail the experimental setup and detector components as well as report on the operation experience. We also present the first results on the achieved charge amplification, prompt scintillation and electroluminescence detection, and purity of the liquid argon from analyses of a collected sample of cosmic ray muons.

The Argon Dark Matter (ArDM-1t) experiment is a ton-scale liquid argon (LAr) double-phase time projection chamber designed for direct Dark Matter searches. Such a device allows to explore the low energy frontier in LAr. After successful operation on surface at CERN, the detector has been deployed underground and is presently commissioned at the Canfranc Underground Laboratory (LSC). In this paper, we describe the status of the installation and present first results on data collected in gas phase.

The Argon Dark Matter experiment is a ton-scale double phase argon Time Projection Chamber designed for direct Dark Matter searches. It combines the detection of scintillation light together with the ionisation charge in order to discriminate the background (electron recoils) from the WIMP signals (nuclear recoils). After a successful operation on surface at CERN, the detector was recently installed in the underground Laboratorio Subterráneo de Canfranc, and the commissioning phase is ongoing. We describe the status of the installation and present first results from data collected underground with the detector filled with gas argon at room temperature.

The treatment of hepatocellular carcinoma (HCC) in cirrhotic patients is challenging: the incidence is increasing, the cirrhosis dramatically limits the tolerance to treatment possibilities, there are many therapeutic modalities but resources are limited, namely in the context of organ shortage for transplantation. Liver transplantation (LT) is the optimal treatment as it combines the largest tumor resection possible and the correction of the underlying liver disease. Due to organ shortage however, LT is reserved for early-stages HCC. Surgical resection and radiofrequency destruction represent potentially curative options in highly selected patients. Arterial embolizations, chemo- or radio-embolizations, allow local tumor control but are not curative. These techniques could be performed before surgical resection or LT, to downstage the tumor and/or to control tumor progression while waiting for a graft. Finally, sorafenib is the only systemic treatment which has shown a survival benefit in advanced HCC. The benefit of combination of sorafenib and surgical treatments remains undetermined. The challenge in the management of HCC in cirrhotic patients is to integrate both individual (age, comorbidities, cirrhosis stage, tumor stage, specific contraindications to LT, etc.) and collective variables (expected waiting time before LT) to determine the best therapeutic option for each patient. In this process, multidisciplinarity is a key for success.

ABSTRACT HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy samples and sera from 22 patients with hepatitis C infection by using the quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay, respectively. The data showed a strong correlation between liver and serum compartments of HCV Ag levels (r = 0.80) and HCV RNA levels (r = 0.87). In summary, the serum HCV Ag and RNA levels reflect the intrahepatic values.

Several surgical techniques have been developed to allow liver transplantation in cases of complete portal vein thrombosis in the recipient. Despite this, these transplantations remain associated with a significant complication rate. We report herein a case of liver transplantation in a patient with complete portal vein thrombosis, underlying the potential pitfalls and the risk of intestinal sutures in case of hepaticojejunostomy. We discuss the technical options and their relative indications in such cases.

The aim of the ArDM project is the development and operation of a one ton double-phase liquid argon detector for direct Dark Matter searches. The detector measures both the scintillation light and the ionization charge from ionizing radiation using two independent readout systems. This paper briefly describes the detector concept and presents preliminary results from the ArDM R&D program, including a 3 l prototype developed to test the charge readout system.

Minimization or withdrawal of immunosuppressive treatments after organ transplantation represents a major objective for improving quality of life and long-term survival of grafted patients. Such a goal may be reached under some clinical conditions, particularly in liver transplantation, making these patients good candidates for tolerance trials. In this context in liver transplantation, the central questions are (1) how to promote the natural propensity of the liver graft to be accepted, (2) which type of immunosuppressive drug should be used for induction and maintenance, and (3) which biomarkers could be used to discriminate tolerant patients from those requiring long-term immunosuppression. Induction therapies using aggressive T-cell-depleting agents may favor graft acceptance. However, persistent and/or rapidly reemerging cell lines, such as memory-type cells or CD8(+) T cells, could represent a significant barrier for induction of tolerance. The type of maintenance drugs also remains questionable. Calcineurin inhibitors may be eventually deleterious in the context of tolerance protocols, through inhibitory effects on regulatory T cells, that are not observed with rapamycin. In conclusion, significant efforts must be made to achieve reliable strategies for immunosuppression minimization or withdrawal after organ transplantation into the clinics.

BACKGROUND AND STUDY AIMS The combination of Pegylated (PEG)interferon alpha-2b and ribavirin is considered to be the standard treatment for naïve chronic hepatitis C patients. Study aims are to evaluate the differences between standard interferon and PEG-interferon by conducting a multi-centre, controlled randomized trial comparing 3 groups. Group A : daily interferon alfa-2b at a dose of 4 MIU + ribavirin, Group B : PEG-interferon alfa-2b at a dose of 100 mcg/week + ribavirin; Group C: interferon alfa-2b at a dose of 3 MIU TIW + ribavirin PATIENTS AND METHODS Multicentrer, open label study including naïve chronic Hepatitis C Virus patients randomised in three groups with a ratio of 2:2:1. Group A: daily interferon alpha-2b (4 MIU s.c. for patients > 65 kg or 0.06 MIU/kg < 65 kg) and ribavirin, group B: PEG-interferon alpha-2b (100 microg s.c. weekly for patients > 65 kg or 1.5 microg/kg weekly for patients < 65 kg) and ribavirin and group C (reference arm) : interferon alpha-2b (3MIU s.c. TWI) and ribavirin. The duration of the treatment was 48 weeks for all 3 groups, with a 6 month follow-up period. 336 patients were enrolled in the study and included in the intention-to-treat analysis; 78 never started treatment (35 in group A, 28 in group B and 15 in group C): 101 in group A, 98 in group B and 59 in group C. RESULTS Demographic data, PCR results and reasons for early withdrawal have been statistically analysed. At baseline, the 3 groups did not show any statistical difference regarding age, gender, race, genotypes and METAVIR score. At week 24 on treatment, HCV ribonucleic acid RNA was undetectable in 87% in group A, in 79% in group B and in 69% in group C. At the end of treatment, 73% 74% and 58% respectively, had a negative PCR result. At week 24 of follow-up, these results were 71%, 64% and 48%, respectively. When comparing the efficacy of the daily interferon (+ ribavirin) and the PEG-interferon (+ ribavirin) regimen, no statistical difference was found (p = 0.32). In group A, 38% of drop-outs were due to adverse events compared to 37% in group B and 58% in group C. No statistical differences were observed regarding safety. CONCLUSION Daily weight based interferon alpha-2b dosing and PEG interferon alpha-2b weighed based dosing once weekly both in combination with Ribavirin offer the same efficacy and safety rates.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. The disease usually presents with high spiking fever, evanescent rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and a high serum level of ferritin with a low glycosylated fraction [ [1] Dino O. Provenzano G. Giannuoli G. Sciarrino E. Pouyet M. Pagliaro L. Fulminant hepatic failure in adult onset Still's disease. J Rheumatol. Apr 1996; 23: 784-785 PubMed Google Scholar ].

Aim of the study: There is a lack of epidemiological data on hepatitis C (HCV) infected patients in Belgium. Therefore our purpose was to address this important question and to evaluate the feasibility of a national HCV observatory.Patients and methods : From November 2003 to November 2004, every new patient prospectively seen for HCV antibody positivity in 9 Belgian hospital centres was recorded and a standardised 10-items questionnaire was completed during the consultation, including a Quality of Live (QOL) visual analogue scale.Results : Three hundred and eighteen consecutive patients were recruited. Fifty five percent were male with a median age of 45 y (11-87 y). The main risk factors for infection were IV drug use (27%), blood transfusion (23%), and invasive medical procedure (11%). On the QOL scale, ranging from 0 and 100, mean value was 61 +/- 31. Transaminases were abnormal in 66% with a median elevation 2 times above normal value. HCV RNA was positive in 87% with a viral load above 800 000 IU/ml in 42%. Genotype 1 was predominant (59%), followed by genotypes 3 (19%) and 4 (14%). A liver biopsy was performed in 190 patients, with minimal fibrosis (METAVIR F0-F1) in 43%, moderate fibrosis (F2) in 35% and advanced stages (F3-F4) in 22%. Antiviral treatment was not considered in 53% because of normal ALT (30%), old age (7%), minimal histological stage (6%) or patient refusal (4%).Conclusions : This study highlights the feasibility of a national HCV survey using a simple questionnaire. This pilot study could be generalised throughout Belgium, and, if repeated, could allow a regular assessment of the changes in epidemiology and management of HCV infection in our country.

Acute liver failure is a challenging clinical condition, associated with high morbidity and mortality. In well-selected patients, LT (LT) is the only therapeutic which has been demonstrated to improve patient survival. Clichy and King's College criteria are the two mains scoring systems used to select the patients for liver transplantation. Both models achieve high specificity but remain associated with limited negative predictive value. Several other predictive factors have been evaluated, but none of them have been strongly validated so far. Globally, whole LT appears as the procedure of choice for patients within Clichy and/or King's College criteria. Due to the severity of the disease and its multisystemic consequences, the results of LT for fulminant liver failure remain inferior to those obtained in elective indications. Accord-ing to local conditions, namely expected waiting time before urgent transplantation and surgical expertise, living donor transplantation and auxiliary transplantations appear as valuable alternatives. These techniques have the respective potential advantages to limit the waiting period before transplantation and to avoid the need for lifelong immunosuppression when native liver recovers, but overall results remain inferior to those obtained with whole LT.

BACKGROUND:Due to the organ shortage, marginal donors are increasingly used in liver transplantation (OLT). These grafts may be safely used in less critical recipients but, the real influence of extended donor criteria (EDC) remains uncertain when graft-recipient matching is not applied. Our study analyzed the impact of EDC on initial graft function within the Eurotransplant patient-driven allocation system.PATIENTS AND METHODS:We reviewed 70 OLT performed between 2004 and 2006. The impact of the following EDC were analyzed: age > 60; intensive care unit (ICU) stay > 4 days; peak serum Na(+) > 160 mEq/L; body mass index (BMI) > 30; cardiac arrest with cardiopulmonary resuscitation, and high doses of vasopressors. Early graft function, as defined according to peak transaminase level and spontaneous prothrombin time within the first 5 posttransplant days, was compared between the donors with none or one criterion (group A = 39) and those with >1 criterion (group B = 31).RESULTS:The most frequent EDC were high vasopressor use, ICU stay > 4 days and BMI > 30, were present in respectively 44%, 27%, and 16% of the donors. No EDC were present in 13 donors, one in 26, three in eight, and four in three. Demographics and origin and severity of the liver disease were similar in both groups. We failed to observe significant differences in initial graft function.CONCLUSION:The presence of EDC did not significantly affect early graft function in a population where donor and recipient were not matched. While this observation must be confirmed in a multicenter analysis, it tends to support the use of marginal liver grafts, even in patient-driven allocation systems.

The MELD score has now been implemented in the United States for liver allocation, but it has not been validated in Europe. Its association with posttransplant outcome is unclear. Optimal cutoff values of MELD and Child-Pugh scores to predict death on the liver waiting list were defined in a series of 137 cirrhotic patients listed for liver transplantation. Six-month actuarial survival while on the waiting list was 90% with a Child-Pugh <11 and MELD <17, whereas it decreased progressively to 40% at 6 months after listing for those having a Child-Pugh and MELD score >10 and >16. Analysis of a series of 112 patients (85 chronic liver disease and 27 hepatocellular carcinoma) revealed no change in MELD value at the time of transplantation compared to the score at the time of listing (mean +/- SD: 15.5 +/- 7.7 vs 15 +/- 5.8) with a mean waiting time of 118 days. Using either the optimal cutoff for MELD score (<17 or >16) or seven different strata (3 to 7, 8 to 10, 11 to 13, 14 to 16, 17 to 19, 20 to 22, 23 to 39), whether measured at listing or just before liver transplantation, there was no significant difference (chi(2) 4.97, P = .58) in survival: 82.7% and 63% at 6 and 60 months, overall. Our data confirm that the MELD score with only three parameters is as good as the Child-Pugh score to predict mortality on the Eurotransplant waiting list. The optimal cutoff to assess higher priority for the bad category is >16. There was no negative impact on short- or long-term prognosis of the bad categories of MELD.

OBJECTIVE:The purpose of our study was to assess the usefulness of manganese dipyridoxyl diphosphate (Mn-DPDP)-enhanced T1-weighted MR cholangiography for evaluating patients with biliary-enteric anastomoses.CONCLUSION:Mn-DPDP-enhanced T1-weighted MR cholangiography may provide useful functional information and may aid in the assessment of the patency of biliary-enteric anastomoses.

Background/Aims: Treatment of chronic hepatitis C with interferon can be ineffective due to relapse. We aimed to reduce the 40% relapse rate of 6 months interferon-ribavirin combination therapy by prolonging treatment to 18 months.Methods: Three hundred patients with treatment-naive hepatitis C, were randomized to 18 months combination therapy with interferon (3 MU tiw) and ribavirin (1000-1200 mg/day), 18 months interferon combined with placebo, or 6 months combination therapy with interferon and ribavirin, in a double blinded manner. All 295 patients who received at least one dose of treatment were included in the intention to treat analysis.Results: At the end of treatment, HCV RNA was undetectable in 55 and 49% of those on 6 and 18 months combination therapy, respectively, versus 26% of those on monotherapy (P < 0.001). The relapse rate was 38% for 6 months combination therapy, 38% for 18 months monotherapy, and only 13% for 18 months combination treatment (P = 0.002). The sustained response rates were 34% for 6 months combination therapy, 16% for 18 months monotherapy and 43% for 18 months combination therapy (P < 0.05).Conclusions: Reduction of relapse rates to 15% or less is feasible by prolongation of interferon-ribavirin treatment to 18 months. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

AIM:To evaluate the efficacy of early interferon alpha-2b in non-post-transfusion acute hepatitis C virus: a prospective study with historical comparison.PATIENTS:Group A: 28 patients prospectively treated for acute hepatitis C virus with daily regimen of interferon 5 million units for 2 months. Group B: historical series of 16 patients with untreated acute hepatitis C virus.RESULTS:There was no significant difference between the two groups with regard to gender, age, icterus, alanine aminotransferase, or genotypes. In group B, hepatitis spontaneously resolved in three of 16 (19%) patients (follow-up 1-7 years). In group A, 21 of 25 patients became sustained viral responders (75%; P = 0.0003 vs. group B). Factors include not predictive of sustained viral response: age, gender, sources of infection, presence of icterus, alanine aminotransferase peak, bilirubin peak, incubation period, presence of hepatitis C virus antibodies at presentation, or genotypes. The time from presentation to the start of therapy was, however, significantly shorter in sustained viral responders (43 +/- 31 days) than in relapsers or non-responders (88 +/- 52 days) (P = 0.016).CONCLUSIONS:Early treatment of acute hepatitis C virus with interferon prevents chronicity. A short waiting time from presentation to treatment appears as the most relevant predictive factor for sustained response.