Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV)

Objective An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. Patients and methods In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. Results At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. Conclusion In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated. © 2018 Wolters Kluwer Health, Inc. All rights reserved

Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV)

Objective An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. Patients and methods In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. Results At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. Conclusion In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated. © 2018 Wolters Kluwer Health, Inc. All rights reserved

Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease

BACKGROUND: The effect of oral and/or parenteral ademetionine (500 mg intravenous [IV] and tablet formulation) on clinical symptoms and biochemical markers of intrahepatic cholestasis (IHC) was investigated in subjects with alcoholic liver disease (ALD) and compensated liver function. METHODS: Prospective, multicenter, open-label study consisting of a screening period and an 8-week treatment period and performed in subjects (18-75 years) with compensated ALD and confirmed IHC. Subjects with a baseline serum coniugated bilirubin value above normal range were initially treated with IV ademetionine for two weeks (500-800 mg daily) and continued with oral ademetionine 1500 mg daily for a further six weeks. Subiects with a baseline serum coniugated bilirubin value within normal range were treated with oral ademetionine for eight weeks. RESULTS: A total of 72 subjects were treated; 41 initially with IV ademetionine and 31 with oral ademetionine. Clinical symptoms status improved from baseline to end of treatment with an increase in the proportion of subiects with no symptoms. Ademetionine showed significant improvements in primary efficacy parameters alkaline phosphatase (ALP) and y-glutamyltransferase (yGT) (P<0.0001). Although decreases of ALP were higher for subjects initially treated with IV ademetionine, these subjects also had higher baseline values. No safety concerns with ademetionine arose with respect to the severity or frequency of adverse events (AEs) during the treatment period, laboratory parameters, and vital signs. CONCLUSIONS: Administration of oral or IV/oral ademetionine step-therapy for 8 weeks to subjects with IHC due to ALD was safe and provided a significant improvement of disease burden. © 2018 EDIZIONI MINERVA MEDICA

Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease

BACKGROUND: The effect of oral and/or parenteral ademetionine (500 mg intravenous [IV] and tablet formulation) on clinical symptoms and biochemical markers of intrahepatic cholestasis (IHC) was investigated in subjects with alcoholic liver disease (ALD) and compensated liver function. METHODS: Prospective, multicenter, open-label study consisting of a screening period and an 8-week treatment period and performed in subjects (18-75 years) with compensated ALD and confirmed IHC. Subjects with a baseline serum coniugated bilirubin value above normal range were initially treated with IV ademetionine for two weeks (500-800 mg daily) and continued with oral ademetionine 1500 mg daily for a further six weeks. Subiects with a baseline serum coniugated bilirubin value within normal range were treated with oral ademetionine for eight weeks. RESULTS: A total of 72 subjects were treated; 41 initially with IV ademetionine and 31 with oral ademetionine. Clinical symptoms status improved from baseline to end of treatment with an increase in the proportion of subiects with no symptoms. Ademetionine showed significant improvements in primary efficacy parameters alkaline phosphatase (ALP) and y-glutamyltransferase (yGT) (P<0.0001). Although decreases of ALP were higher for subjects initially treated with IV ademetionine, these subjects also had higher baseline values. No safety concerns with ademetionine arose with respect to the severity or frequency of adverse events (AEs) during the treatment period, laboratory parameters, and vital signs. CONCLUSIONS: Administration of oral or IV/oral ademetionine step-therapy for 8 weeks to subjects with IHC due to ALD was safe and provided a significant improvement of disease burden. © 2018 EDIZIONI MINERVA MEDICA

<math display="inline"><mrow><mi>ψ</mi><mo stretchy="false">(</mo><mn>2</mn><mi>S</mi><mo stretchy="false">)</mo></mrow></math> Suppression in Pb-Pb Collisions at the LHC

International audienceThe production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sNN=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.5&lt;y&lt;4). The measurement of the ratio of the inclusive production cross sections of the ψ(2S) and J/ψ resonances is reported as a function of the centrality of the collisions and of transverse momentum, in the region pT&lt;12  GeV/c. The results are compared with the corresponding measurements in pp collisions, by forming the double ratio [σψ(2S)/σJ/ψ]Pb-Pb/[σψ(2S)/σJ/ψ]pp. It is found that in Pb-Pb collisions the ψ(2S) is suppressed by a factor of ∼2 with respect to the J/ψ. The ψ(2S) nuclear modification factor RAA was also obtained as a function of both centrality and pT. The results show that the ψ(2S) resonance yield is strongly suppressed in Pb-Pb collisions, by a factor of up to ∼3 with respect to pp. Comparisons of cross section ratios with previous Super Proton Synchrotron findings by the NA50 experiment and of RAA with higher-pT results at LHC energy are also reported. These results and the corresponding comparisons with calculations of transport and statistical models address questions on the presence and properties of charmonium states in the quark-gluon plasma formed in nuclear collisions at the LHC

First measurement of <math><msubsup><mi mathvariant="normal">Λ</mi><mrow><mi>c</mi></mrow><mo>+</mo></msubsup></math> production down to <math><mrow><msub><mi>p</mi><mi>T</mi></msub><mo>=</mo><mn>0</mn></mrow></math> in <math><mrow><mi>p</mi><mi>p</mi></mrow></math> and <math><mi>p</mi></math>-Pb collisions at <math><mrow><msqrt><msub><mi>s</mi><mrow><mi>N</mi><mi>N</mi></mrow></msub></msqrt><mo>=</mo><mn>5.02</mn></mrow></math> TeV

International audienceThe production of prompt Λc+ baryons has been measured at midrapidity in the transverse momentum interval 0&lt;pT&lt;1 GeV/c for the first time, in pp and p–Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=5.02TeV. The measurement was performed in the decay channel Λc+→pKS0 by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT-integrated Λc+ production cross sections in both collision systems were determined and used along with the measured yields in Pb–Pb collisions to compute the pT-integrated nuclear modification factors RpPb and RAA of Λc+ baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Λc+/D0 baryon-to-meson yield ratio is reported for pp and p–Pb collisions. Comparisons with models that include modified hadronization processes are presented, and the implications of the results on the understanding of charm hadronization in hadronic collisions are discussed. A significant (3.7σ) modification of the mean transverse momentum of Λc+ baryons is seen in p–Pb collisions with respect to pp collisions, while the pT-integrated Λc+/D0 yield ratio was found to be consistent between the two collision systems within the uncertainties

Azimuthal correlations of heavy-flavor hadron decay electrons with charged particles in pp and p–Pb collisions at sNN\pmb {\sqrt{s_{\mathrm{{NN}}}}} = 5.02 TeV

International audienceThe azimuthal ($\Delta \varphi$) correlation distributions between heavy-flavor decay electrons and associated charged particles are measured in pp and p–Pb collisions at $\sqrt{s_{\mathrm{{NN}}}} = 5.02$ TeV. Results are reported for electrons with transverse momentum $4<p_{\textrm{T}}<16\textrm{GeV}/c$ and pseudorapidity $|\eta |<0.6$. The associated charged particles are selected with transverse momentum $1<p_{\textrm{T}}<7\textrm{GeV}/c$, and relative pseudorapidity separation with the leading electron $|\Delta \eta | < 1$. The correlation measurements are performed to study and characterize the fragmentation and hadronization of heavy quarks. The correlation structures are fitted with a constant and two von Mises functions to obtain the baseline and the near- and away-side peaks, respectively. The results from p–Pb collisions are compared with those from pp collisions to study the effects of cold nuclear matter. In the measured trigger electron and associated particle kinematic regions, the two collision systems give consistent results. The $\Delta \varphi$ distribution and the peak observables in pp and p–Pb collisions are compared with calculations from various Monte Carlo event generators

Light (anti)nuclei production in Pb-Pb collisions at <math><mrow><msqrt><msub><mi>s</mi><mrow><mi>N</mi><mi>N</mi></mrow></msub></msqrt><mo>=</mo><mn>5.02</mn><mo> </mo><mi>TeV</mi></mrow></math>

International audienceThe measurement of the production of deuterons, tritons and He3 and their antiparticles in Pb-Pb collisions at sNN=5.02TeV is presented in this article. The measurements are carried out at midrapidity (|y|&lt; 0.5) as a function of collision centrality using the ALICE detector. The pT-integrated yields, the coalescence parameters and the ratios to protons and antiprotons are reported and compared with nucleosynthesis models. The comparison of these results in different collision systems at different center-of-mass collision energies reveals a suppression of nucleus production in small systems. In the Statistical Hadronisation Model framework, this can be explained by a small correlation volume where the baryon number is conserved, as already shown in previous fluctuation analyses. However, a different size of the correlation volume is required to describe the proton yields in the same data sets. The coalescence model can describe this suppression by the fact that the wave functions of the nuclei are large and the fireball size starts to become comparable and even much smaller than the actual nucleus at low multiplicities

Measurements of azimuthal anisotropies at forward and backward rapidity with muons in high-multiplicity p–Pb collisions at sNN=8.16 TeV

The study of the azimuthal anisotropy of inclusive muons produced in p–Pb collisions at sNN=8.16 TeV, using the ALICE detector at the LHC is reported. The measurement of the second-order Fourier coefficient of the particle azimuthal distribution, v2, is performed as a function of transverse momentum pT in the 0–20% high-multiplicity interval at both forward (2.032 GeV/c. The v2 coefficient of inclusive muons is extracted using two different techniques, namely two-particle cumulants, used for the first time for heavy-flavour measurements, and forward–central two-particle correlations. Both techniques give compatible results. A positive v2 is measured at both forward and backward rapidities with a significance larger than 4.7σ and 7.6σ, respectively, in the interval 2<pT<6 GeV/c. Comparisons with previous measurements in p–Pb collisions at sNN=5.02 TeV, and with AMPT and CGC-based theoretical calculations are discussed. The findings impose new constraints on the theoretical interpretations of the origin of the collective behaviour in small collision systems

Symmetry plane correlations in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76TeV

International audienceA newly developed observable for correlations between symmetry planes, which characterize the direction of the anisotropic emission of produced particles, is measured in Pb–Pb collisions at $\sqrt{s_\text {NN}}$ = 2.76 TeV with ALICE. This so-called Gaussian Estimator allows for the first time the study of these quantities without the influence of correlations between different flow amplitudes. The centrality dependence of various correlations between two, three and four symmetry planes is presented. The ordering of magnitude between these symmetry plane correlations is discussed and the results of the Gaussian Estimator are compared with measurements of previously used estimators. The results utilizing the new estimator lead to significantly smaller correlations than reported by studies using the Scalar Product method. Furthermore, the obtained symmetry plane correlations are compared to state-of-the-art hydrodynamic model calculations for the evolution of heavy-ion collisions. While the model predictions provide a qualitative description of the data, quantitative agreement is not always observed, particularly for correlators with significant non-linear response of the medium to initial state anisotropies of the collision system. As these results provide unique and independent information, their usage in future Bayesian analysis can further constrain our knowledge on the properties of the QCD matter produced in ultrarelativistic heavy-ion collisions