HCV microelimination in harm reduction centres has benefits beyond HCV cure but is hampered by high reinfection rates

Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices.On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment.Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness.HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates.People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.© 2022 The Author(s)

Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy

Abstract: Information about heart failure with reduced ejection fraction (HFrEF) in women and the potential effects of aging in the female heart is scarce. We investigated the vulnerability to develop HFrEF in female elderly mice compared to young animals, as well as potential differences in reverse remodeling. First, HF was induced by isoproterenol infusion (30 mg/kg/day, 28 days) in young (10-week-old) and elderly (22-month-old) female mice. In a second set of animals, mice underwent isoproterenol infusion followed by no treatment during 28 additional days. Cardiac remodeling was assessed by echocardiography, histology and gene expression of collagen-I and collagen-III. Following isoproterenol infusion, elderly mice developed similar HFrEF features compared to young animals, except for greater cell hypertrophy and tissue fibrosis. After beta-adrenergic withdrawal, young female mice experienced complete reversal of the HFrEF phenotype. Conversely, reversed remodeling was impaired in elderly animals, with no significant recovery of LV ejection fraction, cardiomyocyte hypertrophy and collagen deposition. In conclusion, chronic isoproterenol infusion is a valid HF model for elderly and young female mice and induces a similar HF phenotype in both. Elderly animals, unlike young, show impaired reverse remodeling, with persistent tissue fibrosis and cardiac dysfunction even after beta-adrenergic withdrawal

Community-based screening enhances hepatitis B virus linkage to care among West African migrants in Spain

Hepatitis B virus; Community approach; Screening programsVirus de l'hepatitis B; Abordatge comunitari; Programes de deteccióVirus de la hepatitis B; Abordaje comunitario; Programas de detecciónBackground: Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. Methods:This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. Results: In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days.Conclusions:This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.Antecedents: La infecció crònica pel VHB és responsable del >50% de tots els casos de càncer hepatocel·lular a nivell mundial i afecta desproporcionadament els països de l'Àfrica subsahariana (SAS). La migració d'aquests països a Europa ha augmentat substancialment en els últims anys, plantejant reptes únics per als sistemes de salut. L'objectiu d'aquest estudi va ser dur a terme una intervenció basada en la comunitat per augmentar la detecció del VHB, la vacunació i la vinculació amb l'atenció entre els migrants de SSA a Catalunya, Espanya. Mètodes: Es tractava d'un estudi de cohort prospectiu. Als participants ≥18 anys se'ls va oferir un cribratge comunitari del VHB entre el 20/11/20 i el 21/01/22. Es van dur a terme proves ràpides de VHB i recollida de mostres de sang mitjançant targetes de separació de plasma i es va oferir vinculació a l'atenció a tots els participants. La vacunació contra el VHB i l'assessorament post-test es van realitzar en una segona visita a la comunitat. El resultat principal van ser les probabilitats que les persones amb infecció actual pel VHB estiguin vinculades amb èxit a l'hepatologia. Es van analitzar les taxes de completar la cascada assistencial d'aquest model. Resultats: En el present estudi, 444 persones se sotmeten a cribratge, amb el 50.6% dels participants que mostren evidència d'infecció passada o actual pel VHB, inclosa una prevalença de VHB del 9.2%. Els migrants amb infecció actual pel VHB presenten 5,2 vegades més probabilitats d'èxit en l'atenció en comparació amb aquells que necessiten assessorament o vacunació post-prova. L'estudi aconsegueix una taxa de vinculació reeixida a l'atenció del 72% per a tots els participants, amb cites amb especialistes concertades en un termini de 15,5 dies. Conclusions: Aquest programa de cribratge del VHB basat en la comunitat proporciona proves d'un model reeixit per identificar i proporcionar atenció, inclosa la vacunació, als migrants de l'Àfrica occidental amb alt risc d'infecció pel VHB que d'altra manera podrien no dedicar-se a l'atenció.C.A.P., J.V.L. and Lv.S. acknowledge support to ISGlobal from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and from the Government of Catalonia through the “CERCA Program”. C.A.P. acknowledges support from the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and the European Social Fund as an AGAUR-funded PhD fellow. E.M. thanks the CERCA Program/Generalitat de Catalunya for their support to the Germans Trias i Pujol Research Institute (IGTP). This study was carried out by ISGlobal with competitive funding through the Gilead Sciences global HBV-CARE program (IN-ES-988–5799)

TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6

TRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response

High frequency of acute decompensation and cancer in patients with compensated cirrhosis due to nonalcoholic fatty liver disease : A retrospective cohort study

The natural history of compensated cirrhosis due to nonalcoholic fatty liver disease (NAFLD) has not been completely characterized. The aim of the present study was to assess the incidence and risk factors of acute decompensation of cirrhosis, hepatocellular carcinoma, and extrahepatic cancers. This was a multicenter, retrospective, cohort study including 449 patients with compensated cirrhosis due to NAFLD. We calculated cumulative incidences and used competitive risk analysis to determine the risk factors associated with decompensation and cancer development. Over a median of 39 months of follow-up, 124 patients (28%) presented acute decompensation. The most frequent decompensation was ascites (21%) followed by hepatic encephalopathy (15%), variceal bleeding (9%), and spontaneous bacterial peritonitis (3%). Acute-on-chronic liver failure was diagnosed in 6% of patients during follow-up. Liver function parameters and specifically an albumin level below 40 g/L were independently associated with an increased risk of decompensation. The presence of ischemic heart disease was independently associated with acute decompensation. Seventy-eight patients (18%) developed hepatocellular carcinoma or extrahepatic cancers during follow-up (51 and 27, respectively). Conclusion : Patients with compensated cirrhosis due to NAFLD are at high risk of severe liver complications, such as the development of acute decompensation, in a relative short follow-up time. This population is at high risk of hepatic and extrahepatic cancers. The analysis of a large contemporary cohort of 449 patients with compensated cirrhosis due to non-alcoholic fatty liver disease shows a high frequency of acute decompensations (AD) and development of cancer during 39 months of follow-up. Almost 28% of the cohort developed acute decompensation and 18% developed hepatocellular carcinoma (HCC) or extrahepatic cancer. Predictors of decompensation are mainly related to liver function and portal hypertension

Experimental investigation of ground-state properties of ⁷H with transfer reactions

The properties of nuclei with extreme neutron–to–proton ratios, far from those naturally occurring on Earth, are key to understand nuclear forces and how nucleons hold together to form nuclei. 7H, with six neutrons and a single proton, is the nuclear system with the most unbalanced neutron–to–proton ratio known so far. However, its sheer existence and properties are still a challenge for experimental efforts and theoretical models. Here we report experimental evidences on the formation of 7H as a resonance, detected with independent observables, and the first measurement of the structure of its ground state. The resonance is found at ∼0.7 MeV above the 3H+4n mass, with a narrow width of ∼0.2 MeV and a 1/2+ spin and parity. These data are consistent with a 7H as a 3H core surrounded by an extended four-neutron halo, with a unique four-neutron decay and a relatively long half-life thanks to neutron pairing; a prime example of new phenomena occurring in what would be the most pure-neutron nuclear matter we can access in the laboratory.</p

Study of fission using multi-nucleon transfer reactions

Multi-nucleon transfer channels of the reactions of 18O+232Th, 18O+238U, 18O+248Cm were used to measure fission-fragment mass distribution for various nuclides and their excitation energy dependence. Predominantly asymmetric fission is observed at low excitation energies for all the studied cases, with an increase of the symmetric fission towards high excitation energies. Experimental data are compared with predictions of the fluctuation-dissipation model, where effects of multi-chance fission (neutron evaporation prior to fission) was introduced. It was shown that a reliable understanding of the observed fission fragment mass distributions can be obtained only invoking multi-chance fissions

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice

Background Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. Aims To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). Methods We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. Results Of 255 patients, median follow-up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. Conclusion Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension