Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

URI permanent per a aquesta col·leccióhttps://hdl.handle.net/2445/107206

Estadístiques

Examinar

Mostrant 1 - 20 de 3134

Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry
(Wolters Kluwer, 2024-11-12) Moreno Fajardo, David; Jiménez, Cristina; Escalante, Fernando; Askari, Elham; Castellanos Alonso, Marta; Arnao, Mario; Heredia, Ángela; Canales Albendea, Miguel Ángel; Alcalá, Magdalena; Bermúdez, Arancha; Saus Carreres, Ana; Casanova, María; Palomera Bernal, Luis; Motlló, Cristina; Garcia Sánchez, Ricarda; Rios Rull, P.J.; García Sanz, Ramón; Fernández de Larrea, Carlos
Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2-microglobulin ≥3 mg/L, and albumin <4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low-, intermediate-, and high-risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of MYD88 L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5-year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.
Association of astrocyte-specific gene expression in the dorsolateral prefrontal cortex with clozapine treatment in schizophrenia.
(Nature Publishing Group, 2025-10-31) Prohens Coll, Llucia; Rodriguez Ferret, Natalia; Gonzalez Segura, Àlex; Martínez Pinteño, Albert; Olivares Berjaga, David; Martínez Martín, Irene; Mezquida Mateos, Gisela; Santas Martín, Jon A.; Morentin, Benito; Meana, J. Javier; Callado, Luis F.; Gassó Astorga, Patricia; Rivero, Guadalupe; Mas Herrero, Sergi
Gene expression profiling studies could be a valuable tool in identifying the specific genes and pathways involved in the mechanism of action of clozapine, leading to a better understanding of the molecular biology underlying treatment-resistant schizophrenia (TRS). We aimed to identify the co-expressed modules that reflect the genetic differences between clozapine-treated and non-clozapine-treated patients with schizophrenia as a proxy of TRS. Gene expression of DLPFC samples from 26 subjects with schizophrenia (13 clozapine treated and 13 non-clozapine treated) were analyzed using Clariom S Human Array. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its association with clozapine treatment. As a result of our analysis of the gene co-expression architecture in the DLPFC, among the 13 modules identified, one module (green) was significantly associated with clozapine treatment (p = 3.7 × 10−2). This module was significantly enriched in astrocyte markers (5.7 × 10−29) and genes involved in the polygenic architecture of TRS (1.6 × 10−2). This finding provides cell type-specific associations that could help in the interpretation of the neurobiological basis of TRS. A better understanding of the specific DLPFC cell types involved in clozapine treatment will contribute to the study of potential pathways and ultimately help improve psychiatric classification tools in personalized medicine.
Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia.
(Nature Publishing Group, 2025-01-14) Olivares Berjaga, David; Martínez Pinteño, Albert; Rodriguez Ferret, Natalia; Mas Herrero, Sergi; Morén Núñez, Constanza; Parellada Rodón, Eduard; Gassó Astorga, Patricia
Schizophrenia (SZ) is a deleterious brain disorder characterised by its heterogeneity and complex symptomatology consisting of positive, negative and cognitive deficits. Current antipsychotic drugs ameliorate the positive symptomatology, but are inefficient in treating the negative symptomatology and cognitive deficits. The neurodevelopmental glutamate hypothesis of SZ has opened new avenues in the development of drugs targeting the glutamatergic system. One of these new therapies involves the positive allosteric modulators (PAMs) of metabotropic glutamate receptors, mainly types 2/3 (mGluR2/3). mGluR2/3 PAMs are selective for the receptor, present high tolerability and can modulate the activity of the receptor for long periods. There is not much research in clinical trials regarding mGluR2/3 PAMs. However, several lines of evidence from animal models have indicated the efficiency of mGluR2/3 PAMs. In this review, focusing on in vivo animal studies, we will specifically discuss the utilization of SZ animal models and the various methods employed to assess animal behaviour before summarising the evidence obtained to date in the field of mGluR2/3 PAMs. By doing so, we aim to deepen our understanding of the underlying mechanisms and the potential efficiency of mGluR2/3 PAMs in treating SZ. Overall, mGluR2/3 PAMs have demonstrated efficiency in attenuating SZ-like behavioural and molecular deficits in animal models and could be useful for the early management of the disorder or to treat specific subsets of patients.
Effects of JNJ-46356479 and clozapine on VGLUT1 and GAD65/67 brain levels and expression of genes related to glutamate and GABA in mice postnatally exposed to ketamine.
(Elsevier Masson SAS, 2025-11) Martínez Pinteño, Albert; Olivares-Berjaga, D.; Rodriguez Ferret, Natalia; Mena, Juan Ignacio; Prohens Coll, Llucia; Mas, Sergi; Morén Núñez, Constanza; Parellada Rodón, Eduard; Gassó Astorga, Patricia
Schizophrenia (SZ) is a complex mental disorder influenced by genetic, environmental, and neurobiological factors, with current treatments ineffective for negative symptoms and cognitive deficits. The glutamatergic hypothesis of SZ highlights the N-methyl-D-aspartic acid (NMDA) receptor dysfunction as a key factor, causing excitatory-inhibitory imbalance and synaptic inefficiency. Positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), could be useful in treating these symptoms, especially when used in early stages of the disease. Previous results have shown that JNJ can reverse certain SZ-related behavioral and neuropathological deficits. This study evaluates, for the first time, the effects of early treatment with JNJ or clozapine (CLZ) in reversing molecular deficits related to glutamatergic and GABAergic pathways in mice postnataly exposed to ketamine (KET) on postnatal days (PND) 7, 9, and 11. Animals received JNJ or CLZ daily in the adolescent period (PND 35–60). Specifically, we investigated alterations in brain protein levels of VGLUT1, as a marker of glutamatergic synapses, and GAD65/67, as markers of GABAergic synapses. Changes in brain expression of 240 selected genes involved in glutamate and GABA pathways were also evaluated. Results demonstrated that postnatal KET exposure increased hippocampal VGLUT1 levels which were partially normalized after both pharmacological treatments, especially with JNJ. Additionally, we identified some genes that showed altered brain expression after drug treatment in our mouse model. In conclusion, this study provides evidence of SZ-related glutamate signaling alterations in adult mice postnatally exposed to KET, as well as of the effectiveness of JNJ in improving these alterations when administered during the early stages of the disease.
Time intervals and previous primary care consultations in the pathway to emergency cancer diagnosis
(Elsevier, 2023-10-01) Bosch Genover, Xavier; Montori Palacín, Elisabet; Calvo Jiménez, Júlia; Carbonell, Irene; Naval Álvarez, José; Moreno Lozano, Pedro Juan; López-Soto, Alfonso
Background: Time intervals and number of prior consultations in primary care (PC) are recognised metrics of diagnostic timeliness of cancer and are interrelated. However, whether and how the two measures correlate with each other in the emergency diagnostic pathway is unknown. We investigated the association between the number of prereferral consultations and the length of intervals from PC presentation to cancer diagnosis following emergency referral to hospital. Methods: Patients were eligible if they first consulted in PC and were diagnosed with cancer following emergency or nonemergency referral to hospital. We analysed for differences in PC and diagnostic intervals and number of consultations between emergency and nonemergency presenters and determined their associations by cancer type. Differences in presenting symptoms and stage at diagnosis between populations and according to number of consultations were also examined. Results: There were 796 emergency and 865 nonemergency presenters with comparable sociodemographic and comorbidity data. Correlation analysis in emergency presenters revealed a strong positive association between number of consultations and intervals for seven of 13 different cancers, including cancers characterised by high proportions of > 3 consultations and long intervals (pancreatic, lung, and colorectal cancer) and vice versa for others (e.g., endometrial, cervical, or oesophageal cancer). Additionally, emergency presenters with > 3 consultations were more likely than those with 1-2 to report nonspecific symptoms (60 vs. 40%, respectively) and to be diagnosed at a later stage. Conclusion: System level interventions are needed to reduce unnecessary delays in the emergency diagnostic pathway, particularly in cancer patients with multiple prereferral consultations. The findings also suggest opportunities to reduce the proportion of emergency diagnoses by targeting symptomatic individuals pre-presentation.
Genomic and immune profiling of prognostic risk groups in IgM gammopathy reveals novel biomarkers beyond MYD88 L265P
(Frontiers Media, 2025-07-01) Moreno, David F.; Nadeu Prat, Ferran; Brasó Maristany, Fara; Vaqué, Sergi; Paz, Sara; Mañé Pujol, Joan; Cardús, Oriol; Medina, Elena; Lozano, Ester; Rodríguez Lobato, Luis Gerardo; Daniel, Anna de; Tovar, Natalia; Cibeira, María Teresa; Bladé, J. (Joan); Rosiñol Dachs, Laura; Colomer Pujol, Dolors; Prat Aparicio, Aleix; Fernández de Larrea, Carlos
Background: MYD88 L265P is an early mutation in IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (WM). Given the high prevalence of the MYD88 mutation observed in epidemiological studies, its presence is not sufficient to drive disease progression. In fact, a recent risk model of progression reported that the impact of other laboratory biomarkers was superior to the MYD88 mutation's presence. Due to the low incidence of these clinicopathological entities, there is a need for a better characterization of tumor and immune cells that can help to identify novel biomarkers. We hypothesize that the characterization of the risk groups in asymptomatic patients could improve the discovery of drivers of disease progression. Methods: We characterized the genomic and immune landscape of the most recent prognostic risk categories in 19 IgM MGUS and 17 asymptomatic WM patients. We performed targeted next generation sequencing (NGS) on CD19+ cells from bone marrow samples at diagnosis using a panel of 54 lymphoma-driver genes. Whole bone marrow samples were also used to measure mRNA gene expression in tumor and immune cells using the PanCancer ImmuneProfiling panel on the nCounter platform (NanoString). Results: We observed that low-risk patients were only characterized by the presence of MYD88 L265P, while intermediate- and high-risk groups harbored additional mutations on CXCR4, KMT2D, ARID1A and EP300. Regarding the mRNA expression analyses, we found an increased proportion of myeloid cells in the low-risk group, with monocytes having a significant decrease in low versus high-risk patients. The high-risk group also upregulated genes involved in the activation of NF-κB and B-cell receptor (BCR) signaling, while low-risk patients upregulated genes associated with an alternative activation of B cells or a decrease of the BCR signaling, such as TOLLIP, CEACAM1 and CR1. Conclusions: Beyond the MYD88 mutation, we described novel molecular mechanisms associated with high-risk patients, as an effort moving towards easy-to use new biomarkers in IgM gammopathy.
The Role of Audiometry prior to High-Dose Cisplatin in Patients with Head and Neck Cancer.
(2017-01-01) Grau de Castro, Juan Jose; Caballero Borrego, Miguel; Mackers Iglesias, Paula; Reig Torras, Oscar; Buxo Orra, Elvira; Navarrete Duran, Pilar; Blanch Andreu, Jordi; Grau Junyent, Josep M.
To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients.Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB.A total of 103 patients were included; the median age of the patients was 59 years (range 18-75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab.Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population.© 2017 S. Karger AG, Basel.
Assessment of childhood maltreatment in pharmacotherapy trials for schizophrenia.
(2026-02-18) Fares Otero, Natalia Elena; Leucht S; Seedat S
Schizophrenia spectrum disorders (SSD) are among the leading global causes of disability, owing to chronic trajectories and high rates of treatment resistance. Antipsychotic medications are generally effective, but in up to a third of individuals with an acute episode, their symptoms show insufficient treatment response, underscoring the need to identify predictors of poor outcomes.
Unveiling Drug-Induced Autoimmune-Like Hepatitis in Autoimmune Hepatitis Patients: A Multicenter Retrospective Study
(John Wiley & Sons, 2025-08-26) Arvaniti, Pinelopi; Olivas, Ignasi; Pascual-Dapena, Ana; Riveiro-Barciela, Mar; Esteban, Paula; Aguilar, Anna; Perez-Medrano, Indhira; Horta, Diana; Caballero Marcos, Arancha; Salcedo, Magdalena; Conde, Isabel; Gomez, Elena; Castello, Inmaculada; Barbara, Jesus Santa; Diaz-Gonzalez, Alvaro; Del Barrio, Maria; Lorente, Sara; Mateos, Beatriz; Arencibia, Ana; Jimenez, Miguel; Cuenca, Paqui; Bernal-Monterde, Vanesa; Fernandez, Eva-Maria; Rodríguez Tajes, Sergio; Pocurull, Anna; Hernandez Evole, Helena; Forns Bernhardt, Xavier; Andrade, Raul J; Londoño Hurtado, María Carlota
Background and Aims Acute or chronic exposure to drugs or herbal and dietary supplements (HDS) can cause drug-induced autoimmune-like hepatitis (DI-ALH), a self-limiting condition resembling autoimmune hepatitis (AIH). We investigated the prevalence of drug exposure among AIH patients at diagnosis to recognise cases of DI-ALH and discern features predicting AIH development.Methods We retrospectively included 705 patients diagnosed with AIH. DI-ALH was defined using published criteria. The clinical, biochemical, serological, and histological data of DI-ALH and AIH were analysed to identify predictors of the evolution of each phenotype.Results Most patients were female (n = 496, 70%), with a median age of 57 years and a median follow-up of 55 months. A 59% (n = 417) reported exposure to drugs or HDS, and 8% (n = 58) fulfilled the criteria for DI-ALH. Statins and HDS were the most common culprits. Patients with DI-ALH more frequently had acute severe or fulminant hepatitis (22% vs. 12%, p = 0.013) and higher transaminase levels (ALT: 966 vs. 591, p = 0.001) at diagnosis. In total, 97% of the patients received immunosuppression. DI-ALH patients had a faster biochemical response than i-AIH patients (4 vs. 5, p = 0.031), while treatment withdrawal was attempted in only 29% (n = 17). Approximately 30% (n = 17) of DI-ALH cases presented a flare during follow-up. Neither clinical, histological, nor serological findings nor RUCAM and RECAM could predict a DI-ALH flare.Conclusions DI-ALH is often under-recognised in clinical practice, leading to unnecessary long-term immunosuppression. A causal relationship between drugs and AIH, along with an attempt to withdraw treatment and long-term follow-up, is essential to prevent overtreatment-associated risks.
Hepatic encephalopathy and MELD-Na predict treatment benefit in autoimmune hepatitis-related decompensated cirrhosis.
(2025-04-08) Arvaniti P; Rodríguez Tajes, Sergio; Padilla M; Olivas I; Mauro, Ezequiel Matías; El Maimouni, Cautar; Lytvyak E; Verhelst X; Engel B; Taubert R; Lorente-Pérez S; Conde I; Riveiro-Barciela M; Ruiz-Cobo JC; Álvarez-Navascués C; Salcedo M; Gomez J; Janik MK; Mateos B; Efe C; Granito A; Datji E; Azzaroli F; Horta D; Vila C; Castelló I; Pérez-Medrano I; Arencibia A; Gerussi A; Bruns T; Colapierto F; Lleo A; Van den Ende N; Verbeek J; Díaz-Gonzalez A; Morillas RM; Torner-Simó M; Bernal V; Fernández EM; Gevers TJ; Londoño Hurtado, María Carlota
Management of patients with autoimmune hepatitis (AIH)-related decompensated cirrhosis is challenging because of the risk of treatment-related complications and lack of clinical recommendations. We investigated the predictive factors for treatment benefit in AIH-related decompensated cirrhosis at diagnosis and developed an algorithm to guide treatment decisions in clinical practice. This retrospective, international, multicenter study included 232 patients with histologically confirmed AIH-related decompensated cirrhosis at diagnosis. The sub-hazard ratio (SHR) of mortality was determined by competing risk analysis, considering liver transplantation (LT) as competing event. A decision tree analysis was used to develop a treatment algorithm. At diagnosis, 89% of patients had ascites and 41% overt hepatic encephalopathy (OHE). Treated patients (n=214, 92%) had higher aminotransferases, bilirubin and modified hepatic activity index. The SHR of mortality was lower in treated patients (0.438, 95%CI 0.196-0.981, p=0.045). Patients without OHE grade 3/4 and MELD-Na ≤28 at diagnosis were more likely to benefit from treatment. In these patients, a decline in MELD-Na ≥11 after 4 weeks of treatment had a 100% negative predictive value for death/LT. Forty-nine percent of treated patients recompensated during follow-up. Twenty percent of patients had to discontinue treatment, 65% during the first 4 weeks, and only 4% due to infectious complications. OHE ≥ grade 2 and MELD-Na at diagnosis predicted the need for treatment discontinuation. Immunosuppression is beneficial in patients with AIH-related decompensated cirrhosis and active disease. OHE and MELD-Na at diagnosis, along with a decline in MELD-Na at 4 weeks of treatment, are the most important determinants of outcome and can guide treatment decisions.
Comparison of inferior vena cava filter use and outcomes between cancer and non-cancer patients in a tertiary hospital
(2024-04-01) López, Néstor; Zamora-Martínez, Carles; Montoya-Rodes, Marc; Gabara, Cristina; Ortiz, Maria; Aibar Gallizo, Jesús
Background: While accepted indications for the use of inferior vena cava filter (IVCF) in patients with a venous thromboembolism (VTE) have remained stable, their use continues to be frequent. Retrieval rates are still low, being particularly notable in the population with cancer. This study aims to review the rate of adherence to guidelines recommendation and to compare retrieval rates and complications in both cancer and non-cancer patients. Methods: A retrospective study was performed including 185 patients in whom an IVCF was placed in Hospital Clinic of Barcelona. Baseline characteristics, clinical outcomes, and IVCF-related outcomes were analyzed. A strongly recommended indication (SRI) was considered if it was included in all the revised clinical guidelines and non-strongly if it was included in only some. Results: Overall, 47 % of the patients had a SRI, without differences between groups. IVCF placement after 29 days from the VTE event was more frequent in the cancer group (46.1 vs. 17.7 %). Patients with cancer (48.1 % of the cohort) were older, with higher co-morbidity and bleeding risk. Anticoagulation resumption (75.3 % vs. 92.7 %) and IVCF retrieval (50.6 % vs. 66.7 %) were significantly less frequent in cancer patients. No significant differences were found regarding IVCF-related complications, hemorrhagic events and VTE recurrence. Conclusions: SRI of IVCF placement was found in less than half of the patients. Cancer patients had higher rates of IVCF placement without indication and lower anticoagulation resumption and IVCF retrieval ratios, despite complications were similar in both groups.
HBV Suppression by Nucleos(t)ide Analogues Reduces PD-1 Expression on Liver-Resident T Cells
(2025-10-03) Garcia Lopez, Mireia; Lens García, Sabela; Pallett, Laura J; Pocurull Aparicio, Anna; Leonel Couto, Thais; Belmonte, Ernest; Garcia Pras, Ester; Rodríguez Tajes, Sergio; Mariño Mendez, Zoe; Sàez Palma, Maria; Bartres, Concepcion; Rando-Segura, Ariadna; Rodriguez-Frias, Francisco; Lin, Jonah; Gehring, Adam J; MAINI, MALA K; Forns Bernhardt, Xavier; Pérez Del Pulgar Gallart, Sofía
Background and Aim: PD-1-expressing T cells within the HBV-infected liver constitute a target of novel immunotherapeutics. Our aim was to investigate the impact of viral suppression on PD-1 expression on intrahepatic versus circulating lymphocyte populations from chronic hepatitis B (CHB) patients. Methods: Twenty-two CHB patients, nine of them on nucleos(t)ide analogues (NUCs), had paired blood, liver fine needle aspirations (FNAs) and biopsies. A subset had a follow-up FNA after treatment initiation (n = 4) or discontinuation (n = 4). Intrahepatic (iHBV-DNA and cccDNA) and serum (HBV-DNA, HBsAg, HBcrAg and cirB-RNA) viral markers were quantified. Flow cytometry was used for immunophenotyping PBMCs and intrahepatic lymphocytes. An independent liver FNA scRNAseq dataset was used to consolidate our results. Results: PD-1 expression on tissue-resident memory CD8 T cells (T-RM) correlated with both iHBV-DNA and cccDNA, as well as surrogate markers of cccDNA transcriptional activity (cirB-RNA and HBcrAg) in CHB patients with mild hepatitis. These associations were not reflected in circulating T cells. PD-1 expression intensity on CD8 T-RM was lower in NUC-treated than in naive patients, changes that were again not detectable in the circulation. Longitudinal analysis showed that viral load rebound induced by NUC discontinuation had the potential to drive re-expression of high levels of PD-1 on CD8 T-RM. Conversely, therapy initiation and subsequent viral suppression reversed these changes. scRNAseq results further extended the profiling of these PD-1 + CD8 T-RM, showing a phenotype consistent with bystander activation in response to subclinical liver damage. Conclusions: Intrahepatic viral markers correlate with PD-1 expression on global liver-resident T cells of CHB patients with mild hepatitis, with a reduction after prolonged NUC therapy and re-expression following treatment withdrawal.
Incidence and Clinical Significance of Recompensation After HCV Cure
(2025-11-24) Semmler, Georg; Lens García, Sabela; Hidalgo, Álvaro; Lopez, Sonia Alonso; Perez-Perez, Maria; Dajti, Elton; Kabelitz, Martin; Zanaga, Paola; Hofer, Benedikt Silvester; Mariño Mendez, Zoe; Manzano, Marisa Luisa; Payeras, Isabel; Pons, Monica; Bruni, Angelo; Zanetto, Alberto; Burghart, Lukas; Ecker, Dominik; Simonis, Lucie; Pocurull Aparicio, Anna; Fritz, Laurenz; Collazos Clemente, Cristina; Neumayer, Daniela; Balcar, Lorenz; Jachs, Mathias; Reiberger, Thomas; Russo, Francesco Paolo; Maasoumy, Benjamin; Genesca, Joan; Banares, Rafael; Forns Bernhardt, Xavier; Fernandez, Inmaculada; Mandorfer, Mattias
BACKGROUND & AIMS: Baveno VII has proposed criteria for cirrhosis recompensation, but their prognostic significance in decompensated patients cured of hepatitis C virus (HCV) deserves further investigation. Thus, we studied the incidence and impact of recompensation after HCV cure as well as its predictors. METHODS: A total of 2570 patients with advanced chronic liver disease (ACLD) from 10 European centers were retrospectively included, including 2209 and 361 patients with compensated ACLD and decompensated cirrhosis who achieved sustained virologic response to direct-acting antivirals (DAAs). The association between achieving recompensation and clinical outcomes (hepatocellular carcinoma [HCC], portal vein thrombosis [PVT], and [liver-related] death) was investigated. RESULTS: During a median follow-up of 8.4 years from treatment initiation, 132 patients (36.6%) achieved recompensation. Lower albumin levels and diabetes were negatively associated with achieving recompensation. The incidence rates of liver-related death (4.2 vs 8.8 per 100 patient-years) and PVT (2.7 vs 5.4) were substantially lower after recompensation vs in the nonrecompensated state, while HCC incidence remained high (3.9 vs 5.5). Compared with decompensated cirrhosis, achieving recompensation was independently associated with decreased risks of subsequent liver-related death (adjusted hazard ratio, 0.384; 95% confi-dence interval, 0.225-0.655) and of PVT (adjusted hazard ratio, 0.421; 95% confidence interval, 0.224-0.759), but both risks remained higher than in compensated ACLD. Importantly, HCC incidence was not reduced as compared with decompensated cirrhosis. CONCLUSIONS: Recompensation after HCV cure is associated with substantially decreased risks of (liver-related) mortality and PVT, but not of HCC.
Tracking B cell immunity during perturbation of hepatitis B infection induced by treatment withdrawal
(2025-12-19) Lens García, Sabela; Burton, Alice R; Davies, Jessica; Locatelli, Maëlle; Garcia Lopez, Mireia; Pocurull Aparicio, Anna; Jeffery-Smith, Anna; Novikov, Nikolai; Fletcher, Simon P; Forns Bernhardt, Xavier; Pérez Del Pulgar Gallart, Sofía; MAINI, MALA K
Background Withdrawal of prolonged nucleos(t)ide analogue (NA) treatment results in hepatitis B surface antigen (HBsAg) loss in some subjects with chronic hepatitis B (CHB), potentially revealing immune correlates of functional cure.Objective We investigated whether baseline or longitudinal changes in humoral immunity correlated with outcome of discontinuing prolonged NA treatment.Design Global memory B cells (MBC) and T follicular helper cells (Tfh) were analysed by flow cytometry. HBs (small surface)/HBc (core)-MBC were quantified by ex-vivo bait staining and function assessed by cultured ELISpots (enzyme-linked immunosorbent spots). Immune parameters assessed at end-of-treatment (EOT), 12 and 48 weeks after treatment withdrawal (and at 4-8 years in a subset) were correlated with intrahepatic and longitudinal serum viral markers and alanine transaminase (ALT).Results Individuals on prolonged NA had comparable frequencies of HBc-MBC and HBs-MBC, although the latter were PD-1hi and functionally defective. Following treatment withdrawal, increases in class-switched HBc-MBC were frequently temporally linked with hepatic flares. Subjects achieving HBsAg loss had an increase in activated global MBC detectable at EOT that become more marked by week 48, accompanied by significant increases in plasmablasts. HBs-MBC in those with HBsAg loss showed significant reductions in PD-1, trends to increased activation (CD71) and function and a more robust correlation with Tfh, compared with HBsAg persistence. MBC changes were maintained 4-8 years after HBsAg seroconversion.Conclusion Differences in global and HBs-specific B cell immunity associate with HBsAg loss, whereas HBc-MBC temporally associates with flares, following withdrawal of prolonged NA treatment. Our results underscore the need to further explore the potential of B cell targets for monitoring and enhancing HBV functional cure in larger cohorts.
Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false-positive antibodies
(John Wiley & Sons, 2020-03) Llovet, Laura Patricia; Londoño, María Carlota; Gratacós Ginès, Jordi; Ortiz, Oswaldo; Rodriguez Tajes, Sergio; Lens García, Sabela; Reverter, Enric; Ruiz Ortiz, Estíbaliz; Costa Faidella, Jordi; Viñas, Odette; Forns, Xavier; Parés Darnaculleta, Albert
Background and aims Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. Methods One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). Results Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). Conclusion Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.
Deep Medullary Vein Integrity and Relationships with Small Vessel Disease and Interstitial Diffusivity Measures in Patients with a Recent Small Subcortical Infarct
(2025-05-22) Brenlla, Carla; Sozzi, Caterina; Girona, Andres; Martinez Quintanilla Martinez, Jordi; Laredo Gregorio, Carlos; Rodríguez Vázquez, Alejandro; Amaro Delgado, Sergio; Renú Jornet, Arturo; Doncel-Moriano Cubero, Antonio; Llull Estrany, Laura; Urra Nuin, Xabier; Rudilosso, Salvatore; Chamorro Sanchez, Ángel
BACKGROUND AND PURPOSE: The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary vein (DMV) integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct. MATERIALS AND METHODS: We gathered demographic, clinical, and 3T MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluated the venular integrity by using 2 visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures by using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score. RESULTS: In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter, and DTI along the perivascular spaces, were associated with 1 or both venular scores. In multivariate analysis, free water (OR, 1.33, 95% CI, 1.03-1.73), mean diffusivity (OR, 4.56, 95% CI, 1.32-15.81), fractional anisotropy (OR, 0.77, 95% CI, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (OR, 2.39, 95% CI, 1.06-5.39; OR 0.78, 95% CI, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (OR, 0.48, 95% CI, 0.25-0.94), fractional anisotropy with and without free water correction (OR, 0.82, 95% CI, 0.86-0.99; OR, 0.83, 95% CI, 0.7-0.99, respectively) remained robust for vein count. CONCLUSIONS: In patients with a recent small subcortical infarct, disruption of the DMVs, increased extracellular water, and white matter injury appear to be associated.
Determinants of HBsAg Loss After Nucleos(t)ide Discontinuation in a Prospective Cohort of HBeAg-Negative Caucasian Patients
(2025-10-13) Pocurull Aparicio, Anna; Broquetas, Teresa; Hoyas, Elena; Rodriguez, Manuel; Miquel, Mireia; Rodriguez, Mercedes; Roig, Clara Amiama; Herms Rubió, Queralt; Rodríguez Tajes, Sergio; Garcia-Samaniego, Javier; Suarez, Emilio; Buti, Maria; Forns Bernhardt, Xavier; Carrion, Jose A; Lens García, Sabela
Introduction: Nucleos(t)ide analogues (NAs) discontinuation in HBeAg-negative chronic hepatitis B (CHB) aims at increasing functional cure rates. However, clinical outcomes and predictive factors for HBsAg loss or re-treatment are affected by the heterogeneity of studies. We aimed to analyse baseline factors associated with outcomes after NAs discontinuation in a cohort with homogeneous re-treatment criteria. Methods: Prospective multicenter study of 149 HBeAg-negative CHB with complete viral suppression and absence of cirrhosis recruited from 2016 to 2021. Re-treatment criteria after NAs discontinuation were homogeneous based on liver tests and HBV-DNA levels. Results: In this predominantly Caucasian cohort, 71% received tenofovir with a median treatment duration of 10 (7-13) years. Forty patients (27%) achieved HBsAg loss after 44 (28-54) months. Lower qHBsAg at end of treatment (EOT) and longer treatment duration were independent predictors of HBsAg loss. Combining qHBsAg at EOT (1000 IU/mL) and month 3 after NA interruption (100 IU/mL) stratified patients into high (> 70%) or low (< 10%) likelihood of HBsAg loss. On the other hand, 43 (29%) patients were retreated; HBV-DNA < 100 IU/mL at month 3 was significantly associated with remaining off-therapy. Overall, safety was favourable, with mild or transient ALT flares occurring in 64 patients (43%). However, one patient (0.6%) developed a severe hepatitis and required liver transplantation. Conclusions: NA withdrawal results in functional cure rates exceeding 25%, particularly in patients with long-term antiviral treatment and low qHBsAg levels. Combining qHBsAg levels at EOT and at 3 months accurately stratifies patients according to the probability of HBsAg loss. Close monitoring to detect the need for treatment re-introduction is mandatory.
Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure
(2024-07-01) Semmler G; Lopez, SA; Pons, M; Lens García, Sabela; Dajti, E; Griemsmann, M; Zanetto, A; Burghart, L; Hametner-Schreil, S; Hartl, L; Manzano, M; Rodríguez Tajes, Sergio; Zanaga, P; Schwarz, M; Gutierrez, ML; Jachs, M; Pocurull Aparicio, Anna; Polo, B; Ecker, D; Mateos, B; Izquierdo, S; Real, Y; Ahumada, A; Bauer, DJM; Mauz, JB; Casanova-Cabral, M; Gschwantler, M; Russo, FP; Azzaroli, F; Maasoumy, B; Reiberger, T; Forns Bernhardt, Xavier; Genesca, J; Banares, R; Mandorfer M
Background & Aims: Baveno VII has defined a clinically significant ( i.e. , prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of >-20% associated with a final LSM -20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (-20 kPa: 465 [19.9%]) translating into a median LSM change of-5.3 (-8.8 to-2.4) kPa corresponding to-33.9 (-48.0 to-15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p -20% (p p = 0.550). Conclusions: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
HBcrAg and cirB-RNA Do Not Predict Clinical and Virological Outcomes in Patients With HBeAg-Negative Chronic Infection
(John Wiley & Sons, 2025-04-21) Battistella, Sara; Leonel Couto, Thais; Pocurull Aparicio, Anna; Rodríguez Tajes, Sergio; Sàez Palma, Maria; Rando-Segura, Ariadna; Mariño Mendez, Zoe; Tabernero, David; Hurtado, Juan Carlos; Cortese, Maria Francesca; Pérez Del Pulgar Gallart, Sofía; Lens García, Sabela; Forns Bernhardt, Xavier
Background & Aims: Predicting clinical and virological outcomes in HBeAg-negative (HBeAg-neg) chronic infection often requires long-term monitoring. Our study explored whether a single measurement of quantitative HBsAg (qHBsAg), HBV core-related antigen (HBcrAg), and circulating HBV RNA (cirB-RNA) can define the natural course of untreated HBeAg-neg chronic infection patients. Methods: To this aim, we included 128 na & iuml;ve HBeAg-neg chronic infection patients, stratified according to qHBsAg levels in: (1) 10-1000 IU/mL, (2) 1000-10 000 IU/mL, and (3) > 10 000 IU/mL. Results: HBcrAg and cirB-RNA were detected in 27% and 19% of patients with qHBsAg > 1000 IU/mL but rarely detected in patients with qHBsAg < 1000 IU/mL. After a median follow-up of 5.1 years, 9.4% of patients lost HBsAg, and 8.5% experienced an increase in HBV DNA > 2000 IU/mL. qHBsAg < 1000 IU/mL was the only factor independently associated with functional cure. Conclusions: In untreated HBeAg-neg chronic infection patients, single-point cirB-RNA and HBcrAg do not offer additional predictive value over qHBsAg < 1000 IU/mL for spontaneous HBsAg loss.
Influence of language barrier and cultural background in hepatitis B disease knowledge in a Chinese community of Spain
(2024-04-10) Pocurull Aparicio, Anna; Collazos Clemente, Cristina; Miralpeix Vissi, Anna; Tapias, Laura; Wang, Tao; Moreta, Maria Jose; Mariño Mendez, Zoe; Lens García, Sabela; Forns Bernhardt, Xavier
Introduction Hepatitis B infection (HBV) is prevalent in China. Due to language barriers and cultural differences, it is not always straightforward to evaluate disease knowledge in liver clinics. We aimed to assess the awareness on HBV and its mechanisms of transmission in HBV-infected Chinese patients and their household contacts. Methods HBV-infected Chinese patients and their contacts were interviewed by a native Chinese nurse regarding their knowledge on HBV transmission mechanisms, use of preventive measures and vaccination status. Non-Chinese HBV-infected patients and their household contacts served as a control group. Results In total 182 patients and 398 contacts participated with 85 (47%) patients and 240 (60%) contacts being from China. Language barrier was reported in 80% of Chinese patients and 44% of their contacts. Knowledge on parenteral and sexual HBV transmission was high in all patients (similar to 90%) but Chinese were more aware of vertical transmission than controls (94% vs. 68%; p < 0.01). Regarding the use of preventive measures, Chinese patients were more forewarned in their use to avoid parenteral transmission (93% vs. 74%, p < 0.01). When assessing household contacts, Chinese used preventive measures more frequently than controls for parenteral and sexual transmission (79% vs. 65 and 81% vs. 48%, p < 0.05). Vaccination coverage was slightly lower in Chinese contacts compared to controls (78% vs. 86%, p = 0.05). Conclusion Despite relevant language barriers, Chinese patients are well informed on the mechanisms of HBV transmission. Cultural differences may explain a higher use of preventive measures among the Chinese population. HBV vaccination of household contacts should be reinforced in both groups.

Examinar

Enviaments recents