Cholangiocarcinoma in Latin America: a multicentre observational study alerts on ethnic disparities in tumour presentation and outcomes.

Background: Cholangiocarcinoma (CCA) represents a global health challenge, with rising incidence and mortality rates. This study aimed to elucidate the clinical course and practices of CCA in Latin America.

Methods: This observational cohort study investigated individuals diagnosed with CCA between 2010 and 2023 at five referral centres across Latin America.

Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials.

Background: Severe flares (ALT ≥ 10×ULN) are a well-recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance.

Methods: Data were used from two prospective studies on NA cessation conducted in the Netherlands and Canada.

Low nailfold capillary density in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: biomarker of clinical outcome?

Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls.

B-Cell Activation Gene Signature in Blood and Liver of Hepatitis B e Antigen-Positive Patients With Immune Active Chronic Hepatitis B.

Background: Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and liver of patients with chronic HBV.

Intrahepatic plasma cells, but not atypical memory B cells, associate with clinical phases of chronic hepatitis B.

Studies have traditionally focused on the role of T cells in chronic hepatitis B (CHB), but recent evidence supports a role for B cells. The enrichment of so-called atypical memory (AtM) B cells, which show reduced signaling and impaired differentiation, is believed to be a characteristic feature of CHB, potentially contributing to the observed dysfunctional anti-HBsAg B-cell responses. Our study, involving 62 CHB patients across clinical phases, identified AtM B cells expressing IFNLR1 and interferon-stimulated genes.

Evaluating changes in functioning and psychological distress in visitors of the @ease youth mental health walk-in centres.

Background: Highly accessible youth initiatives worldwide aim to prevent worsening of mental health problems, but research into outcomes over time is scarce.

Aims: This study aimed to evaluate outcomes and support use in 12- to 15-year-old visitors of the @ease mental health walk-in centres, a Dutch initiative offering free counselling by trained and supervised peers.

Method: Data of 754 visitors, collected 2018-2022, included psychological distress (Clinical Outcomes in Routine Evaluation 10 (CORE-10)), social and occupational functioning (Social and Occupational Functioning Assessment Scale (SOFAS)), school absenteeism and support use, analysed with change indicators (first to last visit), and mixed models (first three visits).

Turning 18 in mental health services: a multicountry qualitative study of service user experiences and views.

Background: Worldwide, the division between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) has frequently resulted in fragmented care with an unprepared, non-gradual transition. To improve continuity of care and other service transition experiences, service user input is essential. However, such previous qualitative studies are from a decade ago or focused on one mental disorder or country.

Clinical Correlates of a Nonplexiform Vasculopathy in Patients With a Diagnosis of Idiopathic Pulmonary Arterial Hypertension.

Background: The clinical phenotype of patients with idiopathic pulmonary arterial hypertension (IPAH) has changed. Whether subgroups of patients with IPAH have different vascular phenotypes is a subject of debate.

Research Question: What are the histologic patterns and their clinical correlates in patients with a diagnosis of IPAH or hereditary pulmonary arterial hypertension?

Study Design And Methods: In this this cross-sectional registry study, lung histology of 50 patients with IPAH was assessed qualitatively by two experienced pathologists.

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology.

The incidence of hepatocellular carcinoma (HCC) in non-cirrhotic livers is rising significantly, but clear risk factors for screening remain elusive. This study sought to characterize non-cirrhotic HCC etiologies. HCC cases from 2009 to 2020 in a Dutch referral center were examined, revealing 371 out of 1654 cases (22%) as non-cirrhotic.

Association of HBsAg levels with differential gene expression in NK, CD8 T, and memory B cells in treated patients with chronic HBV.

Background & Aims: HBsAg secretion may impact immune responses to chronic HBV infection. Thus, therapeutic approaches to suppress HBsAg production are being investigated. Our study aims to examine the immunomodulatory effects of high and low levels of circulating HBsAg and thereby improve our understanding of anti-HBV immunity.

Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B: Multicentre Randomized Trial (PAS Study).

We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 μg per week) or continued NA-monotherapy with subsequent follow-up to Week 72.

The Role of PIVKA-II as a Predictor of Early Hepatocellular Carcinoma Recurrence-Free Survival after Liver Transplantation in a Low Alpha-Fetoprotein Population.

Introduction: AFP and the RETREAT score are currently used to predict HCC recurrence after LT. However, superior discriminating models are needed for low AFP populations. The aim of this study is to investigate the predictive value of PIVKA-II on recurrence-free survival after LT in a low AFP population and microvascular invasion on explant.

Sustained response and HBsAg loss after nucleo(s)tide analogue discontinuation in chronic hepatitis B patients: the prospective SNAP study.

Background & Aim(s): Current guidelines suggest that nucleos(t)ide analogues (NA) can be discontinued before HBsAg loss in a selected group of chronic hepatitis B (CHB) patients. We aimed to study the safety and off-treatment response after NA cessation.

Methods: This is a prospective, multicentre, cohort study in which eligible patients discontinued NA therapy.

Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension.

Background: Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described.

Methods: We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA.

Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans.

Introduction And Objectives: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined.

Materials And Methods: Cross-sectional analysis was performed on Latin American and European individuals.

Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma.

Aberrant DNA methylation changes have been reported to be associated with carcinogenesis in cirrhotic HCC, but DNA methylation patterns for these non-cirrhotic HCC cases were not examined. Therefore, we sought to investigate DNA methylation changes on non-cirrhotic HCC using reported promising DNA methylation markers (DMMs), including HOXA1, CLEC11A, AK055957, and TSPYL5, on 146 liver tissues using quantitative methylation-specific PCR and methylated DNA sequencing. We observed a high frequency of aberrant methylation changes in the four DMMs through both techniques in non-cirrhotic HCC compared to cirrhosis, hepatitis, and benign lesions ( < 0.

Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations.

Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe.

Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.

MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort.

Background: The rs641738 C > T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population.

Aims: We provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans.