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Metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease and metabolic dysfunction and alcohol-related liver disease represent the principal subtypes of steatotic liver disease (SLD), together constituting a rapidly growing global health challenge. Latin America bears a disproportionately high burden of SLD, driven by the convergence of increasing prevalence of obesity and type 2 diabetes, high levels of harmful alcohol consumption, and a high frequency of genetic risk variants, particularly in the gene encoding patatin-like phospholipase domain-containing protein 3 (PNPLA3). These factors interact synergistically to accelerate disease progression, increasing the risk of steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma. Despite this substantial burden, the region faces major structural and health-system constraints, including fragmented health-care delivery, limited hepatology capacity, restricted access to diagnostic and therapeutic technologies, and low participation in clinical trials, all of which hinder early detection and the generation of region-specific evidence. This Review summarizes current data on the epidemiology and clinical burden of SLD in Latin America, identifies critical gaps in research and surveillance, and highlights priorities for prevention, harm reduction and health-system strengthening, including the implementation of effective public policies to reduce morbidity and mortality and improve health outcomes in the region.
As a classical prescription, Wuwei Xiaodu Decoction (WWXDD) () is composed of five medicinal components: Lonicerae Japonicae Flos, Taraxaci Herba, Chrysanthemi Indici Flos, Violae Herba, and Semiaquilegiae Radix. Originating from the Qing Dynasty, WWXDD has been widely employed in Traditional Chinese Medicine (TCM) for treating inflammatory diseases. Although numerous studies have explored various aspects of WWXDD, few comprehensive reviews have systematically synthesized its ethnopharmacological basis, phytochemistry, pharmacology, and clinical applications, which hinders the further application and commercialization of WWXDD. This review aims to provide a comprehensive summary of the traditional theory, chemical composition, pharmacological activity, and clinical evidence related to WWXDD, with a focus on current challenges and future perspectives. The literature was systematically searched in databases including Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure (CNKI). The search period covered publications from 2013 to 2025. Keywords included "Wuwei Xiaodu Decoction", "WWXDD", "traditional Chinese medicine", "phytochemistry", "pharmacology", and "clinical application". Original research articles, reviews, and clinical studies relevant to the composition, pharmacological activities, quality control, and clinical applications of WWXDD were included. Duplicates, unrelated studies, and articles lacking sufficient methodological information were excluded. Chemical structures were drawn using ChemDraw 23, and the graphical abstract and schematic illustrations were created using BioRender and PowerPoint. This review firstly summarized the progress of the chemical constituents of WWXDD and discussed the advanced methods in monitoring quality of WWXDD and its herbal ingredients. Meanwhile, the attribution of each herb in WWXDD provides some theoretical basis for its efficacy. Pharmacological investigations reveal that WWXDD exhibits anti-inflammatory, anticancer, and antibacterial properties, attributable to its constituent herbs. Clinically, it has demonstrated efficacy in managing facial acne and preventing postoperative infections. Finally, it is important to note in WWXDD use that even though there is no toxicity, most drugs are cold in nature, so it is important to pay attention to the people for whom the use is contraindicated. Through systematic investigation of WWXDD's herbal components, this study enhances the mechanistic understanding of its therapeutic actions. Both preclinical and clinical evidence underscores its potential in managing complex diseases. On this basis, we summarize an actionable compound-level quality-control framework (chemical fingerprinting/multi-component quantification-spectrum-effect and bioactivity consistency-mutual confirmation with mechanistic and clinical evidence), and highlight that standardization and formula-level indicators remain key bottlenecks. In this review, current issues are discussed to inform and inspire subsequent research of WWXDD and other classical prescriptions.
Esophageal/gastric varices (EV), especially clinically significant varices (CSV), represent life-threatening complications of pediatric portal hypertension (PH), necessitating timely detection. While esophagogastroduodenoscopy (EGD) remains the gold standard, its invasive nature and requirement for sedation in children highlight the need for reliable non-invasive alternatives for screening and risk stratification. Splenic stiffness measurement (SSM) has emerged as a potential tool. This systematic review and meta-analysis aimed to evaluate diagnostic accuracy of SSM for detecting EV and CSV in pediatric PH. A comprehensive search of PubMed, Scopus and Embase was performed up to January 2025. Studies assessing SSM via elastography in pediatric (< 18 years) PH, with EGD as reference standard for EV/CSV detection, were included. Data was synthesized using hierarchical summary receiver operating characteristic (HSROC) model to estimate pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC). Risk of bias was evaluated using Quality Assessment of Studies of Diagnostic Accuracy (QUADAS-2) tool. Ten studies encompassing 618 patients were analyzed. For EV prediction (3 studies, n = 158), pooled sensitivity, specificity and DOR were 0.80 (95% CI: 0.70-0.88), 0.89 (95% CI: 0.80-0.95) and 26.22 (95% CI: 5.39-98.83), respectively, with AUROC 0.838 (95% CI: 0.806-0.864). For CSV (7 studies, n = 460), values were 0.86 (95% CI: 0.81-0.90), 0.82 (95% CI: 0.76-0.87) and 31.00 (95% CI:12.33-80.21) with AUROC 0.905 (95% CI: 0.882-0.924), indicating very good diagnostic performance. Substantial heterogeneity noted for pooled sensitivity (I2 = 69.2%, p = 0.0006) for CSV prediction. Sub-group analysis revealed that etiology of PH, elastography techniques and ethnicity of study population were sources of heterogeneity. SSM showed superior accuracy in non-cirrhotic PH (DOR: 48.61 [95% CI: 13.62-188.37]) than cirrhotic PH (DOR: 18.89 [95% CI: 8.65-40.53]). SSM demonstrates good diagnostic accuracy for non-invasive variceal predictionin pediatric PH. However, further multicentre studies with standardized protocols and disease-specific cut-offs for pediatric population are necessary for its integration in routine clinical practice as a screening tool.
Liver diseases account for 1 in 25 deaths worldwide. Owing to the asymptomatic nature across the dynamic spectrum of steatotic liver disease (SLD) and the absence of targeted screening programmes, individuals at risk of progression to cirrhosis or hepatocellular carcinoma (HCC) are unlikely to pursue liver disease testing. Historically, hepatitis B and C were the leading causes of liver injury that can progress to cirrhosis or HCC. Global efforts to implement screening and vaccination programmes, expand testing and treatment, and encourage active viral hepatitis case finding followed the widespread availability of curative treatment for hepatitis C and effective suppressive therapy and vaccines for hepatitis B, further supported by changes in law, regulation and public policy. With encouraging declines in new viral hepatitis infections in many countries, greater attention should turn to SLD, now the leading global indicator for cirrhosis and HCC. Screening and active case finding for SLD lag far behind its increasing prevalence, leaving most people undiagnosed. This Expert Recommendation draws on lessons learned from legal, regulatory and policy changes required to combat the viral hepatitis public health threat. Our recommendations can contribute to a concerted shift in legal frameworks and policies to enhance screening programmes, increase testing and improve health outcomes.
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The management of hepatocellular carcinoma (HCC) has undergone radical change over the past decade. Immunotherapies now dominate the treatment of advanced-stage disease and are increasingly being evaluated in perioperative and intermediate-stage settings. However, in some instances, positive phase III trials have not translated into adoption by guidelines or regulatory agencies, highlighting the need to harmonize and update the current standards for trial design and end points. In response to these challenges, four scientific societies - the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO) - appointed representatives to develop a consensus recommendations document addressing current unmet needs and future challenges in HCC trial design and end points. Through a modified Delphi process, 102 consensus statements were developed across several distinct domains: surveillance; early-stage, intermediate-stage and advanced-stage disease; transplant-related contexts; regulatory considerations; and emerging topics. The document rigorously defines target populations, stratification factors, control arms and benchmarks for expected clinical benefit. Collectively, this consensus is intended to provide a dynamic, evidence-based, multisociety roadmap for optimizing trial design, accelerating therapeutic development and improving clinically meaningful outcomes in patients with HCC.
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The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.
Epithelial-derived malignancies account for the majority of human tumours and present considerable treatment challenges owing to their heterogeneity, metastatic potential and resistance to therapy. The claudin family of tetra-transmembrane proteins was identified approximately 28 years ago as containing key regulators of epithelial function. These proteins are integral components of tight junctions, which control barrier integrity, selective channel permeability and cellular organization in epithelial tissues. Subsequent murine studies revealed that claudins also have tissue-specific physiological roles, whereas clinical studies demonstrated that their expression is frequently dysregulated in various cancers, highlighting their potential as therapeutic targets. In the past few decades, increasing efforts to exploit claudins in cancer therapy have led to the development of targeted molecules, including zolbetuximab, a first-in-class CLDN-18.2-targeted antibody for the treatment of gastric cancer, which has been recently approved by the United States Food and Drug Administration. This milestone emphasizes the therapeutic potential of targeting this protein family and its possible role in expanding treatment options for cancer. In this review, we discuss the evolving landscape of claudin-targeting therapeutics, examining key advances, emerging challenges and future prospects.
Globally, colorectal cancer (CRC) is the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths, although these epidemiological patterns show substantial geographical variation. In this Review, we discuss the emerging global patterns of CRC incidence, which historically has been the highest among Western, high-income countries but is now increasing globally beyond these regions. This rise has mainly been driven by early-onset CRC - that is, cancers diagnosed in individuals aged <50 years. A birth cohort effect beginning with individuals born in the 1960s indicates that factors beyond genetic susceptibility or changes in screening practice underlie this increase. A changing landscape of established and emerging risk factors occurring worldwide has been proposed to underlie these epidemiological trends in CRC. Hypothesized risk factors include dietary and lifestyle aspects, shifts in the gut microbiota and the rise in environmental contaminants associated with the rapid urbanization occurring globally. Substantial advances in the characterization of genomic and epigenomic profiles of CRCs as well as their gut microbiomes not only hold potential for providing insight on the aetiology of this disease but could also be leveraged for early detection and interception strategies. The under-representation of non-Western populations in these studies, however, greatly limits progress and, if not addressed, could widen the existing gaps in global CRC prevention and control.
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Wearable technologies are increasingly being integrated into clinical trials, offering new tools to capture physiological and behavioural endpoints in real-world settings. By enabling continuous, remote, participant-friendly monitoring, wearables address key limitations of traditional trials, such as frequent site visits, sparse sampling and limited ecological validity, while supporting the development of digital biomarkers. To characterize how wearables are used in drug development, we curated 1,021 interventional trials registered between 2001 and 2025 that incorporated wearable-derived data into study protocols. We identified five application archetypes - drug effects, dosing optimization, adherence, delivery medium and delivery technique optimization - through which wearables are deployed in trials, underscoring a broadening role across study objectives. Adhesive patches, largely driven by continuous glucose monitoring, now dominate trial deployments, with expanding coverage of physiological domains including sleep, cardiovascular function, motor activity and brain signals. Despite this progress, formal regulatory qualification of wearable-derived measures remains rare, with SV95C in Duchenne muscular dystrophy the only such example to date. Looking ahead, we highlight emerging biochemical sensing modalities beyond glucose, as well as transdermal spectroscopy and wearable ultrasound. This Review provides a structured, forward-looking overview of wearables in trials and supports their responsible, effective integration into clinical development.
The rising disease burden of inflammatory bowel disease (IBD) parallels the changing dietary landscape accompanying industrialization, underscoring the growing relevance of nutritional science in disease prevention and management. Precision nutrition has emerged as a promising approach to prevent and manage IBD through tailored dietary recommendations based on multidimensional individual characteristics, including demographics, disease natural history and multiomics traits. In this Review, we investigate the sources of heterogeneity in dietary responses and propose a stepwise framework for precision nutrition: phenotype-based precision nutrition, informed by general phenotypes in clinical and community settings; omics-based precision nutrition, targeting subgroups with shared biological features identified via omics and complementary approaches; and integrated precision nutrition, providing personalized dietary strategies informed by comprehensive, multidimensional phenotypes. Advances in large-scale longitudinal multiomics cohorts, biomarker detection and artificial intelligence are transforming data acquisition and interpretation, thereby facilitating both interventional research and real-world application of precision nutrition. Key considerations for implementing precision nutrition in IBD are discussed. This Review outlines a holistic and translational framework, aiming to advance both research and clinical practice in the prevention and management of IBD.
Cholangiocarcinoma (CCA) is a cancer that originates within the bile ducts. Traditionally considered to be a rare neoplasm, increased awareness of CCA alongside advancements in diagnosis and the rising prevalence of certain risk factors have contributed to a global increase in incidence and mortality. CCAs are highly heterogeneous from the clinical, histomorphological and molecular perspectives but commonly share a poor prognosis. These tumours usually develop and progress silently; by the time they are detected, it is often too late for curative surgical intervention. In such cases, current therapeutic approaches offer modest survival improvements and are generally considered palliative. Although well-known risk factors predispose individuals to developing CCA, the majority of cases are considered sporadic, occurring without any identifiable underlying condition. Over the past decade, substantial collaborative efforts have been made to improve our understanding of the aetiopathogenesis of these tumours, aiming to identify novel biomarkers and therapeutic targets to develop more effective treatments. The ultimate goal is to improve patient outcomes and overall well-being. However, there are significant gaps in our understanding of the molecular mechanisms that drive cholangiocarcinogenesis. In this international Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we provide a critical overview of the latest advancements in the field of CCA. We highlight the key aspects of CCA aetiopathogenesis and clinical management and provide insights into promising new treatments. Finally, we provide a set of consensus recommendations and future research priorities for CCA based on a Delphi panel questionnaire involving international experts.