Humanistic values are usually treated as qualities of clinicians, although modern care is produced by organizations, financing arrangements, regulatory systems, and digital infrastructures. This conceptual and critical integrative review examines how humanistic tenets became embedded beyond the clinical encounter while drawing a boundary between humanistic tenets and health policy that is merely beneficial or efficient. Landmark scholarship, international frameworks, comparative healthcare-system studies, critical accounts of managerialism, and selected primary legal and governmental sources from the United States, United Kingdom, Japan, and China were synthesized by domains of responsibility rather than a presumed universal chronology. The framework distinguishes six non-interchangeable domains-physician, patient, population, organization, a person's life, and healthcare system-defined by different moral qualities, scales, temporal horizons, and governance mechanisms. Technology governance cuts across all six; technology itself is not a moral quality. The Japanese pathway illustrates the institutionalization of universal coverage before autonomy became comparably explicit, whereas China's recent trajectory is interpreted as compressed institutionalization across coverage, rights, quality, reforms in the provision of care, and aging. A humanistic healthcare system is proposed as an ideal and a directional continuum. Its core tenets are dignity, agency, attention to suffering, and responsiveness to person-defined life goals. Safety, equity, solidarity, participation, and trustworthiness acquire humanistic significance when they uphold those tenets rather than functioning only as performance objectives. Institutionalization can make humane care more reliable, but auditing, targets, and digital systems can also produce a predilection for procedures. Professional judgment, institutional capability, public accountability, and contestable technology must therefore remain mutually corrective.
Vascular instability, characterized by impaired pericyte coverage, is a hallmark of tumor progression. ATP6L is highly expressed in colorectal cancer (CRC) tissues and promotes tumor progression by enhancing the tumor microvasculature; however, its direct impact on vascular stability remains unclear. ATP6L expression, microvascular morphology, and pericyte coverage were analyzed by immunohistochemistry in a cohort of 179 CRC specimens, and the role of ATP6L in vascular stability was further investigated by modulating its expression both in vitro and in vivo. In vitro, MC38 and CT26 cells with ATP6L overexpression or knockdown were co-cultured with mouse vascular smooth muscle cells (MOVAS), and MOVAS proliferation, migration, and apoptosis were evaluated using EdU incorporation, transwell migration, and TUNEL staining assays, respectively. PDGFB secretion and PDGFRβ expression were assessed by ELISA, Western blotting, and immunofluorescence. Along the normal colorectal mucosa-adenoma-adenocarcinoma sequence, ATP6L upregulation was closely associated with progressive vascular instability, characterized by loss of pericyte coverage and increasing vascular morphological heterogeneity. Mechanistically, ATP6L overexpression promoted extracellular acidification, suppressed PDGFB secretion, and subsequently reduced PDGFRβ expression in pericytes, thereby impairing their recruitment and survival. Conversely, ATP6L knockdown attenuated extracellular acidification, restored PDGFB/PDGFRβ signaling, and rescued pericyte proliferation, migration, and survival. These findings identify ATP6L as a key mediator of perivascular dysfunction in CRC and demonstrate that ATP6L-induced extracellular acidification disrupts vascular stability by suppressing the PDGFB/PDGFRβ signaling axis and impairing pericyte function.
Portal vein tumor thrombus (PVTT) is a biologically aggressive and clinically heterogeneous form of hepatocellular carcinoma (HCC). Global guidelines generally classify macrovascular invasion as advanced disease and prioritize systemic therapy, whereas selected East Asian practice pathways incorporate hepatic arterial infusion chemotherapy (HAIC), radiotherapy, or resection. This review critically evaluates HAIC combined with an antiangiogenic agent and immune checkpoint inhibitor as a conversion strategy for HCC with PVTT. Randomized trials substantiate the efficacy of HAIC-based treatment in contrast to controls from the days of sorafenib but do not establish the incremental benefit of the contemporary triplet. Across prospective single-arm studies, RECIST 1.1 objective response rates ranged from approximately 36 to 77%, with higher estimates in some studies using mRECIST. Retrospective PVTT-focused comparisons also suggest longer progression-free and overall survival than with dual systemic therapy or HAIC alone, but these figures remain vulnerable to confounding by indication, heterogeneous regimens, inconsistent response criteria, and immortal-time bias related to surgery. Conversion should be defined as a prospectively documented transition from unresectable disease to an R0-resectable state with adequate liver reserve, not as radiological response alone. We propose an explicitly unvalidated multidisciplinary framework for candidate selection, reassessment, and perioperative management. Current evidence supports protocol-based use in clinical trials or experienced centers rather than routine global adoption. Randomized PVTT-stratified trials comparing the triplet to contemporary immunotherapy, with intention-to-treat reporting of resection and pathological response, are required.
Hepatocellular carcinoma (HCC) is governed by malignant progression and deterioration of the organ in which the cancer arises. Modern management has therefore outgrown static stage-to-treatment allocation. We define dynamic therapeutic opportunity as the time-varying set of clinically credible treatment options available to an individual patient, determined by hepatic reserve, oncological tractability, physiological reserve, prior therapeutic exposure, patient goals, and real-world deliverability. This framework does not replace validated staging systems or liver-function scores; it asks how each intervention changes the circumstances under which the next decision will be made. Evidence for curative-intent conversion remains dominated by selected cohorts, although the interim results of the randomized TALENTop trial provide the first prospective comparative signal supporting resection in a narrowly defined post-induction population. We review liver-sparing surgery, locoregional-systemic integration, conversion therapy, and modifiers such as frailty and metabolic dysfunction-associated steatotic liver disease. We then propose a trial architecture that complements tumor endpoints with hepatic decompensation, sustained ALBI deterioration, subsequent-treatment access, curative-intent transition, functional independence, and patient-reported outcomes. Modern HCC management should evaluate not only whether an intervention controls the present tumor but also whether it preserves, expands, or eliminates the patient's future set of clinically meaningful treatment options.
Postoperative complications remain major determinants of outcomes after hepatectomy for hepatocellular carcinoma (HCC), but whether complications that prolong hospitalization are also those that contribute most to mortality remains unclear. This multicentre cohort study included 1,883 patients undergoing curative-intent hepatectomy for HCC across seven tertiary centers. Postoperative complications were categorized by organ system, and adjusted population-attributable fractions (PAFs) were calculated to estimate their contributions to 90-day mortality and prolonged hospital stay. Multivariable Cox models were used to assess associations with overall survival and recurrence-free survival. A divergence between hospitalization burden and mortality burden was observed. Liver surgery-specific complications accounted for the largest population-level burden of prolonged hospitalization (PAF 11.0%) and 90-day mortality (PAF 10.0%). Cardiovascular complications were the leading non-liver contributor to 90-day mortality (PAF 9.4%), despite a smaller contribution to prolonged hospitalization (PAF 4.1%). Pulmonary complications, cardiovascular complications, renal complications, and glucose dysregulation were independently associated with worse overall survival, whereas no complication domain was independently associated with recurrence-free survival. These findings show that postoperative recovery burden and mortality burden are not interchangeable after hepatectomy. Liver surgery-specific complications dominated hospitalization burden, whereas cardiovascular complications represented an underrecognized non-liver contributor to early mortality and worse long-term survival. An integrated perioperative framework incorporating systematic cardiovascular risk assessment may improve risk prioritization after hepatectomy for HCC.
Cholangiocarcinoma (CCA) is a highly aggressive, molecularly heterogeneous biliary tract malignancy and the second most common primary liver cancer, and it has an increasing global incidence and persistently poor prognosis. Recent updates of international guidelines, including those from the NCCN, ESMO, EASL, CSCO, BSG, and Japanese societies, along with rapid advances in precision oncology, have substantially changed the clinical management of CCA. This review systematically compares current global guidelines, highlighting both areas of consensus and regional differences in epidemiology, risk factors, screening strategies, diagnostic approaches, pathological and molecular classification, staging systems, surgical indications, systemic therapy, and multidisciplinary management. This review also summarizes recent advances in molecular diagnostics, including next-generation sequencing, liquid biopsy, circulating tumor DNA, extracellular vesicles, artificial intelligence-assisted imaging, radiomics, and emerging prognostic biomarkers. The evolving roles of immune checkpoint inhibitors, molecularly targeted therapies against FGFR2, IDH1, HER2, BRAF, NTRK, and MSI-H/dMMR, liver transplantation, locoregional treatment, and conversion (translational) therapy are also discussed. Finally, this review addresses current challenges, including drug resistance, limited access to molecular testing, regional disparities in healthcare resources, and the lack of universally accepted screening strategies. By integrating updated guideline recommendations with the latest clinical evidence, this review provides a comprehensive reference for evidence-based clinical decision-making and future translational research in CCA.
Diffuse midline glioma (DMG) is a high-grade malignant brain tumor. The 5-year survival rate for DMG remains close to zero. It is a rare and highly aggressive tumor, which is more common in children than in adults. We here report our retrospective study of 210 cases of DMG. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, ATRX, p53, OLIG2 and Ki-67. The most frequent anatomic locations in patients were the thalamus and brainstem. During follow-up, 169/210 patients (80.5%) died from the disease, with a median survival time of 11 months (range: 0 to 87 months). Kaplan-Meier analysis indicated that the prognosis of adult patients was better than that of the pediatric cohort (P = 0.006). Multivariable Cox regression identified male sex, spinal cord tumor location, and a Ki-67 index of ≤ 10% as independent favorable prognostic factors. Also, meta-analysis indicated that the prognosis of adult patients was better than that of the pediatric cohort (P = 0.002), patients with brainstem tumors had a worse prognosis compared to those with tumors in other locations (P = 0.003). We highlight the aggressive nature of DMG and the critical role of clinical and molecular markers in prognosis. These findings demonstrate substantial clinicopathological heterogeneity in H3 K27M-altered DMG and support the combined consideration of age, tumor location, and proliferative activity in future prognostic stratification. Prospective multicenter validation and more comprehensive molecular profiling are required.
Rare diseases impose a disproportionate clinical burden, and yet therapeutic progress is hindered by small cohorts, biological heterogeneity, and limited disease-specific options. Stem cell-derived extracellular vesicles (EVs), and especially exosome-enriched products, are emerging as adaptable cell-free therapeutics that preserve key paracrine activities of parent cells while offering improved controllability, engineering flexibility, and potentially lower acute immunogenicity than living-cell products. This review proposes a clinically driven bottleneck-to-mechanism framework for rare-disease translation, matching each disease class to its dominant pathological barrier, mechanism-relevant EV function, route-aware delivery strategy, and measurable potency endpoint. Using this framework, EVs may enable immune circuit rewiring in autoimmune disorders, neuroprotection and toxic-protein clearance in neurodegeneration, osteogenic and matrix-supportive repair in skeletal/connective tissue diseases, and metabolic rescue in lysosomal or mitochondrial disorders. We further highlight a key conceptual distinction between EVs as active biologics and EVs as engineered delivery vehicles. Successful translation will depend on integrating cargo design, surface targeting, biodistribution-aware administration, scalable manufacturing, and quality-by-design control, while anticipating repeat-dose pharmacokinetics/pharmacodynamics (PK/PD), immunogenicity, complement activation, procoagulant risk, impurity control, and off-target organ-accumulation challenges. Multi-omics and artificial intelligence may further refine target selection and precision engineering. Overall, stem cell-derived EVs constitute a versatile platform for treating rare diseases, but clinical success requires closer alignment among mechanism, disease specificity, product definition, and translational endpoints.
Recent advances in computerized technologies, neuroscience, and materials and engineering have transformed brain‑computer interfaces (BCIs) from conventional unidirectional signal recording systems (brain-to-device) to bidirectional closed-loop neuromodulation systems (brain-device-brain). BCI-based devices enable direct information exchange between the human central nervous system and external electronic devices, and they are widely used in scenarios such as rehabilitation of patients with dyskinesia or enhancement of the self-care ability of disabled individuals. This editorial discusses the rapidly evolving field of BCIs, highlighting both their transformative potential to restore neurological function and the emerging ethical concerns associated with neural data access, cognitive enhancement, and human autonomy. The academic consensus and future translational prospects are also discussed. This article attempts to provide insightful, balanced, and critical viewpoints to help BCI-related research. Indeed, the future of BCIs will depend not only on technological innovation but also on society's ability to establish robust ethical and regulatory frameworks. Whether BCIs become a lifeline for millions of patients or a source of new societal risks will be determined by the choices made today.
Brain-computer interface (BCI) technology establishes a direct communication pathway between neural activity and external devices. Driven by advances in neuroscience, artificial intelligence (AI), neural signal acquisition, decoding algorithms, and implantable system design, BCIs have progressed rapidly from experimental prototypes toward clinically relevant neurotechnologies. However, the translation of these technical advances into routine clinical practice and equitable real-world access remains substantially slower than technological innovation. This review summarizes the major technological pathways of BCIs and their clinical applications, and it then examines BCI development from the perspective of clinical translation and accessibility. We focus on key barriers across the translational chain, including long-term technical stability, quality of clinical evidence, evaluation standards, reimbursement mechanisms, health-economic evidence, and the feasibility of implementation in real-world healthcare settings. We argue that the central challenge in BCI development has shifted from improving technical performance alone to building the translational infrastructure required for safe, effective, affordable, and sustainable clinical integration.
Patients with end-stage liver disease often exhibit impaired neutrophil function and have an elevated risk for perioperative infections. Liver transplantation (LT) restores hepatic function; however, perioperative neutrophil dynamics and their association with graft size remain unclear. We retrospectively analyzed 71 adult patients who underwent LT between January 2019 and June 2021. Leukocyte, neutrophil, and lymphocyte counts and the neutrophil-to-lymphocyte ratio were assessed at three intraoperative time points: beginning of surgery (BS), anhepatic phase (AP), and abdominal closure (AC), as well as on postoperative days (PODs) 1-3. The patients were stratified by graft-to-recipient weight ratio (GRWR < 1.0 vs. ≥ 1.0), and the correlations between GRWR and leukocyte parameters were evaluated. Neutrophil and leukocyte counts remained unchanged from the BS to AP and increased significantly after graft reperfusion (AC vs. BS: p < 0.01). Lymphocyte counts declined significantly during surgery. On POD 1, both neutrophil counts and their increases from BS correlated significantly with GRWR in the GRWR < 1.0 group (rs = 0.424 and 0.442, respectively; both p < 0.01), although not in the GRWR ≥ 1.0 group. No postoperative infections were observed within 7 days. Graft reperfusion was associated with a robust increase in peripheral neutrophil counts, particularly in the recipients of smaller grafts. These findings suggest an association between graft size and early postoperative neutrophil dynamics, which may help interpret early immune responses after LT.
Long-term care insurance (LTCI) is commonly understood as a social insurance mechanism that compensates care-related costs after disability has occurred. This compensation function remains essential, but it is insufficient in the context of rapid population aging, multimorbidity, cognitive impairment, and long-term family caregiving burden. In older adults, disability often emerges from the cumulative interaction of geriatric syndromes, including frailty, recurrent falls, cognitive decline, malnutrition, depressive symptoms, pressure injuries, together with multimorbidity, environmental vulnerability, and caregiver burden. This article argues that the next stage of LTCI reform should not simply expand coverage or reimbursement, but should incorporate earlier identification of functional risk, comprehensive geriatric assessment, continuous care, caregiver support, and functional outcome evaluation. Existing quasi-experimental studies from China suggest that current LTCI pilots are associated with partial benefits in cognitive and psychological outcomes, changes in healthcare utilization including reduced hospitalization in some studies, modest improvements in health-related quality of life, and favorable frailty-related outcomes. However, these studies do not establish the effectiveness or added value of a geriatric-syndrome-oriented LTCI model. We therefore distinguish between the current evidence base and a proposed reform model, outline potential pathways linking LTCI to healthy aging, and propose operational priorities for future evaluation.
In May 2026, an outbreak of Ebola virus disease caused by Bundibugyo ebolavirus emerged in the Democratic Republic of the Congo and spread to Uganda, prompting a WHO Public Health Emergency of International Concern. With no approved vaccine or specific antiviral treatment, Bundibugyo virus poses an acute importation risk in an era of dense global air travel. This perspective frames imported Ebola as a hospital resilience stress test and proposes the Hospital Resilience 4P Framework, organizing preparedness around Prediction, Preparedness, Protection, and Partnership. We critically analyze the drivers of nosocomial amplification, including diagnostic delay, healthcare worker undertraining, and insufficient infection prevention and control. For China, whose aviation hubs in Guangzhou and Shenzhen sustain dense air links with Africa under the Belt and Road Initiative, this risk is particularly urgent. We further examine the vulnerabilities of East Asian healthcare systems - aging workforces, emergency department overcrowding, and skewed PPE stockpiles - and evaluate emerging technologies (deep-ultraviolet laser disinfection, AI-driven surveillance, differential serology) with explicit evidence grading. A full-chain, multi-layered system from the aircraft cabin to isolation ward, guided by the 4P Framework, can ensure imported cases remain contained clinical events rather than triggers of hospital-based outbreaks.
China is experiencing rapid population aging and a growing burden of disability, creating urgent demand for sustainable long-term care systems. In response, China has progressively developed a long-term care insurance system since the launch of national pilot programs in 2016. China's long-term care insurance has evolved through three major stages: Pilot launch phase (2016-2019), Expansion phase (2020-2025), and Comprehensive implementation phase (2026-present). The system has significantly expanded coverage, improved access to long-term care for severely disabled older adults, reduced the family caregiving burden, and promoted the transformation of elder care from a family-based responsibility to a shared social responsibility. However, substantial structural challenges remain. These include heavy dependence on medical insurance funds, lack of a sustainable financing mechanism, regional disparities in disability assessment standards, a dearth of professional caregivers, fragmented governance structures, and inadequate digital supervision systems. Looking forward, China's long-term care insurance is expected to transition from a supplementary medical insurance arrangement toward an integrated social care security system. Future reforms should focus on establishing diversified financing mechanisms, unified disability assessment standards, delivery of community-centered care, integrated health and social care governance, and digitalized regulatory systems. China's experience may provide an important policy reference for other rapidly aging middle-income countries facing growing long-term care demands.
Previous studies have suggested that low to moderate alcohol exposure can extend Caenorhabditis elegans (C. elegans) lifespan, but early molecular mechanisms linking ethanol exposure to longevity have not been fully characterized. Here, we investigated how ethanol treatment affects transcriptional networks in L4-stage C. elegans by time-resolved RNA-seq. L4-stage C. elegans were exposed to 5% ethanol and time-resolved RNA-seq was performed after 1, 4, and 20 hours in solution cultures, followed by differential gene expression and KEGG pathway-based Gene Set Enrichment Analysis. At 1 hour, GSEA analysis showed significant enrichment of genes in the Longevity regulating pathway (worm) with elevated expression. Core-enrichment genes exhibited coordinated upregulation of redox-defense modules, including glutathione S-transferases (gst) and p38 MAPK components (pmk-2/pmk-3), consistent with upregulation of SKN-1/Nrf2-related stress-response genes. Detoxification (gpx and fmo families) and lipid-remodeling genes were enriched at 1 hour. By 4 hours, sod-3, a canonical DAF-16/FOXO target, was clearly upregulated, suggesting engagement of DAF-16-associated antioxidant responses, whereas Peroxisome and TGF-β signaling pathways were significantly downregulated. Together, these findings provide transcriptomic insights into a temporally structured longevity-associated response to ethanol exposure, in which early detoxification and antioxidant programs, together with membrane-lipid remodeling, are followed by DAF-16-associated gene induction and repression of peroxisome- and development-related signaling. These pathway-level changes highlight candidate biological processes potentially associated with ethanol-linked lifespan modulation in C. elegans.
Advances in biological sciences and technology have continuously reshaped the questions that researchers are able to address. Over the past several decades, developments in DNA sequencing, mass spectrometry, genome analysis, and omics technologies have transformed not only biomedical research itself, but also the interpretation of observations that previously remained unresolved because of technical limitations. This Editorial reflects on how evolving technologies allow long-standing scientific questions to be revisited across generations of research. Two examples illustrate this process. One concerns the structural re-analysis of a Streptomyces lectin first studied in the 1970s, whose molecular features could only later be clarified through advances in mass spectrometry and expanding genetic databases. The second involves a recent transcriptomic re-examination of ethanol-associated lifespan responses in Caenorhabditis elegans, where modern RNA-seq approaches provided pathway-level insights that were not technically accessible in earlier studies. Together, these examples highlight that scientific progress often emerges not only from asking new questions, but also from revisiting unresolved observations using new technologies and perspectives.
Confocal laser endomicroscopy (CLE) is a critical modality for the early, minimally invasive diagnosis of intraluminal diseases. However, its clinical translation is constrained by the inherent optical-mechanical trade-offs between numerical aperture (NA), probe diameter, and clinical maneuverability. Achieving high-performance imaging within the strict dimensional limits of standard biopsy channels remains a significant technical bottleneck. To address these challenges, we propose a clinically constrained optical design strategy. This integrated design approach incorporates anatomical boundary constraints directly into the optical optimization process. Based on this method, the developed miniature immersion objective achieved a 0.78 μm lateral resolution across a 300 μm field of view, while the integrated pCLE probe maintained a 1.1 μm lateral resolution. This system realizes stable cellular-level imaging under constrained geometry. It is bending-compatible and clinically deployable. Animal experiments and representative histology-correlated clinical gastric images demonstrated the feasibility of resolving tissue microstructures and clinically relevant mucosal abnormalities, supporting the translational potential of the integrated pCLE probe.
Liver transplantation has long been the definitive treatment for end-stage liver diseases, and yet its clinical use remains constrained by donor shortages, surgical risks, and the burden of lifelong immunosuppression. Emerging regenerative strategies, and particularly chemically induced liver progenitors (CLiPs), are reshaping this paradigm by enabling functional restoration rather than organ replacement. CLiP technology utilizes small-molecule-mediated partial reprogramming of mature hepatocytes into proliferative progenitor-like cells, which can be expanded and re-differentiated into functional hepatic lineages. This commentary discusses the conceptual shift from replacement to regeneration, it evaluates the clinical positioning of CLiP-based therapies, and it highlights key translational challenges. Rather than serving as a complete substitute for liver transplantation, such approaches may significantly reduce transplant demand by restoring critical hepatic function in selected patients.
Oncolytic adenovirus H101 has shown antitumor activity in hepatocellular carcinoma (HCC), but the molecular determinants of treatment response remain unclear. In this study, a Hepa1-6 subcutaneous tumor model was established in C57BL/6 mice and treated with intratumoral H101, followed by integrated transcriptomic and proteomic analyses to identify candidate genes associated with H101 response. PRXL2B was selected for further investigation using public multi-omics datasets, tissue microarray-based immunohistochemistry, in vitro functional assays, mechanistic analyses, and in vivo validation experiments. Integrated multi-omics analyses identified PRXL2B as a candidate gene downregulated after H101 treatment. Public datasets and tissue-based validation further showed that PRXL2B was upregulated in HCC tissues. In MHCC97H and HCCLM3 cells, PRXL2B knockdown inhibited proliferation, migration, and invasion, promoted apoptosis and cell-cycle arrest, and enhanced the antitumor effect of H101. Mechanistically, PRXL2B silencing reduced AKT phosphorylation and PD-L1 expression. In vivo, PRXL2B knockdown suppressed tumor growth, and the combination of PRXL2B knockdown and H101 produced the strongest antitumor effect. These findings indicate that PRXL2B promotes malignant phenotypes in HCC and may modulate H101 efficacy through the PI3K/AKT/PD-L1 axis. Targeting PRXL2B may therefore represent a potential strategy to enhance the therapeutic efficacy of oncolytic virus therapy in HCC.
Hepatitis B virus (HBV) infection remains a major global health burden, affecting approximately 296 million people worldwide, and yet progress in mechanistic studies and development of antivirals has been limited by the lack of physiologically relevant and sustainable in vitro models. This study established a human induced pluripotent stem cell (hiPSC)-derived multilineage hepatic organoid system that robustly supports the complete HBV life cycle, including viral entry, replication, covalently closed circular DNA (cccDNA) formation, antigen secretion, and production of infectious progeny virus. These organoids exhibit stable expression of sodium taurocholate cotransporting polypeptide (NTCP), a key receptor for HBV entry, and remain viable long term under infection conditions for at least 20 days, with sustained secretion of HBsAg and HBeAg. Importantly, the model recreates key pathological features of chronic HBV infection, including downregulation of hepatocyte functional genes (e.g., ALB and CYP3A4) and induction of fibrosis-associated markers such as COL1A1, reflecting early extracellular matrix remodeling. Moreover, results indicated the utility of this platform in the evaluation of antivirals. Treatment with tenofovir effectively reduced viral DNA and antigen production without affecting cccDNA levels, whereas bulevirtide resulted in stage-specific inhibition of viral entry, highlighting the model's capacity to resolve mechanism-of-action differences. At the same time, drug-induced hepatotoxicity was assessed within the same system. Collectively, this hiPSC-derived hepatic organoid model provides a scalable and physiologically relevant platform that bridges the gap between conventional cell culture and in vivo systems, offering a powerful tool for studying HBV pathogenesis, host-virus interactions, and preclinical antiviral discovery.
