Search Results (337)

Background: Hepatocellular carcinoma (HCC) patients without microvascular invasion (MVI) face significant postoperative early recurrence (ER) risks, yet prognostic determinants remain understudied. Existing models often rely on linear assumptions. This study aimed to develop and validate an interpretable machine learning model using routine clinical parameters to predict early recurrence (ER) in MVI-negative HCC patients. Methods: We retrospectively analyzed 578 MVI-negative HCC patients undergoing radical resection. Seven machine learning (ML) algorithms were systematically benchmarked using clinical/laboratory/imaging features optimized via recursive feature elimination (RFE) and hyperparameter tuning. Model interpretability was achieved via SHapley Additive exPlanations (SHAP). Results: The CatBoost model demonstrated superior performance (AUC: 0.7957, Accuracy: 0.7290). SHAP analysis identified key predictors: tumor capsule absence, elevated HBV-DNA and CA125 levels, larger tumor diameter, and lower body weight significantly increased ER risk. Individualized SHAP force plots enhanced clinical interpretability. Conclusions: The CatBoost model exhibits robust predictive performance for ER in MVI-negative HCC, offering a clinically interpretable tool for personalized risk stratification and optimization of postoperative management strategies. Full article

Virus-associated hepatocellular carcinoma (HCC) remains a major global health burden despite effective antiviral therapies. Chronic infection with hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) promotes malignant transformation through overlapping pathways of fibrosis, immune dysregulation, and microenvironmental remodeling. YKL-40, a glycoprotein secreted by hepatic stellate cells, hepatocytes under stress, macrophages, and endothelial cells, has emerged as a marker that reflects stromal activation rather than direct hepatocyte injury. Its expression is reinforced by profibrotic and angiogenic circuits, and circulating concentrations correlate with advanced fibrosis, residual risk after viral suppression, and oncologic outcomes. This review synthesizes current evidence on YKL-40 across HBV, HCV, and HDV cohorts, with emphasis on its role in bridging molecular mechanisms to clinical applications. We examine its utility in non-invasive fibrosis assessment, longitudinal monitoring after antiviral therapy, and prognostic modeling in HCC. Particular attention is given to its potential in the liver transplant pathway, where YKL-40 may refine eligibility beyond morphology, inform bridging therapy response, and predict post-transplant recurrence or graft fibrosis. Remaining challenges include its lack of disease specificity, assay variability, and limited multicenter validation. Future integration of YKL-40 into multimarker, algorithm-based frameworks could enable risk-adaptive strategies that align surveillance and transplant decisions with the evolving biology of virus-associated liver disease. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

Core fucose is one of the most important glycans in HBV infection. In this study, we investigated whether Pholiota squarrosa lectin (PhoSL), a lectin that specifically binds to core fucose, exerts an inhibitory effect in an HBV infection model of normal human hepatocytes. Similarly to previous studies using hepatocellular carcinoma cells (HepG2-C4), the coexistence of PhoSL during HBV infection inhibited HBe antigen production and HBV cccDNA in normal human hepatocytes in a PhoSL concentration-dependent manner. Furthermore, this effect of PhoSL was found to be able to suppress HBe antigen production in a treatment period-dependent manner, even when PhoSL was administered after HBV infection. Our previous research has revealed that the mechanism by which PhoSL inhibits HBV infection is through physical inhibition by binding to the HBV receptor and inhibition of HBV entry into cells by inhibiting the phosphorylation of EGFR, a co-receptor for NTCP. Furthermore, this study suggested that PhoSL may also inhibit HBV proliferation in cells through other mechanisms that require further investigation. PhoSL is a lectin, derived from edible Pholiota squarrosa (shaggy scalycap) mushrooms, that is resistant to acid and heat. In addition, it has a low molecular weight and can be chemically synthesized, so it is expected to be used clinically as a new carbohydrate therapy for HBV in the future. Full article

Global warming has made water resources more uneven in space and time, making water management harder. This study used the HBV-XGBoost model to see how climate change affects runoff in the Xiangxi River Basin. The HBV model simulated water processes, and XGBoost improved predictions by handling complex relationships. This study used the SDSM to create climate data for 2025–2100 and looked at runoff trends under different emission scenarios. The HBV-XGBoost model performed better than the HBV model in simulating runoff. Future predictions showed big differences in runoff trends under various SSP scenarios in the 2040s and 2080s. For example, under SSP585, the ACCESS-CM2 model projected a May runoff increase from 1527.52 m³/s to 2344.42 m³/s by the 2080s, and ACCESS-ESM1-5 projected an increase from 1462.11 m³/s to 2889.58 m³/s. All GCMs predicted a large rise in annual runoff under SSP585 by the 2080s, with FGOALS-g3 showing the highest growth rate of 76.54%. The model accurately simulated runoff changes and provided useful insights for adapting water management to climate change. However, this study has limitations, including uncertainties in machine learning models, potential input data biases, and varying applicability under different conditions. Future work should explore more climate models and downscaling methods to improve accuracy and consider local policies to better address climate impacts on water resources. Full article

Background/Objectives: Identifying dietary factors influencing liver cancer is crucial for developing preventive measures. While tea polyphenols have demonstrated cancer-preventive activities in animal models, the evidence in humans is not definitive. This study aims to explore the association between tea consumption and liver cancer, as well as the interaction between tea drinking and other risk factors, in China, a country with a high incidence of liver cancer and substantial tea consumption. Methods: A population-based case–control study was conducted in Jiangsu Province from 2003 to 2010. Socio-demographic data, history of tea consumption, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were evaluated. Unconditional logistic regression was used to examine the associations between tea consumption and the odds of liver cancer. Potential interactions between tea consumption and other major liver cancer risk factors were assessed. Results: A total of 2011 incident liver cancer cases and 7933 controls were included in the analysis. Regular tea drinking showed an inverse association with the risk of liver cancer compared with those who never drank tea (OR: 0.79; 95% CI: 0.63–0.99). Current tea drinking showed an inverse association with liver cancer (OR: 0.51; 95% CI: 0.39–0.66), while former tea drinking showed a positive association (OR: 3.56; 95% CI: 2.42–5.23). Current tea consumption was inversely associated with liver cancer incidence among both hepatitis B surface antigen (HBsAg) positive (OR: 0.45; 95% CI: 0.28–0.73) and HBsAg negative participants (OR: 0.51, 95% CI: 0.36–0.73), among both never and ever tobacco smokers, ever alcohol drinkers (OR: 0.46; 95% CI: 0.33–0.63), and among those without family history of liver cancer. Multiplicative and additive interactions were observed between tea drinking and HBsAg, alcohol consumption, and history of raw water drinking. Conclusions: Tea consumption is inversely associated with the development of primary liver cancer, with potential interactions involving HBV infection, alcohol consumption, and raw (unsafe) water drinking. Increasing tea consumption—particularly among high-risk populations such as individuals who consume alcohol—may serve as an additional preventive measure for liver cancer. This should be considered alongside established strategies, including HBV vaccination, alcohol cessation, and avoidance of drinking raw water, to help reduce liver cancer risk. Full article

Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 µg of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB. Full article

Chronic infection with the hepatitis B virus (HBV) results in over 1 million deaths annually. Although currently licensed treatments, including pegylated interferon-α and nucleoside/nucleotide analogs, can inhibit viral replication, they rarely eradicate covalently closed circular DNA (cccDNA) reservoirs. Moreover, vaccination does not offer therapeutic benefit to already infected individuals or non-responders. Consequently, chronic infection is maintained by the persistence of cccDNA in infected hepatocytes. For this reason, novel therapeutic strategies that permanently inactivate cccDNA are a priority. Obligate heterodimeric transcription activator-like effector nucleases (TALENs) provide the precise gene-editing needed to disable cccDNA. To develop this strategy using a therapeutically relevant approach, TALEN-encoding mRNA targeting viral core and surface genes was synthesized using in vitro transcription with co-transcriptional capping. TALENs reduced hepatitis B surface antigen (HBsAg) by 80% in a liver-derived mammalian cell culture model of infection. In a stringent HBV transgenic murine model, a single dose of hepatotropic lipid nanoparticle-encapsulated TALEN mRNA lowered HBsAg by 63% and reduced viral particle equivalents by more than 99%, without evidence of toxicity. A surveyor assay demonstrated mean in vivo HBV DNA mutation rates of approximately 16% and 15% for Core and Surface TALENs, respectively. This study presents the first evidence of the therapeutic potential of TALEN-encoding mRNA to inactivate HBV replication permanently. Full article

Southeast Asia relies heavily on hydropower from dams and reservoir projects, but this dependence comes at the cost of ecological damage and increased vulnerability to extreme events. This dilemma necessitates a choice between continued dam development and adopting alternative renewable options. Concerns over these environmental impacts have already led to halts in dam construction across the region. This study assesses the potential of run-of-river hydropower plants (RHPs) across 199 hydrometric stations in Mainland Southeast Asia (MSEA). The assessment utilizes power duration curves for the historical period and projections from the HBV hydrological model, which is driven by an ensemble of 31 climate models for future scenarios. Energy production was analyzed at four levels (minimum, maximum, balanced, and optimal) for both historical and future periods under varying Shared Socioeconomic Pathways (SSPs). To promote sustainable development, environmental flow constraints and carbon dioxide (CO₂) emissions were evaluated for both historical and projected periods. The results indicate that the aggregate energy production potential during the historical period ranges from 111.15 to 229.62 MW (Malaysia), 582.78 to 3615.36 MW (Myanmar), 555.47 to 3142.46 MW (Thailand), 1067.05 to 6401.25 MW (Laos), 28.07 to 189.77 MW (Vietnam), and 566.13 to 2803.75 MW (Cambodia). The impact of climate change on power production varies significantly across countries, depending on the level and scenarios. At the optimal level, an average production change of −9.2–5.9% is projected for the near future, increasing to 15.3–19% in the far future. Additionally, RHP development in MSEA is estimated to avoid 32.5 Mt of CO₂ emissions at the optimal level. The analysis further shows avoidance change of 8.3–25.3% and −8.6–25.3% under SSP245 and SSP585, respectively. Full article

The global burden of hepatitis B virus (HBV) remains high, with ongoing concerted efforts to eliminate viral hepatitis as a public health concern by 2030. The absence of curative treatment against HBV makes it an active area of research to further study HBV pathogenesis. In vitro cell culture systems are essential in exploration of molecular mechanisms for HBV propagation and the development of therapeutic targets for antiviral agents. The lack of an efficient cell culture system is one of the challenges limiting the development and study of novel antiviral strategies for HBV infection. However, the evolution of cell culture systems to study HBV pathogenesis and treatment susceptibility in vitro has made a significant contribution to public health. The currently available cell culture systems to grow HBV have their advantages and limitations, requiring further optimization. The discovery of sodium taurocholate co-transporting polypeptide (NTCP) as a receptor for HBV was a major breakthrough for the development of a robust cell model, allowing the study of de novo HBV infection through NTCP expression in the HepG2 hepatoma cell line. This review is aimed at highlighting the evolution of cell culture systems to study HBV pathogenesis and in vitro treatment susceptibility. Full article

This study evaluates the impact of precipitation ensembles on flood hazards in the Ouémé River Basin by coupling the hydrological HBV and hydrodynamic HEC–RAS model. Both models were calibrated and validated to simulate hydrological and hydraulic processes. Meteorological and hydrometric data from 1994 to 2016, along with flood maps and DEM are used. Evapotranspiration data are calculated using Hargreaves–Samani formula. The coupling HBV–HEC–RAS models enabled the generation of ensemble hydrographs, flood maps, flood probability maps and additional statistics in West Africa for the first time, offering a comprehensive understanding of flood dynamics under uncertainty. Ensemble hydrographs and maps obtained enhance decision-making by showing discharge scenarios, spatial flood variability, prediction reliability, and probabilities, supporting targeted flood management and resource planning under uncertainty. The findings underline the need for a comprehensive strategy to mitigate both common and rare flood events while accounting for spatial uncertainties inherent in hydrological and hydraulic modeling. Full article

Climate change has intensified the melting of glaciers and permafrost in high-altitude cold regions, leading to more frequent extreme hydrological events. This has caused significant variations in the spatiotemporal distribution of meltwater runoff from the headwater cryosphere, posing a major challenge to regional water security. In this study, the HBV hydrological model was set up and driven by CMIP6 global climate model outputs to investigate the multi-scale temporal variations of runoff under different climate change scenarios in the Tuotuo River Basin (TRB) within the source region of the Yangtze River (SRYR). The results suggest that the TRB will undergo significant warming and wetting in the future, with increasing precipitation primarily occurring from May to October and a notable rise in annual temperature. Both temperature and precipitation trends intensify under more extreme climate scenarios. Under all climate scenarios, annual runoff generally exhibits an upward trend, except under the SSP1-2.6 scenario, where a slight decline in total runoff is projected for the late 21st century (2061–2090). The increase in total runoff is primarily concentrated between May and October, driven by enhanced rainfall and meltwater contributions, while snowmelt runoff also shows an increase, but accounts for a smaller percentage of the total runoff and has a smaller impact on the total runoff. Precipitation is the primary driver of annual runoff depth changes, with temperature effects varying by scenario and period. Under high emissions, intensified warming and glacier melt amplify runoff, while low emissions show stable warming with precipitation dominating runoff changes. Full article

Accurate runoff simulation and prediction are crucial for water resources management, especially under the impact of climate change. In this study, a multi-physics ensemble Bayesian model averaging (MPE-BMA) model is developed to improve runoff prediction accuracy by integrating a soil and water assessment tool (SWAT), hydrologiska byråns vattenbalansavdelning (HBV) model, and Bayesian model averaging (BMA) into a general framework. The MPE-BMA model integrates the strengths of the SWAT and HBV models. This approach enhances the robustness of simulation outputs and reduces uncertainties from single-model methods. MPE-BMA is subsequently employed to simulate and predict runoff for the upper reaches of Xiangxi River Basin (XXRB) in China, where four general circulation models (GCMs) and three shared socioeconomic pathways (SSP126, SSP245, and SSP585) are considered. Multiple statistical metrics (R², NSE, and RMSE) prove that the MPE-BMA model outperforms the single models of SWAT and HBV. Results reveal that higher-emission scenarios generally lead to significant decreases in runoff, particularly by the 2080s. Specifically, under SSP585, runoff is projected to decrease by approximately 4.61–12.68% by the 2040s and 5.96–11.28% by the 2080s compared to the historical period. From the perspective of monthly and seasonal runoff changes, the peak runoff is projected to shift from June to May by the 2080s. Additionally, under SSP585, spring and summer runoffs tend to significantly increase, while winter runoff decreases sharply, leading to wetter summers and drier winters. These findings underscore the importance of enhancing water use efficiency, upgrading hydropower stations, and implementing watershed management practices to ensure sustainable water resources management in the XXRB amidst climate change. Full article

Hepatitis B is a serious infectious disease that threatens the health of all mankind. In this study, we isolated and extracted hydroxytyrosol from Lindernia ruellioides with anti-hepatitis B virus (HBV) activity. The structure of hydroxytyrosol was identified by the nuclear magnetic resonance technique. HepG2.2.15 cell models were used to detect the anti-HBV activity and liver protection of hydroxytyrosol in vitro. Hydroxytyrosol can inhibit hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg). The IC₅₀ values of HBsAg and HBeAg were 4.02 mg/L and 5.19 mg/L, respectively. At the highest concentration of hydroxytyrosol, the inhibition rates of supernatant and intracellular HBV DNA were 75.99% and 66.33%, respectively. Hydroxytyrosol was less toxic to normal human hepatocytes. Molecular docking showed that hydroxytyrosol was bound to three amino acid residues of HBV polymerase with a binding energy of −7.0 kcal/mol. This study provided data for the development and utilization of Lindernia ruellioides and the research and development of anti-hepatitis B virus drugs. Full article

Human viral infections remain a significant global health challenge, contributing to a substantial number of cancer cases worldwide. Among them, infections with oncoviruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are key drivers of hepatocellular carcinoma (HCC). Despite the availability of an effective HBV vaccine since the 1980s, millions remain chronically infected due to the persistence of covalently closed circular DNA (cccDNA) as a reservoir in hepatocytes. Current antiviral therapies, including nucleos(t)ide analogs and interferon, effectively suppress viral replication but fail to eliminate cccDNA, underscoring the urgent need for innovative therapeutic strategies. Direct-acting antiviral agents (DAAs), which have revolutionized HCV treatment with high cure rates, offer a promising model for HBV therapy. A particularly attractive target is the intrinsically disordered region (IDR) of the HBx protein, which regulates cccDNA transcription, viral replication, and oncogenesis by interacting with key host proteins. DAAs targeting these interactions could inhibit viral persistence, suppress oncogenic signaling, and overcome treatment resistance. This review highlights the potential of HBx-directed DAAs to complement existing therapies, offering renewed hope for a functional HBV cure and reduced cancer risk. Full article