Hepatocellular carcinoma (HCC) stands as one of the most prevalent and deadliest malignancies on a global scale. Its complex pathogenesis arises from multifactorial etiologies, including viral infections, metabolic syndromes, and environmental carcinogens, all of which drive genetic and molecular aberrations in hepatocytes. This intricate condition is associated with multiple causative factors, resulting in the abnormal activation of various cellular and molecular pathways. Given that HCC frequently manifests within the context of a compromised or cirrhotic liver, coupled with the tendency of late-stage diagnoses, the overall prognosis tends to be unfavorable. Systemic therapy, especially conventional cytotoxic drugs, generally proves ineffective. Despite advancements in therapeutic interventions, conventional treatments such as chemotherapy often exhibit limited efficacy and substantial systemic toxicity. In this context, nanomedicine, particularly lipid-based nanoparticles (LNPs), has emerged as a promising strategy for enhancing drug delivery specificity and reducing adverse effects. This review provides a comprehensive overview of the molecular and metabolic underpinnings of HCC. Furthermore, we explored the role of lipid-based nano-formulations including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers in targeted drug delivery for HCC. We have highlighted recent advances in LNP-based delivery approaches, FDA-approved drugs, and surface modification strategies to improve liver-specific delivery and therapeutic efficacy. It will provide a comprehensive summary of various treatment strategies, recent clinical advances, receptor-targeting strategies and the role of lipid composition in cellular uptake. The review concludes with a critical assessment of existing challenges and future prospects in nanomedicines-driven HCC therapy.

Pien Tze Huang (PTH), a well-established traditional Chinese medicine compound, has exhibited anti-hepatic fibrosis properties both in vitro and in vivo animal models, but the randomized clinical trials to evaluate anti-hepatic fibrosis efficacy of PTH are deficient. Chronic hepatitis B (CHB) is a leading cause of hepatic fibrosis in China. Although antiviral therapies have demonstrated significant effectiveness in arresting the progression of fibrotic disease, complete regression of established fibrosis is limited to only a subset of treated patients.

To assess the efficacy of PTH in improving hepatic fibrosis in CHB patients.

We conducted a randomized, double-blind, placebo-controlled clinical trial involving 144 CHB patients with hepatic fibrosis. This study was carried out from September 2020 to April 2023. (Clinical Trials Registration: ChiCTR2000035128) METHODS: CHB patients with an Ishak score of 2-5 points were recruited from ten hospitals across China. Participants were randomized in 1:1 ratio to receive either oral PTH (0.6 g per dose, three times/day) or placebo for 48 weeks, in addition to the standard treatment of entecavir (0.5 mg/day). The primary endpoint was the change in Ishak score. Secondary outcomes included changes in Knodell HAI score, liver stiffness measurement, AST- to -platelet ratio index, Fibrosis-4 index and hepatic function indices.

Of the 144 randomized patients, 142 patients (71 in the PTH group and 71 in the placebo group) were included in the primary analysis. The PTH group exhibited lower Ishak score compared to the control group (2.37 ± 0.94 vs. 2.87 ± 1.04, F = 6.072, p = 0.015). Notably, in treatment-naive patients, the PTH group showed significant improvement in Ishak score post-treatment compared with the control group (2.13 ± 0.72 vs. 2.74 ± 1.07, F = 6.336, p = 0.014). However, no significant changes were observed in these parameters among patients already receiving antiviral therapy.

The combination of PTH and entecavir demonstrates significant improvement in hepatic fibrosis among CHB patients, especially those who are treatment-naive patients.

Background: Hepatitis B virus infection is the most prevalent cause of serious liver infection. During pregnancy, hepatitis B virus has a higher vertical transmission rate that may later impair the physical and cognitive development of a child. The main objective of this study was to investigate the seroprevalence of hepatitis B viral infection and identify the associated factors among pregnant women attending antenatal care at Demartino Hospital.

This is an institution-based, cross-sectional study that involved pregnant women to ascertain the seroprevalence of HBsAg among them between January and February 2024. Participants were interviewed for data using an interviewer-administered structured questionnaire. Each participant had a venous blood sample of five milliliters taken. Plasma was extracted from the blood samples and subjected to investigation using the advanced quality one-step HBsAg test kit, If the results were positive, additional testing using ELISA was conducted to determine hepatitis seroprevalence. The data were analyzed by SPSS, version 25, and both bivariate and multivariate logistic regression analyses were performed to assess the independent predictors of HBsAg seroprevalence, at a p-value of < 0.05.

The overall sero-prevalence of HBV among the pregnant women was 13.3%. History of blood transfusion (AOR = 4.271; 95% CI = 1.488-12.254), history of abortion (AOR = 3.822; 95% CI = 2.009-7.271), family history of hepatitis B infection (AOR = 5.104; 95% CI = 1.900-13.713), and history of sharing sharp materials (AOR = 3.427; 95% CI = 1.153-10.186) were found to be independently significantly associated with HBsAg seropositivity.

In WHO classification, the seroprevalence rate of HBsAg among pregnant women in this present study was highly endemic. History of abortion, history of blood transfusion, history of shared sharp materials, and family history of hepatitis B infection were risk factors which significantly predict HBsAg seropositivity. The Federal Ministry of Health needs to establish hepatitis B health education campaigns, Screening Programmes, Vaccination Programs, and treatment should be given for those already infected to save their lives and prevent Mother to Child transmission.

Hepatocellular carcinoma (HCC) is the sixth most prevalent malignancy worldwide, and represents a major global health challenge. While surgical resection at early stages offers favorable prognosis with 5-year survival rates exceeding 70%, the clinical reality in China reveals a contrasting scenario, where over 60% of patients present with advanced disease, resulting in a dramatic decline in 5-year survival to below 12.5%. The immunological landscape plays a pivotal role in HCC pathogenesis and progression, comprising two complementary arms: the innate immune system's rapid-response mechanism for immediate tumor surveillance and the adaptive immune system's antigen-specific targeting with immunological memory capabilities. Emerging evidence has highlighted ubiquitination, a sophisticated post-translational modification system, as a critical regulator of immune homeostasis in HCC pathogenesis. This molecular process exerts precise control through three primary mechanisms: (1) Modulation of immune cell activation thresholds via proteasomal degradation of signaling proteins, (2) Orchestrating immune cell differentiation through stability regulation of transcriptional factors, and (3) Maintenance of immune tolerance by dynamic modification of checkpoint regulators. Such multifaceted regulation affects both innate immune recognition pathways (e.g., NF-κB and STING signaling) and adaptive immune effectors (particularly T cell receptor signaling cascades). This comprehensive review establishes a threefold Objective: First, to elucidate the mechanistic interplay between ubiquitination networks and HCC-related immune dysregulation; Second, to systematically analyze how innate immune-associated ubiquitination events drive hepatocarcinogenesis through chronic inflammation modulation; and third, to critically evaluate recent clinical advances combining ubiquitination-targeted therapies (e.g., proteasome inhibitors and E3 ligase modulators) with immunotherapeutic regimens. Our synthesis revealed that strategic manipulation of ubiquitination pathways can potentiate PD-1/PD-L1 blockade efficacy while mitigating therapeutic resistance, particularly through modulation of tumor-associated macrophages and exhausted T cell populations. By integrating fundamental mechanistic insights with translational clinical data, this review provides a conceptual framework for the development of next-generation diagnostic biomarkers and rational therapeutic combinations. The proposed strategy of ubiquitination-immune axis modulation holds significant potential to transform current HCC management paradigms, offering new avenues for precision immunotherapy for this challenging malignancy.

Currently, nanomedicines have been widely applied in the treatment of various types of tumors. However, due to the complexity of the tumor microenvironment, conventional nanomedicines often exhibit poor efficacy, insufficient site specificity, and susceptibility to off-target effects. In contrast, dual-ligand nanomedicines demonstrate superior targeting ability and drug penetration in tumor therapy. These nanomedicines are equipped with two ligands on their surface, enabling targeting of specific receptors on the same or different cells. The specific binding between ligands and receptors significantly enhances the selectivity and targeting of dual-ligand nanomedicines towards tumors. This review systematically describes the preparation of dual-ligand nanomedicines, the influencing factors, and the types of delivered drugs, focusing on the application of dual-ligand nanomedicines in targeting the treatment of various tumors. We highlight the comprehensiveness of dual-ligand nanomedicines for the treatment of tumors, including glioblastoma, lung cancer, breast cancer, gastric cancer, and many other types of tumors. Finally, the possible challenges for the future development of dual-ligand nanomedicines in terms of preparation, clinic, and safety are further analyzed. We look forward to exploring dual-ligand nanomedicines in greater depth to provide references for their future development and clinical applications.

Hepatocellular carcinoma (HCC) is recognized for its high growth rate, high degree of invasiveness, and tendency to spread, leading to a significant number of deaths. In the course of studying the transcriptome of HCC tissues, the protein coiled-coil domain-containing 110 (CCDC110) was identified. By employing tandem mass tag (TMT) quantitative proteomics, this research identified transforming growth factor beta receptor 1 (TGFBR1) as a potential target influenced by CCDC110. The purpose of this study was to examine the role of CCDC110 in the growth and invasion of HCC and to identify new potential targets for the treatment of HCC.

In vitro and in vivo experiments were conducted to investigate the role and mechanism of CCDC110 in promoting the malignant behaviors of hepatocellular carcinoma through the regulation of TGFBR1.

We determined that the mRNA and protein levels of CCDC110 are elevated in hepatocellular carcinoma tissues and cell lines, which is correlated with a worse patient prognosis. CCDC110 enhances the proliferation of hepatocellular carcinoma cells, reduces their apoptosis, and increases their migration and invasion capabilities. In the cytoplasm, CCDC110 interacts with TGFBR1, enhancing stability of TGFBR1, promoting proliferation, and reducing the apoptosis, migration, and invasion of hepatocellular carcinoma cells through TGFBR1 both in vivo and in vitro. The CCDC110-TGFBR1 axis stimulates EMT, thereby enhancing the malignant biological behavior of hepatocellular carcinoma by activating the TGF-β/SMAD signaling pathway. The protein levels of CCDC110/TGFBR1 in hepatocellular carcinoma tissues are highly expressed and positively correlated. A combined analysis of CCDC110 and TGFBR1 provides improved guidance for the prognosis of patients with hepatocellular carcinoma.

CCDC110 is highly expressed in hepatocellular carcinoma tissues and cell lines, and the CCDC110-TGFBR1 axis facilitates EMT and the malignant biological behavior of hepatocellular carcinoma through the activation of the TGF-β/SMAD signaling pathway.

Multiple risk factors for HCC have been identified, however, not all individuals exposed to these factors will develop HCC, suggesting that genetic predisposition also contributes to hepatocarcinogenesis. Despite the identification of numerous single-nucleotide polymorphisms (SNPs) in HCC risk loci and several protein-coding susceptibility genes through genome-wide association studies (GWAS), the potential mechanisms are still not fully understood. In this study, we used The Updated Integrative Functional Genomics Approach (TUIFGA) method to investigate functional causal genetic variants in HCC. We identified one SNP rs399283 associated with HCC risk, which locates in CREB1 binding motif of the LYRM4 intronic enhancer. The rs399283 genetic variation may affect the binding of CREB1 to the enhancer of the oncogene LYRM4 in HCC, leading to allele-specific gene expression changes. Mechanistically, elevated levels of LYRM4 enhance the enzymatic activities of succinate dehydrogenase (SDH), thereby promoting fumarate accumulation in cells and playing a key role in HCC tumorigenesis. Our results offer valuable insights into the genetic complexity of HCC and emphasize the significant potential of fumarate regulation as a novel approach for cancer therapy.

Mongolia has the highest incidence of liver cancer worldwide, largely driven by a high prevalence of hepatitis virus infections. Mutations in oncogenes and tumor suppressor genes provide valuable insights into the molecular mechanisms of hepatocellular carcinoma (HCC).

This study aimed to investigate the prevalence of mutations in key oncogenes and tumor suppressor genes in Mongolian HCC patients and to explore their molecular mechanisms, particularly in relation to hepatitis virus infections.

We analyzed 55 tumor tissue samples from Mongolian HCC patients (2019-2021), identifying mutations in TP53, CTNNB1, AXIN1, KRAS, and JAK1 through sequencing. Western blotting was used to assess β-catenin and p53 protein levels. Our findings showed p53 overexpression in tumors with TP53 mutations (F270I and S362S), while mutations such as R213* and a short-sequence deletion upstream of intron 7 produced premature stop codons, resulting in truncated p53 and loss of tumor suppressor function. β-catenin accumulation was observed in tumors with CTNNB1 mutations (D32N/Y, S33C/Y, S34V, S37P, T41A, and S45P). CCND1 expression, a key target of the Wnt/β-catenin pathway, was significantly upregulated in tumors harboring CTNNB1 and AXIN1 mutations (p = 0.02213). Statistical analysis revealed a positive correlation between β-catenin and CCND1 expression levels (r = 0.42703). Hepatitis virus infections were significantly associated with these mutations (p < 0.01), suggesting a link between viral infection and genetic alterations in HCC development. Compared to TCGA data, our cohort displayed a significantly higher mutation frequency (p < 0.001 and p < 0.05), indicating potential regional genetic and environmental influences.

This study provides insights into the molecular mechanisms of HCC in Mongolia, highlighting distinct mutational patterns in TP53, CTNNB1, AXIN1, and KRAS. The association between hepatitis virus infections and these mutations underscores their potential oncogenic impact and may inform future therapeutic strategies for HCC in this population.

Hepatitis B virus (HBV) infects cells by attaching to heparan sulfate proteoglycans (HSPG) and Na+/taurocholate cotransporting polypeptide (NTCP). The endothelial lipase LIPG bridges HSPG and HBV, facilitating HBV attachment. From a randomized peptide expression library, we identified a short sequence binding to LIPG. This identified sequence closely resembled a sequence in the V domain of netrin-1, a protein known to bind heparin through its V domain. We designed two synthetic peptides based on this sequence and found that both synthetic peptides and netrin-1 suppressed HBV infection in chimeric mice with humanized livers and in primary hepatocytes isolated from them. The data reveal an antiviral function of the peptides and netrin-1 in HBV infection that is independent of LIPG lipase activity.

Hepatocellular carcinoma (HCC) frequently involves metabolic reprogramming, which promotes oncogenesis and metastasis. However, the underlying molecular mechanisms remain insufficiently explored. In this study, we aim to investigate the metabolic abnormalities in c-Myc-driven HCC development and their potential therapeutic implications.

RNA sequencing and metabolomics were performed on HCC and adjacent tissues in a murine HCC model established by hydrodynamic tail-vein injection of c-Myc and sgTrp53/Cas9 plasmids. Key catalytic enzyme gene knockout was used to assess tumor formation and murine survival. Gene expression was analyzed using quantitative polymerase chain reaction, immunohistochemistry, and Western blot. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction and luciferase assays verified c-Myc regulation.

RNA sequencing data revealed that the hexosamine biosynthetic pathway was significantly activated in c-Myc-driven HCC. The rate-limiting enzyme GFPT1 (rather than GFPT2) was up-regulated in the first step of this pathway. Knocking out GFPT1 reduces tumor growth and prolongs murine survival. Human specimens showed that GFPT1 was overexpressed in HCC tissues and was associated with advanced Edmondson-Steiner grades and short patient survival. Further luciferase reporter assays confirmed that c-Myc binds directly to the promoter region of GFPT1 and activates its transcription. Subsequent examination of the downstream pathways of the hexosamine biosynthetic pathway showed that the sialic acid synthesis (but not O-GlcNac glycosylation) pathway was enhanced, which was mediated by a key enzyme, N-acetylneuraminic acid synthase. Knockout of N-acetylneuraminic acid synthase also inhibits tumor growth and extends murine survival in c-Myc-driven HCC models.

These findings indicate that the activation of the hexosamine biosynthetic pathway/sialic acid pathway is an important mechanism underlying the development of c-Myc-driven HCC. Inhibitors of GFPT1, along with anti- N-acetylneuraminic acid synthase may offer a promising therapeutic strategy.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to have an influential role in HCC progression and the development of an aggressive phenotype. AEG-1 has been shown to be upregulated in many cancers, including HCC. Studies have shown that it plays a crucial role in the proliferation, invasion and metastasis, and evasion of apoptosis in HCC. Its relationship with proteins and pathways, such as MYC, SND1, PI3K/AKT, and other signaling pathways demonstrates its pertinent role in oncogenic development and relevance as a biomarker and therapeutic target. Recent studies have shown that AEG-1 is present in tumor tissues, and the anti-AEG-1 antibody is detected in the blood of cancer patients, demonstrating its viability as a diagnostic/prognostic marker. This review paper shines light on recent findings regarding the molecular implications of AEG-1, with emphasis on its role of regulating metabolic dysfunction-associated steatohepatitis (MASH), a key predisposing factor for HCC, new treatment strategies targeting AEG-1, and challenges associated with analyzing this intriguing molecule.

Cyclin-dependent kinase 1 (CDK1) has emerged as a critical regulator of cell cycle progression, yet its role in liver fibrosis-associated hepatocellular carcinoma (LF-HCC) remains underexplored. This study aimed to systematically evaluate CDK1's prognostic significance, immune regulatory functions, and therapeutic potential in LF-HCC pathogenesis. Integrated bioinformatics approaches were applied to multi-omics datasets from GEO, TCGA, and TIMER databases. Differentially expressed genes were identified through enrichment analysis and protein-protein interaction networks. Survival outcomes were assessed via Kaplan-Meier analysis, while immune cell infiltration patterns were quantified using CIBERSORT. Molecular docking simulations evaluated CDK1's binding affinity with pharmacologically active compounds (alvocidib, seliciclib, alsterpaullone) using AutoDock Vina. CDK1 demonstrated significant overexpression in LF-HCC tissues compared to normal controls (p < 0.001). Elevated CDK1 expression correlated with reduced overall survival (HR = 2.41, 95% CI:1.78-3.26, p = 0.003) and advanced tumor staging (p = 0.007). Immune profiling revealed strong associations between CDK1 levels and immunosuppressive cell infiltration, particularly regulatory T cells (r = 0.63, p = 0.001) and myeloid-derived suppressor cells (r = 0.58, p = 0.004). Molecular docking confirmed high-affinity binding of CDK1 to kinase inhibitors through conserved hydrogen-bond interactions (binding energy ≤ -8.5 kcal/mol), with alvocidib showing optimal binding stability. This multimodal analysis establishes CDK1 as both a prognostic biomarker and immunomodulatory regulator in LF-HCC pathogenesis. The enzyme's dual role in driving tumor progression and reshaping the immune microenvironment positions it as a promising therapeutic target. Computational validation of CDK1 inhibitors provides a rational basis for developing precision therapies against LF-HCC, bridging translational gaps between biomarker discovery and clinical application.

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the third leading cause of cancer-related mortality, primarily driven by viral infections (HCV, HBV) and steatotic liver diseases (SLD). Despite advances in treatment, early detection and accurate prognosis remain challenging. The Human leukocyte antigen G (HLA-G) molecule is dysregulated in various conditions, including cancers and viral infections. This study aimed to investigate HLA-G's role in viral-related and SLD-driven HCC. We analyzed a cohort of 116 HCC patients and 140 healthy controls to assess HLA-G genetic variants and soluble levels. Results showed significantly higher levels of soluble HLA-G in HCC patients compared to controls (Pc = 0.003). Moreover, overall survival (OS) was significantly lower in patients with the extended HLA-G*01:01:01/UTR-1 haplotype (Log-rank test, p = 0.002), a trend consistent in both HCV and/or HBV-related HCC (p = 0.025) and SLD-related HCC (p = 0.018). Elevated sHLA-G levels were associated with shorter OS across both subgroups (p = 0.034 (HBV/HCV) and p = 0.010 (SLD), respectively). The findings suggest that elevated levels of soluble HLA-G and specific genetic variants are associated with poor prognosis in HCC patients, highlighting the potential of HLA-G as a prognostic biomarker in both viral-related and steatotic liver disease-related HCC.

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). This study aimed to construct a novel nomogram model for predicting the risk of HCC in patients with HBV infection.

This retrospective study analyzed clinical data from healthcare databases in Xiamen, encompassing 5161 adults with HBV infection without HCC and 2819 adults with HBV-related HCC between January 2016 and December 2020. Subsequently, the patients were randomly divided into a training set (n=5586) and testing set (n=2394). The training set was used to identify the risk factors for HCC development and to construct an HCC risk prediction nomogram model. The predictive accuracy of the model was assessed using the receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) in both sets. Furthermore, the performance of the nomogram model was compared with that of the existing models.

Multivariate analysis revealed that age, sex, liver cirrhosis, neutrophil/platelet count ratio (NLR), serum bilirubin (TBIL), aspartate aminotransferase (AST), serum albumin (ALB), serum alpha-fetoprotein (AFP), and HBV DNA were independently associated with HCC. A nomogram model was developed by incorporating these risk factors. The the receiver operating characteristic curve (AUC) of the nomogram model were 0.897 and 0.902 for the training and testing sets, respectively. Analysis of the AUC demonstrated that the nomogram model exhibited significantly enhanced predictive performance for HCC compared to the alternative risk scores in both sets. Furthermore, DCA indicated that the nomogram model provided a broad range of threshold probabilities related to the net clinical benefits. A web-based calculator was developed(https://nomogram-model-hcc.shinyapps.io/DynNomapp/).

The novel nomogram model, which includes age, sex, liver cirrhosis, NLR, TBIL, AST, ALB, AFP, and HBV DNA as factors, precisely predicts the risk of HCC in patients with chronic hepatitis B(CHB) and outperforms the existing models.

Ubiquitination, a critical post-translational modification, plays a pivotal role in regulating protein stability and activity, influencing various aspects of cancer development, including metabolic reprogramming, immune evasion, and tumor progression. However, the specific role of ubiquitination in hepatocellular carcinoma (HCC), particularly in relation to the tumor microenvironment (TME), remains poorly understood. This study aims to systematically explore the role of ubiquitination in shaping the TME of HCC, with a focus on its impact on cancer progression and immune modulation.

We performed bioinformatics analysis by integrating multiple publicly available HCC datasets to assess the ubiquitination status across various cell types in the TME, including plasma cells, fibroblasts, endothelial cells, and epithelial-mesenchymal transition (EMT) cells. Ubiquitination scores were calculated to categorize these cell types, and survival data, along with spatial transcriptomics, were employed to evaluate how different levels of ubiquitination influence HCC progression. In vitro experiments, such as transwell, CCK8, and wound healing assays, were used to further investigate the role of the key ubiquitination gene UBE2C in HCC phenotypes.

Our study revealed that ubiquitination-related genes are significantly upregulated in HCC tissues, with high expression levels correlating with poor prognosis in patients. Pathway analysis showed that these genes are enriched in key processes such as cell cycle regulation, DNA repair, metabolic reprogramming, and p53 signaling. These pathways contribute to the TME by promoting tumor cell proliferation, facilitating matrix remodeling, and enhancing angiogenesis. Notably, UBE2C, a critical ubiquitination enzyme, appears to play a key role in immune evasion, potentially by inhibiting anti-tumor immune responses and reducing the immune system's ability to recognize and eliminate tumor cells. Furthermore, experimental data confirmed that UBE2C overexpression promotes HCC cell proliferation, invasion, and metastasis, further supporting its role in tumor progression and TME remodeling.

This study reveals the multifaceted regulatory roles of ubiquitination in HCC. Ubiquitination not only supports proliferation and anti-apoptotic functions within tumor cells but also promotes tumor progression by modulating the activity of immune and stromal cells. Among all ubiquitination-related genes, UBE2C emerges as a potential prognostic biomarker and therapeutic target in HCC, offering new directions for precision treatment of HCC in the future.

As a chronic condition, liver fibrosis is characterized by diverse etiological factors, and the pivotal event to its pathogenesis is the activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts. Mesenchyme homeobox 1 (MEOX1) is a transcription factors central to cellular development and differentiation. However, the role of MEOX1 signaling in hepatic fibrosis still remains largely unknown. In this study, we investigated the potential role and mechanism of MEOX1 in liver fibrosis using different models in vivo and in vitro. The hepatic expression of MEOX1 exhibited a positive correlation with the degree of fibrosis in patients diagnosed with non-alcoholic steatohepatitis (NASH), as determined through bioinformatics analysis. Furthermore, MEOX1 demonstrated high expression levels in activated HSCs and fibrotic liver tissues induced by methionine and choline-deficient diet (MCD), thioacetamide (TAA), or carbon tetrachloride (CCl4) treatment in C57/BL6 mice. Mechanistically, MEOX1 facilitated HSC activation, proliferation, and migration. The comprehensive analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing data revealed that connective tissue growth factor (CTGF) served as a target gene for MEOX1 in HSCs. Specifically, MEOX1 bound to the promoter region of CTGF and enhanced its transcriptional activity, thereby mediating the exacerbating effect of MEOX1 on hepatic fibrosis. In conclusion, our current findings elucidate the role of MEOX1 in exacerbating hepatic fibrosis progression through transcriptional activation of CTGF. Our findings provide valuable insights into the therapeutic potential of targeting MEOX1 for the treatment of hepatic fibrosis.

Few studies have examined the risk of de novo hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-infected patients with cirrhosis who received interferon (IFN)-free direct-acting antiviral (DAA) therapy relative to patients who received IFN-containing therapy or remained untreated.

To estimate the risk of de novo HCC with DAA treatment in cirrhotic HCV patients compared to no anti-HCV treatment and those treated with IFN-based therapy.

We identified patients with chronic HCV infection and compensated cirrhosis in the US Department of Veterans Affairs healthcare system treated with IFN (2005 to 2013) or DAAs (2013 to 2017). We compared the risk of de novo HCC for patients treated with DAAs, IFN-containing regimens or no treatment after accounting for differences in demographics, alcohol and drug abuse, comorbidities, laboratory values, healthcare utilisation, prior HCV treatment and HCC surveillance.

A total of 53,847 patients contributed to untreated time, 27,147 patients contributed to DAA-treated time (15,641 contributed to both untreated and DAA-treated times) and 6809 patients contributed to IFN-treated time. HCC risk associated with DAA treatment was significantly lower than untreated [adjusted HR: 0.70 (95% CI: 0.65-0.74)]. The risk of HCC was not significantly different for patients treated with DAA compared with those treated with IFN [adjusted HR: 0.98 (95% CI: 0.87-1.10)].

The study shows a reduced risk of de novo HCC among patients with chronic HCV-related compensated cirrhosis who received DAA treatment compared to that of untreated patients. There were no differences in HCC risk between DAA-treated and IFN-treated patients.

The correlation between intrahepatic covalently closed circular DNA (cccDNA) levels and serum hepatitis B virus (HBV) markers in patients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative and antibody to hepatitis B core antigen [anti-HBc]-positive) is unclear. We therefore examined the utility of anti-HBc titers as a surrogate marker of intrahepatic cccDNA levels in patients with resolved HBV infections.

Among 1005 patients who underwent hepatectomy between 2010 and 2018, a retrospective review was performed in 114 patients (76 with resolved HBV infection and 38 HBsAg-positive) with frozen specimens of the background liver. Clinical, biochemical, and virological data, including intrahepatic cccDNA levels, were retrospectively evaluated. Intrahepatic cccDNA levels were measured using droplet digital polymerase chain reaction.

Intrahepatic cccDNA levels positively correlated with serum HBsAg levels (r = 0.609, p < 0.001) and anti-HBc titers (r = 0.542, p < 0.001). An intrahepatic cccDNA level of 22.2 copies/μg was the optimal cut-off for HBsAg positivity, with a sensitivity of 86.8% and specificity of 89.5%. Of the 76 cases with resolved HBV infection, 8 had high levels of intrahepatic cccDNA (≥22.2 copies/μg). Multivariate analyses showed that anti-HBc ≥ 11.0 sample/cut-off (S/CO) was an independent risk factor for high intrahepatic cccDNA levels (odds ratio, 12.6; 95% confidence interval, 2.4-66.156; P = 0.003).

Anti-HBc titers were positively correlated with intrahepatic cccDNA levels. Even in patients with resolved HBV infection, anti-HBc ≥ 11.0 S/CO was considered to indicate high intrahepatic cccDNA levels, comparable to those in HBsAg-positive cases. In this group, careful monitoring is required during immunosuppressive therapy to prevent HBV reactivation.

Relapse after radical treatment remains a major concern in hepatocellular carcinoma (HCC), affecting 50-75 % of early-stage cases within 5 years. Early recurrence prediction is a clinical unmet need. Circulating blood biomarkers could provide a minimally invasive approach to detect minimal residual disease (MRD) post-intervention. Although alpha-fetoprotein has been the primary biomarker in this setting, its MRD sensitivity is limited to 50-70 %. This systematic review aims to summarize available evidence regarding the clinical validity and potential utility of emerging circulating blood biomarkers for MRD detection in HCC patients.

We searched PubMed and Embase for peer-reviewed articles and abstracts published up to 2025, and ClinicalTrials.gov for ongoing trials on circulating blood biomarkers for MRD in HCC.

A total of 91 studies (74 with results and 17 ongoing, out of 2,386) were retrieved. We evaluated various blood biomarkers, including circulating DNA (cDNA, N = 24), circulating tumor cells (CTCs, N = 20), circulating RNA (cRNA, N = 8), and other miscellaneous (N = 22) for MRD detection in HCC. These biomarkers demonstrated encouraging results, albeit with notable heterogeneity. In particular, circulating tumor DNA (ctDNA) and CTCs stand as the most robust novel approaches, with 50-80 % sensitivity and specificity up to 94 %. Nonetheless, none of the 17 ongoing studies involve biomarker-driven intervention to prove clinical utility.

Novel circulating blood biomarkers are mature for MRD detection in HCC. However, variability in methodologies and results highlights the need for further validation. We encourage the investigation of CTCs and/or ctDNA in interventional trials to assess clinical utility. This biomarker-driven approach may enhance adjuvant treatment effectiveness in MRD-positive cases while minimizing toxicity in MRD-negative patients.

To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.

We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.

The annual incidence of HCC was 2.1/100 person-years after a follow-up period of over 4840.5 person-years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55-5.81; p = 0.001), male sex (2.98/1.51-5.90; p = 0.02), body mass index (1.11/1.04-1.18; p = 0.002) and age (1.06/1.04-1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00-4.25; p = 0.04) and NO2 (per one-unit increment, parts per billion; 1.07/1.01-1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO2 exposure had more than a three-fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34-7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79-19.23; p = 0.004), age (1.12/1.07-1.17; p < 0.001) and platelet count (0.99/0.98-1.00; p = 0.04).

Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long-term NO2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.

Chronic hepatitis B virus (HBV) infection is a global health issue with limited therapeutic options given the persistence of viral episomal DNA (cccDNA). Previously, we investigated the effects of adeno-associated virus 2 (AAV2) vector-mediated delivery of three guide (g)RNAs/Cas9 selected from 16 gRNAs. AAV2/WJ11-Cas9 effectively suppressed HBV replication in vitro and in humanized chimeric mouse livers. In the present study, we examined the effect of AAV2/WJ11-Cas9 on the acute phase of HBV genotype F infection in an immunocompetent northern tree shrew (Tupaia belangeri; hereafter, "tupaia") model. AAV2/WJ11-Cas9 treatment significantly reduced the HBV viral load in serum at 1, 7, 10, and 14 days post-infection (dpi). HBV-F infection caused enlargement of hepatocytes and mild lymphocytic infiltration in the interlobular connective tissue. Thus, the virus damages hepatocytes and drives infection progression and HBV core antigen (HBcAg) accumulation, which were not observed in AAV2/WJ11-Cas9 treated and normal liver tissues. AAV2/WJ11-Cas9 treatment reduced HBV DNA and cccDNA in liver tissues, as well as serum levels of HBV surface antigen and HBV core-related antigen (HBcrAg), including HBcAg and HBeAg at 14 dpi. Anti-HBc, anti-HBs, and anti-AAV Abs production was also detected. AAV2/WJ11-Cas9 treatment suppressed inflammatory cytokines and TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, and TLR9 mRNA levels. Thus, WJ11/Cas9 delivered by AAV2 vectors may provide a new therapeutic approach for inhibiting HBV infection in immunocompetent animal models, which could be developed for use in humans through further translational research.

Autoimmune hepatitis (AIH) is a rare, heterogeneous liver disease marked by autoantibodies, hypergammaglobulinemia, and distinct histological features. Predominantly affecting women, its incidence and prevalence show significant regional variability globally. Therefore, our aim is to examine the trends of AIH and to assess its demographics, management, and disease progression using an extensive population-based database.

This retrospective, population-based study analyzed data from 2.7 million adults in Clalit Health Services, focusing on autoimmune hepatitis (AIH) diagnoses between 2009 and 2023. Data reordered included demographics, clinical details, and treatment regimens. Key outcomes tracked were the development of cirrhosis and its complications.

This study included 992 AIH patients with a median age of 51.5 years, 80.4 % female, and a median follow-up of 6.1 years. Obesity was present in 23.2 %, and 10.9 % had thyroid disease. At diagnosis, 22.9 % had cirrhosis, and an additional 137 patients developed cirrhosis during follow-up, leading to a total prevalence of 36.5 %. Among cirrhotic patients, 29.9 % experienced decompensation, 25.3 % developed ascites, 9.3 % had variceal bleeding, and 10.4 % developed hepatic encephalopathy. Hepatocellular carcinoma (HCC) occurred in 5.24 % of cirrhotic patients, with an incidence rate of 6.32 cases per 1000 patient-years. Overall, 11.2 % of cirrhotic patients underwent liver transplantation. The proportion of AIH patients diagnosed with cirrhosis at the time of diagnosis significantly decreased over the study period (p = 0.0028).

This study demonstrates a decreasing trend in AIH patients diagnosed with cirrhosis, suggesting earlier detection and improved management, alongside a lower documented incidence of HCC.

Liver cancer or hepatocellular carcinoma (HCC) remains the most common cancer in global epidemiology. Both the frequency and fatality of this malignancy have shown an upward trend over recent decades. Liver cancer is a significant concern due to its propensity for both intrahepatic and extrahepatic metastasis. Liver cancer metastasis is a multifaceted process characterized by cell detachment from the bulk tumor, modulation of cellular motility and invasiveness, enhanced proliferation, avoidance of the immune system, and spread either via lymphatic or blood vessels. MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) playing a crucial function in the intricate mechanisms of tumor metastasis. A number of miRNAs can either increase or reduce metastasis via several mechanisms, such as control of motility, proliferation, attack by the immune system, cancer stem cell properties, altering the microenvironment, and the epithelial-mesenchymal transition (EMT). Besides, two other types of non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can competitively bind to endogenous miRNAs. This competition results in the impaired ability of the miRNAs to inhibit the expression of the specific messenger RNAs (mRNAs) that are targeted. Increasing evidence has shown that the regulatory axis comprising circRNA/lncRNA-miRNA-mRNA is correlated with the regulation of HCC metastasis. This review seeks to present a thorough summary of recent research on miRNAs in HCC, and their roles in the cellular processes of EMT, invasion and migration, as well as the metastasis of malignant cells. Finally, we discuss the function of the lncRNA/circRNA-miRNA-mRNA network as a crucial modulator of carcinogenesis and the regulation of signaling pathways or genes that are relevant to the metastasis of HCC. These findings have the potential to offer valuable insight into the discovery of novel therapeutic approaches for management of liver cancer metastasis.

Microvascular invasion (MVI) is an important risk factor for early postoperative recurrence of hepatocellular carcinoma (HCC). Based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) images, we developed a novel radiomics model. It combined bi-regional features and two machine learning algorithms. The aim of this study was to validate its potential value for preoperative prediction of MVI.

This retrospective study included 304 HCC patients (training cohort, 216 patients; testing cohort, 88 patients) from three hospitals. Intratumoral and peritumoral volumes of interest were delineated in arterial phase, portal venous phase, and hepatobiliary phase images. Conventional radiomics (CR) and deep learning radiomics (DLR) features were extracted based on FeAture Explorer software and the 3D ResNet-18 extractor, respectively. Clinical variables were selected using univariate and multivariate analyses. Clinical, CR, DLR, CR-DLR, and clinical-radiomics (Clin-R) models were built using support vector machines. The predictive capacity of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.

The bi-regional CR-DLR model showed more gains and gave better predictive performance than the single-regional models or single-machine learning models. Its AUC, accuracy, sensitivity, and specificity were 0.844, 76.9%, 87.8%, and 69.1% in the training cohort and 0.740, 73.9%, 50%, and 84.5% in the testing cohort. Alpha-fetoprotein (odds ratio was 0.32) and maximum tumor diameter (odds ratio was 1.270) were independent predictors. The AUCs of the clinical model and the Clin-R model were 0.655 and 0.672, respectively. There was no significant difference in the AUCs between all the models (P > 0.005).

Based on Gd-EOB-DTPA-enhanced MRI images, we focused on developing a radiomics model that combines bi-regional features and two machine learning algorithms (CR and DLR). The application of the new model will provide a more accurate and non-invasive diagnostic solution for medical imaging. It will provide valuable information for clinical personalized treatment, thereby improving patient prognosis.

Not applicable.

Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.

Hepatitis B virus (HBV) infection is a well-documented independent risk factor for developing hepatocellular carcinoma (HCC). Consequently, extensive research has focused on elucidating the mechanisms by which HBV induces hepatocarcinogenesis. The majority of studies are dedicated to understanding how HBV DNA integration into the host genome, viral RNA expression, and the resulting protein transcripts affect cellular processes and promote the malignant transformation of hepatocytes. However, considering that most acute HBV infections are curable, immune suppression potentially contributes to the critical challenges in the treatment of chronic infections. Regulatory T cells (Tregs) are crucial in immune tolerance. Understanding the interplay of Tregs within the liver microenvironment following HBV infection could offer novel therapeutic approaches for treating HBV infections and preventing HBV-related HCC. Two viewpoints to targeting Tregs in the liver microenvironment include means of reducing their inhibitory function and decreasing Treg frequency. As these strategies may disrupt the immune balance and lead to autoimmune responses, careful and comprehensive profiling of the patient's immunological status and genetic factors is required to successfully employ this promising therapeutic approach.

Hepatocellular Carcinoma (HCC) is one of the most common and fatal types of liver cancer worldwide; in this sense, Diethylnitrosamine (DEN) has been established as a potent carcinogen affecting the development and progression of this disease. The present work focused on determining whether phosphodiesterase (PDE) enzymes, especially PDE5, may serve as targets in the therapeutic treatment of DEN-induced HCC. PDE5 inhibitors, widely used as therapeutic drugs for cardiovascular diseases and erectile dysfunction, have recently been found to be promising in preclinical cancer models through the modulation of key signaling pathways implicated in the progression of tumors, such as the cGMP-PKG, JNK, and MAPK pathways. These pathways are very important for cell proliferation, apoptosis and metastasis, and their dysregulation contributes to the aggressive nature of HCC. This study assessed the potential of PDE5 inhibitors to suppress proliferation, induce apoptosis, and alter the tumor microenvironment, thus potentially improving standard chemotherapy and immunotherapy interventions. By inhibiting certain PDE isoforms with these drugs, an anticancer response might occur as part of a complex mechanism that acts on both cancer cells and the microenvironment favorable for tumor growth. A preliminary review indicated that PDE inhibitors may be a promising therapeutic approach for overcoming some of the shortcomings of current treatments, particularly the development of resistance and the toxic effects of these treatments. Additional clinical investigations are necessary to determine the safety profile, appropriate amount of Osage, and long-term efficacy of these agents in the treatment of HCC, particularly in DEN-induced animal models. This study contributes to the expanding body of evidence supporting the use of PDE inhibitors in cancer treatment.

Exosomes, spherical lipid-bilayered particles secreted by cells, have recently emerged as a novel and highly promising drug delivery system, attracting extensive attention in the field of biomedical research. Dendritic-cell-derived exosomes (DC-Exos) possess surface protein and ligands characteristic of DC cells, such as functional MHC-I and MHC-II, CD80, CD86. These components play a crucial role in immune responses, facilitating antigen uptake, presentation, and the activation of antigen-specific CD4 and CD8 T cells. These properties make them striking and excellent drug delivery vehicles for use in various immune diseases and cancer therapy. This review summarizes and discusses the characteristics, current methods and types of drug loading of DC-Exos. Its surface modifications and application in disease treatment were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment. These modifications enable CSCs to exhibit plasticity, differentiating into various resistant tumor cell types. Addressing this challenge requires urgent efforts to develop personalized treatments guided by biomarkers, with a specific focus on targeting CSCs. The lack of effective precision treatments for PLCs is partly due to the scarcity of ex vivo preclinical models that accurately capture the complexity of CSC-related tumors and can predict therapeutic responses. Fortunately, recent advancements in the establishment of patient-derived liver cancer cell lines and organoids have opened new avenues for precision medicine research. Notably, patient-derived organoid (PDO) cultures have demonstrated self-assembly and self-renewal capabilities, retaining essential characteristics of their respective in vivo tissues, including both inter- and intratumoral heterogeneities. The emergence of PDOs derived from PLCs serves as patient avatars, enabling preclinical investigations for patient stratification, screening of anticancer drugs, efficacy testing, and thereby advancing the field of precision medicine. This review offers a comprehensive summary of the advancements in constructing PLC-derived PDO models. Emphasis is placed on the role of CSCs, which not only contribute significantly to the establishment of PDO cultures but also faithfully capture tumor heterogeneity and the ensuing development of therapy resistance. The exploration of PDOs' benefits in personalized medicine research is undertaken, including a discussion of their limitations, particularly in terms of culture conditions, reproducibility, and scalability.

The study aimed to gather information about the target population's knowledge, attitudes, and behaviors regarding HCV screening to develop effective communication strategies and improve service offerings.

This was a Cross-Sectional study.

A target population random sample was submitted a phone questionnaire based on the Health Belief Model (HBF), containing 4 sections on perceived HCV susceptibility and severity, screening benefits and barriers. Each person interviewed was finally invited to adhere to the screening. Prevalence was estimated using a 95 % C.I., and association between sociodemographic characteristics, HBF attitudes, and screening adherence following the interview was assessed.

Survey involved 641 participants. HCV susceptibility was perceived by 4.8 % (95 % CI 3.23-6.57) and HCV severity by 69.4 % (95 % CI 65.83-72.97), 95 % (95 % CI 93.3-96.6) acknowledged screening benefits and 88 % (95 % CI 85.4-90.5) perceived no barriers. Insufficient or no information about HCV or the screening was received by the 49.0 % (95 % CI 45.1-52.8) of people interviewed. Among these people, in the 2 months aftermath, 17.6 % carried out the HCV screening. Perception of screening barriers was associated with low education level (OR 1.83, P = 0.02).

Low adherence to the HCV screening could be explained with a poor perception of HCV susceptibility and gravity by the target population particularly with socioeconomic hurdles. Forthcoming communication campaign would need to focus on those factors to improve adherence.

This systematic review aimed at identifying oncoviruses associated with head and neck malignant neoplasms (HNC).

Five databases and grey literature sources were searched following PRISMA guidelines. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist, and the certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool.

One hundred and 19 studies were included in the qualitative synthesis. Gathered results of 57 studies were combined in a meta-analysis revealing a significant link between oncoviruses and the development of head and neck cancer, with the most common viruses identified were human papillomavirus (HPV)-16, HPV-18, and Epstein-Barr virus. More studies are needed to clarify the association of human cytomegalovirus and Merkel Cell Polyomavirus with HNC.

Although the role of viruses in cancer onset has been studied for years, our results demonstrated using a meta-analysis that these viruses are associated with HNC.

Conflicting results have been reported on the impact of tenofovir versus entecavir on liver-related outcomes.

To explore trends in clinical outcomes in chronic hepatitis B virus (HBV)-infected patients and compare the impact of tenofovir versus entecavir on the risk of hepatocellular carcinoma (HCC), liver transplantation (LT) and mortality.

We used the French National Health Insurance Databases (SNDS) to identify HBV-infected patients. We quantified the excess clinical burden from 2012 to 2021 by comparing the HBV-infected cohort with a general population cohort, using 1:1 exact matching on birth date, sex, social deprivation index and follow-up start date. The risks of mortality, HCC and LT were compared between patients treated with tenofovir and entecavir using inverse probability weighting.

A total of 101,740 patients were matched to the general population. From 2012 to 2021, the average annual decreases in excess mortality, incidence of HCC and LT were 3.7%, 8.0% and 11.9%, respectively (p for trend < 0.001). During the same period, the nucleos(t)ide analog (NUC) treatment coverage significantly increased, particularly after 2016 (p < 0.001). Among 14,054 treatment-naïve patients starting tenofovir (n = 7426) or entecavir (n = 6628), we observed no difference in the composite outcome of mortality, LT or HCC (HR, 1.09; 95% CI, 0.95-1.24). Tenofovir was associated with an increased risk of HCC compared with entecavir (HR, 1.31; 95% CI, 1.07-1.62).

Tenofovir was associated with a higher risk of HCC compared with entecavir, although no difference in the composite outcome of mortality or liver-related events was observed between the two treatments.

Hepatitis C (HCV) testing innovations such as dried blood spot (DBS) and point-of-care testing should have fewer client-related barriers than traditional diagnostic pathways, yet there is limited evidence on their acceptability among people who inject drugs. To address this gap, this study sought to evaluate the acceptability of DBS and point-of-care testing among people at risk of HCV infection and understand the circumstances in which such testing is most preferred.

Participants were recruited from community sites involved in the Australian HCV Point-of-Care Testing Program. Inclusion criteria were aged ≥18 years, sufficient proficiency in the English language, history of HCV testing at least once, and informed consent. Between June and August 2023, in-depth, semi-structured interviews were conducted via telephone with clients on their perceptions and experiences of HCV DBS and point-of-care testing. Data were coded and analysed thematically with Sekhon's theoretical framework of acceptability.

Forty participants were interviewed: 18 had previously received HCV DBS testing, 8 had received HCV point-of-care testing, 8 had experience with both, and 6 had no prior experience with either test. Most participants preferred point-of-care compared to DBS and venepuncture due to the shorter time to result and some identified that this reduced anxiety while waiting for results (burden). Among participants in this study, many felt that the provision of non-judgemental care was more important than whether testing was performed by peers (ethicality). Many participants indicated a preference for assisted collection when compared to self-collected or mail testing service (self-efficacy).

Applying Sekhon's acceptability framework highlighted remaining service gaps to bridge client HCV testing experiences, including enhanced education on testing modalities and their results, an increased need for non-judgemental care, and the use of peer support in community settings.

Recently, studies have reported that pan-viral serology signatures may be predictive for liver cancer development. However, whether these same findings are observed for prospective studies has not been previously investigated. The nested case-control analysis included 191 persons who developed liver cancer and 382 controls from the PLCO prospective cohort. The presence of circulating antibodies, measured by VirScan, was determined in serum samples obtained at study recruitment. The presence of antibodies was compared between cases and controls using multivariable conditional logistic regressions, and prediction models were used to estimate whether exposures predicted liver cancer development. No significant associations were found between antibodies to viruses, bacteria or allergens and liver cancer risk after adjustment for multiple testing. The agent most significantly associated with risk was hepatitis C virus (HCV), but it was only detected among 23 participants (odds ratio (OR): 3.98; 95% confidence intervals (CI):1.59-9.99; p = 0.0032, False Discovery Rate (FDR) = 0.35). In prediction models based on 109 antibody features, no associations with liver cancer risk were observed (area under the curve [AUC]: 0.52-0.54). In analyses restricted to the most common type of liver cancer, hepatocellular carcinoma, the association with HCV was stronger (OR: 23.16, 95% CI: 4.55-117.68; FDR p-value = 0.0016), although prediction models based on all detected antibodies were similar (AUC = 0.55; 95% CI:0.43-0.68). Antibodies to no infectious agents, other than HCV, were found to be prospectively associated with liver cancer risk. The utility of using an antibody exposure signature prospectively for liver cancer development needs to be further explored.