Liver Hepatocellular Carcinoma Research Articles

The expression of VEGF and cyclin D1/EGFR in common primary liver carcinomas in Egypt: an immunohistochemical study.

The most common types of primary malignant liver tumours are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Treatment options for patients who are inoperable/advanced, or recurring are challenging. Cyclin D1, epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGR) are common carcinogenic proteins that have potential therapeutic targets in various cancers. They have been implicated in the development of HCC and CCA. In this study, we aimed to evaluate the oncogenic function expression of cyclin D1, EGFR and VEGF in HCC and CCA of Egyptian patients. This could help to validate their therapeutic potential. Tumour cases were selected from 82 cases of primary liver carcinomas, with 58 cases being from HCC and 24 cases from CCA compared to 51 non-tumour adjacent liver cases and 18 from normal liver tissue. The immunohistochemical study of cyclin D1, EGFR and VEGR was conducted. Cyclin D1, EGFR and VEGF are overexpressed in HCC and CCA as compared to the control group (p < 0.001). Cyclin D1 was related to well-differentiated grade and early pathologic stage in HCC (p = 0.016 and p = 0.042, respectively). The well-differentiated grade showed significantly higher VEGF levels (p = 0.04). In the CCA group, however, EGFR was strongly related to high tumour size (p = 0.047). EGFR and VEGF were overexpressed in HCC raised in the non-cirrhotic liver compared to those developed in post-hepatitic liver cirrhosis (p = 0.003 and p = 0.014). Cyclin D1, EGFR and VEGF shared significant overexpression in HCC and CCA. EGFR and VEGF may play an oncogenic function in the development of HCC in non-cirrhotic liver. Furthermore, cyclin D1 and VEGF may play a good prognostic function in HCC, but EGFR may play a bad prognostic role in CCA.

GPNMB+ Gal-3+ hepatic parenchymal cells promote immunosuppression and hepatocellular carcinogenesis.

Hepatocellular carcinoma (HCC) formation is a multi-step pathological process that involves evolution of a heterogeneous immunosuppressive tumor microenvironment. However, the specific cell populations involved and their origins and contribution to HCC development remain largely unknown. Here, comprehensive single-cell transcriptome sequencing was applied to profile rat models of toxin-induced liver tumorigenesis and HCC patients. Specifically, we identified three populations of hepatic parenchymal cells emerging during HCC progression, termed metabolic hepatocytes (HCMeta ), Epcam+ population with differentiation potential (EP+Diff ) and immunosuppressive malignant transformation subset (MTImmu ). These distinct subpopulations form an oncogenic trajectory depicting a dynamic landscape of hepatocarcinogenesis, with signature genes reflecting the transition from EP+Diff to MTImmu . Importantly, GPNMB+ Gal-3+ MTImmu cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 is required for the generation and malignant transformation of GPNMB+ Gal-3+ MTImmu cells. Enrichment of the GPNMB+ Gal-3+ MTImmu subset was found to be associated with poor prognosis and a higher rate of recurrence in patients. Collectively, we unraveled the single-cell HCC progression atlas and uncovered GPNMB+ Gal-3+ parenchymal cells as a major subset contributing to the immunosuppressive microenvironment thus malignance in HCC.

Identification and validation of palmitoylation metabolism-related signature for liver hepatocellular carcinoma

BackgroundProtein S-palmitoylation is a reversible posttranslational modification widely involved in tumor progression. Nevertheless, the function of palmitoylation metabolism in prognosis and tumor microenvironment characteristics in liver hepatocellular carcinoma (LIHC) patients is not fully understood. MethodsmRNA and clinical data of LIHC patients were obtained from the TCGA and ICGC databases. Consensus clustering was used to construct palmitoylation metabolism-related clusters. Univariate Cox and Lasso regression analyses were employed to establish a palmitoylation metabolism-related signature (PMS). ssGSEA was applied to evaluate the immune cell score in each LIHC sample. Functional enrichments were accessed through GO, KEGG and GSVA. Drug sensitivity data were downloaded from the GDSC database. ResultsThree palmitoylation metabolism-related clusters with different prognostic and immune infiltration characteristics were constructed in LIHC. We identified PMS with distinct survival, clinical, and tumor immune microenvironment characteristics. The high PMS group had a poorer prognosis, higher infiltration of immunosuppressive cells and higher expression of immune checkpoints. ZDHHC20 exerted a tumor-promoting role in LIHC and was significantly associated with immunosuppressive cells and immunosuppressive checkpoints. Additionally, in HepG-2 and SMCC-7721 cells, si-ZDHHC20 boosted apoptosis but decreased proliferation and migration when compared to si-NC. ConclusionOur research revealed that PMS may accurately predict the prognosis and immune characteristics of LIHC patients. ZDHHC20 has significant clinical and immune relevance in LIHC and may contribute to the formulation of new targets for LIHC immunotherapy.

MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?

Alcohol-related Liver Disease (ALD) is the primary cause of chronic liver disorders and hepatocellular carcinoma (HCC) development in developed countries and thus represents a major public health concern. Unfortunately, few therapeutic options are available for ALD and HCC, except liver transplantation or tumor resection for HCC. Deciphering the molecular mechanisms underlying the development of these diseases is therefore of major importance to identify early biomarkers and to design efficient therapeutic options. Increasing evidence indicate that epigenetic alterations play a central role in the development of ALD and HCC. Among them, microRNA importantly contribute to the development of this disease by controlling the expression of several genes involved in hepatic metabolism, inflammation, fibrosis, and carcinogenesis at the post-transcriptional level. In this review, we discuss the current knowledge about miRNAs’ functions in the different stages of ALD and their role in the progression toward carcinogenesis. We highlight that each stage of ALD is associated with deregulated miRNAs involved in hepatic carcinogenesis, and thus represent HCC-priming miRNAs. By using in silico approaches, we have uncovered new miRNAs potentially involved in HCC. Finally, we discuss the therapeutic potential of targeting miRNAs for the treatment of these diseases.

Unraveling the molecular links between benzopyrene exposure, NASH, and HCC: an integrated bioinformatics and experimental study

Benzopyrene (B[a]P) is a well-known carcinogen that can induce chronic inflammation and fibrosis in the liver, leading to liver disease upon chronic exposure. Nonalcoholic steatohepatitis (NASH) is a chronic liver condition characterized by fat accumulation, inflammation, and fibrosis, often resulting in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the intricate connections between B[a]P exposure, NASH, and HCC. Through comprehensive bioinformatics analysis of publicly available gene expression profiles, we identified differentially expressed genes (DEGs) associated with B[a]P exposure, NASH, and liver cancer. Furthermore, network analysis revealed hub genes and protein–protein interactions, highlighting cellular metabolic dysfunction and disruption of DNA damage repair in the B[a]P-NASH-HCC process. Notably, HSPA1A and PPARGC1A emerged as significant genes in this pathway. To validate their involvement, we conducted qPCR analysis on cell lines and NASH mouse liver tissues and performed immunohistochemistry labeling in mouse and human HCC liver sections. These findings provide crucial insights into the potential regulatory mechanisms underlying benzopyrene-induced hepatotoxicity, shedding light on the pathogenesis of B[a]P-associated NASH and HCC. Moreover, our study suggests that HSPA1A and PPARGC1A could serve as promising therapeutic targets. Enhancing our understanding of their regulatory roles may facilitate the development of targeted therapies, leading to improved patient outcomes.

High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma

NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a computational analysis method for quantifying cell fractions from bulk tissue gene expression profiles, was used to estimate the infiltrating immune cell composition of the tumor microenvironment from gene expression profiles of a large cohort of 225 HCCs in the public GEO database. Decidual-like CD49a+ NK cells, in addition to another 22 immune cell populations, were characterized and thoroughly investigated so that HCC cell heterogeneity in a large cohort of 225 HCCs from the public GEO database could be studied. An inverse correlation of the expression of CD49a+ NK-cells and CD8+ T-cells suggested a negative association with clinical outcomes. This result was confirmed in a further validation cohort of 100 HCC patients from The Cancer Genome Atlas, Liver Hepatocellular Carcinoma (TCGA-LIHC). Cox regression analysis did not identify CD49a+ cells as a variable independently associated with survival. However, a more abundant infiltrate of this subset was present in patients at a more advanced pathological and clinical HCC stage. In conclusion, we found that NK cells, with a decidual-like gene expression profile, are enriched in HCC, and their abundance increases not only in tumor size but also at advanced stages of the disease suggesting that these cells play a role in tumor growth. For this reason, these NK cells may represent a possible new target for immunotherapeutic approaches in HCC.

EMT-related gene risk model establishment for prognosis and drug treatment efficiency prediction in hepatocellular carcinoma

This study was designed to evaluate the prognosis and pharmacological therapy sensitivity of epithelial mesenchymal transition-related genes (EMTRGs) that obtained from the EMTome database in hepatocellular carcinoma (HCC) using bioinformatical method. The expression status of EMTRGs were also investigated using the clinical information of HCC patients supported by TCGA database and the ICGC database to establish the TCGA cohort as the training set and the ICGC cohort as the validation set. Analyze the EMTRGs between HCC tissue and liver tissue in the TCGA cohort in the order of univariate COX regression, LASSO regression, and multivariate COX regression, and construct a risk model for EMTRGs. In addition, enrichment pathways, gene mutation status, immune infiltration, and response to drugs were also analyzed in the high-risk and low-risk groups of the TCGA cohort, and the protein expression status of EMTRGs was verified. The results showed a total of 286 differentially expressed EMTRGs in the TCGA cohort, and EZH2, S100A9, TNFRSF11B, SPINK5, and CCL21 were used for modeling. The TCGA cohort was found to have a worse outcome in the high-risk group of HCC patients, and the ICGC cohort confirmed this finding. In addition, EMTRGs risk score was shown to be an independent prognostic factor in both cohorts by univariate and multivariate COX regression. The results of GSEA analysis showed that most of the enriched pathways in the high-risk group were associated with tumor, and the pathways enriched in the low-risk group were mainly associated with metabolism. Patients in various risk groups had varying immunological conditions, and the high-risk group might benefit more from targeted treatments. To sum up, the EMTRGs risk model was developed to forecast the prognosis for HCC patients, and the model might be useful in assisting in the choice of treatment drugs for HCC patients.

Association of elevated autoantibody to high expression of GNAS in hepatocellular carcinoma

PurposeThis study was based on hepatocellular carcinoma (HCC) patients of early-stage to explore the diagnostic capability and possible production causes of anti-GNAS autoantibody. MethodsWe evaluated the frequency of anti-GNAS autoantibody in sera from patients with early-stage HCC by enzyme-linked immunosorbent assay (ELISA) and the expression of GNAS protein in early-stage HCC tissues by immunohistochemistry. Western blotting (WB) and real-time polymerase chain reaction (RT-PCR) were utilized to examine the expressions of GNAS protein and mRNA in cell lines. GEO and International Cancer Genome Consortium (ICGC) databases were inquired to explore mRNA expression and mutation of GNAS in HCC tissues. ResultsThe positive rates of anti-GNAS autoantibody in HCC patients at clinical stage I (78.1 %) and clinical stage II (57.1 %) were all significantly higher than that in healthy control (20 %). There was also a significant difference in GNAS protein expression between HCC and its adjacent normal liver tissues. The results from WB and RT-PCR showed a significant difference at the mRNA level but no statistical difference at the protein level between HCC and normal liver cell lines. The difference in mRNA level between HCC and adjacent normal liver tissues was verified to be significant. Furthermore, the ICGC database demonstrated a 10.6 % mutation frequency for GNAS in HCC patients. ConclusionThe coordination of elevated anti-GNAS autoantibody, high expression of GNAS in the mRNA and protein levels in HCC, and high frequency of GNAS mutation indicates that anti-GNAS autoantibody may be used as an early indicator of HCC.

Is the anterior approach recommended for liver resection of hepatocellular carcinoma? A systematic review and meta-analysis.

The anterior approach (AA) in liver resection has proven more effective with regard to short-term outcomes than the conventional approach (CA). However, its superiority over the CA concerning long-term outcomes remains unclear. This meta-analysis compared the short- and long-term outcomes of the AA and CA. Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing the AA and CA for hepatocellular carcinoma (HCC) liver resection. The primary outcomes were the in-hospital mortality, in-hospital morbidity, disease-free survival (DFS), and overall survival (OS). Secondary outcomes were operative time, blood loss, blood transfusion, R0 rate, and length of hospital stay. Ten studies involving 1369 patients were included (AA, n = 595; CA, n = 774). Despite no significant differences in the in-hospital mortality or morbidity, the AA demonstrated a superior DFS (hazard ratio [HR], 0.63; 95% confidence interval [CI]: 0.51-0.77) and OS (HR, 0.56; 95% CI: 0.48-0.65) and was associated with a longer operative time, less blood loss, and less transfusion than the CA. No marked differences in other outcomes were noted. The AA for HCC liver resection helped reduce blood loss and need for transfusion, improving the DFS and OS.

Сhanges in the composition of gut microbiota in patients with chronic hepatitis С, non-alcoholic fatty liver disease at different stages of liver disease: a review

INTRODUCTION. The human gut microbiota is a set of microorganisms that are in symbiosis with the host organism. The predominance of bacteria of Bacteroidetes, Firmicutes, Actinobacteria types is a characteristic feature of human gut microbiota. However, the composition of the gut microbiota is subject to change under the influence of a number of factors. The influence of the gut-liver axis on the pathogenesis of many chronic liver diseases of various etiologies, both infectious and metabolic, has been proven. At the same time, in the analyzed literature, the data on the relationship between the nature of GM changes and the stage of liver damage are quite controversial.&#x0D; OBJECTIVE. Updating and systematization of ideas about the nature of changes in the composition of intestinal microbiota in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) at different stages of the disease.&#x0D; MATERIALS AND METHODS. We analyzed the scientific literature on GM changes in chronic liver diseases with regard to their etiology and disease stage, in particular in chronic viral hepatitis C and NAFLD. The search was conducted in PubMed, Google Scholar, and eLIBRARY databases for 2000-2023 using the following keywords: gut microbiota; microbiota in hepatitis C; microbiota in NAFLD; microbiota in liver fibrosis; liver fibrosis progression. Sixty scientific articles were analyzed and 42 sources were selected, of which more than 60% were published within the last five years.&#x0D; RESULTS. This review presents the results of original studies describing the main taxonomic differences between the microbiomes of healthy individuals and patients with CHC complicated by the formation of liver cirrhosis and hepatocellular carcinoma (HCC). Thus, patients with viral cirrhosis showed impoverishment of intestinal commensals Lachnospiraceae and Ruminococcaceae and significant enrichment of Streptococcaceae, Lactobacillaceae and Enterobacteriaceae. In patients with non-alcoholic steatohepatitis (NASH) and FII, enrichment of GM Phylum Bacteroides and Proteobacteria, Families Lachnospiraceae and Enterobacteriaceae, Genera Blautia and Escherichia, with a concomitant decrease of Prevotella was detected.&#x0D; DISCUSSION. The analysis of GM taxonomic units in the previously described studies did not reveal significant differences depending on the etiology of the underlying disease. However, a decrease in the representative of the phylum Firmicutes - Ruminococcaceae was observed in CHC in contrast to NAFLD. A more distinct relationship can be observed in the changes of intestinal microbiota in F(III-IV) irrespective of etiology. Thus, in advanced liver fibrosis and cirrhosis of both CHC and NAFLD etiologies, enrichment of GM has been described due to an increase in phylum Proteobacteria, in particular the genus Escherichia and phylum Firmicutes (Blautia, Veillonellaceae). In the studies analyzed, at F(III-IV), an enrichment of the microbiota is observed due to an increase in the phylum Bacteroidetes. Regarding the genus Prevotella, contradictory results were found. In addition, there are ambiguous data regarding the genera Lactobacillus, Ruminococcaceae and Bifidobacteria.&#x0D; CONCLUSION. Based on the results of the literature review, we obtained contradictory data on GM composition in patients with CHC and NAFLD. This may be due to the size of samples, heterogeneity of initial data during the selection of patients in the study. The relationship between the composition of microbiota and persistent inflammatory process, expressed liver fibrosis is observed. GM reflects not only functional disorders in chronic liver diseases of various etiologies, but can also serve as a diagnostic indicator of their progression.

HPB P11 Hepatic vein reconstruction during hepatectomy – a feasible and underused technique?

Abstract Background Hepatic vein involvement can be a contraindication to resection of liver tumours. This study aimed to assess the feasibility, long term outcomes and vein patency among patients who underwent hepatic vein reconstruction during liver resections for liver tumour(s). Methods Retrospective analysis of patients who underwent circumferential hepatic venous reconstruction identified from a prospectively maintained database. Standard volumetric analysis was performed using software to estimate volumetry with and without hepatic venous reconstruction. Long term vein patency was established using review of available radiology. Results 15 patients underwent 17 venous reconstructions for colorectal liver metastases (n=13), cholangiocarcinoma (n=1) and hepatocellular carcinoma (n=1). The median FLR without and with venous reconstruction were 32 (range 18.0-74.5) and 96% (range 26.9-97.7) respectively; the median increase in FLR was 34% per patient. Venous patency was 89% at a median follow-up of 25 months (Range 1-53) with 2 graft thrombosis. No patient developed PHLF. Conclusions Hepatic venous reconstruction during liver resection is safe and feasible. It has the potential to expand the scope of liver resection and preserve liver and venous drainage if needed in the future.

HPB P03 Stereoractic ablative radiotherapy provides a safe and feasible treatment alternative for non-surgical candidates with primary hepatocellular carcinoma

Abstract Background Stereotactic ablative radiotherapy (SABR) is a highly focused radiation treatment that delivers an intense dose of radiation to a tumour whilst limiting exposure of surrounding tissues. SABR has been associated with improvement in overall survival and local control in non-surgical candidates with primary hepatocellular carcinoma (HCC). The aim of this study was to evaluate the outcomes of HCC patients treated with SABR in a tertiary referral hepatobiliary centre. Methods A total of 33 patients (median age 72 years {range 47-85}, 79% male) who received SABR for primary HCC liver lesions over a 2-year period between July 2020 and August 2022 were retrospectively analysed. Patient, treatment and follow-up details were obtained from online patient records and imaging. Patients underwent SABR either due to co-morbidity precluding surgery (23/33), lack of suitable treatment alternatives (9/33) or due to patient choice (1/33). Five patients had previously undergone liver resection, eight transarterial chemoembolisation (TACE) and three microwave ablation (MWA). Results Table 1 shows patient demographics and treatment details of the study cohort. Overall survival was 79% at a median follow-up of 12 months (range 3-25). A total of seven patients died at a median of 8 months post SABR (range 4-18). Only 10/33 (30%) reported toxicity including gastrointestinal upset (n=5), fatigue (n=4) and localised rib discomfort (n=3). No Grade 3/4 toxicities were reported. Of those where radiological outcomes were available, two thirds (20/30) achieved local control at the treatment site while local disease progression occurred in 10/30 (33%). Overall, 6/20 (20%) of patients developed metastatic disease. Conclusions These data suggest SABR is a viable, well-tolerated and potentially effective treatment for HCC in patients unsuitable for surgical therapy. Longer-term follow-up data and prospective studies, including randomised trials, are required to assess survival benefit, and optimise patient selection and dose-fractionation regimens.

Identification of topoisomerase 2A as a novel bone metastasis-related gene in liver hepatocellular carcinoma.

Bone is the second most frequent site of metastasis for Liver hepatocellular carcinoma (LIHC), which leads to an extremely poor prognosis. Identifying novel biomarkers and therapeutic targets for LIHC patients with bone metastasis is urgently needed. In this study, we used multiple databases for comprehensive bioinformatics analysis, including TCGA, GEO, ICGC, GTEx, TISIDB, and TIMER, to identify key genes related to bone metastasis of LIHC. Clinical tissues and tissue microarray were adopted to assess the expression of TOP2A through qRT-PCR and immunohistochemistry analyses in LIHC. Gene enrichment analysis, DNA methylation, gene mutation, prognosis, and tumor immunity associated with TOP2A in LIHC were investigated. In vitro and in vivo experiments were performed to explore the functional role of TOP2A in LIHC bone metastasis. We identified that TOP2A was involved in LIHC bone metastasis. Clinically, TOP2A was highly expressed in LIHC tumoral specimens, with the highest level in the bone metastasis lesions. TOP2A was an independent prognostic factor that higher expression of TOP2A was markedly associated with poorer prognosis in LIHC. Moreover, the abnormal expression of TOP2A might be related to DNA hypomethylation, often accompanied by TP53 mutation, immune escape and immunotherapy failure. Enrichment analysis and validation experiments unveiled that TOP2A stimulated the Hippo-YAP signaling pathway in LIHC. Functional assays confirmed that TOP2A could promote bone-specific metastatic potential and tumor-induced osteolysis in LIHC. These findings unveil that TOP2A might be a novel prognostic biomarker and therapeutic target for LIHC bone metastasis.

Development and validation of multi-omic prognostic signature of anoikis-related genes in liver hepatocellular carcinoma.

Liver hepatocellular carcinoma (LIHC) is characterized by high morbidity, rapid progression and early metastasis. Although many efforts have been made to improve the prognosis of LIHC, the situation is still dismal. Inability to initiate anoikis process is closely associated with cancer proliferation and metastasis, affecting patients' prognosis. In this study, a corresponding gene signature was constructed to comprehensively assess the prognostic value of anoikis-related genes (ARGs) in LIHC. Using TCGA-LIHC dataset, the mRNA levels of the differentially expressed ARGs in LIHC and normal tissues were compared by Student t test. And prognostic ARGs were identified through Cox regression analysis. Prognostic signature was established and then externally verified by ICGC-LIRI-JP dataset and GES14520 dataset via LASSO Cox regression model. Potential functions and mechanisms of ARGs in LIHC were evaluated by functional enrichment analyses. And the immune infiltration status in prognostic signature was analyzed by ESTIMATE algorithm and ssGSEA algorithm. Furthermore, ARGs expression in LIHC tissues was validated via qRT-PCR and IHC staining from the HPA website. A total of 97 differentially expressed ARGs were detected in LIHC tissues. Functional enrichment analysis revealed these genes were mainly involved in MAP kinase activity, apoptotic signaling pathway, anoikis and PI3K-Akt signaling pathway. Afterward, the prognostic signature consisting of BSG, ETV4, EZH2, NQO1, PLK1, PBK, and SPP1 had a moderate to high predictive accuracy and served as an independent prognostic indicator for LIHC. The prognostic signature was also applicable to patients with distinct clinical parameters in subgroup survival analysis. And it could reflect the specific immune microenvironment in LIHC, which indicated high-risk group tended to profit from ICI treatment. Moreover, qRT-PCR and IHC staining showed increasing expression of BSG, ETV4, EZH2, NQO1, PLK1, PBK and SPP1in LIHC tissues, which were consistent to the results from TCGA database. The current study developed a novel prognostic signature comprising of 7 ARGs, which could stratify the risk and effectively predict the prognosis of LIHC patients. Furthermore, it also offered a potential indicator for immunotherapy of LIHC.

Prevalence of Hepatitis B and Hepatitis C Viral Infections and Their Associated Factors among Diabetic Patients Visiting Debre Tabor Referral Hospital, Northwest Ethiopia, 2021: A Cross-Sectional Study.

Viral hepatitis is a global public health problem that affects millions of people each year, causing disability and death. Hepatitis B and C viruses are the most common causes of viral hepatitis and are associated with chronic liver disease, cirrhosis, and hepatocellular carcinoma. The primary site of infection for these viruses is the liver, the primary site of hormone and glucose metabolism closely linked to diabetes mellitus (DM), which is associated with increased morbidity and mortality worldwide. As a result, assessing the coexistence of viral hepatitis and DM could be important in disease management, prevention, and control measures in DM patients. The aim of our study is to assess the prevalence and associated factors of HBV and HCV among diabetes patients attending Debre Tabor Referral Hospital. An institutional-based, cross-sectional study was conducted from December 1, 2021, to February 30, 2021. A systematic sampling technique was used for selecting study participants. Serum samples were screened with a rapid test kit for hepatitis B (HBV) and hepatitis C (HCV) infections. A pretested structured questionnaire was constructed to collect the data, which were later analyzed using SPSS version 23. Inferential statistics were used to evaluate the associated risk factors for the outcome variable. A p value of <0.05 was considered statistically significant. A total of 152 diabetes patients were included in this study, with 78 (51.3%) males and 74 (48.7%) females, with a mean age of 39.24 ± 17.90 years. The prevalence of HBV and HCV was 6 (3.9%) and 2 (1.3%), respectively. Most of potential risk factors such as, histories of surgical procedures, tooth extraction, hepatitis infection in the family, blood transfusion, alcohol consumption, body tattooing, and multiple sexual partners were not statistically significant for HBV and HCV infections. In this study, no association was obtained between sociodemographic, clinical, and behavioural factors and the prevalence of hepatitis B and C viruses. Furthermore, there is no significant association detected between HBV or potential HCV infection and DM. Despite these results, continuing professional training programs on HBV and HCV infection, including increased vaccination coverage rates for HBV, are required.

Insights on epithelial cells at the single-cell level in hepatocellular carcinoma prognosis and response to chemotherapy.

Background: Hepatocellular carcinoma (HCC) originates from Epithelial cells, and epithelial lineage plasticity has become a promising research direction for advancing HCC treatment. This study aims to focus on Epithelial cells to provide target insights for detecting HCC prognosis and response to drug therapy. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE149614 were clustered using Seurat, and the differentiation and evolution of epithelial cells were analyzed by Monocle 2. Scissor+ and Scissor- Epithelial cells associated with the prognostic phenotypes of bulk RNA-seq of HCC were screened using the Scissor algorithm for differential analysis to screen candidate genes. Candidate genes were overlapped with prognostic related genes screened by univariate Cox regression, and the Least Absolute Shrinkage and Selection Operator (LASSO) sparse penalty was imposed on the intersection genes to construct a risk assessment system. Results: Eight major cell subpopulations of HCC were identified, among which the proportion of epithelial cells in non-tumor liver tissues and HCC tissues was significantly different, and its proportion increased with advanced clinical stage. During the progression of HCC, the whole direction of epithelial cells differentiation trajectory was towards enhanced cell proliferation. Differential analysis between Scissor+ and Scissor- epithelial cells screened 1,265 upregulated and 191 downregulated prognostic candidate genes. Wherein, the upregulated genes were enriched in Cell processes, Genetic information processing, Metabolism and Human disease with Infection. Nevertheless, immune system related pathways took the main proportions in downregulated genes enriched pathways. There were 17 common genes between upregulated candidate genes and prognostic risk genes, of which CDC20, G6PD and PLOD2 were selected as components for constructing the risk assessment system. Risk score showed a significant correlation with tumor stage, epithelial-mesenchymal transition (EMT) related pathways and 22 therapeutic drugs, and was an independent prognostic factor for HCC. Conclusion: This study revealed the cellular composition of HCC, the differentiation evolution and functional landscape of epithelial cells in the further deterioration of HCC, and established a 3-gene risk model, which was closely related to clinical features, EMT, and drug sensitivity prediction. These findings provided insights in patient prognosis and drug therapy detection for HCC.

Chimeric antigen receptors of HBV envelope proteins inhibit hepatitis B surface antigen secretion

ObjectivesChronic hepatitis B (CHB) caused by HBV infection greatly increases the risk of liver cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) plays critical roles in the pathogenesis of...

Novel breath biomarkers identification for early detection of hepatocellular carcinoma and cirrhosis using ML tools and GCMS.

According to WHO 2019, Hepatocellular carcinoma (HCC) is the fourth highest cause of cancer death worldwide. More precise diagnostic models are needed to enhance early HCC and cirrhosis quick diagnosis, treatment, and survival. Breath biomarkers known as volatile organic compounds (VOCs) in exhaled air can be used to make rapid, precise, and painless diagnoses. Gas chromatography and mass spectrometry (GCMS) are utilized to diagnose HCC and cirrhosis VOCs. In this investigation, metabolically generated VOCs in breath samples (n = 35) of HCC, (n = 35) cirrhotic, and (n = 30) controls were detected via GCMS and SPME. Moreover, this study also aims to identify diagnostic VOCs for distinction among HCC and cirrhosis liver conditions, which are most closely related, and cause misleading during diagnosis. However, using gas chromatography-mass spectrometry (GC-MS) to quantify volatile organic compounds (VOCs) is time-consuming and error-prone since it requires an expert. To verify GC-MS data analysis, we present an in-house R-based array of machine learning models that applies deep learning pattern recognition to automatically discover VOCs from raw data, without human intervention. All-machine learning diagnostic model offers 80% sensitivity, 90% specificity, and 95% accuracy, with an AUC of 0.9586. Our results demonstrated the validity and utility of GCMS-SMPE in combination with innovative ML models for early detection of HCC and cirrhosis-specific VOCs considered as potential diagnostic breath biomarkers and showed differentiation among HCC and cirrhosis. With these useful insights, we can build handheld e-nose sensors to detect HCC and cirrhosis through breath analysis and this unique approach can help in diagnosis by reducing integration time and costs without compromising accuracy or consistency.

Hepatocellular Carcinoma in Non-Fibrotic Liver: A Narrative Review.

Hepatocellular carcinoma (HCC) in a non-fibrotic liver (F0) is considered to be rare, and there is a marked paucity of studies in the literature on this HCC type. A review of the literature shows some important clinical and tumor characteristics: (a) it occurs mainly in young female and elder male patients; (b) clinically, under normal hepatic function, alpha-fetoprotein level is often normal, and there are no risk factors; (c) associated with metabolic disease; (d) macroscopically, single large lesions are noted; and (e) microscopically, the lesions are well-differentiated and encapsulated. Radiological imaging results are straightforward, showing arterial hyperenhancement and later wash-out. The combined use of B-mode and contrast-enhanced (CE) ultrasound (US) is the most reliable and cost-effective diagnostic method. Few peri-and post-operative complications are noted and 5-year survival is not inferior to patients with HCC on fibrosis liver despite the lesion's large size. Most clinicians believe that HCC is unlikely to occur if patients have no symptoms and normal hepatic function. Although detailed clinical data are very limited, we expect that this review will help to improve the clinical management of HCC in non-fibrotic livers.

A surveillance for advanced liver disease and characterization of hyperechogenic lesions after Fontan surgery in a prospective cohort of cases with congenital univentricular heart

Abstract Background The congenital univentricular heart (UH) is a rare disease corrected with the palliative Fontan’s intervention, that restores the survival of most child and young patients up to adultwood. Unlikely, these patients develop a series of complications, among all, the Fontan associated liver disease (FALD), that causes the occurrence of liver cirrhosis and hepatocellular carcinoma (HCC), that negatively impacts the life expectancy in the majority of cases. Purpose Our primary aim was to identify the presence of severe FALD in our patients by liver fibrosis and portal hypertension scores (FORNS, liver and spleen-platelet score or LSPS and SSPS), and by liver (LS) and spleen (SS) stiffness measurement in relation to time since Fontan, and secondarly to characterize all the abdominal-US hyperechogenic lesions (US-HL) according to the LI-RADS (LR) CT/MRI categories. Method One-hundred-46 outpatients (83 m/63 f, aged 25,2±11.0 yrs) born with UH corrected with Fontan circuit have been recruited prospectively from 2019 to 2023 (FUmean 24.5±15.1 mos). Each patient underwent a complete clinical history and instrumental examination, by imaging obtained with US, CT and MRI, a specific lab-test profile, and the LS and SS evaluation by transient elastography (VCTE, Fibroscan). ROC curves were built to select the scores cut-off proved to be the most accurate to diagnose and grade FALD. Based on the presence of US-HL found in 43 cases (29,5%), we grouped: 23 cases with LR-1 or 2 (benign), 15 with LR-3 (suspect) and 5 with LR-4 or 5 (malign). Results Features for definition of failing-Fontan appeared in 17.5%, 47.5% and 80% of cases with &amp;lt;15; 15-25 or &amp;gt;25yrs since Fontan surgery, respectively (p&amp;lt;0.01). All the scores used (FORNS with cut-off ≥4, LSPS ≥1.4, SSPS ≥2.3, LS ≥20.2 and SS ≥30.7) showed high sensitivity and specificity, improving FALD diagnostic accuracy and staging (all p&amp;lt;0.001). Moreover by identification of selective criteria related to advanced liver disease and portal hypertension, we applied a novel risk-score for failing-Fontan, that predicted a low-moderate risk profile (HR 0.30;CI 0.18-0.52) in 72 patients and a high risk profile (HR 3,29,CI 1.93-5.60) in 74 (51%). During FU, 13 patients (8.9%) died, 5 received OHT (3.4%) and 5 had HCC occurrence (3.4%). Finally, cases with US-HL stratified by classes LR-3-4-5 (20 cases, 46.5%) appeared significantly associated with a more advanced FALD (16/4, 75% vs. 68/58, 46%; p=0,004) and a longer time since Fontan (26.3±9.4 vs. 19.8±10.8; p=0,025). Conclusion The novel risk score proposed may help to predict the development of cirrhosis in high risk patients and focussed on the need for surveillance by imaging methods to characterized the US-HL, that appeared at risk of malignity (nodule size &amp;gt;20mm and/or presence of wash-out into portal-hepatocellular phase or into LR ≥3 classes).