Virus-associated Hepatocellular Carcinoma Research Articles

Dose-dependent Relationship between Alcohol Consumption and the Risks of Hepatitis B Virus-associated Cirrhosis and Hepatocellular Carcinoma: A Meta-analysis and Systematic Review

Dose-dependent Relationship between Alcohol Consumption and the Risks of Hepatitis B Virus-associated Cirrhosis and Hepatocellular Carcinoma: A Meta-analysis and Systematic Review

Abstract A019: Identification and Genomic Analysis of miRNA-mRNA Binding Site SNPs in Hepatitis C Virus-Associated Hepatocellular Carcinoma

Abstract Hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally. MicroRNAs (miRNAs) play critical roles in gene regulation, and single nucleotide polymorphisms (SNPs) within miRNA binding sites can disrupt this regulation, potentially influencing HCC pathogenesis. The present study aims to identify and characterize SNPs within miRNA binding sites of genes associated with HCV- induced HCC (HCV-HCC). A comprehensive bioinformatics analysis workflow was devised. HCV-specific differentially expressed (DE) miRNAs and mRNAs were extracted from literature and databases. SNPs in the 3' UTRs of HCV-HCC genes were identified, and their impact on miRNA binding was predicted using PoymiRTS and TargetScan. RNAhybrid was used to estimate minimum folding energy (MFE) differences (ΔMFE) between mutant and wild types. Functional enrichment analysis was conducted to elucidate the biological processes affected by these SNPs. Our analysis revealed several significant alterations in miRNA-mRNA binding pairs due to SNPs within genes associated with HCV-HCC. For instance, among the downregulated genes in HCV-HCC, the SNP in CTSB (rs3088245; 193T>C) predicted to increase the stability of the miR-27b - CTSB duplex (ΔMFE: 1.4), suggesting enhanced binding and potentially improved repression of CTSB. Conversely, the SNP in EGR2 (rs61865883; 287 T>A) decreased the stability of the miR-140-5p - EGR2 mRNA interaction (ΔMFE: -1.9), suggesting a weaker binding affinity and potentially reduced repression of EGR2 expression. Considering the tumor suppressor role of EGR2, presence of this SNP is likely to reflect good prognosis. For the upregulated gene oncogene, XIAP, the SNP (rs6648556; 5892 T>C) is predicted to enhance the binding of miR- 200c (ΔMFE: 1.5), likely resulting in increased suppression of XIAP expression in patients carrying this SNP and improved prognosis. Our study emphasizes the importance of considering genetic variations in miRNA binding sites in the context of HCV-HCC. These SNPs may serve as genetic modifiers influencing disease susceptibility and progression. Further experimental studies are warranted to explore their potential as therapeutic agents and predictors of prognosis in HCV-HCC patients. Citation Format: Azeem M Butt, Anum Qamar, Shafiqa Siddique. Identification and Genomic Analysis of miRNA-mRNA Binding Site SNPs in Hepatitis C Virus-Associated Hepatocellular Carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A019.

Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma.

In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

Mechanism of emodin in treating hepatitis B virus-associated hepatocellular carcinoma: network pharmacology and cell experiments.

Hepatocellular carcinoma (HCC) is a pressing global issue, with Hepatitis B virus (HBV) infection remaining the primary. Emodin, an anthraquinone compound extracted from the natural plant's. This study investigates the moleculartargets and possible mechanisms of emodin in treating HBV-related HCC based on network pharmacology and molecular docking and validates the screened molecular targets through in vitro experiments. Potential targets related to emodin were obtained through PubChem, CTD, PharmMapper, SuperPred, and TargetNet databases. Potential disease targets for HBV and HCC were identified using the DisGeNET, GeneCards, OMIM, and TTD databases. A Venn diagram was used to determine overlapping genes between the drug and the diseases. Enrichment analysis of these genes was performed using GO and KEGG via bioinformatics websites. The overlapping genes were imported into STRING to construct a protein-protein interaction network. Cytoscape 3.9.1 software was used for visualizing and analyzing the core targets. Molecular docking analysis of the drug and core targets was performed using Schrodinger. The regulatory effects of emodin on these core targets were validate through in vitro experiments. A total of 43 overlapping genes were identified. GO analysis recognized 926 entries, and KEGG analysis identified 135 entries. The main pathways involved in the KEGG analysis included cancer, human cytomegalovirus infection and prostate cancer. The binding energies of emodin with HSP90AA1, PTGS2, GSTP1, SOD2, MAPK3, and PCNA were all less than -5 kcal/mol. Compared to normal liver tissue, the mRNA levels of XRCC1, MAPK3, and PCNA were significantly elevated in liver cancer tissue. The expression levels of XRCC1, HIF1A, MAPK3, and PCNA genes were closely related to HCC progression. High expressions of HSP90AA1, TGFB1, HIF1A, MAPK3, and PCNA were all closely associated with poor prognosis in HCC. In vitro experiments demonstrated that emodin significantly downregulated the expression of HSP90AA1, MAPK3, XRCC1, PCNA, and SOD2, while significantly upregulating the expression of PTGS2 and GSTP1. This study, based on network pharmacology and molecular docking validation, suggests that emodin may exert therapeutic effects on HBV-related HCC by downregulating the expression of XRCC1, MAPK3, PCNA, HSP90AA1, and SOD2, and upregulating the expression of PTGS2 and GSTP1.

Elevated nuclear expression of ZHX1 correlates with poor prognosis in hepatocellular carcinoma (HCC): Comparison of nuclear and cytoplasmic distribution of the ZHX family in HCC cells.

The role of the zinc fingers and homeoboxes family (ZHX1-3), transcriptional repressors, through their subcellular localization in hepatocellular carcinoma (HCC), is not fully understood. The present study aimed to examine the differential nuclear and cytoplasmic expression of ZHXs in HCC tissues. Immunohistochemistry was utilized to detect the expression of ZHXs in 54 liver tissues from HCC (n=33), hepatitis C (n=16), and the normal liver tissue surrounding hepatic metastasis of colorectal cancer (n=5). Next-generation sequencing and digital polymerase chain reaction identified gene mutations associated with HCC. Kaplan-Meier curves were constructed to evaluate the relationship between ZHX expression and survival. The results were validated using data from The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were undertaken to identify independent prognostic factors. High nuclear expression of ZHX1 was associated with poor overall survival (OS), while high nuclear expression of ZHX2 correlated with higher recurrence. Conversely, patients with high cytoplasmic expression of ZHX3 had lower recurrence and better OS. Hepatitis B virus-associated HCC was related to high cytoplasmic expression of ZHX1, which was marginally related to telomerase reverse transcriptase (TERT) promoter mutation-negative HCC. In contrast, low nuclear expression of ZHX3 was associated with TERT promoter mutation-positive HCC and HCC patients over 70years old. These results suggest that the expression and localization of different ZHXs may be related to HCC progression, potentially inferring genetic backgrounds such as TERT promoter mutation. Further studies on the relationship between HCC and ZHXs will enhance our understanding and control of HCC.

Expression and clinical significance of NLRC5 in hepatocellular carcinoma

ABSTRACT NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03–3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

Computational design and validation of siRNA molecules to silence oncogenic CTNNB1 mRNA as a potential therapeutic strategy against hepatitis B/C virus-associated hepatocellular carcinoma

The majority of hepatocellular carcinoma cases are caused by infection with hepatitis B (HBV) or C (HCV) viruses. CTNNB1 is the most mutated oncogene in HBV- and HCV-associated tumors. CTNNB1 mutations can lead to β-catenin accumulation, resulting in tumor progression. Small interfering RNAs (siRNAs) can be used to silence CTNNB1 mRNA. After prediction and evaluation, four siRNAs were found to have the highest silencing potential. All four siRNAs had an acceptable GC content, no palindromic sequences, no off-targets, were thermostable, and had accessible target sites. Molecular docking of the siRNAs to Argonaute 2 demonstrated favorable docking scores within the binding pocket for three siRNAs. Molecular dynamics simulations and binding energy calculations demonstrated that the siRNAs steadily remained in the binding pocket. In this study, three siRNAs were successfully designed to silence oncogenic CTNNB1 mRNA as a therapeutic strategy against hepatocellular carcinoma and warrant further in vitro and in vivo validation.

Clinical significance of LINC02532 in hepatitis B virus-associated hepatocellular carcinoma and its regulatory effect on tumor progression

Background and aimLong non-coding RNAs (lncRNAs) play an important role in tumor progression, including in hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV). Therefore, the aim of this study was to investigate the role of LINC02532 in HCC, mainly for diagnostic prognostic value and cellular function, as well as mechanistic aspects. MethodsInitially, GEO and VirBase databases were used to screen for aberrant lncRNAs in HBV-HCC.Then, HBV-HCC persons followed up in our center were retrospectively studied to investigate the diagnostic, prognostic value of LINC02532 in HBV-HCC. Subsequently, the role of LINC02532 in HBV-HCC was measured using cellular function assay methods and possible mechanisms were analyzed in conjunction with bioinformatic predictive science. ResultsLINC02532 was a lncRNA abnormally expressed in HBV-HCC. LINC02532 was significantly up-regulated in the expression level in HBV-HCC tissues compared with normal tissues from patients. Moreover, LINC02532 could distinguish HBV-HCC and predict the prognosis of HBV-HCC. In vitro experiments showed that LINC02532 could regulate miR-455–3p and promote the malignant characterization of HBV-HCC cells. CHEK2 was a target gene of miR-455–3p. Conclusions: The prognosis and diagnosis of HBV-HCC can rely on the expression of LINC02532. LINC02532 was important for further progression of HBV-HCC, by moderating miR-455–3p/CHEK2.

Prognostic and therapeutic potential of imbalance between PD-1+CD8 and ICOS+Treg cells in advanced HBV-HCC.

Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOShi) and low-ratio (PD-1/ICOSlo) groups according to ratio median. Compared with PD-1/ICOSlo patients, the PD-1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOShi patients exhibited a higher proportion of tissue-resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOSlo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.

Hepatitis B virus-associated hepatocellular carcinoma with invasion into right atrium

Hepatitis B virus-associated hepatocellular carcinoma with invasion into right atrium

Identification of hub genes and pathways in hepatitis B virus-associated hepatocellular carcinoma: A comprehensive in silico study.

The hepatitis B virus (HBV) is one of the most common causes of liver cancer in the world. This study aims to provide a better understanding of the mechanisms involved in the development and progression of HBV-associated hepatocellular carcinoma (HCC) by identifying hub genes and the pathways related to their functions. GSE83148 and GSE94660 were selected from the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) with an adjusted p-value < 0.05 and a |logFC| ≥1 were identified. Common DEGs of two data sets were identified using the GEO2R tool. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) databases were used to identify pathways. Protein-protein interactions (PPIs) analysis was performed by using the Cytoscap and Gephi. A Gene Expression Profiling Interactive Analysis(GEPIA) analysis was carried out to confirm the target genes. One hundred and ninety-eight common DEGs and 49 hub genes have been identified through the use of GEO and PPI, respectively. The GO and KEGG pathways analysis showed DEGs were enriched in the G1/S transition of cell cycle mitotic, cell cycle, spindle, and extracellular matrix structural constituent. The expression of fourgenes (TOP2A, CDK1, CCNA2, and CCNB2) with high scores in module 1 were more in tumor samples and have been identified by GEPIA analysis. In this study, the hub genes and their related pathways involved in the development of HBV-associated HCC were identified. These genes, as potential diagnostic biomarkers, may provide a potent opportunity to detect HBV-associated HCC at the earliest stages, resulting in a more effective treatment.

Comparative analysis of liver resection in Non-B Non-C and hepatitis virus-associated hepatocellular carcinoma

BackgroundThe incidence of non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC) is increasing in our country. This study assesses the feasibility of employing an identical surgical treatment strategy for resectable NBNC-HCC as that for hepatitis virus-associated HCC (HV-HCC). MethodsA retrospective analysis (1993–2023) of 1321 curative liver resections for HCC at a single institution was performed. Propensity score matching ensured a balanced comparison of preoperative clinical factors, including tumor status and background liver condition. ResultsThe proportion of NBNC-HCC cases has gradually increased, reaching up to 70 %. After matching, 294 of 473 NBNC-HCC patients and 294 of 848 HV-HCC patients were compared. Operative outcomes, including operation time, blood loss, type of surgical procedure, and morbidity, were comparable. Long-term outcome analysis showed similar recurrence-free survival (HR: 0.86, 95 % CI: 0.70–1.06, P = 0.167) and overall survival (HR: 0.98, 95 % CI: 0.79–1.23, P = 0.865) for NBNC-HCC. Multivariable analysis identified ICGR15 ≥ 15 %, ALBI grade 2 or 3, aspartate aminotransferase ≥40, tumor size > 5 cm, multiple tumors, macrovascular invasion, and microvascular invasion as independent prognostic factors for overall survival, while hepatitis B or C virus status lost significance. ConclusionsDespite the increasing incidence of NBNC-HCC, comparable outcomes were achieved between the two groups of matched cohort.

The Adaptive Immune Response in Hepatitis B Virus-Associated Hepatocellular Carcinoma Is Characterized by Dysfunctional and Exhausted HBV-Specific T Cells.

This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.

Deciphering the latent biomarkers in HBV and HDV- associated HepatoCellular carcinoma – An integrated bioinformatics analysis

Abundant studies convey chronic viral hepatitis (HBV and HDV) infection to be associated with development and promotion of HepatoCellular Carcinoma (HCC), making HBV and HDV contamination as one of the foremost source of HCC development worldwide. In the present study we intended to identify potential therapeutic biomarkers for HBV and HDV induced HCC development and progression. Hereby, we executed meta-analysis of micro-array datasets: GSE121248 comprising 107 viral infected samples categorized as 37 normal adjacent samples and 70 tumor samples along with GSE107170 containing 307 virus-positive tissue samples of which 155 samples were considered for further analysis encompassing 105 normal tissues and 50 HCC tumor samples. Eventually by analyzing an aggregate of 262 samples through GeneSpring Software, 486 Differentially Expressed Genes (DEGs) were identified among HBV and HDV infected samples leading to HCC including 152 up-regulated and 334 down-regulated genes. Subsequently resulted DEGs were processed for functional annotation by using OmicsBox, Pathway enrichment and disease association analysis by using EnrichR webserver. Additionally, Protein-Protein Interaction Network was constructed to identify top 10 most significant hub nodes by using Cytoscape tool and cytohubba plugin. Furthermore the identified top 10 noteworthy hub nodes were analyzed for overall survival, disease free survival and expression validation in HCC samples by employing GEPIA2 and HPA databases. Consequently hub genes were assessed for diagnostic efficacy by Receiver Operating Characteristic curves (ROC) which demonstrates promising performance of all the hub genes. Conclusively, our findings postulate TOP2A, PBK, NUF2, CCNB1, CDC20, BUB1B, NDC80, MAD2L1, DLGAP5 and KIF4A as the plausible biomarkers occupied in oncogenic pathways having a probable function in progression of HBV and HDV contaminated cells to HCC, proliferation of HCC and tumorogenesis. The present study also aids for elevated understanding of virus-associated HCC progression.

Fonction de l'ARNnc exosomal HEIH dans le carcinome hépatocellulaire associé au virus de l'hépatite B

Long non-coding RNA-HEIH (lncRNA-HEIH) is a potential biomarker for patients with hepatocellular carcinoma (HCC), but exosomal lncRNA-HEIH in patients with hepatitis B virus-associated HCC (B-HCC) is unclear. This study aimed to investigate the expression of exosomal lncRNA-HEIH in B-HCC patients and explore its clinical significance. We collected blood samples from 60 B-HCC patients, 60 non-hepatitis virus-associated HCC (N-HCC) patients, and 50 healthy volunteers. Exosomal lncRNA-HEIH levels were measured by real-time PCR and analyzed for their correlation with patient prognosis using Kaplan-Meier analysis. Multivariate COX regression analysis was conducted to identify factors affecting patient outcomes. The effects of lncRNA-HEIH on carcinogenesis were also investigated by constructing a Huh7 cell line stably expressing the hepatitis B virus. In the B-HCC group, there was a positive correlation between hepatitis B virus and exosomal lncRNA-HEIH. The 5-year survival rate of the exosomal lncRNA-HEIH high-expression group was significantly lower than that of the low-expression group in the B-HCC group, but not in the N-HCC group. Exosomal lncRNA-HEIH level was related to the TNM stage, lymph node metastasis and AFP. Exosomal lncRNA-HEIH level was independent risk factors for poor prognosis in B-HCC patients. In Huh7-HBV cells, lncRNA-HEIH level was significantly higher than in control, and the migration capacity of Huh7-HBV cells decreased significantly after down-regulating lncRNA-HEIH. Our findings suggest that exosomal lncRNA-HEIH is abnormally expressed and closely related to poor prognosis in B-HCC patients, indicating its potential as a diagnostic and therapeutic target for HBV-associated HCC.

Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker.MethodsAn integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC.ResultsBioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis.ConclusionsThe findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.

Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide.

Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.

Entecavir versus tenofovir for prevention of hepatitis B virus-associated hepatocellular carcinoma after curative resection: study protocol for a randomized, open-label trial

BackgroundEntecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection.MethodsThis study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery.DiscussionThis study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study.Trial registrationClinicalTrials.gov NCT02650271. Registered on January 7, 2016.

Predictive Value of Peripheral Blood Eosinophil Count on the Efficacy of Treatment with Camrelizumab in Combination with Lenvatinib in Patients with Advanced Hepatitis B-Associated Hepatocellular Carcinoma.

Objective: To examine the effects of peripheral blood eosinophil (EOS) count and its dynamic alterations on the treatment efficacy and prognosis of patients with advanced hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) receiving camrelizumab combined with lenvatinib (C + L) therapy. Methods: A retrospective analysis was performed on 200 patients with advanced HBV-HCC who were admitted to two centers from January 2018 to August 2023 and treated with C + L. EOS, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were determined before C + L treatment (EOS0, NLR0, and PLR0) and after three cycles of treatment (EOS3, NLR3, and PLR3). The area under the curve was calculated using the receiver operating characteristic (ROC) curve. NLR and PLR served as references to analyze the effect of differences in EOS in predicting the survival efficacy of patients with HBV-HCC treated using C + L. The independent risk factors affecting progression-free survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate Cox proportional risk models. Results: The ROC curve revealed that the predictive value of EOS3 was better than those of NLR3 and PLR3 for the long-term treatment efficacy of patients with intermediate and advanced HBV-HCC receiving C + L. Statistically significant differences were observed between groups with different levels of EOS0 and EOS3 and the evaluation of treatment efficacy after 3 weeks (P < 0.05). The median PFS of the high-EOS0 group was higher than that of the low-EOS0 group (P = 0.027); median PFS of the high EOS3 group was higher than that of the low EOS3 group (P = 0.018); median OS of the high EOS0 group was higher than that of the low EOS0 group (P = 0.032); median OS of the high EOS3 group was higher than that of the low EOS3 group (P < 0.0001). Multifactorial Cox analysis revealed that EOS3 was an independent predictor of PFS and that EOS0 was an independent predictor of OS (P < 0.05). Conclusion: EOS may be an ideal indicator for predicting the treatment efficacy and prognosis of patients with advanced HBV-HCC receiving C + L.