ACG Clinical Guideline: Focal Liver Lesions.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning.

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

Myxoinflammatory fibroblastic sarcoma of the liver: Case report and literature review.

RATIONALE: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade malignant soft tissue sarcoma that primarily affects the distal extremities in adults, with the highest incidence in patients in their 40s and 50s. It has a high local recurrence rate and a low metastasis rate. Although MIFSs have been documented in other sites, an MIFS in the liver is highly unusual. Herein, we present a case of a patient with hepatic MIFS. PATIENT CONCERNS: The patient was a 58-year-old Chinese man with abdominal pain as the primary symptom. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the right posterior lobe of the liver. The patient underwent surgical excision, and the excised specimen was identified as MIFS. Three years later, the patient returned to our hospital for abdominal pain. Computed tomography and magnetic resonance imaging revealed a mass in liver segments 2/3/4. DIAGNOSIS: Postoperative pathological examination of the tumor revealed the recurrence of MIFS. INTERVENTIONS: The patient underwent surgical resection of the MIFS. OUTCOMES: The patient received multiple pirarubicin-based chemotherapy treatments and an ALK inhibitor (anlotinib) within 6 months after surgery, but the tumor recurred. LESSONS: MIFS can not only occur in the proximal limbs, trunk, head, and neck but can also affect the abdominal organs. Surgical resection remains the primary treatment option for MIFS in the absence of any contraindications. Because the recurrence rate of MIFS is high, meticulous long-term monitoring is required.

Hepatocellular carcinoma outcomes and potential implications for surveillance in elderly patients.

International liver societies recommend hepatocellular carcinoma (HCC) surveillance for those at high-risk of developing HCC. While previous studies have shown the benefits of surveillance for middle-aged patients, but its necessity for elderly patients is unclear. This study aimed to assess the benefits of HCC surveillance in the elderly by comparing diagnosis mode of HCC. Consecutive, elderly patients aged 75 years or older who were newly diagnosed with HCC were screened at our institution between January 2009 and December 2021. Patients were grouped into those who were diagnosed with HCC during surveillance (n = 235, surveillance group) and those who were diagnosed with HCC due to symptoms (n = 184, symptomatic group). The study outcome was overall survival. It was compared in the overall cohort and a propensity score (PS)-matched cohort. Early-stage diagnosis was more frequent in the surveillance group than in the symptomatic group (mUICC stage I/II: 72.3% vs. 39.1%, p < 0.001). The overall survival rate was better in the surveillance group than in the symptomatic group (median 4.4 vs. 2.1 years, log-rank p < 0.001). In multivariable-adjusted models, the hazard ratio (HR) of mortality of the surveillance group compared to the symptomatic group was 0.64 (95% confidence interval (CI): 0.47-0.87). However, further adjustment for the tumor stage markedly attenuated this association, which was no longer statistically significant (adjusted HR = 0.75; 95% CI: 0.54-1.02). In the PS-matched cohort analysis, outcomes were similar when the PS matching variables included the tumor stage. In contrast, when PS matching variables did not include the tumor stage, outcomes were better for the surveillance group. The surveillance group of elderly patients showed better survival than the symptomatic group, which was largely explained by earlier tumor stage at diagnosis. This suggests that the overall outcome of elderly HCC patients could be improved by increasing surveillance-detected cases compared to symptom-driven cases.

DNA tetrahedral scaffold-corbelled self-feedback circuit for dual-mode ratiometric biosensing with Ru@COF-LZU1 accelerator.

Sensitive, reliable, and specific detection of microRNAs (miRNAs) is a key objective for disease diagnosis and prognosis. Here, a ratiometric fluorescent/electrochemiluminescent (FL/ECL) sensor was designed for the dual-mode detection of miRNA-122, a hepatocellular carcinoma biomarker. The strong ECL emission was achieved from imine-linked covalent organic framework (COF-LZU1) accelerator enriched Ru(bpy)32+ molecules (Ru@COF-LZU1), which was applied as a delimited reaction micro-reactor to enhance ECL emission. Impressively, to construct an efficient sensing platform, self-feedback circuit was grafted at the vertex of DNA tetrahedral scaffold (DTS), which could provide a solution-phase-like environment and transform miRNA-122 into abundant single-stranded DNAs on the disposable electrode. Simultaneously, the carboxyfluorescein (FAM) tagged DNA segment was cleaved and released into the reaction solution, bringing in the recovery of FL response (FL on). Finally, the introduction of glucose oxidase (GOD) could generate H2O2 by in situ catalyzing GOD to glucose, resulting in the decrease of ECL signal (ECL off). Relying on FL/ECL ratio value, miRNA-122 was quantified with high sensitivity, well selectivity, stability and favorable practicability, suggesting that the proposed biosensor hold great potential for clinical diagnosis.

The Staging of Newly Diagnosed Hepatocellular Carcinoma in Romania. A National Multicentric Study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy. METHODS: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020. RESULTS: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%). CONCLUSIONS: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

Label-free electrochemical aptasensor for the detection of HepG2 hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the screening and diagnosis of HCC exhibit inherent limitations, highlighting the ever-growing need for the development of new methods for the early diagnosis of HCC. The aim of this work was to develop a novel electrochemical aptasensor for the detection of HepG2 cells, a type of circulating tumor cells that can be used as biomarkers for the early detection of HCC. A carbon screen-printed electrode was functionalized with a composite suspension containing graphene oxide, chitosan, and polyaniline nanoparticles to increase the electrode surface and provide anchoring sites for the HepG2 cell-specific aptamer. The aptamer was immobilized on the surface of the functionalized electrode using multipulse amperometry, an innovative technique that significantly reduces the time required for aptamer immobilization. The innovative platform was successfully employed for the first time for the amplification-free detection of HepG2 cells in a linear range from 10 to 200,000 cells/mL, with a limit of detection of 10 cells/mL. The platform demonstrated high selectivity and stability and was successfully used for the detection of HepG2 cells in spiked human serum samples with excellent recoveries.

KLF15-activated MARCH2 boosts cell proliferation and epithelial-mesenchymal transition and presents diagnostic significance for hepatocellular carcinoma.

PURPOSE: Membrane associated ubiquitin ligase MARCH2 majorly involves in inflammation response and protein trafficking. However, its comprehensive role in hepatocellular carcinoma (HCC) is largely unknown. METHODS: Firstly, multiple bioinformatic analyses were applied to determine MARCH2 mRNA level, its expression comparison in diverse molecular and immune subtypes, and diagnostic value in HCC. Subsequently, RNA-seq, real-time quantitative PCR, immunohistochemistry and cell proliferation assay are used to explore the epithelial-mesenchymal transition (EMT) and proliferation by gene-silencing or overexpressing in cultured HCC cells or in vivo xenograft. Moreover, dual luciferase reporter assay and immunoblotting are delved into verify the transcription factor that activating MARCH2 promoter. RESULTS: Multiple bioinformatic analyses demonstrate that MARCH2 is upregulated in multiple cancer types and exhibits startling diagnostic value as well as distinct molecular and immune subtypes in HCC. RNA-seq analysis reveals MARCH2 may promote EMT, cell proliferation and migration in HepG2 cells. Furthermore, overexpression of MARCH2 triggers EMT and significantly enhances HCC cell migration, proliferation and colony formation in a ligase activity-dependent manner. Additionally, above observations are validated in the HepG2 mice xenografts. For up-stream mechanism, transcription factor KLF15 is highly expressed in HCC and activates MARCH2 expression. CONCLUSION: KLF15 activated MARCH2 triggers EMT and serves as a fascinating biomarker for precise diagnosis of HCC. Consequently, MARCH2 emerges as a promising candidate for target therapy in cancer management.

A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel.

The lack of non-invasive methods for detection of early metastasis is a crucial reason for the poor prognosis of lung cancer (LC) liver metastasis (LM) patients. In this study, the goal was to identify circulating biomarkers based on a biomarker model for the early diagnosis and monitoring of patients with LCLM. An 8-gene panel identified in our previous study was validated in CTC, cfRNA and exosomes isolated from primary lung cancer with & without metastasis. Further multivariate analysis including PCA & ROC was performed to determine the sensitivity and specificity of the biomarker panel. Model validation cohort (n = 79) was used to verify the stability of the constructed predictive model. Further, clinic-pathological factors, survival analysis and immune infiltration correlations were also performed. In comparison to our previous tissue data, exosomes demonstrated a good discriminative value with an AUC of 0.7247, specificity (72.48%) and sensitivity (96.87%) for the 8-gene panel. Further individual gene patterns led us to a 5- gene panel that showed an AUC of 0.9488 (p = < 0.001) and 0.9924 (p = < 0.001) respectively for tissue and exosomes. Additionally, on validating the model in a larger cohort a risk score was obtained (RS > 0.2) for prediction of liver metastasis with an accuracy of 95%. Survival analysis and immune filtration markers suggested that four exosomal markers were independently associated with poor overall survival. We report a novel blood-based exosomal biomarker panel for early diagnosis, monitoring of therapeutic response, and prognostic evaluation of patients with LCLM.

A new label free spiral sensor using impedance spectroscopy to characterize hepatocellular carcinoma in tissue and serum samples.

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer, predominantly affecting patients with chronic liver diseases such as hepatitis B or C-induced cirrhosis. Diagnosis typically involves blood tests (assessing liver functions and HCC biomarkers), imaging procedures such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), and liver biopsies requiring the removal of liver tissue for laboratory analysis. However, these diagnostic methods either entail lengthy lab processes, require expensive imaging equipment, or involve invasive techniques like liver biopsies. Hence, there exists a crucial need for rapid, cost-effective, and noninvasive techniques to characterize HCC, whether in serum or tissue samples. In this study, we developed a spiral sensor implemented on a printed circuit board (PCB) technology that utilizes impedance spectroscopy and applied it to 24 tissues and sera samples as proof of concept. This newly devised circuit has successfully characterized HCC and normal tissue and serum samples. Utilizing the distinct dielectric properties between HCC cells and serum samples versus the normal samples across a specific frequency range, the differentiation between normal and HCC samples is achieved. Moreover, the sensor effectively characterizes two HCC grades and distinguishes cirrhotic/non-cirrhotic samples from tissue specimens. In addition, the sensor distinguishes cirrhotic/non-cirrhotic samples from serum specimens. This pioneering study introduces Electrical Impedance Spectroscopy (EIS) spiral sensor for diagnosing HCC and liver cirrhosis in clinical serum-an innovative, low-cost, rapid (< 2 min), and precise PCB-based technology without elaborate sample preparation, offering a novel non-labeled screening approach for disease staging and liver conditions.

Anti-BIRC5 autoantibody serves as a valuable biomarker for diagnosing AFP-negative hepatocellular carcinoma.

Background: Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.

Identification of 1-Methylnicotinamide as a specific biomarker for the progression of cirrhosis to hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, often arising from hepatitis induced by the hepatitis B virus (HBV) in China. However, effective biomarkers for early diagnosis are lacking, leading to a 5-year overall survival rate of less than 20% among patients with advanced HCC. This study aims to identify serum biomarkers for early HCC diagnosis to enhance patient survival rates. METHODS: We established an independent cohort comprising 27 healthy individuals, 13 patients with HBV-induced cirrhosis, 13 patients with hepatitis B-type HCC, and 8 patients who progressed from cirrhosis to hepatocellular carcinoma during follow-up. Serum metabolic abnormalities during the progression from cirrhosis to HCC were studied using untargeted metabolomics. Liquid chromatography-mass spectrometry-based metabolomics methods characterized the subjects' serum metabolic profiles. Partial least squares discriminant analysis (PLS-DA) was employed to elucidate metabolic profile changes during the progression from cirrhosis to HCC. Differentially expressed metabolites (DEMs) between cirrhosis and HCC groups were identified using the LIMMA package in the R language. Two machine learning algorithms, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest Classifier (RF), were used to identify key metabolic biomarkers involved in the progression from cirrhosis to HCC. Key metabolic biomarkers were further validated using targeted metabolomics in a new independent validation cohort comprising 25 healthy individuals and 25 patients with early-stage hepatocellular carcinoma. RESULTS: A total of 155 serum metabolites were identified, of which 21/54 metabolites exhibited significant changes in HCC patients compared with cirrhosis patients and healthy individuals, respectively. PLS-DA clustering results demonstrated a significant change trend in the serum metabolic profile of patients with HBV-induced cirrhosis during the progression to HCC. Utilizing LASSO regression and RF algorithms, we confirmed 10 key metabolic biomarkers. Notably, 1-Methylnicotinamide (1-MNAM) exhibited a persistent and significant decrease in healthy individuals, cirrhosis, and HCC patients. Moreover, 1-MNAM levels in developing patients were significantly higher during the cirrhosis stage than in the HCC stage. Targeted metabolomic validation in an external cohort further confirmed the good diagnostic performance of 1-MNAM in early HCC detection. CONCLUSION: Our findings imply that 1-MNAM may be a specific biomarker for the progression of cirrhosis to HCC.

Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.

Introduction: This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment. Methods: We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance. Results: The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Conclusion: Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Comparison of the Ability of Gadobenate Dimeglumine and Gadolinium Ethoxybenzyl Dimeglumine to Display the major Features for Noninvasively Diagnosing Hepatocellular Carcinoma According to the LI-RADS 2018v.

OBJECTIVE: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). CONCLUSION: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.

Precision detection of hepatocellular carcinoma-associated telomerase RNA with SA@Comb-HCR nanosystem.

Accurate intracellular visualization of human telomerase RNA (hTR) is imperative for early diagnosis and treatment monitoring of hepatocellular carcinoma (HCC). While isothermal amplification-based DNA cascade strategies are promising, challenges persist in achieving great intake efficiency of detection probes within tumor cells and enhancing intracellular reaction efficiency. This study introduces a SA@Comb-HCR nanosystem, a highly effective approach for in situ hTR detection in HCC cells. Sodium alginate-coated liposomes ensures efficient nanoprobe delivery, which are then combined with proximity effect-inspired signal amplification. The coating of sodium alginate facilitates receptor-mediated endocytosis, prevents serum protein adhesion, and mitigates cationic liposome cytotoxicity. The designed Comb-like consolidated hairpin probe enhances the concentration of the local reactant, resulting in cascade amplification upon hTR activation. This technique achieves precision detection of intracellularly overexpressed hTR in HCC cells with a remarkable detection limit of 0.7 pM. This approach holds great promise for advancing targeted and sensitive early clinical diagnosis of HCC.

Prognostic value of tertiary lymphoid structures in hepatocellular carcinoma: a meta-analysis and systematic review.

Background: Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC. Methods: We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords "tertiary lymphoid structures" and "hepatocellular carcinoma." The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR). Results: Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients. Conclusion: The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Identification and validation of immune-related gene signature models for predicting prognosis and immunotherapy response in hepatocellular carcinoma.

Background: This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize the assessment of immunotherapy response. Methods: A training set comprising 305 HCC cases was obtained from The Cancer Genome Atlas (TCGA) database. Initially, a screening process was undertaken to identify prognostically significant immune-related genes (IRGs), followed by the application of logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods for gene modeling. Subsequently, the final model was constructed using support vector machines-recursive feature elimination (SVM-RFE). Following model evaluation, quantitative polymerase chain reaction (qPCR) was employed to examine the gene expression profiles in tissue samples obtained from our cohort of 54 patients with HCC and an independent cohort of 231 patients, and the prognostic relevance of the model was substantiated. Thereafter, the association of the model with the immune responses was examined, and its predictive value regarding the efficacy of immunotherapy was corroborated through studies involving three cohorts undergoing immunotherapy. Finally, the study uncovered the potential mechanism by which the model contributed to prognosticating HCC outcomes and assessing immunotherapy effectiveness. Results: SVM-RFE modeling was applied to develop an OS prognostic model based on six IRGs (CMTM7, HDAC1, HRAS, PSMD1, RAET1E, and TXLNA). The performance of the model was assessed by AUC values on the ROC curves, resulting in values of 0.83, 0.73, and 0.75 for the predictions at 1, 3, and 5 years, respectively. A marked difference in OS outcomes was noted when comparing the high-risk group (HRG) with the low-risk group (LRG), as demonstrated in both the initial training set (P <0.0001) and the subsequent validation cohort (P <0.0001). Additionally, the SVMRS in the HRG demonstrated a notable positive correlation with key immune checkpoint genes (CTLA-4, PD-1, and PD-L1). The results obtained from the examination of three cohorts undergoing immunotherapy affirmed the potential capability of this model in predicting immunotherapy effectiveness. Conclusions: The HCC predictive model developed in this study, comprising six genes, demonstrates a robust capability to predict the OS of patients with HCC and immunotherapy effectiveness in tumor management.

Two Concepts of Hepatitis B Core-Related Antigen Assay: A Highly Sensitive and Rapid Assay or an Effective Tool for Widespread Screening.

Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B patients in whom serum HBV DNA or hepatitis B surface antigen is undetectable. The HBcrAg measurement system was developed based on two concepts. One is a fully-automated and highly-sensitive HBcrAg assay (iTACT-HBcrAg) and the other is a point-of-care testing (POCT) that can be used in in resource-limited areas. iTACT-HBcrAg is an alternative to HBV DNA for monitoring HBV reactivation and predicting the development of hepatocellular carcinoma. This validated biomarker is available in routine clinical practice in Japan. Currently, international guidelines for the prevention of mother-to-child transmission recommend anti-HBV prophylaxis for pregnant women with high viral loads. However, over 95% of HBV-infected individuals live in countries where HBV DNA quantification is widely unavailable. Given this situation, a rapid and simple HBcrAg assay for POCT would be highly effective. Long-term anti-HBV therapy may have potential side effects and appropriate treatment should be provided to eligible patients. Therefore, a simple method of determining the indication for anti-HBV treatment would be ideal. This review provides up-to-date information regarding the clinical value of HBcrAg in HBV management, based on iTACT-HBcrAg or POCT.