Alpha-fetoprotein Research Articles

Ultrasensitive dynamic light scattering immunodetection of alpha-fetoprotein using heptamer-amplified nanoparticle crosslinking aggregation.

Anovel construction strategy is introducedfor an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies on a self-assembled heptamer fusion protein (A1-C4bpα), incorporating the dual functions of multivalent recognition and crosslinking aggregation amplification due to the presence of seven AFP-specific A1 nanobodies on the A1-C4bpα heptamer. Leveraging antibody-functionalized magnetic nanoparticles for target AFP capture and DLS signal output, the proposed heptamer-assisted DLS immunosensor offers high sensitivity, strong specificity, and ease of operation. Under the optimized conditions, the designed DLS immunosensor demonstrates excellent linear detection of AFP in the concentration range 0.06 ng mL-1 to 512 ng mL-1, with a detection limit of 15 pg mL-1. The selectivity, accuracy, precision, practicability, and reliability of this newly developed method were further validated through an assay of AFP levels in spiked and actual human serum samples. Thiswork introduces a novel approach for constructing ultrasensitive DLS immunosensors, easily extendable to the sensitive determination of other targets via simply replacing the nanobody sequence, holding great promise in various applications, particularly in disease diagnosis.

Electrochemiluminescence Immunosensor for Alpha-Fetoprotein Based on Polypyrrole-Luminol Nanoparticles

The study of luminol electrochemiluminescence (ECL) is commonly conducted in alkaline solutions. However, many substances, especially biomolecules, are only stable in neutral or weakly acidic media. In this study, a sensitive ECL immunosensor was developed using polypyrrole-luminol (PPY-Lu) nanoparticles for the determination of alpha-fetoprotein (AFP) in a neutral buffer. Polypyrrole (PPY) nanoparticles were synthesized by chemical oxidation. Subsequently, luminol was attached to the PPY nanoparticles via electrostatic interaction, resulting in the formation of the desired nanoparticles which exhibited strong and stable electrochemiluminescence in neutral solution. Furthermore, the PPY-Lu nanoparticles have abundant amino groups suitable for immobilizing biomolecules. An ECL immunosensor for AFP was fabricated by immobilizing anti-AFP on the PPY-Lu-modified electrode surface. The electrochemiluminescence decreased when AFP was captured. The immunosensor exhibited a linear range from 1.0 × 10−11 to 1.0 × 10−6 mg/mL with a low detection limit of 8.5 × 10−12 mg/mL and excellent specificity, reproducibility, and long-term stability. This designed immunosensor provides a new method for the determination of biomarkers in clinical analysis.

Novel Cadmium Telluride Quantum Dot (QD) Fluorescent Probe for the Sensitive Determination of the Hepatocellular Carcinoma (HCC) Biomarker Alpha-Fetoprotein (AFP)

The concentration of alpha-fetoprotein (AFP) generally increases in the serum of hepatocellular carcinoma (HCC) patients. Hence, AFP is a biomarker for HCC detection, diagnosis, and treatment. However, the sensitivity is unsatisfactory. Here a fluorescent probe based on CdTe quantum dots (QDs-AFPAb) was prepared and a simple sensitive fluorescence immunoassay on nitrocellulose membranes (NFIA) was developed for alpha-fetoprotein. This method exhibited a low detection limit of 2.18 pg/mL with a linear range from 10 to 1.0 × 107 pg/mL. In addition, the sensitivity allowed the identification of HCC and non-HCC serum. This method is sensitive, easy, and low-cost for the diagnosis of HCC.

Tumor Mutational Burden From Circulating Tumor DNA Predicts Recurrence of Hepatocellular Carcinoma After Resection: An Emerging Biomarker for Surveillance.

Describe the utility of circulating tumor DNA in the postoperative surveillance of hepatocellular carcinoma (HCC). Current biomarkers for HCC like alpha-fetoprotein (AFP) are lacking. Circulating tumor DNA (ctDNA) has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown. Patients with HCC undergoing curative-intent resection from November 1, 2020, to July 1, 2023, received ctDNA testing using the Guardant360 platform. Tumor mutational burden (TMB) is calculated as the number of somatic mutations-per-megabase of genomic material identified. Forty-seven patients had postoperative ctDNA testing. The mean follow-up was 27 months, and the maximum was 43.2 months. Twelve patients (26%) experienced recurrence. Most (n=41/47, 87.2%) had identifiable ctDNA postoperatively; 55.3% (n=26) were TMB-not detected versus 45.7% (n=21) TMB-detectable. Postoperative identifiable ctDNA was not associated with RFS ( P =0.518). Detectable TMB was associated with reduced RFS (6.9 vs 14.7mo, P =0.049). There was a higher rate of recurrence in patients with TMB (n=9/21, 42.9%, vs n=3/26, 11.5%, P =0.02). Area under the curve for TMB-prediction of recurrence was 0.752 versus 0.550 for AFP. ROC analysis established a TMB cutoff of 4.8mut/mB for predicting post-operative recurrence ( P =0.002) and RFS ( P =0.025). AFP was not correlated with RFS using the lab-normal cutoff (<11ng/mL, P =0.682) or the cutoff established by ROC analysis (≥4.6ng/mL, P =0.494). TMB-high was associated with poorer RFS on cox-regression analysis (hazard ratio=5.386, 95% CI: 1.109-26.160, P =0.037), while microvascular invasion ( P =0.853) and AFP ( P =0.439) were not. Identifiable TMB on postoperative ctDNA predicts HCC recurrence and outperformed AFP in this cohort. Perioperative ctDNA may be a useful surveillance tool following curative-intent hepatectomy. Larger-scale studies are needed to confirm this utility and investigate additional applications in HCC patients, including the potential for prophylactic treatment in patients with residual TMB after resection.

Micro-RNA-371a-3p in Germ Cell Testicular Tumors on Diagnosis: A Prospective Case-Control Study in Turkish Population.

We aimed to evaluate the diagnostic sensitivity and specificity of the miRNA-371a-3p for the primary diagnosis of germ cell tumors (GCT) and to investigate its relationship with pathological factors and clinical stage in the Turkish population. In this prospective study, a total of 60 patients with GCTs, and 40 healthy male controls were examined for serum levels of miRNA-371a-3p before orchiectomy and again two weeks after surgery. The miRNA-371a-3p, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (bHCG) levels in the preoperative and postoperative periods were compared at different clinical stages. Receiver operating characteristics curve analyses were performed to determine the sensitivity and specificity of miRNA-371a-3p. Clinical and pathological factors such as clinical stage (CS), tumor size, histology, rete testis invasion, and lymphovascular invasion, potentially impacting miRNA-371a-3p expression levels (relative quantity, RQ), were evaluated statistically. The sensitivity of miR-371a-3p in GCT patients was 98.3%, and the specificity was 95% (AUC = 0.997 [95%Cl:0.99-1], p < .001). miR-371a-3p expression was not detected in two patients with teratoma. The median miR-371a-3p RQ was 489 times in GCT and 2.2 times in the Control group (p < .001). In the postoperative period, there was a significant decrease in AFP and bHCG levels in all CS-1 (p = .01) and 30% of the other CS (p = .3). Throughout this time there was a decrease of 19 times at the miR-371a-3p RQ in CS-1(p < .001) and 1.6 times in the other CS (p < .001). The miR-371a-3p RQs were correlated with tumor size and CS. The miR-371a-3p seems to have higher diagnostic accuracy than classical serum tumor markers in GCT.

A novel aptasensor platform for the detection of carcinoembryonic antigen using quartz crystal microbalance

In this study, a quartz crystal microbalance (QCM) aptasensor for carcinoembryonic antigen (CEA), a well-known biomarker for various cancer types, was reported, utilizing two different aptamers. To achieve this, a nanofilm of 4-mercaptophenyl was electrochemically attached to gold-coated QCM crystal surfaces via the reduction of 4-mercaptobenzenediazonium salt (4 MB-DAT) using cyclic voltammetry. Subsequently, gold nanoparticles (AuNP) were affixed to this structure, and then aptamers (antiCEA1 and antiCEA2) modified with SH-functional ends bound to AuNPs completed the modification. The analytical performance of the CEA sensor was evaluated through simultaneous QCM measurements employing CEA solutions ranging from 0.1 ng/mL to 25 ng/mL. The detection limit (LOD) for CEA was determined to be 102 pg/mL for antiCEA1 and 108 pg/mL for antiCEA2 aptamers. Interday and intraday precision and accuracy tests yielded maximum results of 4.3 and + 3.8, respectively, for both aptasensors, as measured by relative standard deviation (RSD%) and relative error (RE%). The kinetic data of the aptasensors resulted in affinity values (KD) of 0.43 ± 0.14 nM for antiCEA1 and 0.75 ± 0.42 nM for antiCEA2. These values were lower than the reported values of 3.9 nM and 37.8 nM for both aptamers, respectively. The selectivity of the aptasensor was evaluated by measuring the signal changes caused by alpha-fetoprotein (AFP), cancer antigen (CA-125), and vascular endothelial growth factor (VEGF-165) individually and together at a concentration of 500 ng/mL, resulting in a maximum 4.1 % change, which was comparable to precision and accuracy values reported in the literature. After confirming the selectivity of the aptamers, recovery experiments were conducted using spiked commercial serum samples to simulate real samples, and the lowest recovery value obtained was 95.4 %. It was determined that two different aptasensors could be successfully used for the QCM-based detection of CEA in this study.

Preoperative and postoperative MRI-based models versus clinical staging systems for predicting early recurrence in hepatocellular carcinoma

BackgroundTo predict the early recurrence of HCC patients who received radical resection using preoperative variables based on Gd-EOB-DTPA enhanced MRI, followed by the comparison with the postoperative model and clinical staging systems. MethodsOne hundred and twenty-nine HCC patients who received radical resection were categorized into the early recurrence group (n = 48) and the early recurrence-free group (n = 81). Through COX regression analysis, statistically significant variables of laboratory, pathologic, and Gd-EOB-DTPA enhanced MRI results were identified. The preoperative and postoperative models were established to predict early recurrence, and the prognostic performances and differences were compared between the two models and clinical staging systems. ResultsSix variables were incorporated into the preoperative model, including alpha-fetoprotein (AFP) level, aspartate aminotransferase/platelet ratio index (APRI), rim arterial phase hyperenhancement (rim APHE), peritumoral hypointensity on hepatobiliary phase (HBP), CERHBP (tumor-to-liver SI ratio on hepatobiliary phase imaging), and ADC value. Moreover, the postoperative model was developed by adding microvascular invasion (MVI) and histological grade. The C-index of the preoperative model and postoperative model were 0.889 and 0.901 (p = 0.211) respectively. Using receiver operating characteristic curve analysis (ROC) and decision curve analysis (DCA), it was determined that the innovative models we developed had superior predictive capabilities for early recurrence in comparison to current clinical staging systems. HCC patients who received radical resection were stratified into low-, medium-, and high-risk groups on the basis of the preoperative and postoperative models. ConclusionThe preoperative and postoperative MRI-based models built in this study were more competent compared with clinical staging systems to predict the early recurrence in hepatocellular carcinoma.

Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

BACKGROUND At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM To develop a model for predicting prognosis after LT in patients with HCC. METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P &lt; 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.

Radiomics model based on contrast-enhanced computed tomography imaging for early recurrence monitoring after radical resection of AFP-negative hepatocellular carcinoma

BackgroundAlthough radical surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), the high rate of postoperative recurrence remains a major challenge, especially in patients with alpha-fetoprotein (AFP)-negative HCC who lack effective biomarkers for postoperative recurrence surveillance. Emerging radiomics can reveal subtle structural changes in tumors by analyzing preoperative contrast-enhanced computer tomography (CECT) imaging data and may provide new ways to predict early recurrence (recurrence within 2 years) in AFP-negative HCC. In this study, we propose to develop a radiomics model based on preoperative CECT to predict the risk of early recurrence after surgery in AFP-negative HCC.Patients and methodsPatients with AFP-negative HCC who underwent radical resection were included in this study. A computerized tool was used to extract radiomic features from the tumor region of interest (ROI), select the best radiographic features associated with patient’s postoperative recurrence, and use them to construct the radiomics score (RadScore), which was then combined with clinical and follow-up information to comprehensively evaluate the reliability of the model.ResultsA total of 148 patients with AFP-negative HCC were enrolled in this study, and 1,977 radiographic features were extracted from CECT, 2 of which were the features most associated with recurrence in AFP-negative HCC. They had good predictive ability in both the training and validation cohorts, with an area under the ROC curve (AUC) of 0.709 and 0.764, respectively. Tumor number, microvascular invasion (MVI), AGPR and radiomic features were independent risk factors for early postoperative recurrence in patients with AFP-negative HCC. The AUCs of the integrated model in the training and validation cohorts were 0.793 and 0.791, respectively. The integrated model possessed the clinical value of predicting early postoperative recurrence in patients with AFP-negative HCC according to decision curve analysis, which allowed the classification of patients into subgroups of high-risk and low-risk for early recurrence.ConclusionThe nomogram constructed by combining clinical and imaging features has favorable performance in predicting the probability of early postoperative recurrence in AFP-negative HCC patients, which can help optimize the therapeutic decision-making and prognostic assessment of AFP-negative HCC patients.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Case analysis of hepatotoxicity caused by vancomycin

BackgroundAlthough the correlation between liver toxicity and vancomycin is generally considered low, it has been observed that the use of vancomycin can lead to abnormal liver function indicators, such as elevated aspartate aminotransferase, alanine aminotransferase, alpha fetoprotein, and jaundice. To further understand the clinical features associated with vancomycin-induced liver toxicity and to provide clinical guidance, we conducted an analysis of the characteristics and clinical manifestations of vancomycin-induced liver injury.MethodsPatients with liver function injury who received vancomycin treatment at the Third Xiangya Hospital of Central South University and Hunan Maternal and Child Health Hospital between 2016 and 2021 were selected for retrospective analysis of their general characteristics, vancomycin course, dose, liver function index, severity of liver injury, and concomitant medications.ResultsOf the 4562 patients who received vancomycin, 17 patients were finally included, with an incidence rate of 0.37%. Of these patients, 12 were male (70.6%) and 5 were female (29.4%), ranging in age from 17 to 84 years with a mean average age of 45.41 ± 20.405 years. All patients were evaluated using Naranjo’s score, with score ≥ 3. The dosage, time, and plasma concentration of vancomycin were analyzed and it was found that nine patients (52.94%) had abnormal liver function when initially given a dose of 1 g every 12 hours. In total, 14 patients (82.35%) with liver injury were taking vancomycin in combination with two to four drugs, and severe liver injury occurred in patients taking vancomycin in combination with two drugs. The occurrence time of liver injury was 2–12 days after starting vancomycin, with a mean of 4.53 ± 2.401 days. Of these patients, 16 patients (94.1%) showed liver function abnormalities within 7 days of taking the drug, and 2 patients with grade 3–4 liver injury both showed liver function abnormalities within 3 days of taking the drug. Only 4 of the 17 patients (23.53%) had vancomycin blood concentrations within the normal range, and there was no correlation found between blood concentration and severity of liver injury. Analysis of the correlation between the severity of liver injury and vancomycin showed that none of the patients had allergies such as rash, two patients (11.76%) had jaundice, and fatigue occurred in five patients (29.41%). The remaining ten patients (58.82%) had no symptoms related to liver injury. All 17 patients had abnormal aspartate aminotransferase/alanine aminotransferase levels and 9 patients also had abnormal bilirubin levels. In 15 patients (88.24%), the severity of liver injury was grade 1, indicating mild liver injury, and no correlation was observed between the severity of liver injury and creatinine. Of the 17 patients, 1 patient received no intervention, 4 patients stopped taking vancomycin after developing liver injury, 1 patient reduced the dose, and 11 patients (64.7%) were treated with hepatic protectant.ConclusionAlthough the study concluded that the incidence of liver injury was not high, the liver toxicity of vancomycin should still be considered and liver function indicators should be monitored during the clinical use of vancomycin.

Alpha-fetoprotein and APRI as predictive markers for patients with Type C hepatitis B-related acute-on-chronic liver failure: a retrospective study

BackgroundType C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF.MethodPatients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model.ResultsA total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH‐ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer.ConclusionsA new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.

Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.

e16162 Background: Serum alpha-fetoprotein (AFP) is widely accepted as a crucial tool for clinical diagnosis and screening of HCC. However, there are cases where patients test negative for AFP but are confirmed to have Hepatocellular Carcinoma through imaging or pathological examinations. Despite these findings, there is limited research focusing on the medicine selection for AFP-negative patients. Methods: This retrospective cohort study, involving 223 untreated advanced HCC patients, and the first-line regimen consisted of targeted therapy and TKI+ICIs therapy. Patients are categorized into negative and positive AFP groups based on initial serum levels. Main efficacy endpoint was progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: According to the level of serum AFP, they were divided into negative group(100) and positive group(123). The two groups showed no statistically significant differences in age, gender, Child-Pugh score and other baseline clinical characteristics( P&gt; 0.05). At data cut-off at February 2023, median OS was not matured and mPFS in negative group was higher than positive group(8.2 vs 5.3months, P&lt; 0.0001). In the ICIs+TKI therapy cohort, mPFS in the negative AFP group(52) was significantly higher than in the positive AFP group(70) (10 vs. 5.8 months, P = 0.0021). Considering all patients in the negative AFP group as a subgroup, an analysis of survival benefits between those receiving targeted therapy and those receiving TKI+ICIs therapy revealed no significant difference in PFS( P&gt; 0.05). Moreover, AEs were compared between the negative and positive group, with no significant differences observed in Any Grade or Grade 3/4( P&gt; 0.05). Conclusions: Patients with negative AFP exhibited superior survival benefits compared to those with positive AFP in first-line therapy. Regarding PFS, the TKI+ICIS therapy did not demonstrate a better benefit over targeted therapy in the negative AFP subgroup.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume

BackgroundIn many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits.MethodsWe reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan–Meier method.ResultsIn all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria.ConclusionPatients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

Predictors of short-term death and long-term survival in advanced hepatocellular carcinoma (HCC) treated with contemporary tyrosine kinase inhibitors (TKI) or immunotherapy: A multicenter analysis from the HCC-CHORD consortium.

4098 Background: Advances in systemic therapy for HCC have increased treatment options, including TKIs and immunotherapy combinations. Variables that predict patient outcomes may be helpful in personalizing treatment decisions. The aim of this study was to identify predictors of short-term death (STD) and long-term survival (LTS) for HCC patients. Methods: Retrospective review of patients with advanced HCC who received a TKI or immunotherapy combinations was conducted between Aug 2018 to Aug 2022 in the Canadian provinces of British Columbia, Alberta, Nova Scotia, Manitoba, as well as from select institutions in Ontario (n = 2). Prior locoregional therapies were permitted. Variables examined were: Barcelona Clinic Liver Cancer (BCLC) stage, Child-Pugh class, albumin-bilirubin (ALBI) grade, alpha fetoprotein (AFP) level, microvascular invasion (MVI), and distant metastases. Multivariate logistic regression was used to determine independent predictors of STD (patient survival &lt; 6 months vs others) and LTS (patient survival &gt; 18 months vs others). Results: 520 patients with the following baseline characteristics were included: median age 66, 84.6% male, 87.4% ECOG performance status 0-1, 69.7% BCLC stage C, and 88.7% Child-Pugh A. First-line treatments were primarily: lenvatinib 57.3%, sorafenib 8.1%, and atezolizumab/bevacizumab 31.7%. Median progression-free survival was 7.4 months (95% CI: 6.2 to 8.4), and overall survival was 17.1 months (95% CI:, 15.1 to 18.8). Independent predictors of STD were (odds ratio): ALBI grade (2.26), MVI (2.13), and distant metastases (2.14). These three factors were also predictive for LTS: ALBI grade (0.45), MVI (0.49), and distant metastases (0.36). Child-Pugh class, AFP, and BCLC stage were not predictive of STD nor LTS (Table). Conclusions: This study supports higher ALBI grade, MVI and distant metastases as predictors of STD, while lower ALBI grade, absence of MVI and lack of distant metastases were predictive of LTS in HCC patients treated with contemporary TKIs or immunotherapy combination regimens. These predictors may help guide treatment decisions in patient populations underrepresented in clinical trials, including patients with Child-Pugh B7 score who are often excluded. [Table: see text]

A cross-sectional study of synchronous liver metastasis in patients with gastric cancer.

e16015 Background: The specific organ microenvironment can promote the colonization of tumor cells. However, lack of research shed light on the liver microenvironment in synchronous liver metastasis in patients with gastric cancer (synGCLM). With the epidemic of hepatitis B virus (HBV) infection in China, we aim to explore the influence of hepatitis B surface antigen (HBsAg) on the risk of synGCLM. Methods: It was a cross-sectional study that enrolled 858 cases of newly diagnosed gastric cancer (GC). SynGCLM confirmed by biopsy or imaging evaluation reported by two senior radiologists. HBsAg-positive was defined as the detection of serum HBsAg more than 10 IU/mL. The prevalence of synGCLM was compared between patients with HBsAg (HBsAg+) and those without HBsAg (HBsAg-). The risk factors for synGCLM were analyzed by univariate and multivariate logistic regression analyses. Especially in the HBsAg+ GC patients, aspartate aminotransferase to platelet ratio index (APRI), liver fibrosis-4 index (FIB-4) levels and hepatitis B e antigen (HBeAg) status were further analyzed. Results: The prevalence of synGCLM of the HBsAg+ group was 16.7%, higher compared to 7.0% of the HBsAg- group, which was of statistical significance (p = 0.014). Multivariate logistic regression analysis demonstrated that HBsAg (Odds ratio (OR) = 3.359, p = 0.008), the elevated level of carcinoembryonic antigen (CEA) (OR = 3.775, p &lt; 0.001), alpha-fetoprotein (AFP) (OR = 6.204, p &lt; 0.001), γ-glutamyltransferase (GGT) (OR = 5.081, p &lt; 0.001), alkaline phosphatase (ALP) (OR = 3.968, p = 0.002) and age (OR = 1.028, p = 0.033) were risk factors for synGCLM. Among the HBsAg+ patients, both ARPI and FIB-4 were statistically higher in the patients with synGCLM (synGCLM+) compared to those without synGCLM (synGCLM-) (ARPI: p = 0.045; FIB-4: p = 0.047); HBeAg positivity was detected in 20.0% of synGCLM+ patients compared to 6.0% of synGCLM- patients, but the difference was of no significance (p = 0.190). Conclusions: HBV infection is a risk factor for synGCLM whereas elevated ARPI and FIB-4 may be pro-metastatic especially among the HBsAg+ GC patients. Age, preoperative CEA, AFP, GGT and ALP levels are associated with increased risk of synGCLM.

Bifunctional iron-porphyrin metal-organic frameworks for organic photoelectrochemical transistor gating and biosensing

Iron-porphyrin metal-organic frameworks (MOFs) have emerged as a remarkable class of semiconductors with adjustable photoelectrical properties and peroxidase-mimicking activities, yet their full potential remains largely unexplored. The organic photoelectrochemical transistor (OPECT) has been proven to be a prominent platform for diverse applications. Herein, iron-porphyrin MOFs, as bifunctional photo-gating module and horseradish peroxidase-mimicking nanozyme, is explored for novel OPECT bioanalysis. Exemplified by alpha-fetoprotein (AFP)-dependent sandwich immunorecognition and therein glucose oxidase (GOx)-generated H2O2 to etch CdS quantum dots on the surface of iron-porphyrin MOFs, this OPECT bioanalysis achieved high-performance AFP detection with a low detection limit of 24 fg/mL. This work featured a bifunctional iron-porphyrin MOFs gated OPECT, which is envisioned to inspire more interest in developing the diverse MOFs-nanozymes toward novel optoelectronics and beyond.

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1years (0.8-16.4years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

A rare case report: multiple intrahepatic masses in a pediatric patient with citrin deficiency

Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

A preliminary study on the reference intervals of serum tumor marker in apparently healthy elderly population in southwestern China using real-world data

BackgroundThe aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method.MethodsData from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method.ResultsIn the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0–6.75 ng/ml, carcinoembryonic antigen (CEA) 0–4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0–22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0–28.10 U/ml, carbohydrate antigen125 (CA125) 0–20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0–4.66 U/ml, neuron-specific enolase (NSE) 0–19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0–5.26 ng/ml and 0–1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes.ConclusionThis study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.