Transjugular Intrahepatic Portosystemic Shunt Is Associated With Better Waitlist Management of Liver Transplant Candidates With Hepatocellular Carcinoma.

Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension complications. Its impact on hepatocellular carcinoma (HCC) remains unclear. We evaluated 42,843 liver transplant candidates with HCC from the Scientific Registry of Transplant Recipients (2002-2022). 4,484 patients with and without TIPS were propensity score-matched 1:3. Analysing wait-list changes in total tumor volume, HCC count, and alpha-fetoprotein levels, and assessing survival from listing and transplantation; TIPS correlated with a decreased nodule count (-0.24 vs. 0.04, p = 0.028) over a median wait period of 284 days (IQR 195-493) and better overall survival from listing (95.6% vs. 91.5% at 1 year, p < 0.0001). It was not associated with changes in tumor volume (0.28 vs. 0.11 cm³/month, p = 0.58) and AFP (14.37 vs. 20.67 ng/mL, p = 0.42). Post-transplant survival rates (91.8% vs. 91.7% at 1 year, p = 0.25) and HCC recurrence (5.1% vs. 5.9% at 5 years, p = 0.14) were similar, with a median follow-up of 4.98 years (IQR 2.5-8.08). While TIPS was associated with a reduced nodule count and improved waitlist survival, it did not significantly impact HCC growth or aggressiveness. These findings suggest potential benefits of TIPS in HCC management, but further studies need to confirm TIPS safety.

Super-resolution Multispectral Imaging Nanoimmunosensor for Simultaneous Detection of Diverse Early Cancer Biomarkers.

In medical diagnosis, relying on only one type of biomarker is insufficient to accurately identify cancer. Blood-based multicancer early detection can help identify more than one type of cancer from a single blood sample. In this study, a super-resolution multispectral imaging nanoimmunosensor (srMINI) based on three quantum dots (QDs) of different color conjugated with streptavidin was developed for the simultaneous screening of various cancer biomarkers in blood at the single-molecule level. In the experiment, the srMINI chip was used to simultaneously detect three key cancer biomarkers: carcinoembryonic antigen (CEA), C-reactive protein (CRP), and alpha-fetoprotein (AFP). The srMINI chip exhibited 108 times higher detection sensitivity of 0.18-0.5 ag/mL (1.1-2.6 zM) for these cancer biomarkers than commercial enzyme-linked immunosorbent assay kits because of the absence of interfering signals from the substrate, establishing considerable potential for multiplex detection of cancer biomarkers in blood. Therefore, the simultaneous detection of various cancer biomarkers using the developed srMINI chip with high diagnostic precision and accuracy is expected to play a decisive role in early diagnosis or community screening as a single-molecule biosensor.

Use of Maternal Race and Weight Provides Equitable Performance in Serum Screening for Open Neural Tube Defects.

BACKGROUND: Maternal serum alpha-fetoprotein (AFP) levels are used in screening for open neural tube defects (ONTD). Historical reports show that AFP levels and maternal weights are higher in self-reported Black than White individuals, but recent reports question the need to account for these variables in screening. Our study compares screening performance with and without accounting for race. METHODS: Retrospective analysis was performed on deidentified prenatal screening records including maternal weight and self-reported race of White or Black. Gestational age-specific medians and weight-adjusted multiples of the median levels were calculated separately for each group and using a race-agnostic analysis. Outcome measures included the proportion of screen-positive results. RESULTS: Records for analysis (n = 13 316) had an ultrasound confirmed gestational age between 15 and 21 completed weeks, singleton pregnancy, and self-reported race. Race was Black for 26.3%. AFP levels for pregnancies in Black individuals were higher than in White individuals: 6% to 11% depending on gestational age. Race-specific gestational age and maternal weight analyses resulted in similar screen-positive rates for self-reported White and Black individuals at 0.74% vs 1.00%, respectively (P = 0.14). However, use of race-agnostic analyses resulted in a screen-positive rate that was 2.4 times higher in Black than White individuals (P < 0.001). CONCLUSION: These data show that the historical method of accounting for maternal race and weight in prenatal screening for ONTD provides equitable performance. Using a race-agnostic methodology results in an increased screen-positive rate and a disproportionate rate of required follow-up care for individuals who self-identify as Black.

Design of U-shaped peptides with long-lasting antifouling efficacy: Toward a feasible electrochemical aptasensor for robust detection in human serum.

BACKGROUND: Developing biosensors with antifouling properties is essential for accurately detecting low-concentration biomarkers in complex biological matrix, which is imperative for effective disease diagnosis and treatment. Herein, an antifouling electrochemical aptasensor qualifying for probing targets in human serum was explored based on newly-devised peptides that could form inverted U-shaped structures with long-term stability. RESULTS: The inverted U-shaped peptides (U-Pep) with two terminals of thiol groups grafted onto the Au-modified electrode showcase superior antifouling properties in terms of high stability against enzymatic hydrolysis and long acting against biofouling in actual biofluids. The construction of the outlined antifouling electrochemical aptasensor just involved the fabrication of Au-deposited poly(3,4 ethylenedioxythiophene) (Au/PEDOT) modified electrode, followed by one-step co-incubation in the peptides and the aptamer probes with the Au/PEDOT electrode. Taking a typical biomarker of alpha-fetoprotein (AFP) for detection, this elegant antifouling aptasenor demonstrated a nice response for probing the target AFP with a low detection limit of 0.27 pg/mL and a wide linear scope of 1.0 pg/mL to 1.0 µg/mL, and furthermore qualified for assaying of AFP in human serum samples with satisfactory accuracy and feasibility. SIGNIFICANCE: This engineering strategy of U-Pep with long-lasting antifouling efficacy opens a new horizon for high-performance antifouling biosensors suitable for detection in complex bifluids, and it could spark more inspiration for a follow-up exploration of other featured antifouling biomaterials.

Early prediction of microvascular invasion (MVI) occurrence in hepatocellular carcinoma (HCC) by 18F-FDG PET/CT and laboratory data.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in China. Microvascular invasion (MVI) often indicates poor prognosis and metastasis in HCC patients. 18F-FDG PET-CT is a new imaging method commonly used to screen for tumor occurrence and evaluate tumor stage. PURPOSE: This study attempted to predict the occurrence of MVI in early-stage HCC through 18F-FDG positron emission tomography (PET)/computed tomography (CT) imaging findings and laboratory data. PATIENTS AND METHODS: A total of 113 patients who met the inclusion criteria were divided into two groups based on postoperative pathology: the MVI-positive group and MVI-negative group. We retrospectively analyzed the imaging findings and laboratory data of 113 patients. Imaging findings included tumor size, tumor maximum standard uptake value (SUVmaxT), and normal liver maximum standard uptake value (SUVmaxL). The ratios of SUVmaxT to SUVmaxL (SUVmaxT/L) and an SUVmaxT/L > 2 were defined as active tumor metabolism. The tumor size was indicated by the maximum diameter of the tumor, and a diameter greater than 5 cm was defined as a mass lesion. The laboratory data included the alpha-fetoprotein (AFP) level and the HBeAg level. An AFP concentration > 20 ng/mL was defined as a high AFP level. A HBeAg concentration > 0.03 NCU/mL was defined as HB-positive. RESULTS: The SUVmaxT/L (p = 0.003), AFP level (p = 0.008) and tumor size (p = 0.015) were significantly different between the two groups. Patients with active tumor metabolism, mass lesions and high AFP levels tended to be MVI positive. Binary logistic regression analysis verified that active tumor metabolism (OR = 4.124, 95% CI, 1.566-10.861; p = 0.004) and high AFP levels (OR = 2.702, 95% CI, 1.214-6.021; p = 0.015) were independent risk factors for MVI. The sensitivity of the combination of these two independent risk factors predicting HCC with MVI was 56.9% (29/51), the specificity was 83.9% (52/62) and the accuracy was 71.7% (81/113). CONCLUSION: Active tumor metabolism and high AFP levels can predict the occurrence of MVI in HCC patients.

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

PURPOSE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. CONCLUSION: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

The ARH score, a practical guide to decision-making for retreatment with hepatic arterial infusion chemotherapy in hepatocellular carcinoma patients.

BACKGROUND: Hepatic arterial infusionchemotherapy (HAIC) is a promising option for large unresectable hepatocellular carcinoma (HCC). Identifying patients who could benefit from continuous HAIC remains a challenge. We aimed to establish an objective model to guide the decision for retreatment with HAIC. METHODS: Between 2015 and 2020, the data of patients with large unresectable HCC without macrovascular invasion or extrahepatic spread undergoing multiple HAIC cycles from 3 different centers were retrieved. We investigated the basic tumor parameters and the effect of HAIC on liver function and tumor response, and their impact on overall survival (OS). A point score (ARH, Assessment for Retreatment with HAIC) was built by using a stepwise Cox regression model in the training cohort (n = 112) and was validated in an independent validation cohort (n = 71). RESULTS: The high α-fetoprotein before the second cycle of HAIC, an increase in Child-Pugh score, and undesirable radiologic tumor responses remained independent negative prognostic factors and were used to create the ARH score. The prognosis of HCC patients deteriorated significantly with the increase in ARH score. The median OS of patients with ARH score 0-2 points and ≥ 2.5 points were 19.37 months and 11.60 months (P < 0.001). All of these results had been confirmed in the external validation cohort and demonstrated significance across multiple subgroups. CONCLUSIONS: The ARH score makes an excellent prediction of the prognosis of HCC patients who received retreatment of HAIC. Patients with an ARH score ≥ 2.5 prior to the second cycle of HAIC may not profit from further sessions.

Misdiagnosis Based on Neoplastic Markers-Extremely High Alpha-Fetoprotein in Patients with Intrahepatic Cholangiocarcinoma with Literature Review of the Published Cases.

Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid "washout" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.

Exonuclease III/Cas12a Cascade Amplification Strategy and Smartphone-Based Portable Fluorescence Detector to Repurpose the Commercial AFP Strip for the POCT of Multiple RNAs.

Point of care testing (POCT) of nucleic acid (NA) contributes to the timely disease diagnosis, like bacteria and virus screening in households or resource-constrained areas, but its development has always been stagnant. Herein, we proposed an exonuclease III cascaded with CRISPR/Cas12a (Exo-III/Cas12a) amplification strategy and constructed a smartphone-based portable fluorescence detector (SPFD) to repurpose the commercial alpha-fetoprotein (AFP) strip for the ultrasensitive and hand-held detection of NA samples. In detail, the target-initiated-Exo-III/Cas12a strategy realizes the signal amplification and liberates AFP from magnetic beads through the trans-cleavages of activated Cas12a toward the AFP aptamer. After magnetic separation and migration, the fluorescence signals of the test (FT) and control (FC) lines on the AFP strip were digitally output by the SPFD, and the FT/FC was employed for the quantitative analysis to minimize external disturbances and improve accuracy. We experimentally assessed the universe applicability of the proposed NA-POCT platform toward miRNA-155, 16S rRNA of Staphylococcus aureus, and ORF1a/b RNA of Covid-19 pseudovirus, achieving favorable detection limits of 42 aM, 18 CFU/mL, and 87 copies/µL, respectively. Moreover, its simplicity, universality, and admirable detection performance demonstrate a great potential in the aspect of rapidly transforming the existing POCT devices for multiple new applications at the time of need.

An efficient DNAzyme-locked leakless enzyme-free amplification system for alpha-foetoprotein detection in liver cancer and breast cancer.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

Establishment of a multi-line immunochromatography based on magnetic nanoparticles for simultaneous screening of multiple biomarkers.

Biomarkers screening is a benefit approach for early diagnosis of major diseases. In this study, magnetic nanoparticles (MNPs) have been utilized as labels to establish a multi-line immunochromatography (MNP-MLIC) for simultaneous detection of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 19-9), and alpha-fetoprotein (AFP) in a single serum sample. Under the optimal parameters, the three biomarkers can be rapidly and simultaneously qualitative screening within 15 min by naked eye. As for quantitative detection, the MNP-MLIC test strips were precisely positioned and captured by a smartphone, and signals on the test and control lines were extracted by ImageJ software. The signal ratio of test and control lines has been calculated and used to plot quantitative standard curves with the logarithmic concentration, of which the correlation coefficients are more than 0.99, and the limit of detection for CEA, CA 19-9, and AFP were 0.60 ng/mL, 1.21 U/mL, and 0.93 ng/mL, respectively. The recoveries of blank serum were 75.0 ~ 112.5% with the relative standard deviation ranging from 2.5 to 15.3%, and the specificity investigation demonstrated that the MNP-MLIC is highly specific to the three biomarkers. In conclusion, the developed MNP-MLIC offers a rapid, simple, accurate, and highly specific method for simultaneously detecting multiple biomarkers in serum samples, which provides an efficient and accurate approach for the early diagnosis of diseases.

BALAD score predicts the recurrence and survival in the patients who underwent initial hepatectomy for HCC.

BACKGROUNDS: Several studies have indicated that BALAD score which includes the HCC tumor markers of HCC, AFP, AFP-L3%, DCP, and serum albumin and bilirubin value were good predictors of HCC patients for all treatment modalities. In this study, we aim to clarify the impact of BALAD score as the prognostic factor for HCC patients after curative surgery. METHODS: This study investigated 578 patients who underwent hepatectomy for HCC between January 2003 and May 2013. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to the level of BALAD score. RESULTS: In patients with higher BALAD score, recurrence rate and OS was poor (p = 0.0015 and p < 0.0001, respectively). Multivariate analyses revealed independent risk factors for recurrence to be male (hazard ratio [HR] 1.52, P = 0.011), HCV-antibody positive (HR 1.33, P = 0.019), multiple tumors (HR 2.16, P < 0.0001), microvascular invasion (HR 1.45, P = 0.0035) and higher BALAD score (RR 1.70, P = 0.015). The independent risk factors for OS were multiple tumors (HR 1.52, P = 0.014), microvascular invasion (HR 1.53, P = 0.012), and higher BALAD score (RR 2.51, P = 0.0012). CONCLUSION: BALAD score is associated with high recurrence rate and poor overall survival of the patients who underwent curative liver resection for HCC.

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 < 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.

Rapid and High-Density Antibody Immobilization Using Electropolymerization of Pyrrole for Highly Sensitive Immunoassay.

Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.

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

BACKGROUND: Although 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 METHODS: Patients 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. RESULTS: A 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. CONCLUSION: The 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.

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.

The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

Evaluation of the risk of developing hepatocellular carcinoma in chronic Hepatitis C patients receiving antiviral treatment.

INTRODUCTION: Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC. The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment. METHODOLOGY: The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients. RESULTS: At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients. CONCLUSIONS: It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs.

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

BACKGROUND: Type 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. METHOD: Patients 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. RESULTS: A 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. CONCLUSIONS: A 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.

HEPPAR1 and PIWIL2 as Panel Markers for Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in Hepatocellular Carcinoma (HCC), and determine their correlation with clinicopathological parameters of this type of cancer to determine their diagnostic value in combination. METHODS: Seventy-five patients with HCC were assessed for the expression of PIWIL2 in serum and tissue using real-time polymerase chain reaction (RT-PCR) and IHC was performed for PIWIL2 and HepPar1 was performed on all patients. RESULTS: A statistically significantly higher level of PIWIL2 was found in HCC compared to controls (p≤0.001). Both HepPar1 and PIWIL2 were detected in 84% of HCC cases, the diagnostic and prognostic factors for PIWIL2 were found to be significant in liver tumour tissue samples and non-tumorous sections p<0.001, and the same was observed for serum samples and results of healthy serum controls (p<0.001) when compared to AFP. CONCLUSION: Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development, and that a possible panel maybe used for these markers HCC diagnosis.