Serum Alpha-fetoprotein Levels Research Articles

Efficacy and safety of transarterial chemoembolization plus lenvatinib in the treatment of advanced hepatocellular carcinoma: A meta-analysis.

The benefits of transarterial chemoembolization (TACE) plus lenvatinib in advanced hepatocellular carcinoma (HCC) remain controversial. Therefore, we performed a meta-analysis to evaluate the efficacy and safety of TACE plus lenvatinib in the treatment of advanced HCC. Up to February 26, 2023, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang were searched, and clinical studies of TACE plus lenvatinib (experimental group) versus TACE or lenvatinib (control group) in the treatment of advanced HCC were included. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Revman5.4 software was used for meta-analysis. A total of 1855 patients were included in 18 studies. The results of the meta-analysis showed that TACE plus lenvatinib could increase the objective response rate (ORR) (odds ratio [OR] = 3.25, 95% confidence interval [CI]: 2.46-4.31; OR = 3.55, 95%CI: 2.53-4.97) and disease control rate (DCR) (OR = 3.27, 95%CI: 2.44-4.38; OR = 3.45, 95%CI: 2.28-5.24), 12-month (OR = 3.43, 95%CI: 2.08-5.65; OR = 2.78, 95%CI: 1.90-4.05) and 18-month (OR = 2.97, 95%CI: 1.77-5.00; OR = 2.62, 95%CI: 1.54-4.47) progression-free survival (PFS) rate, 12-month (OR = 2.34, 95%CI: 1.53-3.58; OR = 3.64, 95%CI: 2.65-5.01) and 18-month (OR = 2.27, 95%CI: 1.48-3.48; OR = 3.23, 95%CI: 2.33-4.48) overall survival (OS) rate compared with TACE or lenvatinib alone. In addition, the experimental group could significantly reduce the expression levels of serum alpha-fetoprotein (AFP) (standard mean difference [SMD] = 1.22, 95%CI: 0.67-1.78) and vascular endothelial growth factor (VEGF) (SMD = 1.27, 95%CI: 0.87-1.67). In terms of adverse events of drugs, the incidence of grade ≥ 3 hypertension and elevated aspartate aminotransferase and alanine aminotransferase in the experimental group was higher than that in the control group (P < .05). Compared with TACE or lenvatinib alone, TACE plus lenvatinib has achieved remarkable efficacy in patients with advanced HCC, and the efficacy versus risk need to be carefully balanced in clinical application.

Correlation Between Serum ESPL1 and Hepatitis B Virus-related Hepatocellular Carcinoma Histological Grade: A Chinese Single-center Case-control Study.

Serum markers to determine the histological grade of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still limited. This study aimed to investigate if serum extra spindle pole bodies-like 1 (ESPL1) protein could reflect the histological grade of HBV-related HCC. A total of 154 patients with HBV-related HCC were enrolled in the experimental group and 41 non-HBV-related patients in the control. Enzyme-linked immunosorbent assay was used to detect serum ESPL1 levels. The differences in serological ESPL1, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) were compared between the two groups. HCC tumor diameter was measured, and pathological examination was performed to compare the relationship between ESPL1, AFP, and DCP and tumor size and histological grade. Serum AFP and DCP levels showed no significant difference between experimental group and control group, and increased when the tumor diameter increased but were not related to HCC histological grade. Serological ESPL1 levels were higher in the experimental group than those in the control group, and positively correlated with the histological grade. In the experimental group, tumor size and histological grade were almost independent (Kappa=0.000); patients with medium size tumors had the highest serum ESPL1 levels and the highest proportion of poorly differentiated carcinomas, whereas 75.6% of patients with small size tumors had moderately differentiated carcinomas and only 20% well differentiated carcinomas. Serum ESPL1 can reflect the malignant degree of HBV-related HCC and is helpful in identifying small size HCC tumors.

Fibrolamellar Hepatocellular Carcinoma in Young Adult: A Case Report and Literature Review

Fibrolamellar carcinoma (FLC), a truly unique and uncommon variation of hepatocellular carcinoma (HCC), accounting for barely 1%–9% of all HCC cases. Fibrolamellar carcinoma, an unclear malignancy, appears to be more commonly observed in youthful individuals without any preexisting liver conditions. The nomenclature "fibrolamellar" originates from the presence of dense fibrous collagen bands enveloping the neoplastic cells. Contrary to hepatocellular carcinoma (HCC), cirrhosis and viral hepatitis infection do not serve as predisposing factors for fibrolamellar carcinoma (FLC). Additionally, FLC is not typically associated with increased levels of serum alpha-fetoprotein. Patients with FLC frequently manifest with nonspecific abdominal discomfort, queasiness, general discomfort, and decreased in body mass. Surgical intervention, specifically resection or liver transplantation, serves as the cornerstone of treatment and represents the sole potentially curative avenue. FLCs, or fibrolamellar carcinomas, have historically exhibited lower responsiveness to chemotherapy compared to conventional hepatocellular carcinomas (HCC). Nevertheless, it is important to note that in cases of advanced FLCs, the utilization of multi-modality treatments has shown promising effectiveness. The purpose of this review is to explain the clinical characteristics, diagnostic techniques, and therapeutic approaches for this uncommon tumor in order to enhance the knowledge of healthcare professionals.

Profile and clinical significance of interferon gamma-inducible protein-10 (IP-10) and its receptor in patients with hepatocellular carcinoma.

Chemokines play a vital role in tumor progression, metastasis and prognosis; however, the profile and clinical significance of gamma interferon-inducible protein-10 (IP-10) and its receptor (CXCR3) in patients with hepatocellular carcinoma (HCC) have not been well evaluated. Liquid-phase chip technology was used to detect the serum IP-10 in 85 patients with HBV-related HCC, 50 patients with chronic hepatitis B (CHB) and 50 liver cirrhosis subjects (CS); simultaneously, the CXCR3 and Alpha fetoprotein (AFP) were determined. Additionally, their mRNA or protein expression levels in peripheral blood mononuclear cells (PBMC), liver tumor and paracancerous tissues were quantified using qRT-PCR or ELISA. Moreover, the IP-10 and CXCR3 expression was verified by the online data from Gene Expression Omnibus. Furthermore, the relationships of serum IP-10, CXCR3 and AFP levels with their overall survival rate were also analyzed. The levels of IP-10 and CXCR3 in HCC group were significantly higher than those in CHB and CS groups, and their mRNA of PBMC is significantly positive correlation with those in their liver tissues or HBV DNA load (P < 0.0001), respectively. The serum IP-10 and CXCR3 in HCC were significantly correlated with tumor differentiation, metastases staging and distant metastasis (P < 0.05), but not related to gender, age and tumor size (P > 0.05, except IP-10 based on age). The serum IP-10 (142.6 pg/mL) and CXCR3 (241.2 pg/mL) could be differential diagnostic surrogates that distinguish HCC from CS, and the lower IP-10 level may be conducive to the postoperative survival of HCC patients. Moreover, the IP-10 and CXCR3 would be related to anti-tumor immunity in HCC patients and be a potential target for treatment of HCC.

Approach and Technique for Cesarean Section to Immediate Resection for High-Risk Sacrococcygeal Teratomas

IntroductionEx-utero intrapartum treatment has been established as an option for fetal and perinatal surgeons to deliver patients with sacrococcygeal teratomas (SCTs) which are causing significant fetal distress and possible in-utero fetal demise. However, ex-utero intrapartum treatment procedures carry significant maternal risk and morbidity. Herein, we report an alternative technique of Cesarean section to immediate resection (CSIR) for managing high-risk SCTs. MethodsA retrospective institutional review board–approved review was performed on all SCTs evaluated at our fetal center from May 2014 to September 2020. Demographics; prenatal imaging characteristics; prenatal interventions; and postnatal surgery data including operative time, estimated blood loss, pathology, and outcomes were collected. Outcomes of interest included surveillance serum alpha-fetoprotein levels, imaging surveillance, developmental milestones, and the presence or absence of constipation or fecal incontinence. ResultsA total of 20 patients with prenatal diagnosis of SCT were evaluated. Mothers who transferred their care to another institution after diagnosis were excluded from this study. Twelve neonates underwent standard postnatal resection. Three neonates underwent emergent CSIR for high output cardiac failure, fetal anemia, or concerns for in-utero hemorrhagic rupture. The median (interquartile range) operative time was 231.5 (113) minutes for the standard operative group versus 156 min in the CSIR group. We present three patients who underwent immediate resection after emergent Cesarean section. We report 100% survival for the three consecutive cases. ConclusionsCSIR is a safe and feasible approach for managing appropriately selected high-risk SCTs with signs of hydrops, fetal distress, or fetal anemia. Despite patient prematurity, we demonstrated 100% survival of three consecutive cases. We suggest that CSIR be considered an option in the management algorithm for high-risk SCTs.

Value of CT and MR Imaging in Assessment of Loco-regional Ablated Hepatocellular Carcinoma using LI-RADS Treatment Response Algorithm (version 2018)

Aim: The aim of this work is to evaluate the role of multiphasic CT and dynamic contrast enhanced MRI using LI-RADS treatment response algorithm (version 2018) and the added values of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in the assessment of loco-Regional ablated Hepatocellular Carcinoma (HCC). Methods: This study included 45 patients with 50 loco-Regional ablated HCC lesions. All patients underwent multiphasic CT scan, diffusion weighted and dynamic contrast enhanced MRI. The reference standards for assessment were based on serum alpha-fetoprotein level and dynamic contrast enhanced MRI. Results: Multi-phasic CT had moderate sensitivity (87.5%) and high specificity (100%) for assessment of HCC LI-RADS treatment response algorithm. Dynamic contrast enhanced MRI had high sensitivity (100%) and specificity (100%) for the assessment of HCC LI-RADS treatment response algorithm. The sensitivity and specificity of DWI to diagnose HCC malignant residual or recurrence were 93.7% and 100%, respectively, with very good performance. The mean ADC values of the malignant residual or recurrence were significantly lower than that of benign post-ablation tissue changes areas and the best ADC cutoff value for differentiation between viable and nonviable lesions was 1.1x10-3 mm²/s. Conclusion: Performance of dynamic contrast enhanced MRI is better than that of multiphasic CT in the assessment of LIRADS treatment response algorithm. DWI and ADC maps could be used as ancillary methods for differentiation between viable and non-viable loco-regional ablated HCC lesions and should be included in LR-TR treatment response algorithm.

Nomogram for Predicting Microvascular Invasion in Hepatocellular Carcinoma Using Gadoxetic Acid-Enhanced MRI and Intravoxel Incoherent Motion Imaging

Microvascular invasion (MVI) is an important risk factor in hepatocellular carcinoma (HCC), but it can only be determined through histopathological results. The aim of this study was to develop and validate a nomogram for preoperative prediction MVI in HCC using gadoxetic acid-enhanced magnetic resonance imaging (MRI) and intravoxel incoherent motion imaging (IVIM). From July 2017 to September 2022, 148 patients with surgically resected HCC who underwent preoperative gadoxetic acid-enhanced MRI and IVIM were included in this retrospective study. Clinical indicators, imaging features, and diffusion parameters were compared between the MVI-positive and MVI-negative groups using the chi-square test, Mann-Whitney U test, and independent sample t test. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance in predicting MVI. Univariate and multivariate analyses were conducted to identify the significant clinical-radiological variables associated with MVI. Subsequently, a predictive nomogram that integrates clinical-radiological risk factors and diffusion parameters was developed and validated. Serum alpha-fetoprotein level, tumor size, nonsmooth tumor margin, peritumoral hypo-intensity on hepatobiliary phase (HBP), apparent diffusion coefficient value and D value were statistically significant different between MVI-positive group and MVI-negative group. The results of multivariate analysis identified tumor size (odds ratio [OR], 0.786; 95% confidence interval [CI], 0.675-0.915; P<.01), nonsmooth tumor margin (OR, 2.299; 95% CI, 1.005-5.257; P<.05), peritumoral hypo-intensity on HBP (OR, 2.786; 95% CI, 1.141-6.802; P<.05) and D (OR, 0.293; 95% CI,0.089-0.964; P<.05) was the independent risk factor for the status of MVI. In ROC analysis, the combination of peritumoral hypo-intensity on HBP and D demonstrated the highest area under the curve value (0.902) in prediction MVI status, with sensitivity 92.8% and specificity 87.7%. The nomogram exhibited excellent predictive performance with C-index of 0.936 (95% CI 0.895-0.976) in the patient cohort, and had well-fitted calibration curve. The nomogram incorporating clinical-radiological risk factors and diffusion parameters achieved satisfactory preoperative prediction of the individualized risk of MVI in patients with HCC.

Differential diagnostic value of tumor markers and contrast-enhanced computed tomography in gastric hepatoid adenocarcinoma and gastric adenocarcinoma.

This study aimed to investigate the effectiveness of tumor markers and contrast-enhanced computed tomography (CE-CT) in differentiating gastric hepatoid adenocarcinoma (GHA) from gastric adenocarcinoma (GA). This retrospective study included 160 patients (44 with GHA vs. 116 with GA) who underwent preoperative CE-CT. Preoperative serum concentrations of tumor biomarkers and CT imaging features were analyzed, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), tumor location, growth pattern, size, enhancement pattern, cystic changes, and mass contrast enhancement. Multivariate logistic regression analyses were performed to evaluate useful tumor markers and CT imaging features for differentiating GHA from GA. When compared to GA, GHA showed a higher serum AFP [13.27 ng/ml (5.2-340.1) vs. 2.7 ng/ml (2.2-3.98), P <0.001] and CEA levels [4.07 ng/ml (2.73-12.53) vs. 2.42 ng/ml (1.38-4.31), P <0.001]. CT imaging showed GHA with a higher frequency of tumor location in the gastric antrum (P <0.001). GHA had significantly lower attenuation values at the portal venous phase [PCA, (82.34 HU ± 8.46 vs. 91.02 HU ± 10.62, P <0.001)] and delayed phase [DCA, (72.89 HU ± 8.83 vs. 78.27 HU ± 9.51, P <0.001)] when compared with GA. Multivariate logistic regression analyses revealed that tumor location, PCA, and serum AFP level were independent predictors of differentiation between GHA and GA. The combination of these three predictors performed well in discriminating GHA from GA, with an AUC of 0.903, a sensitivity of 86.36%, and a specificity of 81.90%. Integrated evaluation of tumor markers and CT features, including tumor location, PCA, and serum AFP, allowed for more accurate differentiation of GHA from GA.

Discordance among aggressiveness characteristics of hepatocellular carcinoma: Portal vein thrombosis and multifocality, related to tumor size, but not to serum alpha-fetoprotein level

Background and aimsHepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database. MethodsAn 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels. ResultsThe percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters. ConclusionsA statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.

Stereotactic radiosurgery for tumors of the pineal region: A single-center experience.

Tumors of the pineal region (TPRs) are rare neoplasms that are surgically challenging to resect. Conventional treatment strategies are available, but gamma knife radiosurgery (GKRS) is an alternative approach. This study presents a single-center experience with GKRS performed for TPR with and without histopathological diagnoses. The cases of 25 patients with TPRs treated with GKRS were retrospectively analyzed. Thirteen of these 25 patients had histopathological confirmation, and 13 had elevated serum alpha-fetoprotein and beta-human chorionic gonadotropin levels. The 25 patients had a mean follow-up duration of 61 months. The total response rate to GKRS was 60%, and a 53.8% decrease in the alpha-fetoprotein and beta human chorionic gonadotropin levels was observed. The findings of this study indicate that GKRS is a safe procedure for TPRs, even in the event of insufficient histopathological findings. This treatment approach provides increased Karnofsky performance scores and an extended life expectancy.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter > 4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules > 4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Factors influencing the prognosis patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma undergoing salvage surgery after conversion therapy.

The aim of this study was to investigate the prognostic factors influencing the outcome of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (HCC) receiving salvage surgery after conversion therapy based on tyrosine kinase inhibitors (TKIs) and anti-programmed death-1 (PD-1) antibodies. From June 2018 to December 2022, patients receiving salvage surgery after conversion therapy based on PD-1 and TKIs at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital were retrospectively recruited for this study. Overall survival (OS) and recurrence-free survival (RFS) were observed as the primary end point in the Cox analysis of prognostic factors among this study. The 6- and 12-month RFS rates were 77.0% and 64.8%, respectively, while the 6-, 12-, 24-, and 36-month OS rates were 98.4%, 93.4%, 76.8%, and 69.8%, respectively. The median OS and RFS were not reached. On multivariable Cox regression analyses, low serum alpha fetoprotein (AFP) level (≤20 ng/mL) after conversion therapy [hazard ratio (HR) 0.186, 95% CI: 0.039-0.887; P=0.035) and microvascular invasion (MVI) grade II (HR 3.054, 95% CI: 1.000-9.329; P=0.050) were independent factors associated with a higher OS and RFS. For patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) HCC, lower AFP level after conversion therapy (<20 ng/mL) and MVI II were associated with a higher OS and lower RFS rate, respectively.

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Impact of frailty on long-term outcomes after liver resection for hepatocellular carcinoma in elderly patients: A prospective study

BackgroundsFrailty affects short-term outcomes after liver resection in elderly patients. However, frailty's effects on long-term outcomes after liver resection in elderly patients with hepatocellular carcinoma (HCC) are unknown. MethodsThis prospective, single-center study included 81 independently living patients aged ≥65 years scheduled to undergo liver resection for initial HCC. Frailty was evaluated according to the Kihon Checklist, a phenotypic frailty index.” We investigated and compared postoperative long-term outcomes after liver resection between patients with and without frailty. ResultsOf the 81 patients, 25 (30.9%) were frail. The proportion of patients with cirrhosis, high serum alpha-fetoprotein level (≥200 ng/mL), and poorly differentiated HCC was higher in the frail group than in the nonfrail group (n = 56). Among the patients with postoperative recurrence, the incidence of extrahepatic recurrence was higher in the frail group than in the nonfrail group (30.8% vs. 3.6%, P = 0.028). Moreover, the proportion of patients who underwent repeat liver resection and ablation for recurrence who met the Milan criteria tended to be lower in the frail group than in the nonfrail group. Although there was no difference in disease-free survival between the two groups, the overall survival rate in the frail group was significantly worse than that in the nonfrail group (5-year overall survival: 42.7% vs. 77.2%, P = 0.005). Results of the multivariate analysis indicated that frailty and blood loss were independent prognostic factors for postoperative survival. ConclusionFrailty is associated with unfavorable long-term outcomes after liver resection in elderly patients with HCC.

Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence

We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

The clinical value of serum GPC3 level in predicting recurrence of patients with primary hepatocellular carcinoma

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ2=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ2=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ2=4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ2=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.

An exceptional finding in an explanted liver: a case report of cirrhotomimetic hepatocellular carcinoma

We present a case of cirrhotomimetic hepatocellular carcinoma (HCC) diagnosed on an explant following a liver transplantation (LT). The pre-LT computerized tomography (CT) scan demonstrated a nodular, cirrhotic-appearing liver; there was no evidence of lesions consistent with HCC. The level of serum alpha fetoprotein (AFP) 1 month pre LT was 4 ng/dL. Following LT, the patient underwent surveillance for HCC. Eight months post LT, he was noted to have lytic osseous lesions in his sternum and T10 vertebral body. Biopsies of these lesions demonstrated metastatic poorly differentiated carcinoma, which was concerning for progression to metastatic HCC. It is important to spread awareness of cirrhotomimetic HCC as it often evades detection by current screening methods, and if patients are inadvertently transplanted with a liver with cirrhotomimetic HCC, this can have significant consequences downstream. A multidisciplinary team approach is critical to ensure early detection of any recurrence and timely treatment.

Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients have either normal or marginally increased AFP levels in serum, and the underlying mechanisms are not fully understood. In the present study, we provided in vitro and in vivo evidence that heat shock protein gp96 promoted AFP expression at the transcriptional level in HCC. NR5A2 was identified as a key transcription factor for the AFP gene, and its stability was enhanced by gp96. A further mechanistic study by co-immunoprecipitation, GST pull-down, and molecular docking showed gp96 and the SUMO E3 ligase RanBP2 competitively binding to NR5A2 at the sites spanning from aa 507 to aa 539. The binding of gp96 inhibited SUMOylation, ubiquitination, and subsequent degradation of NR5A2. In addition, clinical analysis of HCC patients indicated that gp96 expression in tumors was positively correlated with serum AFP levels. Therefore, our study uncovered a novel mechanism that gp96 regulates the stability of its client proteins by directly affecting their SUMOylation and ubiquitination. These findings will help in designing more accurate AFP-based HCC diagnosis and progression monitoring approaches.

Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients.

Background and Objectives: Non-invasive methods for evaluating liver fibrosis have been a crucial focus of clinical research. The aim of the current study is to assess the accuracy of serum alpha-fetoprotein (AFP) in determining the stage of liver fibrosis in patients with chronic hepatitis B (CHB) who are positive for HBeAg. Materials and Methods: The current study included a total of 276 HBeAg-positive CHB patients who underwent liver biopsy. The levels of serum AFP were measured in these patients using electrochemiluminescence immunoassays. The correlations between serum AFP levels and other laboratory parameters were analyzed using Spearman's correlation analysis. Binary logistic regression analysis was performed to determine the independent associations between serum AFP levels and liver fibrosis. The diagnostic performance of serum AFP and other non-invasive markers was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 59 (21.4%) patients were found to have elevated levels of serum AFP (>7 ng/mL). These patients displayed a significantly higher proportion of both advanced fibrosis and cirrhosis compared to those with normal serum AFP levels (0-7 ng/mL). The level of serum AFP was positively associated with levels of serum globulin (GLB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL), as well as the AST-to-platelet ratio (APRI), fibrosis-4 (FIB-4), and Scheuer's classification, and negatively correlated with platelet (PLT) counts. Furthermore, serum AFP was found to be independently associated with significant fibrosis, advanced fibrosis, and cirrhosis. The results of the ROC analysis showed that serum AFP was an effective predictor of significant fibrosis, advanced fibrosis, and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% CI: 0.721-0.821), 0.889 (95% CI: 0.847-0.923), and 0.925 (95% CI: 0.887-0.953), respectively. These values are higher than those of the APRI and FIB-4. Conclusions: Serum AFP could serve as a valuable supplemental biomarker for determining the severity of liver fibrosis in HBeAg-positive patients with chronic hepatitis B.

Visualizing alpha-fetoprotein level in undiluted serum based on microfluidic particle accumulation

Alpha-fetoprotein (AFP) is an abundant plasma protein produced by the liver of the human fetus. When abnormally elevated in adult serum, its level can be an essential biomarker for various cancers. In addition, maternal AFP serum levels can be used to screen congenital disorders such as down syndrome and neural tube defects. Here, we report a portable method for visualizing AFP levels in serum. Magnetic microparticles (MMPs) and polystyrene microparticles (PMPs) are designed to bind with AFP simultaneously. By loading the particle solution into a microfluidic chip with a magnetic separator, unconnected PMPs can be separated and continue flowing forward until being trapped at a particle dam. Ultimately, the accumulation length of PMPs enables visualization of AFP levels. This device can be adapted to sensitive mode (70 min incubation) with a limit of detection (LOD) of 15.8 ng/ml and rapid mode (15 min incubation) with a LOD of 34.3 ng/ml in undiluted serum samples, providing a strategy for fast and visual quantitative detection of serum AFP.