Differences In Alpha-fetoprotein Research Articles

Comparative Clinicopathologic and Genomic Analysis of Hepatocellular Neoplasm, Not Otherwise Specified, and Hepatoblastoma

Accurate diagnosis and treatment of hepatocellular neoplasm, not otherwise specified (HCN-NOS), poses significant challenges. Our study aimed to investigate the clinicopathological and genomic similarities and differences between HCN-NOS and hepatoblastoma (HB) to guide diagnostic and treatment strategies. The clinicopathological characteristics of 16 patients with HCN-NOS and 23 patients with HB were compared. Molecular studies, including the OncoKids® DNA and RNA-based next-generation sequencing panel, chromosomal microarray, and targeted Sanger sequencing analyses of CTNNB1 and TERT promoter, were employed. We found that patients with HCN-NOS were older (p<0.001) and more frequently classified as high-risk (p<0.01), yet they showed no significant differences in alpha-fetoprotein (AFP) levels or survival outcomes compared to those with HB. HCN-NOS and HB had a comparable frequency of sequence variants, with CTNNB1 mutations being predominant in both groups. Notably, TERT promoter mutations (37.5%) and rare clinically significant variants (BRAF, NRAS, and KMT2D) were exclusive to HCN-NOS. HCN-NOS demonstrated a higher prevalence of gains in 1q, encompassing the MDM4 locus (17/17 vs. 11/24, p<0.001), as well as loss/loss of heterozygosity (LOH) of 1p (11/17 vs. 6/24, p<0.05) and chromosome 11 (7/17 vs. 1/24, p<0.01) when compared to HB. Furthermore, recurrent loss/LOH of chromosome 3, 4p, 9, 15q, and Y were only observed in HCN-NOS. However, no significant differences were noted in gains of chromosomes 2, 8, and 20, or loss/LOH of 4q and 11p between the two groups. Notably, no clinically significant gene fusions were detected in either group. In conclusion, our study reveals that HCN-NOS exhibits high-risk clinicopathological features and greater structural complexity compared to HB. However, patients with HCN-NOS exhibit comparable AFP levels at diagnosis, CTNNB1 mutation rates, and survival outcomes when subjected to aggressive treatment, as compared to those with HB. These findings have the potential to enhance diagnostic accuracy and inform more effective treatments for HCN-NOS.

The clinical outcomes of patients with vascular invasion after deceased donor liver transplantation.

Vascular invasion is a major risk factor for poor prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC), and this study aimed to evaluate the feasibility and efficacy of deceased donor LT (DDLT) for the treatment of microvascular invasion (MVI) and segmental portal vein tumor thrombus (PVTT). We retrospectively analyzed 141 patients who received DDLT for HCC combined with vascular invasion from January 2016 to December 2023 at Shulan (Hangzhou) Hospital. To assess the risk of vascular invasion associated with the LT prognosis, we evaluated various clinicopathologic variables. The recurrence-free survival (RFS) and overall survival (OS) based on different types of vascular invasion were also analyzed. A total of 141 patients were enrolled in this study, including patients with MVI (MVI group, n=60), segmental PVTT with segmental branches of the portal vein or above (segmental PVTT group, n=13), and lobar PVTT involving the left and right branches of the portal vein or the main portal vein (lobar PVTT group, n=68). Between the tumor recurrence group and the no recurrence group, there were significant differences in alpha-fetoprotein (AFP) level, tumor total diameter, pretransplant treatment, histological grade, and types of vascular invasion. Subgroup analyses were performed according to the types of vascular invasion, the lobar PVTT group had a significantly higher recurrence rate (lobar vs. MVI: 88.2% vs. 35.0%, lobar vs. segmental: 88.2% vs. 30.8%, both P<0.001), but there was no difference in recurrence rate between the MVI group and the segmental PVTT group (35.0% vs. 30.8%, P>0.99). The 3-year RFS rate and OS rate were as low as 9.1% and 45.9% in the lobar PVTT group, compared with 65.5% and 76.0% in the MVI group, 58.3% and 75.0% in the segmental PVTT group. Multivariate analysis showed that Child-Pugh classification, tumor total diameter, histological grade, and lobar PVTT were the main risk factors affecting RFS, whereas Child-Pugh classification, tumor total diameter, and lobar PVTT were the main risk factors affecting OS. Finally, analysis of the segmental PVTT group revealed that RFS was significantly higher in well and moderately-differentiated patients than in poor-differentiated patients (P=0.01). Lobar PVTT remains a contraindication to LT, whereas segmental PVTT can still be considered for LT after careful screening.

Efficacy of transcatheter arterial chemoembolization using pirarubicin-loaded microspheres combined with lobaplatin for primary liver cancer.

BACKGROUNDDrug-eluting beads show good safety and promising efficacy when used as part of a transarterial chemoembolization regimen for primary liver cancer. However, data on the clinical efficacy and safety of pirarubicin-loaded beads combined with lobaplatin are lacking in China.AIMTo evaluate the efficacy and safety of transcatheter arterial chemoembolization using pirarubicin-loaded beads combined with lobaplatin for primary liver cancer.METHODSBetween January 2019 and March 2020, 60 patients with primary liver cancer were selected at Hebei North University Affiliated First Hospital. According to different treatment methods, the participants were categorized into two groups with 30 patients treated with pirarubicin-loaded microspheres combined with lobaplatin included in an observation group and 30 patients treated with pirarubicin emulsion with lipiodol combined with lobaplatin were included in a control group. The progression-free survival, overall survival, clinical response rate, disease control rate, liver and kidney function and adverse reactions were compared between the two groups.RESULTSThe progression-free survival was 14 mo in the observation group, which was significantly higher than 9 mo of the control group (P < 0.05). The 6-mo, 12-mo and 18-mo survival rates were 93.33% (28/30), 66.67% (20/30) and 23.33% (7/30), respectively in the observation group, which were significantly higher than 83.33% (25/30), 50.00% (15/30) and 13.33% (4/30), respectively, of the control group (all P < 0.05). The clinical efficacy rate and disease control rate were 73.33% and 93.33%, respectively, in the observation group, which were significantly higher than those of the control group (53.55% and 80.00%, respectively, all P < 0.05). There was no significant difference in alpha-fetoprotein between the two groups before the treatment (P > 0.05). After the treatment, alpha-fetoprotein was 289.06 ± 76.21 ng/mL in the observation group and 365.01 ± 73.11 ng/mL in the control group, which were low in both groups compared with those before the treatment (all P < 0.05). The incidence of nausea and vomiting was significantly lower in the observation group than in the control group (P < 0.05). There was no significant difference for the adverse reactions of pain and fever between the two groups (P < 0.05).CONCLUSIONThe combination of pirarubicin-loaded beads and lobaplatin can improve treatment efficacy resulting in mild liver function damage and postoperative complications in patients with primary liver cancer. It can be used in clinical practice.

Neutrophil-to-Lymphocyte Ratio Predicts High-Risk Explant Features and Waitlist Survival But Is Not Independently Associated With Recurrence or Survival Following Liver Transplantation for Hepatocellular Carcinoma.

We assessed the prognostic significance and the clinical stability of the neutrophil-to-lymphocyte ratio (NLR) before liver transplantation (LT) in a large cohort of patients with hepatocellular carcinoma (HCC) from a region with a long waitlist time. A high preoperative NLR ≥5 has been reported to predict poor outcomes following LT for HCC, and the NLR has been incorporated into several prognostic models. We evaluated 758 patients with HCC with Model for End-Stage Liver Disease exceptions and listed for LT from 2002 to 2015 at a single LT center, of which 505 underwent LT and 253 dropped out before LT. The NLR was collected in all patients at LT and, if available, between 15 and 90days before LT (NLR2) or at dropout. An NLR≥5 was associated with microvascular invasion (MVI), poorer tumor differentiation, and more advanced pathology on explant. Patients with an NLR≥5 exhibited no differences in alpha-fetoprotein, tumor burden at listing, or number of locoregional therapies compared with patients with an NLR<5. After a median post-LT follow-up of 4.7years, overall survival and recurrence rates were similar for patients with an NLR≥5 versus patients with an NLR<5. The NLR changed frequently, and 47% of patients whose NLR2 was≥5 had an NLR<5 by LT. The NLR was≥5 in 47.6% of patients at dropout compared with 14.9% of patients undergoing LT. Although the NLR at LT correlated with MVI and tumor stage at explant, the NLR did not predict post-LT survival or HCC recurrence. The NLR appeared to be a relatively unstable inflammatory marker during the immediate 3 months before LT for HCC.

Evaluation of the Effect of Hemolysis on Quantitative Chemiluminescent Immunoassay Results for 10 Analytes.

The aim is to evaluate the effect of hemolysis on the quantitative chemiluminescent immunoassay results of 10 analytes and to provide a basis for formulating specific sample rejection criteria and reviewing report results. Hemolysis based on the clinical hemolysis index, hemolysis 1+, 2+, and 3+ samples and matched normal samples were collected. The quantitative chemiluminescent immunoassay results of 10 analytes from the two samples (hemolysis and normal) were determined and differences between the results obtained from samples with different degrees of hemolysis and those obtained from normal samples were evaluated. A total of 34 pairs of samples were collected, including 10 pairs of 1+ hemolysis samples, 10 pairs of 2+ hemolysis samples, and 14 pairs of 3+ hemolysis samples. The quantitative chemiluminescence immunoassay detection results for the 10 analytes showed that regardless of the degree of hemolysis, the differences in alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9), luteinizing hormone (LH), folli-cle-stimulating hormone (FSH), and ferritin (FER) between the hemolysis and normal samples were all lower than the total allowable error (TEa) based on biological variation; there were no statistically significant differences between the samples. However, the results for insulin (INS) began to decrease significantly at a hemolytic index of 1+, folic acid (FOL) showed an increase at a hemolytic index of 2+, and there was a significant difference at a he-molytic index of 3+. This research identified the analytes that are susceptible to hemolysis interference in chemiluminescent immunoassays. The influence of hemolysis on hemolytic clinical laboratory tests was closely related to the assay system used; thus, laboratories should evaluate the effect of hemolysis on their own analysis systems and define assay-specific hemolysis warning indices.

149P - Evaluation and diagnostic potential of plasma biomarkers in bladder cancer

BackgroundWhile urine biomarkers are widely used to diagnose bladder cancer (BLC), little is known about plasma protein levels in patients with BLC. The current research is aimed to evaluate diagnostic potential of 13 plasma markers including tumor antigens, inflammatory markers and apolipoproteins (Apo) as well as combinations of thereof. MethodsIn total 203 healthy volunteers (HV) and 59 patients with BLC were enrolled into the study. Concentrations of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (СА 19-9), prostate-specific antigen (PSA), beta 2 microglobulin (B2M), human-specific C-reactive protein (hsCRP), D-dimer, сytokeratin 19-fragments (CYFRA 21-1), ApoA1, ApoA2, ApoВ, transthyretin (TTR), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in plasma were measured via ELISA. t-test after log-transformation was used to identify between-group differences in biomarker levels. Diagnostic accuracy of the single biomarkers as well as trained random forest (RF), linear discriminant analysis (LDA) and support vector machine (SVM) classifiers was assessed by ROC analysis. ResultsPlasma levels of ApoB, B2M, CA 19-9, CYFRA 21-1, D-dimer, hsCRP, sVCAM-1 and TTR were significantly higher (p-value<0.001) whereas ApoA1 and ApoA2 levels were significantly lower (p-value<0.0005) in patients with BLC vs HV. No differences in AFP, CEA and PSA was found between the groups. The highest discriminative power was shown for sVCAM-1 and ApoA1 with area under ROC curve (AUROC) 0.92 and 0.90, respectively, whereas AUROC for several classifiers based on measurements of 2-12 biomarkers was higher than 0.95. ConclusionsNumerous abnormalities in plasma biomarker levels were detected in patients with BLC, hence, blood-based tests represent a promising strategy to improve performance of urinary-based tests and cystoscopy in BLC detection and prognosis. Combining several biomarkers allows to increase diagnostic test accuracy. Legal entity responsible for the studyI.M. Sechenov First Moscow State Medical University. FundingI.M. Sechenov First Moscow State Medical University. DisclosureAll authors have declared no conflicts of interest.

The therapeutic value of alpha-fetoprotein and cholinesterase in patients with hepatitis B virus related acute onset chronic liver failure

To evaluate the therapeutic value of alpha-fetoprotein (AFP) and cholinesterase (ChE) in patients with hepatitis B virus related acute onset chronic liver failure (HBV-ACLF). A case-control observation was conducted. Sixty-seven patients with HBV-ACLF admitted to Tianjin Second People's Hospital from January 2009 to October 2015 were enrolled. According to the diagnostic criteria of ACLF, the patients were divided into early, middle, and late groups, and alternatively, according to the outcome, they were divided into survival group and death group. Serum samples were collected after 0, 2, 4, 8 weeks to determine the value of AFP and ChE and analyze the value of AFP and ChE in reflecting the changes during HBV-ACLF progression. The differences in AFP and ChE between the survival group and the death group were compared. The prognostic values of AFP and ChE for HBV-ACLF patients were evaluated. Among 67 patients, there were 24, 24, and 19 patients in the early, middle and late stage, respectively, and there were 0, 9, 18 deaths at 8 week. With the advance of HBV-ACLF, the levels of both AFP and ChE were decreased in the early, middle, and late stage, with the AFP value of 40.205 (14.663, 90.550), 23.445 (8.233, 64.213), 8.990 (6.120, 14.340) μg/L (F = 36.149, P = 0.000) and the ChE value of (4.217±1.408), (3.619±1.200), (2.503±1.248) kU/L, respectively (F = 19.575, P = 0.000). In the death group, the levels of serum AFP at 0, 2, 4, 8 weeks were significantly lower than those in survival group [μg/L: 21.540 (7.670, 50.470) vs. 60.680 (16.383, 146.100), 10.560 (6.170, 20.100) vs. 60.090 (27.662, 100.700), 8.750 (3.045, 10.105) vs. 51.875 (16.778, 88.833), 3.900 (2.120, 7.660) vs. 20.400 (12.950, 50.430), P < 0.05 or P < 0.01]. The levels of serum ChE at 2, 4, 8 weeks in the death group were significantly lower than those in the survival group (kU/L: 3.206±1.480 vs. 4.008±1.227, 2.893±1.478 vs. 4.140±1.236, 2.948±1.355 vs. 4.329±1.390, P < 0.05 or P < 0.01). The levels of AFP in 67 patients were 30.100 (10.100, 90.100) μg/L, and ChE was (3.685±1.382) kU/L at 2 weeks, and they showed no correlation between AFP and ChE according to the linear correlation analysis (r = 0.082, P = 0.508), suggesting that AFP and ChE could be used as two independent prognostic factors for HBV-ACLF patients. It was showed by receiver operating characteristic curve (ROC) analysis that the area under the curve of AFP (AUC) was 0.847 (P = 0.000), while the AUC of ChE was 0.681 (P = 0.012). The highest values of Youden index and the maximum effectiveness of testing were obtained when AFP and ChE reached 20.520 μg/L and 2.924 kU/L, respectively, with the sensitivity and the specificity of AFP being 85.0% and 77.8%, respectively, and of ChE being 77.5% and 59.3%, respectively. When using the value of AFP ≥ 20.520 μg/L combined with the value of ChE ≥ 2.924 kU/L, the sensitivity for predicting HBV-ACLF outcome was 65.9%, and its specificity was 91.0%. Both AFP and ChE were helpful in providing accurate information for the progression and prognosis of HBV-ACLF patients due to the facts that their values were less interfered by the clinical treatment and that they have higher specificity.

Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal

Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear. Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan–Meier analysis and multivariable Cox proportional hazards regression models. Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4-4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30-1.98), disease-free survival (HR = 1.26; 95 % CI 1.10-1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07-1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1-5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7-327,560.0 ng/mL) and Ishak stage 6 cirrhosis. Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.

Triple-test screening in in vitro fertilization pregnancies.

To determine whether the results of triple-test analysis differ between spontaneous and IVF pregnancies. The study population consisted of 140 women with singleton pregnancies, 70 by IVF, and 70 by spontaneous conception. The groups were matched for maternal age, gestational week, and laboratory batch. The levels of all triple-test markers--alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (u-E3)--were compared between the groups. Significantly higher HCG levels were detected in the patients with IVF pregnancies than in the control group (1.31 +/- 0.8 vs. 0.95 +/- 0.5 multiple of the medians, respectively, (p < 0.006), but there were no significant differences in AFP or u-E3 levels. Overall, 18.5% of the IVF group were found to be screen-positive as compared with 11.4% of the control group (difference not statistically significant). Only 8 IVF pregnancies (11.4%) reached the lowest calculated risk possible (1:9999) compared with 17 (24.2%) in the control group (p < 0.05). Our findings support previous data demonstrating elevated maternal serum HCG in IVF patients in comparison with spontaneous ones.

Role of alpha-fetoprotein in the diagnosis and management of hepatocellular carcinoma.

Thirty-five years after its first description, alpha-fetoprotein (AFP) remains the gold standard by which other markers are judged. Serum levels above the reference range of 10 ng/mL occur in approximately 75% of cases of hepatocellular carcinoma (HCC). In individual patients, the serum AFP level behaves as if it reflects tumour mass. However, the specificity of AFP is relatively low because moderately raised levels are also found in some patients with uncomplicated chronic liver disease. Recently, tumour-specific AFP assays have been developed. These are based on the carbohydrate side-chains on the AFP molecule which exhibit characteristic differences in AFP of different origins. Monitoring response to treatment may often be more effectively carried out by serial estimation of AFP than by conventional imaging techniques. The relative specificity of AFP for HCC has also been employed to detect circulating HCC cells and to target gene therapy.