Alpha-fetoprotein Values Research Articles

Prognostic value of AFP-L3 and Des-γ-carboxy prothrombin in advanced primary liver cancer treated with Sorafenib and transarterial chemoembolization.

To evaluate the prognostic value of serum alpha-fetoprotein (AFP-L3) and Des-γ-carboxy prothrombin (DCP) in advanced primary liver cancer (PLC) undergoing combined treatment with Sorafenib and transarterial chemoembolization (TACE). This retrospective analysis included 82 patients with advanced PLC treated at the Second Affiliated Hospital, Guangzhou Medical University from January 2018 to January 2020. The patients were divided into an observation group (41 cases) and a control group (41 cases) based on their treatment method. The control group received TACE, while the observation group received a combination of Sorafenib and TACE. Both groups were evaluated after 12 weeks of treatment. Serum AFP-L3 and DCP levels were measured using a chemiluminescence immunoassay with magnetic particles. Short-term efficacy was compared between the two groups after 12 weeks of treatment. Additionally, Karnofsky Performance Status (KPS) scores, serum AFP-L3 and DCP levels before and after 12 weeks of treatment, and the survival rate after 2 years of follow-up were recorded. Serum AFP-L3 and DCP levels were compared between surviving and deceased patients. The objective response rate in the observation group (68.29%) was higher than in the control group (46.34%) (P<0.05). KPS scores in both groups were significantly higher 12 weeks post-treatment compared to pre-treatment (P<0.05); the observation group had higher post-treatment KPS scores than the control group (P<0.05). Serum AFP-L3 and DCP levels were reduced in both groups after 12 weeks of treatment compared to pre-treatment levels (P<0.05). However, post-treatment serum AFP-L3 and DCP levels were lower in the observation group compared to the control group (both P<0.05). After 2 years of follow-up, the survival rate was higher in the observation group compared to the control group (P<0.05). AFP-L3 and DCP levels were higher in deceased patients compared to surviving patients after 2 years of follow-up (both P<0.05). Combination therapy with Sorafenib and TACE is effective for patients with advanced PLC, reducing AFP-L3 and DCP levels and improving patient survival rates. Additionally, higher levels of serum AFP-L3 and DCP are associated with poor prognosis.

Predictive Value of Preoperative 18 Fludeoxyglucose Positron Emission Tomography–Computed Tomography for Survival in Liver Transplantation Due to Hepatocellular Cancer

We aimed to study the predictive value of preoperative perform [18F] Fludeoxyglucose positron emission tomography-computed tomography ([18] FDG PET-CT) for survival in liver transplantation due to hepatocellular cancer. Ninety-six patients who underwent liver transplantation for hepatocellular cancer (HCC) after preoperative PET-CT evaluation were examined for the study. All patients' ages, genders, body mass index, blood groups, Child-Pugh and Model for End-Stage Liver Disease scores, etiologies, median Alpha Fetoprotein values, Milan Criteria and T stages, grades, macrovascular and microvascular invasions, multicentricities, maximum and total tumor sizes, tumor number findings in explant specimens, and recurrence rates were analyzed statistically. Statistically, microvascular (P = .002) and macrovascular invasions (P = .034) were observed more frequently in patients who are PET-CT (+) compared with patients who are PET-CT (-). PET-CT positivity was associated with shortened disease-free survival (DFS) statistically (P = .004). Positron emission tomography-CT positivity may be important for predicting prognostic markers such as DFS and vascular invasion in the preoperative evaluation. Before transplantation, PET-CT should be applied to all patients with HCC.

Raised Alpha-Fetoprotein Level and its Association with Hepatocellular Carcinoma

Objective: To evaluate raised alpha feto-protein levels for socio-demographic and clinicopathological features in hepatocellular carcinoma. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medical Oncology, Jinnah Postgraduate Medical Center, Karachi Pakistan, from Jan 2019 to Jan 2020. Methodology: Two hundred and thirty-six patients of age more than 20 years, of either gender diagnosed with hepatocellular carcinoma were included. Detailed demographic data, information regarding addiction and medical history were collected. According to The National Comprehensive Cancer Network, Hepatocellular carcinoma was diagnosed using a multiphasic liver protocol CT scan with intravenous contrast. The alpha-fetoprotein levels were checked after confirmation of hepatocellular carcinoma on a multiphasic CT scan. The cut-off value for elevated alpha feto-protein was ≥20 ng/mL. Results: The median alpha protein levels were reported as 411 ng/mL. About 183(78%) patients had elevated alpha protein levels. In univariate analysis, age, gender, diabetes mellitus, hepatitis B, hepatitis C, portal vein thrombosis, number of lesions, cirrhotic liver, features of portal hypertension, anti-viral treatment status, cigarette smoking, and segment of the liver showed a statistically significant relationship with elevated alpha protein levels (p&lt;0.05). On the multivariate model, age, hepatitis C, number of lesions, portal vein thrombosis, and Child Pugh score showed statistically significant association with elevated alpha protein (p&lt;0.05). Conclusions: The elevated alpha protein levels level was found to be higher among hepatocellular carcinoma and associated with age, hepatitis C, number of lesions, portal vein thrombosis and Child Pugh score.

Predictive value of PIVKA-II and AFP for the non-objective response of HBV-associated hepatocellular carcinoma after transarterial chemoembolization: a prospective study.

To determine the predictive value of serum abnormal prothrombin (PIVKA-II) and alpha-fetoprotein (AFP) for the non-objective response of HBV-associated hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). This prospective study included HBV-associated HCC patients who underwent TACE at the Fourth People's Hospital of Qinghai Province between December 2021 and July 2022. According to contrast-enhanced ultrasound and upper abdomen contrast-enhanced MRI, the patients were divided into the objective response group and the non-objective response group 3 months after TACE. There were 54 patients, of whom 31 experienced non-objective responses. The PIVKA-II levels in the objective response group were significantly lower than in the non-objective response group at 1 month [352.00 (142.16-722.54) vs. 528.58(241.32-1681.23) mAU/ml, P = 0.005] and 3 months [28.96 (20.01-42.49) vs. 2082.55 (52.63-10 057.30) mAU/ml, P = 0.016] after TACE. The Spearman rank correlation analysis showed no significant correlation between PIVKA-II and AFP (r = 0.315, P > 0.05). The areas under the curve (AUCs) of AFP and PIVKA-II before TACE were 0.632 and 0.529. One month after TACE, the AUC of PIVKA-II combined with AFP (AUC = 0.787) was higher than for PIVKA-II (AUC = 0.658) and AFP (AUC = 0.749). PIVKA-II does not outperform AFP in predicting non-objective response after TACE in HCC patients. The combination of PIVKA-II and AFP might improve the diagnosis of HCC non-objective response after TACE.

Rapid and Label-Free Analysis of Antigen-Antibody Dynamic Binding of Tumor Markers Using Piezoelectric Quartz Crystal Biosensor.

Quantitative biomacromolecular diagnosis is rapidly developing in molecular oncology. In this study, we developed a continuous flow immunoassay device based on a piezoelectric (PZ) quartz crystal biosensor fabricated with whole-electrode occupation for the quantitative molecular diagnosis of tumor markers such as alpha-fetoprotein (AFP). Only one face of the crystal was in contact with the serum sample during the assays. First, the characteristics of AFP and anti-AFP binding kinetics, such as the optimal time for immune response, the average antigen binding rate, the kinetic constants and the optimal standard curve, were investigated. The overall immunoreaction time was only 12 min, the average antigen binding rate of AFP was 45.9 ng/min, the concentration range of AFP detection was 18.8-1100 ng/mL and the association rate constant (kon), dissociation rate constant (koff) and equilibrium dissociation constant (KD) were 5.58×104 M-1s-1,1.79×10-5 s-1 and 3.21×10-10 M, respectively. This sensing system was further validated by detecting AFP values from clinical serum samples, which were obtained from pregnant women, liver and lung cancer patients and those undergoing liver cancer screening. No cross-reactivity with lung cancer markers were found, and the detection results were in good agreement with the radioimmunoassay (RIA) results, with a relative deviation of no more than 3.7% and correlation coefficient r of 0.9998. Therefore, the developed immunoassay device has the potential to be used in large-scale screening for cancers, as well as in novel high-affinity binding drug development.

Prediction of Preterm Delivery among Low-risk Indian Pregnant Women: Discriminatory Power of Cervical Length, Serum Ferritin, and Serum Alpha-fetoprotein.

Around 80% of preterm births (PTBs) occur spontaneously. Various biomarkers are being evaluated to assess the possible role of chorioamniotic inflammation in PTBs. The aim of this study was to establish the accuracy of serum bio-markers( cut off values of ferritin and alpha-fetoprotein [AFP] at midtrimester) along with cervical length [CL] assessment to predict preterm delivery among low-risk women. Three hundred low-risk pregnant women attending the antenatal clinic of a tertiary health care facility were included and underwent CL measurement during mid-trimester by transvaginal ultrasonography and their serum levels of ferritin and AFP were recorded. All were followed up till delivery. Receptor-operated characteristic curves for ferritin, AFP, and CL were constructed. Area under curves and Youden Index calculated for each marker were very low (<0.5) which is statistically considered very poor for a screening test. Serum ferritin and AFP together with CL measurement in the second trimester of pregnancy had poor discriminatory value in predicting preterm delivery among low-risk asymptomatic pregnant women.

Beyond liver cancer, more application scenarios for alpha-fetoprotein in clinical practice.

Alpha-fetoprotein (AFP) is a commonly used clinical biomarker. Before 1970, the two-way agar diffusion method was mainly used, and the specificity of AFP in the diagnosis of primary liver cancer was satisfactory. However, its positivity rate was not very high. The diagnostic value of AFP is changing with the evolution of detection methods. Here, we performed a literature search to identify English-language publications. The search was performed from January 2015 to April 2023 using the PubMed database and the following terms in [Titles/Abstracts]: alpha-fetoprotein, clinical practice, detection, etc. The references of retrieved articles were also screened to broaden the search. Studies referring to liver cancer and AFP detection methods were excluded. In this review, several clinical application scenarios for AFP were systematically reviewed, and its potential detection value in the future was discussed.

Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

Alpha-Fetoprotein Response after First Transarterial Chemoembolization (TACE) and Complete Pathologic Response in Patients with Hepatocellular Cancer.

Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively (p = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively (p = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, p = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE.

Analysis of Alfa-Fetoprotein as A Staging Determiner of Hepatocellular Carcinoma Progresivity

Hepatocellular carcinoma (HCC) is the most common malignant tumor with a poor prognosis and is known as the silent killer. The currently recommended HCC staging system is Barcelona Clinic Liver Cancer (BCLC). The Alpha-fetoprotein (AFP) test is still used to manage HCC patients. The purpose was to find out the AFP comparations and to decide cut-off values for each stage according to BCLC. Cross-sectional retrospective study using secondary data from medical records of Outpatients Clinic and Inpatients from January 2016 to October 2021 at Dr. Wahidin Sudirohusodo Hospital. A total of 432 samples based on BCLC were taken with AFP values and analyzed in this study. The male sample was 72.7%. The highest age is 46-65 years (62.7%). The etiology of HCC mostly is hepatitis B (72.5%). The most BCLC systems were BCLC B (53.7%), followed by BCLC A (25.9%), BCLC D (12.5%), and BCLC C (7.87%). There was a significant difference in AFP values between BCLC stages and the highest significance was BCLC D, followed by BCLC C, B, and A (p=0.05). The cut-off results values at the BCLC stage were BCLC A &lt;21.84 ng/mL, BCLC B: 21.84 ng/mL (sensitivity 90.3%, specificity 85.7%), BCLC C: 478 ng/mL (sensitivity and specificity 100%), BCLC D: 7.693 ng/mL (sensitivity and specificity 100%). There was a significant difference in AFP values between BCLC stages and the highest is BCLC D. Based on the results of calculating the cut-off value, which has good sensitivity and specificity, AFP can be used as a determinant of stage progression of HCC.

Primary endodermal sinus tumor originating from the sacral ligament: a case report and review of the literature

BackgroundEndodermal sinus tumor (EST) is a malignant tumor originating from the ovary or testis. In most case, ultrasound examination shows ovarian mass. But there is a special kind of extra-gonadal endodermal sinus tumor, which occur in organs other than gonads with insidious onset. Here we reported a case of endodermal sinus tumor, which originated from the sacral ligament presenting as an acute lower abdominal pain.Case presentationA 14-year-old girl was admitted to the hospital because of acute lower abdominal pain. The ultrasound showed a mass with 72 mm × 64 mm × 50 mm in Douglas, and there was no abnormality in bilateral ovaries and fallopian tubes. Laparoscopic exploration showed a large amount of blood clots in the pelvic cavity. After removal of the blood, we found rotten fish-like tissue in the left sacral ligament, rapid pathology suggested endodermal sinus tumor. After the operation, we retrospectively examined the value of alpha-fetoprotein (AFP), which was found to be elevated, and post-operative paraffin pathology confirmed the diagnosis. After four cycles of BEP chemotherapy, exploratory laparotomy was performed to remove the visible lesion, but postoperative pathology showed no abnormality. At the one-year follow-up, the patient remained recurrence-free.ConclusionExtra-gonadal germ cell tumors are rarely reported. When young teenagers complain of acute lower abdominal pain with elevated AFP, but there was no lesion in bilateral ovaries and fallopian tubes, we must think about the possibility of endodermal sinus tumors. Accurate diagnosis facilitates complete resection of lesions and improves patient’s outcomes.

Dynamic changes in three biomarkers predict early-stage hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma during antiviral therapy. We aimed to clarify the values of alpha-fetoprotein (AFP), lectin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) for early warning of HCC. A total of 1348 CHB patients received antiviral therapy and follow-up every 26weeks. Eighty-four patients with HCC were age-, sex-, and cirrhosis-matched with 168 controls. AFP, AFP-L3, and DCP were compared between the groups from 104weeks before HCC diagnosis (- 104w) to the time of diagnosis (0w). Of the 84 HCC patients, 60 (71.4%) had early-stage HCC, AFP increased from - 26w, and AFP-L3 and DCP increased from - 78w. However, levels were unchanged in controls. ΔAFP, ΔAFP-L3, and ΔDCP showed similar abilities for predicting HCC (P > 0.05). Receiver operating characteristic curve analysis showed that AFP had better diagnostic performance for HCC than AFP-L3, DCP, or their combination. The cut-off values of AFP, AFP-L3, and DCP were 5.3ng/mL, 1.05%, and 31.5 mAU/mL, respectively. Notably, lower AFP values were required to diagnose HCC in patients with detectable HBV DNA (4.1ng/mL) or elevated alanine aminotransferase (5.2ng/mL). Changes in AFP, AFP-L3, and DCP can help to predict HCC in CHB patients receiving antiviral therapy. A lower AFP value is needed to diagnose HCC, especially in patients with detectable HBV DNA or elevated alanine aminotransferase.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures

Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p=0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

Response Prediction Model of Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Retrospective Study

Introduction: Atezolizumab plus bevacizumab (ATZ+BV) treatment has become the first-line regimen for unresectable hepatocellular carcinoma (u-HCC). Prediction of response to it might be clinically beneficial. Using peripheral blood parameters, we aimed to construct a prediction model for ATZ+BV treatment. Methods: Clinical records of 119 patients with u-HCC treated by ATZ+BV were retrospectively analyzed. The primary outcome measurement was defined as any-size reduction at the initial image evaluation. Using baseline values of peripheral blood parameters, a prediction model was constructed by univariate and multivariate logistic regression analysis. Validation was performed internally by bootstrap method. Results: The primary outcome was achieved in 46 patients. Univariate analysis showed that C-reactive protein (CRP), alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were possible predictors. CRP and DCP, and NLR and PLR had correlation (correlation coefficient >0.3), so we used CRP and NLR as representative factors, respectively. Multivariate analysis constructed the following prediction model: Logit = 1.62–0.61×[CRP] −0.38×[Log₁₀AFP] −0.37×[NLR]. Bootstrapped median (95% confidence interval) of coefficients of CRP, Log₁₀AFP, NLR were −0.64 (−1.46 ∼ −0.11), −0.40 (−0.82 ∼ −0.03), and −0.38 (−0.74 ∼ −0.05), respectively. The area under the receiver operating characteristic curve (95% confidence interval) was 0.73 (0.60–0.80). Median overall survival of the favorably and unfavorably predicted groups were 17.0 and 11.0 months (p = 0.03), respectively. Discussion: In patients with u-HCC treated by ATZ+BEV, a prediction model constructed using baseline values of CRP, AFP, and NLR had impact on any-size reduction at the initial image evaluation and on prognosis.

Evaluation of Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma Using the Combination of Response Evaluation Criteria in Solid Tumors and Alpha-Fetoprotein

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child-Pugh Score of 5-7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy.

Treatment outcomes and prognostic factors in children with hepatoblastoma using a risk‐stratified approach

Not all the significant progress made in the management of children with hepatoblastoma (HB) has translated into improved outcomes in limited-resource settings. There are limited data on outcomes in children with HB from India. All patients diagnosed with HB between July 2013 and December 2020 were risk-stratified and treated as per International Liver Tumor Strategy Group (SIOPEL). Patients with standard-risk HB received cisplatin monotherapy and those with high-risk HB received alternating cycles of cisplatin and the combination of carboplatin plus doxorubicin. Data regarding demographic details, chemotherapy, surgery, liver transplantation, outcomes, prognostic factors, and toxicity were collected. Of 157 patients with HB, 117 (74%) were high risk, 31 (20%) were standard risk, and nine (6%) unknown. Patients with standard-risk disease had excellent outcomes, with 3-year event-free survival (EFS) and overall survival (OS) of 96% and 100%, respectively. Among high-risk HB, six underwent orthotopic liver transplantation of which four were alive at last follow-up. The 3-year EFS and OS of patients with high-risk disease was 56% and 66%, respectively. Outcomes of patients with PRETEXT IV (3-year EFS: 42%, 3-year OS: 50%) and metastatic disease (3-year EFS: 30%, 3-year OS: 50%) were dismal. Patients with serum alpha-fetoprotein (AFP) reduction greater than 90% following two courses of chemotherapy had favorable outcomes; 3-year EFS: 80% versus 58% (p=.013) and 3-year OS: 95% vs. 68% (p<.01). Only two (6%) of 31 patients with relapse/refractory HB were alive at a median follow-up of 36months, and both had received salvage chemotherapy and surgery. While children with standard-risk HB had excellent outcomes, those with high-risk disease continue to do poorly. Serial monitoring of serum AFP values is a cost-effective and reliable predictor of outcomes. Orthotopic liver transplantation remains a viable option for inoperable disease in resource-limited settings as well.

Combining serum AFP and CEUS LI-RADS for better diagnostic performance in Chinese high-risk patients.

To evaluate and compare the diagnostic performance of revised contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System version by combining LR-M category and serum alpha-fetoprotein (AFP) under different cut-off values. This retrospective study enrolled 152 high-risk patients with 152 histology-proven nodules. For revised LI-RADS, nodules in LR-M with different elevated AFP thresholds have been reclassified as the LR-5 category. The diagnostic performances of original and revised CEUS LI-RADS were evaluated and compared. To compare with the original version, the sensitivity of revised LR-5 (adjusted with AFP value > 200ng/ml or 400ng/ml) for the diagnosis of hepatocellular carcinoma (HCC) improved from 52.5 to 69.2% or 65.0%, respectively (both p < 0.001) without compromising specificity (87.5% vs. 71.9% or 78.1%, respectively, both p > 0.05). For the diagnosis of non-HCC malignancy, the specificity of the LR-M after reclassification was improved (69.6% vs. 84.4% or 80.7%, respectively, both p < 0.001) with a non-significant sensitivity reduction (100.0 vs. 70.6% or 82.4%, respectively, both p > 0.05). After modification, the sensitivity of LR-5 also increased to 69.1% or 64.9% (both p < 0.001), while the specificity and PPV did not change (both p > 0.05) for larger nodules (> 20mm). The diagnostic performance of CEUS LI-RADS can be further improved by reclassifying LR-M nodules with elevated AFP thresholds to LR-5.

PIVKA-II or AFP has better diagnostic properties for hepatocellular carcinoma diagnosis in high-risk patients.

Hepatocellular carcinoma (HCC) is a lethal cancer. Two biomarkers were used for HCC diagnosis including alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II or antagonist (PIVKA-II). However, data on biomarkers and HCC diagnosis are not consistent. This study aimed to evaluate if PIVKA-II, AFP, or a combination of both biomarkers had the best diagnostic properties for HCC. This was a prospective study and enrolled patients 18 years or over with a high risk for HCC. AFP and PIVKA-II levels were calculated for HCC diagnosis. Diagnostic properties of both biomarkers were reported with sensitivity, specificity, and a receiver operating characteristic (ROC) curve. There were 260 patients with high risk for HCC in this cohort. Of those, 219 patients were diagnosed with HCC: confirmed by biopsy in 7 patients (2.69%) and by imaging in the others. Median values of AFP and PIVKA-II were 56 ng/mL and 348 mAU/mL, respectively. PIVKA-II level of 40 mAU/mL had sensitivity of 80.80%, while AFP of 10 ng/mL had sensitivity of 75.80%. A combination of PIVKA-II at 100 mAU/mL or over and AFP of 11 ng/mL gave sensitivity of 60.30%. The ROC curve of PIVKA-II plus AFP was significantly higher than the AFP alone (0.855 vs. 0.796; p = 0.027), but not significantly different from the PIVKA-II alone (0.855 vs. 0.832; p = 0.130). PIVKA-II may have more diagnostic yield for HCC compared with AFP. It can be used alone without a combination with AFP.

Reconsidering Race Adjustment in Prenatal Alpha-Fetoprotein Screening.

Black racial designation is the only race for which adjustment is recommended for maternal prenatal serum alpha-fetoprotein (AFP) screening. The objective of this study is to reevaluate the relationship between maternal race and maternal serum AFP values in prenatal analyte screening. This was a single-center retrospective analysis of patients who underwent prenatal analyte screening between January 2007 and December 2020. Nomograms for raw maternal serum AFP values by gestational age were created and compared between patients identified as "Black" and "non-Black" on the laboratory requisition. Multivariable linear regression models were created to evaluate the relationship among gestational age, maternal weight, and maternal race on maternal serum AFP levels. The new models were compared with the laboratory-derived calculations, which used historically determined race adjustments. A total of 43,997 patients underwent analyte screening, and 27,710 patients had complete data for analysis. Of these, 6% were identified as Black. Black patients had laboratory blood draws at a mean gestational age of 123 days, compared with 120 days in non-Black patients ( P <.001), and had higher maternal weight (mean 170 vs 161 lbs, P <.001). Nomograms for raw maternal serum AFP values did not differ between Black and non-Black patients ( P =.065). When adjusted for gestational age and maternal weight, no difference in maternal serum AFP values was identified between Black and non-Black individuals ( P =.81). No difference in maternal serum AFP values was identified between Black and non-Black pregnant individuals when adjusted by maternal weight and gestational age at blood draw. These findings suggest that routine race-based adjustment of maternal serum AFP screening should be discontinued.

Diagnostic Efficacy and Possible Underlying Mechanisms of Noninvasive Clinical Markers in Hepatocellular Carcinoma.

In this study, we aimed to evaluate the diagnostic values of alpha-fetoprotein (AFP), soluble AXL (sAXL), des-γ-carboxy prothrombin (DCP), the aspartate aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma (HCC) and the possible underlying mechanisms of the correlations between them. We collected serum samples from 190, 128, and 75 patients with HCC, cirrhosis, and chronic viral hepatitis, and from 82 healthy subjects. Serum levels of AFP, sAXL, and DCP were determined, and APRI and GPR values were calculated. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of single and combined biomarkers. We detected significant differences between the HCC group and other groups regarding serum AFP, sAXL, DCP, and APRI levels. GPR significantly differed between the HCC group and other groups, except for the liver cirrhosis group. AFP, sAXL, DCP, APRI, and GPR had positive correlations with each other, and AFP showed a higher area under the curve (AUC) and Youden index values, while APRI and DCP showed the highest sensitivity and specificity. Also, when AFP was combined with sAXL, DCP, APRI, and GRP, the highest AUC (0.911) and a higher net reclassification improvement value were obtained compared with those obtained for the individual biomarkers. AFP, sAXL, DCP, APRI, and GPR are independent risk factors for HCC, and the diagnostic performance of AFP combined with sAXL, DCP, APRI, and GPR for HCC diagnosis was superior to that of the individual biomarkers.