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Liv-52, an herbal formulation consisting of seven distinct plants and Mandur Bhasma, is recognized for its hepatoprotective, anti-inflammatory, and antioxidant properties. To investigate the pharmacological potential of each phytochemical from these plants, we conducted ADMET analysis, molecular docking, and molecular dynamic simulations to identify potent molecules capable of inhibiting the interaction between Alpha-fetoprotein (AFP) and Cysteine aspartyl protease 3 (Caspase-3/CASP3). In our study, we have used molecular docking of all the compounds against AFP and filtered them on the basis of ADME properties. Among the compounds analyzed, (-) Syringaresinol from Solanum nigrum, exhibited good binding interactions with AFP, the highest binding free energy, and maintained stability throughout the simulation along with favorable drug likeness properties based on ADME and Toxicity analysis. These findings have strongly indicated that (-) Syringaresinol is a potential inhibitor of AFP, providing a promising therapeutic avenue for hepatocellular carcinoma (HCC) treatment by inhibiting the interaction between AFP and CASP3, thereby reinstating normal CASP3 activity. Further in vitro studies are imperative to validate the therapeutic efficacy of (-) Syringaresinol as an AFP inhibitor, potentially impeding the progression of HCC. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy combined with intra-arterial therapy (IAT) has shown great potential in the treatment of unresectable hepatocellular carcinoma (uHCC). However, there are currently no available biomarkers that can predict the prognosis of immune-based combined therapy. Objectives: To establish a scoring method to predict prognosis in uHCC patients undergoing IAT plus immunotherapy. Methods: Between March 2019 and August 2022, uHCC patients undergoing IAT in combination with programmed cell death (ligand) 1 (PD-1)/PD-L1-based immunotherapy were retrospectively analyzed. Results: Among 1046 patients included, 780 patients were enrolled into hepatic arterial infusion chemotherapy immunotherapy cohorts (training set: n = 546, one center; external testing set: n = 234, three centers) and 266 patients were treated with trans-arterial chemoembolization (TACE) plus immunotherapy were enrolled into TACE immunotherapy cohort (validation set: n = 266). We developed the easy-to-apply alpha-fetoprotein (AFP), C-reactive protein (CRP), and platelet-to-lymphocyte ratio (PLR) in immunotherapy (AFCRPLITY) score and investigated the prognostic value of baseline variables on the disease control rate (DCR) and progression-free survival (PFS). HCC patients with low AFCRPLITY scores would have better PFS and DCRs than patients with high AFCRPLITY scores (AFCRPLITY 0: vs AFCRPLITY 1: vs AFCRPLITY 2: vs AFCRPLITY 3: p < 0.001 for PFS, p = 0.001 for DCRs) in the training set, which was confirmed in the external testing set and validation set. The highest level of CD8+ T cells was in the AFCRPLITY score = 0 group than the other two groups. Conclusion: The AFCRPLITY score is associated with PFS and DCR in uHCC patients receiving IATs plus immunotherapy. This score may be helpful for counseling, but prospective validation is needed. Design: A retrospective, multi-institutional study. Trial registration: The study has been retrospectively registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, ChiCTR2300075828). [ABSTRACT FROM AUTHOR]

An electrochemical biosensor was created to identify the liver cancer marker alpha-fetoprotein (AFP) by employing nanocomposite materials. A combination of reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) was selected as the substrate material for the sensor to prepare the PtNPs/MoS2@rGO electrochemical immunosensor. Among them, rGO has strong conductivity and MoS2 provides a large surface area for the anchoring of PtNPs for better attachment to the hybridized nanomaterials. Meanwhile, PtNPs exhibit consistent biocompatibility and excellent electrocatalytic activity. PtNPs also attach to hybrid nanomaterials and bind the antibody via the Pt–S bond, thereby furnishing the antibody with multiple binding sites for enhanced antibody adhesion. The immunosensor achieved ultra-sensitive AFP detection by exploiting the specific antigen–antibody binding. The structure and morphology of the PtNPs/MoS2@rGO composites were investigated by transmission electron microscopy (TEM), energy dispersive X-ray (EDS) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy, and the sensor was electrochemically characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, using differential pulse voltammetry the biosensor detected AFP in serum within a linear range of 1 ~ 105 pg/mL, with a correlation coefficient (r2) of 0.9989, and a detection limit of 0.12 pg/mL (S/N = 3). The method offers a new approach for the ultrasensitive detection of serum AFP and is extremely selective, accurate, and precise with a relative standard deviation (RSD) of less than 6%. It has been successfully applied to the analysis of real human blood samples. [ABSTRACT FROM AUTHOR]

To assess the diagnostic efficacy of the CEUS LI-RADS combined with a model constructed on the basis of age, sex, AFP, and PIVKA-II (ASAP) for the diagnosis of HCC in high-risk patients. This retrospective study included 366 liver lesions from 366 patients who underwent liver CEUS. All liver lesions were characterized and categorized according to CEUS LI-RADS v2017. Two modified methods were applied: LR-3/4/M nodules accompanied by AFP > 200 ng/mL (Criterion 2) or ASAP model score > 0.5256 and CA 19-9 in the normal range (Criterion 3) were recategorized as LR-5. The reference criteria included histopathological or comprehensive imaging and the clinical follow-up results. The diagnostic performance was evaluated and compared by the sensitivity, specificity, PPV, and NPV. The incidence of HCC in LR-3, LR-4, LR-5, and LR-M was 33.3% (4/12), 86.4% (38/44), 98.5% (191/194) and 82.7% (81/98), respectively. After using Criterion 2 compared to CEUS LI-RADS v2017, the sensitivity of the modified LR-5 for diagnosing HCC increased from 60.8% to 70.7% (p < 0.01) with little effect on its specificity (94.2% vs. 92.3%, p = 1.00) or PPV (98.5% vs. 98.2%, p = 0.86). After using Criterion 3, the sensitivity of the modified LR-5 for the diagnosis of HCC was further improved to 86.9% (p < 0.01), and its specificity and PPV were not significantly changed (92.3% and 98.6%, both p > 0.05). CEUS LI-RADS combined with the serum biomarker-based ASAP model improved the sensitivity of LR-5 in diagnosing HCC with little effect on its specificity and PPV. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. Patients and Methods: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. Results: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium =3.5 mmol/L, direct bilirubin >6.8 mmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity= 0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity= 0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. Conclusions: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP. [ABSTRACT FROM AUTHOR]

Background: The accurate measurement of α-fetoprotein (AFP) is critical for clinical diagnosis. However, different AFP immunoassays may yield different results. Appropriate AFP reference materials (RMs) were selected and assigned accurate values for applications with external quality assessment (EQA) programs to standardize AFP measurements. Methods: Forty individual clinical samples and six different concentrations of candidate RMs (Can-RMs, L1–L6) were prepared by the Beijing Center for Clinical Laboratories. The Can-RMs were assigned target values by performing five immunoassays, using WHO International Standard 72/225 as a calibrator, and sent to 45 clinical laboratories in Beijing for AFP measurements. The commutability of all RMs was assessed based on CLSI and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approaches. Analytical performance was assessed for compliance based on accuracy (total error, TE), trueness (bias), and precision (CV). Results: The Can-RMs were commutable for all immunoassays using the CLSI approach and for 6 of 10 assay combinations using the IFCC approach. RMs diluted in WHO RM 72/225 were commutable among all assays with the CLSI approach, except for serum matrix (Autolumo vs. Roche analyzer) and diluted water matrix (Abbott vs. Roche/Mindray analyzer), whereas some inconclusive and non-commutable results were found using the IFCC approach. The average pass rates based on the TE, bias, and CV were 91%, 81%, and 95%, respectively. Conclusions: The commutability of the RMs differed between both evaluation approaches. The Can-RMs exhibited good commutability with the CLSI approach, suggesting their suitability for use with that approach as commutable EQA materials with assigned values and for monitoring the performance of AFP measurements. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite significant advancements in screening, diagnosis, and treatment modalities for HCC, the mortality-to-incidence ratio remain unacceptably high. A recent study indicates that a minor population of HCCs are AFP negative or express the normal range of AFP levels. Although it is a gold standard and a more reliable biomarker in the advanced stage of HCC and poorly differentiated tumors, it does not serve as a suitable means for screening HCC. AFP plays a significant role in the development and progression of HCC and understanding its role is crucial. By examining the molecular mechanisms involved in AFP-mediated tumorigenesis, we can better understand HCC pathogenesis and identify potential therapeutic targets. This article details the role of alpha-fetoprotein (AFP) in the carcinogenic transformation of hepatocytes. The article also focuses on information about the structure, biosynthesis, and regulation of AFP at the gene level. Additionally, it discusses the immune evasion, metastasis, and control of gene expression that AFP mediates during HCC. [ABSTRACT FROM AUTHOR]

Herein a split‐type photoelectrochemical (PEC) immunosensor based on in situ grown gold nanoparticles (Au NPs) on the surface of ZnO microrods (ZnO MRs) was devised for the detection of alpha‐fetoprotein (AFP) by employing dopamine (DA)‐loaded liposomes as the signal amplification strategy. Specifically, as the level of AFP rises, a proportional number of sandwich‐type immunocomplexes form in the well of the microplate, which can introduce a corresponding amount of DA‐encapsulated liposomes at the same time. Encapsulated DA molecules will be released with the stimulation of Triton X‐100, thereby resulting in the marked enhancement of the PEC signal. Under optimized conditions, the proposed PEC immunosensing platform displays specific photocurrent responses toward AFP in a broad dynamic working range of 0.05 −50 ng mL−1, achieving an impressively low limit of detection (LOD) of 18.7 pg mL−1. Furthermore, this methodology not only displays high specificity, and satisfactory storage stability but also ensures acceptable accuracy and practicality for the analytical applications of human serum samples. [ABSTRACT FROM AUTHOR]

Alpha‐fetoprotein (AFP) is a structural serum glycoprotein that plays vital roles in reproduction and mammalian development. Analysis of serum prolactin (PRL) is considered one of the useful methods for diagnosing pregnancy in Asian elephants. However, the expression profiles of AFP in pregnant and nonpregnant Asian elephants remain unclear, nor is the relationship with PRL. In this study, serum seven gonadal hormones and AFP in three pregnant and seven nonpregnant Asian elephants were analysed by via radioimmunoassay (RIA) and enzyme‐linked immunosorbent (ELISA) assay. We found that the mean (±SD) concentration of prolactin (PRL) in pregnant (136.782 ± 30.987 ng/mL) elephants was significantly higher than that in nonpregnant elephants (52.803 ± 21.070 ng/mL; p ≤ 0.0005). The mean (±SD) concentration of AFP in pregnant elephants (11.598 ± 0.824 ng/mL) was significantly higher than that in nonpregnant elephants (7.200 ± 2.283 ng/mL; p ≤ 0.05). Furthermore, the AFP concentration was positively correlated with the PRL concentration in the 10 Asian elephants studied. In conclusion, our findings suggest that serum AFP concentration is a potential biomarker of pregnancy outcomes in Asian elephants. [ABSTRACT FROM AUTHOR]

We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that "endometrioid carcinoma with yolk sac tumor differentiation" or "endometrioid carcinoma with a primitive phenotype" may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium. [ABSTRACT FROM AUTHOR]

Serum alpha-fetoprotein (AFP) is often used as tumour marker for recurrent sacrococcygeal teratoma (SCT). We aimed to assess the normal dynamics of serum AFP levels after initial resection and diagnostic accuracy of serum AFP levels the follow-up for recurrence in SCT. This retrospective study included 57 patients treated for SCT in the six pediatric surgical centers in the Netherlands from 1980 to 2018. 57 patients were included in the study of whom 19 children developed 20 recurrences at a median of 14.0 months after initial resection. No significant difference was found in serum AFP level dynamics between the recurrence and non-recurrence group after initial resection (p = 0.950). Serum AFP levels did not significantly increase before recurrence (p = 0.106) compared to serum AFP levels of children without recurrence at the same time. However, serum AFP levels did significantly increase in malignant recurrences (n = 7) (p = 0.03) compared to patients without recurrence. A cut-off value of 55 μg/L was found to be predictive for recurrent SCT with an Area Under the Curve (AUC) of 0.636 with sensitivity of 50% and specificity of 100%. Dynamics of serum AFP levels are not different between patients with and without recurrence after initial resection of SCT. Serum AFP levels are not predictive for mature or immature recurrent SCT and normal AFP levels do not rule out recurrent SCT. However, serum AFP levels exceeding 55 μg/L can indicate recurrent SCT, especially malignant recurrences. [ABSTRACT FROM AUTHOR]

Introduction: Patients with hepatitis virus-related hepatocellular carcinoma (viral HCC) are decreasing as hepatitis control improves, but those with non-viral-related HCC (non-viral HCC) are increasing in Japan. No established surveillance system exists for patients with non-viral HCC, so they are often diagnosed at an advanced stage. To address this, we performed this study. Methods: We collected serum samples from 516 participants (154 healthy subjects, 93 chronic liver disease [CLD] patients without HCC, and 269 HCC patients). Participants were divided into a control group comprising healthy subjects and patients with CLD and an HCC group. We evaluated serum methylated HOXA1 (m-HOXA1) copy numbers using modified combined restriction digital PCR (CORD) assay (1-step CORD assay). We assessed diagnostic performance of m-HOXA1 compared to HCC tumor markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) and created a novel index to improve HCC prediction. Results: Serum m-HOXA1 level was significantly higher in each HCC stage group versus the control group. Its sensitivity was 69.1% and specificity was 78.5% for diagnosing HCC. The area under the curve (AUC) of m-HOXA1 was superior to that of AFP and equal to that of DCP. Multivariate logistic regression analysis revealed independent contributions of m-HOXA1, DCP, and AFP, in that order of strength, to diagnose HCC after adjustment for age and sex. We designated the predictive probability of HCC based on the regression model as the ASDAm-H1 (Age, Sex, DCP, AFP, and m-HOXA1) index. Its diagnostic accuracy was 0.96 by AUC with a sensitivity of 86.2% and specificity of 93.9%. Sensitivity was identical for viral and non-viral HCCs. When limited to early-stage HCC, sensitivity of the ASDAm-H1 index was 76.3%. Conclusions: We showed distinguished performance of the ASDAm-H1 index to detect viral and non-viral HCC, even at an early stage. This index might have potential as a non-viral HCC surveillance system. [ABSTRACT FROM AUTHOR]

An ovarian Sertoli–Leydig cell tumor is a rare type of sex cord–stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli–Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 × 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli–Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB–IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli–Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) is the most common malignant liver tumor, with an increasing incidence rate. Since alpha-fetoprotein (AFP), the traditional serum marker for HCC, has a low sensitivity, there is a critical need for novel molecular biomarkers to enable early detection of HCC. Objective To detect the protein expression level of serum polyadenosine diphosphate ribose polymerase 2 (PARP2) in HCC patients in the blood of HCC patients and investigate its potential as a diagnostic marker for HCC. Methods PARP2 mRNA levels of 50 healthy individuals and 371 HCC patients were analyzed in the TCGA database, and the diagnostic efficacy was analyzed by plotting the receiver operating characteristic (ROC) curve of subjects diagnosed with HCC by PARP2 expression. The levels of PARP2 mRNA and protein expression were assessed in both HCC cells and normal hepatocytes. Serum samples from 38 newly diagnosed HCC patients and 38 healthy individuals undergoing physical examinations at the First Affiliated Hospital of Xinjiang Medical University from March 2021 to July 2022 were collected to measure serum PARP2 protein levels by using the enzyme-linked immunosorbent assay (ELISA) method, and their correlation with HCC clinical characteristics was analyzed. Additionally, the characteristics of serum PARP2 expression levels in diagnosing HCC, particularly in alpha-fetoprotein (AFP) -negative HCC (AFP

The aim of the publication. The case of abnormal elevation of alpha-fetoprotein (AFP) in a patient with autoimmune hepatitis (AIH) of the 1-st type is submitted.Features of clinical case. At a 17 years old female patient AIH of 1-st type debuted by jaundice, severe rise of transaminase activity and level of gamma-globulins. Manifestations of AIH, at first glance were typical, accompanied by over 200-fold elevation of serum concentration of AFP that required differential diagnostics with hepatocellular carcinoma. Achievement of immunosuppressor-induced remission resulted in normalization of AFP level.Conclusion. Derepression of respective gene may serve as the mechanism of serum AFP concentration increase at active hepatitis which, however, in absence of neoplastic proliferation is under control of certain regulatory factors. Over 200-fold elevation of AFP level in presented case, that rapidly decreased up to normal level under the influence of successful immune suppressive treatment, can be hard to explain from traditional point of view. Apparently, it is necessary to take into account specific features of AFP synthesis regulation, manifested at vast destruction of hepatic parenchyma.

Fetal ventriculomegaly (VM) is a relatively common finding during prenatal examinations and occurs in approximately 0.2% of live births. Although there are various causes, obstructive VM due to cerebellar hemorrhage is exceedingly rare. A 33-year-old primigravida presented at 32 weeks of gestation with VM. At 36 weeks of age, a male infant was delivered via cesarean section. Postnatal imaging revealed severe bilateral hydrocephalus and space-occupying lesions in the cerebellum. Initial concerns about a potential germ cell tumor were raised due to elevated alpha-fetoprotein levels in both serum and cerebrospinal fluid. An external ventricular drain was placed to manage obstructive hydrocephalus. When the baby was 1 month old, surgical exploration revealed an old blood clot without any evidence of a tumor. Histopathological examination confirmed an old hemorrhage with no malignant cells. This case underscores the diagnostic challenges in distinguishing between hemorrhages and tumors in the context of fetal VM. Despite elevated alpha-fetoprotein levels, no tumors were identified. The underlying cause of cerebellar hemorrhage remains unclear despite extensive workups. Nevertheless, this case report details multifaceted diagnostic efforts to address the rare occurrence of cerebellar hemorrhage related to fetal VM, leading to a comprehensive case presentation.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder. Its pathogenesis is multifactorial, and different pathogenic mechanisms cause differences in its course and outcomes at different clinical stages. This study evaluated serum levels of alpha-fetoprotein (AFP), lipids, and liver enzymes in Sudanese patients with NAFLD. Methods and Results: This study was conducted at the Advance Diagnostic Center, Bihari Hospital, Khartoum State, Sudan, from September 2021 to November 2022. A total of 80 participants (56 women and 24 men) were divided into two groups: The study group included 40 patients diagnosed with NAFLD, and the control group comprised 40 healthy individuals. All patients underwent an ultrasound examination. The serum levels of AST, ALT, triglycerides (TG), and total cholesterol (TC) were measured using a spectrophotometric method, while AFP levels were assessed using an enzyme-linked immunosorbent assay (ELISA). Our study revealed a significant increase in the levels of AST, ALT, TG, and AFP in NAFLD patients compared to the control group (P

Bi-allelic pathogenic variants in GRID2 have been initially associated to an autosomal recessive form of spinocerebellar ataxia, namely SCAR18. Subsequently, few monoallelic cases have been described. Here we present a new subject harboring a novel de novo heterozygous GRID2 missense variant presenting with progressive ataxia together with cerebellar atrophy and, for the first time, alpha-fetoprotein (AFP) elevation. We retrospectively collected data of the patient followed at our clinic. Genetic analysis was performed through clinical exome sequencing with an in-house in-silico ataxia-related genes panel. Variant effect prediction was performed through in silico modeling. The patient had normal psychomotor development except for mild fine and gross motor impairment. In adolescence, he started presenting dysarthria and progressive ataxia. Blood tests showed significant AFP elevation. Brain MRI showed cerebellar atrophy mainly involving the vermis. The novel de novo heterozygous GRID2 (c.1954C>A; p.Leu652Ile) missense variant was disclosed. This variant is located within a highly conserved site with low tolerance to variation and it is predicted to cause protein structure destabilization. GRID2 expression appears to be influenced by other genes related with ataxia and AFP elevation, like ATM and APTX, suggesting a possible shared mechanism. This additional patient increases the scarce literature and genotypic spectrum of the GRID2-related ataxia and evidences a fairly homogeneous phenotype of ataxia with oculomotor abnormalities for the autosomal-dominant form. Alfa-fetoprotein elevation is a novel finding in this condition and this data must be confirmed in larger case-series to definitively state that GRID2-related ataxia can be included among ataxias with AFP increase. [ABSTRACT FROM AUTHOR]

Background: Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial for such patients. We investigated key predictors for refractoriness to Atezo/Bev therapy, particularly in the first-line setting. Methods: We retrospectively analyzed 302 patients with HCC who received Atezo/Bev therapy between October 2020 and September 2022 across nine hospitals in Japan. Refractoriness was defined as best overall response (BOR) of progressive disease or stable disease and a progression-free survival (PFS) of < 180 days (RECIST v1.1). Clinical benefit was defined as BOR of partial/complete response or stable disease with PFS of ≥ 180 days. Baseline characteristics and potential predictors, identified through literature review, were compared between these groups. Stratifications of overall survival (OS), and PFS were also assessed. Results: Refractoriness was observed in 126 (41.7%) patients, while 154 (51.0%) achieved clinical benefit. Due to a significant association between the treatment line and refractory rate, the subsequent analysis focused on the first-line cohort (n = 214; 72 [33.6%] patients showed refractoriness). Among 13 potential predictors, the CRP and AFP in immunotherapy (CRAFITY) score had the best predictive performance, with refractory rates of 24.6%, 44.6%, and 57.9% in CRAFITY-0, 1, and 2 patients, respectively (p < 0.001). OS and PFS were also well-stratified by this scoring system. Conclusions: Approximately one-third of patients were refractory to first-line Atezo/Bev therapy. The CRAFITY score demonstrated superior performance in predicting refractoriness. [ABSTRACT FROM AUTHOR]

Objectives: Although serum screening for aneuploidies has become less prevalent, maternal‐serum alpha‐fetoprotein (MSAFP) screening for body‐wall defects remains widespread. We explored whether MSAFP screening is associated with earlier omphalocele detection than ultrasound alone. Methods: This is a retrospective cohort study of prenatally detected omphalocele cases at our center from 2007 to 2023. We explored the association between MSAFP screening, gestational age at omphalocele detection, and clinical outcomes. Results: Among 101 pregnancies with prenatally diagnosed omphalocele, 27 (26.7%) had MSAFP screening. The median gestational age at MSAFP screening was 17 weeks 4 days. Of those who received MSAFP screening, 11 (41%) had values ≥2.5 multiples of the median (MoM) and 16 (59%) were not elevated. MSAFP results did not correlate with omphalocele size and were not associated with prenatal or postnatal outcomes. MSAFP screening did not result in earlier suspicion for or confirmation of omphalocele (P =.97 and P =.87, respectively). In contrast, first‐trimester ultrasound screening was associated with earlier suspicion for and confirmation of omphalocele (P <.01 and P =.01, respectively). There were no clinical or demographic differences between those who received MSAFP screening and those who did not (including body mass index or commute distance to an urban center). Conclusion: MSAFP screening is not associated with earlier omphalocele detection. Furthermore, in pregnancies with prenatally diagnosed omphalocele, the results of MSAFP screening are not predictive of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The implication of human Schistosoma mansoni (S. mansoni) infection in concomitance with other risk factors such as hepatitis C virus (HCV) and hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC) is still under controversy. This work aimed. to evaluate the role of S. mansoni infection in association with hepatitis B virus (HBV), hepatitis C virus (HCV) and other risk factors in the development and/or progress of HCC. Methods: The present study was carried out on 90 HCC patients recruited from Kafr El-Sheikh Liver Disease Research Institute. After obtaining their informed consents, socio-demographic and clinical data were collected and patients were examined for S. mansoni by Kato-Katz and indirect hemagglutination (IHA) techniques. Alpha-fetoprotein (AFP) level was determined. The Child-Pugh scoring system and Barcelona Clinic Liver Cancer (BCLC) staging system were used to evaluate the pathological features of the studied patients. Results: All participants were negative for active S. mansoni by Kato-Katz. Based on IHA, the participants were categorized into two groups: group I: sixty-two patients negative for S. mansoni and group II: twenty-eight schistosomiasis positive. The patients' age ranged between 40->60, HCC was more prevalent in the age range of > 50–60 years in both groups. Males were more than females and rural participants were more than urban patients in both groups. Most of the patients (88.9%) had HCV while 7.8% had HBV. A higher proportion of HCC patients showed concomitant HCV and S. mansoni (92.6%) than the S. mansoni negative group. The frequency of upper gastrointestinal bleeding (GIB) was four-fold higher among HCC patients positive for schistosomiasis compared to negative schistosomiasis cases (64% vs. 16%). Alpha-fetoprotein (AFP) level was higher in group II than that in group I with no significant difference. Statistical analysis showed no difference between the two studied groups regarding Child scores. On the contrary, BCLC class D was significantly higher among HCC positive schistosomiasis cases compared to the negative group. Conclusion: Concomitant S. mansoni with HCV and HBV potentiate HCC progression. [ABSTRACT FROM AUTHOR]

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.

Yongqiang Xiao,1– 3,&ast; Wanqing Chen,4,&ast; Wei Deng,1,&ast; Guoqing Zhu,1 Jin Xie,1 Laihui Luo,1 Liucong Lin,1 Jiahao Tao,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Surgery, Ganjiang New Area People’s Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of General Surgery, Ganjiang New Area Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Gastroenterology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a > 20% decrease in AFP within 4 weeks, and AFP response as a > 75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated.Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p< 0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p< 0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333– 6.585, p=0.008, and HR 6.182, 95% CI 1.780– 21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107– 4.318, p=0.024, and HR 3.078, 95% CI 1.407– 6.730, p=0.005), serving as significant prognostic values.Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Objective To explore the clinical diagnostic value of combined serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ), hepatic fibrosis 4 index (FIB-4) and tyrosine urine test (TUT) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Fifty patients with HBV-related HCC, 50 patients with HBV-related benign liver diseases and 50 healthy people in the First Hospital of Changsha from January 2021 to December 2022 were selected as the study subjects. The differences of serum AFP, PIVKA-Ⅱ, FIB-4, and the positive rates of TUT among three groups were compared. The area under the receiver operating characteristic curve (AUC) of individual detection and combined detection in the diagnosis of HCC were analyzed, and the clinical application value of combined detection in the diagnosis of HBV-related HCC was evaluated. Results The levels of serum AFP, PIVKA-Ⅱ, FIB-4 and the positive rate of TUT among three groups were significantly different (P＜0.05). The levels of AFP, PIVKA-Ⅱ, FIB-4 and the positive rate of TUT in the HBV-related HCC were higher than those in the healthy control group (P＜0.05). The levels of AFP, PIVKA-Ⅱ and the positive rate of TUT in the HBV-related HCC group were higher than those in the HBV-related benign liver disease group (P＜0.05), but there was no significant difference in FIB-4 (P＞0.05). The levels of PIVKA-Ⅱ and FIB-4 in HBV-related benign liver disease group were significantly higher than those in healthy control group (P＜0.05), while the levels of serum AFP and the positive rates of TUT were not significantly different (P＞0.05). Receiver operating characteristic (ROC) curve analysis showed that the AUC of AFP, PIVKA-Ⅱ, FIB-4 and TUT were 0.812, 0.827, 0.722 and 0.761, respectively. The best cut-off values of serum AFP, PIVKA-Ⅱ and FIB-4 for diagnosing HCC were 21.1 ng/mL, 41.32 mAU/mL and 3.27, respectively. In the single test for diagnosis of HBV-related HCC, the TUT had the highest sensitivity of 82.00% and the AFP had the highest specificity of 95.00%. In the combined test for diagnosis of HBV-related HCC, the serum AFP+PIVKA-Ⅱ+FIB-4+TUT had the maximum AUC of 0.935 and the highest sensitivity of 90.00%, while AFP+PIVKA-Ⅱ+FIB-4 had the highest specificity of 97.00%. Conclusion The combined test of serum AFP, PIVKA-Ⅱ, FIB-4 and TUT can improve the diagnostic efficacy of HCC and has a significant clinical value in the early diagnosis of HBV-related HCC.

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

Objectives: This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. Design: This was a clinical study. Participants: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. Setting: The review was conducted in a Jiaxing First Hospital. Methods: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with CIN (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA, and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA, and AFP and the clinicopathological characteristics of patients with early stage cervical cancer were analyzed, and the receiver operating characteristic (ROC) curves were plotted to identify the value of the single and triple tests of serum HE4, CEA, and AFP for the early stage diagnosis of cervical cancer. Results: The levels of serum HE4, CEA, and AFP in the early stage cervical cancer group were higher than those in the disease control and the healthy control groups (p < 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early stage cervical cancer (p < 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early stage cervical cancer were 0.725, 0.679, 0.663, and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (p < 0.05). Limitations: There is a lack of larger sample sizes to test whether the combined HE4, CEA, and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV-DNA detection and compare it with the levels of serum markers. Conclusion: The combination of HE4, CEA, and AFP has good clinical reference value analysis in the auxiliary diagnosis of early stage cervical cancer, and it is worthy of further validation and popularization. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia occurs as a result of poor perfusion of the placental vessels, which in turn, arises from insufficient regeneration of the spiral arteries of the maternal uterus. Early diagnosis and prediction of preeclampsia (PE) may prevent fetal and maternal complications. The present study was conducted with aim to determine the diagnostic value of screening tests in the second trimester of pregnancy regarding the incidence of preeclampsia in late pregnancy. Methods: This cross-sectional study was conducted during 2021-2022 in the Perinatology Clinic of Sabzevar. In this study, 150 patients with high risk of preeclampsia in the screening of the second trimester of pregnancy were included. Preeclampsia was diagnosed using hospitalization documents. Data were analyzed using descriptive tests, ROC curve, and the Area under the Curve (AUC). P<0.05 was considered statistically significant. Results: Of 150 high-risk individuals in terms of preeclampsia, only 12 (8%) were diagnosed with preeclampsia. The accuracy of different factors to predict preeclampsia was obtained: 0.45 for AFP, 0.43 for inhibin a, 0.27 for beta HCG, and 0.57 for UE3. With 95% confidence, UE3 level between 0.42 and 0.73 had the best diagnostic value for preeclampsia. The highest sensitivity and specificity of UE3 for predicting preeclampsia was 66% and 49%, respectively for 0.74 MOM. Conclusion: The reduction of unconjugated estriol can be used as a biomarker in predicting preeclampsia. The high risk of screening in the second trimester of pregnancy cannot merely predict the risk of preeclampsia. [ABSTRACT FROM AUTHOR]

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre. [ABSTRACT FROM AUTHOR]

Background: To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors. Methods: A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP. Results: The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone. Conclusions: The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance. Trial registration: Clinical Trials, NCT03645655. Registered 20 August 2018, https://www.clinicaltrials.gov/ct2/show/NCT03645655. [ABSTRACT FROM AUTHOR]

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

Highly sensitive and specific biomarker detection is of outstanding importance for the diagnosis and treatment of cancers. Herein, we developed robust photoelectrochemical (PEC) biosensors with low background noise and high sensitivity based on a heterojunction, which can improve semiconductor photoelectric properties by limiting the recombination of photogenerated electron–hole pairs and successfully widening the range of light absorption. Alpha-fetoprotein (AFP) was used as a target model to examine the analytical performances of the designed PEC biosensors. ZnO/Cs3MnBr5 heterogeneous film with a uniform porous structure and large surface area enhanced electron transfer and biomolecule immobilization, and significantly increased the photocurrent response. Under the optimal conditions, the designed PEC biosensor exhibited a linear detection range of 0.01–500 ng/mL and a detection limit of 12 pg/mL. In addition, this PEC biosensor performed well when testing human serum samples and exhibited good repeatability, stability over time, and specificity, showing enormous potential for the detection of cancer markers in future biological and clinical research. [ABSTRACT FROM AUTHOR]

Objective: To analyze the predictive value of contrast-enhanced ultrasound (CEUS) combined with serum alpha-fetoprotein (AFP), γ-glutamyl transpeptidase (GGT) and lymphocyte count ratio (GLR) for microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods: 177 HCC patients who underwent hepatectomy in The 73rd Group Army Hospital of the Chinese People's Liberation Army from October 2018 to October 2023 were selected, all patients underwent CEUS and serum AFP, GGT and GLR examinations 1 week before operation. According to the results of postoperative pathological examination of MVI, patients were divided into MVI positive group (n=52) and MVI negative group (n=125). The risk factors affecting MVI in HCC patients were analyzed by multivariate Logistic regression analysis, the predictive value of CEUS combine with AFP, GGT and GLR for MVI in HCC patients were analyzed by receiver operating characteristic (ROC) curve. Results: The onset time, peak time and clearance time in MVI positive group were shorter than those in MVI negative group (P<0.05). AFP, GGT and GLR in MVI positive group were significantly higher than those in MVI negative group(P<0.05). Multivariate Logistic regression analysis showed that elevated AFP, elevated GGT, elevated GLR, irregular lesion morphology, shortened onset time, shortened peak time, and shortened clearance time were independent risk factors for MVI in HCC patients (P<0.001). The ROC results showed that, the area under the curve of MVI in HCC patients predicted by the combination of serum AFP, GGT and GLR was 0.901, which was significantly larger than that of single detection(P<0.05). Conclusion: The levels of serum AFP, GGT and GLR in patients with MVI after HCC operation increased, and the time of initial increase, peak time and clearance time were shortened, which were independent risk factors for MVI in HCC patients. CEUS combined with AFP, GGT and GLR has a high predictive value for MVI in HCC patients. [ABSTRACT FROM AUTHOR]

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

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

Background: The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib. Methods: This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression‐free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort. Results: We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS. Conclusions: The CRAFITY score, utilizing C‐reactive protein and alpha‐fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions. [ABSTRACT FROM AUTHOR]

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

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

Aim: Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. Methods: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. Results: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis‐4 performed similarly to alpha‐fetoprotein and ultrasound. In G2, Fibrosis‐4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87–0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95–1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis‐4 score. Conclusions: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis‐4 score in identifying individuals at high risk of HCC. [ABSTRACT FROM AUTHOR]

ARV1 mutation is known to present as developmental and epileptic encephalopathy (DEE)-38. However, the phenotypic spectrum has been expanding ever since it was reported in 2016. Along with seizures and developmental delay, other unique clinical features include ophthalmological abnormalities and movement disorders in the form of ataxia and dystonia, especially in those with missense mutation. These manifestations closely mimic ataxia telangiectasia. Elevation of alpha-fetoprotein levels is an important investigative marker in the diagnosis of ataxia telangiectasia and ataxia with oculomotor apraxia syndromes. ARV1 can also be associated with increased alpha-fetoprotein. There are no reports evaluating alpha-fetoprotein levels in cases with ARV1 mutation, which is significant in the context of ocular abnormalities with ataxia. We report a case of ARV1 mutation presenting with ataxia, ocular abnormalities, and elevated alpha-fetoprotein levels, thus mimicking autosomal recessive cerebellar ataxias. This study provides a comprehensive literature review of the cases reported so far, thus expanding the understanding of the spectrum of presentation, and helps in correlating the clinical picture with the underlying causative genetic mutation. ARV1 gene is another example of one gene with phenotypic pleiotropy. Though presentation with DEE is common, a few, especially those with missense mutations, can present with ataxia and ocular abnormalities. All cases presenting with ataxia who have increased alpha-fetoprotein levels and seizures should be tested for the ARV1 gene, when testing for ataxia genes is negative. The underlying genetic mechanism can explain the varying clinical manifestations of the ARV1 gene. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of the magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) version 2018 features and clinical-pathological factors for predicting the prognosis of alpha-fetoprotein (AFP)-negative (≤ 20 ng/ml) hepatocellular carcinoma (HCC) patients, and to compare with other traditional staging systems. Methods: We retrospectively enrolled 169 patients with AFP-negative HCC who received preoperative MRI and hepatectomy between January 2015 and August 2020 (derivation dataset:validation dataset = 118:51). A prognostic model was constructed using the risk factors identified via Cox regression analysis. Predictive performance and discrimination capability were evaluated and compared with those of two traditional staging systems. Results: Six risk factors, namely the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin–bilirubin grade, were associated with recurrence-free survival. The prognostic model constructed using these factors achieved C-index of 0.705 and 0.674 in the derivation and validation datasets, respectively. Furthermore, the model performed better in predicting patient prognosis than traditional staging systems. The model effectively stratified patients with AFP-negative HCC into high- and low-risk groups with significantly different outcomes (p < 0.05). Conclusion: A prognostic model integrating the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin–bilirubin grade may serve as a valuable tool for refining risk stratification in patients with AFP-negative HCC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. Methods: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan–Meier curve methods were used. Results: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. Conclusions: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS. [ABSTRACT FROM AUTHOR]

We aimed to examine the potential protective effects of Iraqi H. tiliaceus L. chloroform leaves extract on DEN-induced HCC in male Wistar Albino rats. Rats were assigned to four groups, six in each group. Group I: rats were administered a daily oral dose of 1 mL/kg/day of distilled water. Group II: rats were intraperitoneally injected with 70 mg/kg DEN once per week for 10 consecutive weeks. Group III: rats received 250 mg/kg of chloroform leaves extract. Groups IV: the rats were administered 500 mg/kg of chloroform leaves extract, along with their food, for five days per week over 20 weeks, with a subsequent dose of DEN once per week for 10 consecutive weeks. The results indicate that the extract demonstrated a significant reduction (p<0.05) in oxidative stress, pro-inflammatory mediators, and HCC parameters, the extract also had a beneficial effect on liver function tests, and there was a significant elevation (p<0.05) of antioxidant parameters in a dose-dependent manner. This study supports the protective properties of the chloroform extract of Iraqi H. tiliaceus L. leaves in HCC. [ABSTRACT FROM AUTHOR]

Abstract Alpha‐fetoprotein (AFP) is a structural serum glycoprotein that plays vital roles in reproduction and mammalian development. Analysis of serum prolactin (PRL) is considered one of the useful methods for diagnosing pregnancy in Asian elephants. However, the expression profiles of AFP in pregnant and nonpregnant Asian elephants remain unclear, nor is the relationship with PRL. In this study, serum seven gonadal hormones and AFP in three pregnant and seven nonpregnant Asian elephants were analysed by via radioimmunoassay (RIA) and enzyme‐linked immunosorbent (ELISA) assay. We found that the mean (±SD) concentration of prolactin (PRL) in pregnant (136.782 ± 30.987 ng/mL) elephants was significantly higher than that in nonpregnant elephants (52.803 ± 21.070 ng/mL; p ≤ 0.0005). The mean (±SD) concentration of AFP in pregnant elephants (11.598 ± 0.824 ng/mL) was significantly higher than that in nonpregnant elephants (7.200 ± 2.283 ng/mL; p ≤ 0.05). Furthermore, the AFP concentration was positively correlated with the PRL concentration in the 10 Asian elephants studied. In conclusion, our findings suggest that serum AFP concentration is a potential biomarker of pregnancy outcomes in Asian elephants.

Abstract Background A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection. Methods Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined. Results A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69–0.85) compared to 0.73 (95% CI: 0.65–0.80); specificity of 0.89 (95% CI: 0.81–0.95) compared to 0.86 (95% CI: 0.77–0.91); PLR of 7.4 (95% CI: 3.7–14.9) compared to 5.1 (95% CI: 3.3–8.1); NLR of 0.24 (95% CI: 0.16–0.37) compared to 0.31 (95% CI: 0.24–0.41); DOR of 30.19 (95% CI: 10.68–85.37) compared to 16.34 (95% CI: 9.69–27.56); and AUC of 0.90 (95% CI: 0.87–0.92) compared to 0.85 (95% CI: 0.82–0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82–0.95), 0.94 (95% CI: 0.82–0.98), 14.5 (95% CI: 4.6–45.4), 0.11 (95% CI: 0.06–0.20), 133.34 (95% CI: 29.65–599.61), and 0.96 (95% CI: 0.94–0.98) for the combination of HSPs and AFP. Conclusion Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.

Dongfang Huang,1– 3 Jianhuai Zhang,3 Jianbo Xu,3 Qiang Niu,2 Dinghua Zhou2 1Department of Hepatobiliary Surgery, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, People’s Republic of ChinaCorrespondence: Dinghua Zhou, Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, No. 16 Xinjiekou Outer Street, Xicheng District, Beijing, 100088, People’s Republic of China, Tel +86 010-66343003, Fax +86 010-66343055, Email zhoudinghua3528@126.comObjective: To investigate the utility of alpha-fetoprotein (AFP) and ultrasound in the diagnosis and prognosis of patients with hepatocellular liver cancer (HCC).Methods: Using retrospective convenience sampling, 401 patients with HCC who underwent transarterial chemoembolisation at the Department of Oncology of The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University between June 2015 and January 2020 were recruited and assigned to the case group. Simultaneously, patients matched to the case group in terms of gender and age but excluded for HCC were enrolled at a 1:1 ratio and classified as the control group. Relevant parameters were collected from both groups for comparison.Results: Both AFP levels and ultrasound results demonstrated diagnostic value for patients with HCC (P < 0.05). Their combined use exhibited the highest diagnostic accuracy for the cancer, with an area under the curve of 0.896 (95% confidence interval [CI]: 0.876, 0.923), a sensitivity of 67.65% and a specificity of 91.22%. In terms of overall survival (OS), statistically significant differences in the OS rates were observed between the low-AFP (L-AFP) group and high-AFP (H-AFP) group as well as between the low-tumour-diameter (LTD) group and high-tumour-diameter (HTD) group (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Regarding the progression-free survival (PFS), significant differences in the PFS rates were also noted between the L-AFP and H-AFP groups and between the LTD and HTD groups (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05).Conclusion: Ultrasound and AFP display notable distinctions when used in the diagnosis of HCC. The sensitivity of ultrasound as a standalone diagnostic tool surpasses that of AFP alone. However, their combined use results in much higher specificity than the use of either test individually. In addition, both techniques hold predictive value for patients’ OS and PFS, enabling timely prognostic assessment.Keywords: alpha-fetoprotein, hepatocellular liver cancer, ultrasound, survival analysis, prognosis

Hepatoid adenocarcinoma (HAC) is a rare form of adenocarcinoma that is diagnosed based on immuno-histochemical findings reminiscent of hepatocellular carcinoma (HCC). The clinical characteristics of HAC include increased levels of serum alpha-fetoprotein and a poor prognosis due to early liver metastasis. In particular, diagnosing liver metastasis of HAC can be challenging owing to radiological findings similar to those of HCC. Although HAC can occur in various organs, the stomach is the most common site. We present the case of a 64-year-old femalewho presented with multiple tumors in the liver. During subsequent examination, rectal cancer was identified and diagnosed as HAC through a biopsy. Herein, we report this case along with a literature review.