GALAD score as a prognostic model for recurrence of hepatocellular carcinoma after local ablation.

BACKGROUND: Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC. METHODS: This study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan-Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: The ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility. CONCLUSION: This research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

Lysyl oxidase-like 2 as a predictor of hepatocellular carcinoma in patients with hepatitis C virus after sustained virological response.

Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.

Development of a machine learning-based model to predict prognosis of alpha-fetoprotein-positive hepatocellular carcinoma.

BACKGROUND: Patients with alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) have aggressive biological behavior and poor prognosis. Therefore, survival time is one of the greatest concerns for patients with AFP-positive HCC. This study aimed to demonstrate the utilization of six machine learning (ML)-based prognostic models to predict overall survival of patients with AFP-positive HCC. METHODS: Data on patients with AFP-positive HCC were extracted from the Surveillance, Epidemiology, and End Results database. Six ML algorithms (extreme gradient boosting [XGBoost], logistic regression [LR], support vector machine [SVM], random forest [RF], K-nearest neighbor [KNN], and decision tree [ID3]) were used to develop the prognostic models of patients with AFP-positive HCC at one year, three years, and five years. Area under the receiver operating characteristic curve (AUC), confusion matrix, calibration curves, and decision curve analysis (DCA) were used to evaluate the model. RESULTS: A total of 2,038 patients with AFP-positive HCC were included for analysis. The 1-, 3-, and 5-year overall survival rates were 60.7%, 28.9%, and 14.3%, respectively. Seventeen features regarding demographics and clinicopathology were included in six ML algorithms to generate a prognostic model. The XGBoost model showed the best performance in predicting survival at 1-year (train set: AUC = 0.771; test set: AUC = 0.782), 3-year (train set: AUC = 0.763; test set: AUC = 0.749) and 5-year (train set: AUC = 0.807; test set: AUC = 0.740). Furthermore, for 1-, 3-, and 5-year survival prediction, the accuracy in the training and test sets was 0.709 and 0.726, 0.721 and 0.726, and 0.778 and 0.784 for the XGBoost model, respectively. Calibration curves and DCA exhibited good predictive performance as well. CONCLUSIONS: The XGBoost model exhibited good predictive performance, which may provide physicians with an effective tool for early medical intervention and improve the survival of patients.

SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

DGPRI, a new liver fibrosis assessment index, predicts recurrence of AFP-negative hepatocellular carcinoma after hepatic resection: a single-center retrospective study.

Although patients with alpha-fetoprotein-negative hepatocellular carcinoma (AFPNHCC) have a favorable prognosis, a high risk of postoperative recurrence remains. We developed and validated a novel liver fibrosis assessment index, the direct bilirubin-gamma-glutamyl transpeptidase-to-platelet ratio (DGPRI). DGPRI was calculated for each of the 378 patients with AFPNHCC who underwent hepatic resection. The patients were divided into high- and low-score groups using the optimal cutoff value. The Lasso-Cox method was used to identify the characteristics of postoperative recurrence, followed by multivariate Cox regression analysis to determine the independent risk factors associated with recurrence. A nomogram model incorporating the DGPRI was developed and validated. High DGPRI was identified as an independent risk factor (hazard ratio = 2.086) for postoperative recurrence in patients with AFPNHCC. DGPRI exhibited better predictive ability for recurrence 1-5 years after surgery than direct bilirubin and the gamma-glutamyl transpeptidase-to-platelet ratio. The DGPRI-nomogram model demonstrated good predictive ability, with a C-index of 0.674 (95% CI 0.621-0.727). The calibration curves and clinical decision analysis demonstrated its clinical utility. The DGPRI nomogram model performed better than the TNM and BCLC staging systems for predicting recurrence-free survival. DGPRI is a novel and effective predictor of postoperative recurrence in patients with AFPNHCC and provides a superior assessment of preoperative liver fibrosis.

Biosensing of Alpha-Fetoprotein: A Key Direction toward the Early Detection and Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Evaluating the diagnostic accuracy of heat shock proteins and their combination with Alpha-Fetoprotein in the detection of hepatocellular carcinoma: a meta-analysis.

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.

Laser-printed paper ELISA and hydroxyapatite immobilization for colorimetric congenital anomalies screening in saliva.

BACKGROUND: Alpha-fetoprotein (AFP) is a fetal protein that can indicate congenital anomalies such as Down syndrome and spinal canal blockage when detected at abnormal levels in pregnant women. Current AFP detection methods rely on invasive blood or serum samples, which require sophisticated equipment. From the many solutions proposed, colorimetric paper-based assays excel in point-of-care settings. The concept of paper-based ELISA (p-ELISA) enhances traditional methods, aligning with the ASSURED criteria for diagnostics in resource-limited regions. Despite success in microfluidic paper-based assay devices, laser printing remains underexplored for p-ELISA. Additionally, modifying the paper surface provides an additional layer of sensitivity enhancement. RESULTS: In this study, we developed a novel laser-printed paper-based ELISA (LP-pELISA) for rapid, sensitive, and noninvasive detection of AFP in saliva samples. The LP-pELISA platform was fabricated by printing hydrophobic barriers on filter paper using a laser printer, followed by depositing hydroxyapatite (HAp) as an immobilization material for the antibodies. The colorimetric detection was achieved using AuNPs functionalized with anti-AFP antibodies and silver nitrate enhancement. The LP-pELISA exhibited a linear response for AFP detection in both buffer and saliva samples over a range of 1.0-800 ng mL-1, with a limit of detection (LOD) reaching 1.0 ng mL-1. The assay also demonstrated good selectivity, repeatability, reproducibility, and stability. The LP-pELISA was further validated by testing spiked human saliva samples, showing its potential for point-of-care diagnosis of congenital disabilities. SIGNIFICANCE: The LP-pELISA is a noninvasive platform showcasing simplicity, cost-effectiveness, and user-friendliness, utilizing laser printing, hydroxyapatite modification, and saliva samples to efficiently detect AFP. Beyond its application for AFP, this method's versatility extends to other biomarkers, positioning it as a catalyst for the evolution of paper-based biosensors. The LP-pELISA holds promise as a transformative tool for point-of-care diagnostics, fostering advancements in healthcare with its innovative technology.

Placental metastasis from maternal NUT carcinoma: diagnostic pitfalls and challenges.

We report a young pregnant woman with large midline thoracic mass and markedly elevated serum alpha-fetoprotein (AFP) levels. Initially suspected as a germ cell tumour (GCT) due to age, site, and high AFP levels, a biopsy unveiled a high-grade malignant tumour characterised by undifferentiated monotonous cells. Although tumour cells exhibited positive AFP, the overall immunoprofile did not provide additional evidence to support GCT. Further work-up showed positive for NUT (nuclear protein in testis) immunostaining and the presence of BRD4-NUT1 fusion, confirming the diagnosis of NUT carcinoma. On radiology, there were extensive metastases to lungs, liver, vertebrae, and placenta. Despite aggressive chemotherapy, radiotherapy and immunotherapy, she did not respond to the therapies. Fortunately, her child was not affected by the carcinoma. This is the first case highlighting that thoracic lung primary NUT carcinoma can spread to the placenta and manifest with elevated serum AFP levels, potentially leading to misdiagnosis as GCT both clinically and pathologically.

Surveillance To Track Progress Toward Polio Eradication - Worldwide, 2022-2023.

The reliable and timely detection of poliovirus cases through surveillance for acute flaccid paralysis (AFP), supplemented by environmental surveillance of sewage samples, is a critical component of the polio eradication program. Since 1988, the number of polio cases caused by wild poliovirus (WPV) has declined by >99.9%, and eradication of WPV serotypes 2 and 3 has been certified; only serotype 1 (WPV1) continues to circulate, and transmission remains endemic in Afghanistan and Pakistan. This surveillance update evaluated indicators from AFP surveillance, environmental surveillance for polioviruses, and Global Polio Laboratory Network performance data provided by 28 priority countries for the program during 2022-2023. No WPV1 cases have been detected outside of Afghanistan and Pakistan since August 2022, when an importation into Malawi and Mozambique resulted in an outbreak during 2021-2022. During 2022-2023, among 28 priority countries, 20 (71.4%) met national AFP surveillance indicator targets, and the number of environmental surveillance sites increased. However, low national rates of reported AFP cases in priority countries in 2023 might have resulted from surveillance reporting lags; substantial national and subnational AFP surveillance gaps persist. Maintaining high-quality surveillance is critical to achieving the goal of global polio eradication. Monitoring surveillance indicators is important to identifying gaps and guiding surveillance-strengthening activities, particularly in countries at high risk for poliovirus circulation.

Exploring the association between regional fat distribution and atrial fibrillation risks: a comprehensive cohort study.

Background: The contribution of total fat mass and regional fat distribution to the risk of AF has rarely been studied. Methods: This prospective cohort study(N=494,063) evaluated the association of total fat mass measured by fat percentage (FP) and regional fat measured by arm fat percentage (AFP), trunk fat percentage (TFP), and leg fat percentage (LFP) with incident AF. A subgroup (N = 25,581) underwent MRI, which allowed us to further assess whether visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) of the trunk fat exert different effects on AF incidence. Results: Over, a median 12.9 ± 1.86 years of follow-up, 29,658 participants (cumulative rate: 6.0%) developed AF. Each 1-standard deviation (SD) increase in LFP was associated with a 16% lower risk of AF (HR: 0.84, 95% CI: 0.82, 0.85). The association between FP and AF was weaker than that between LFP and AF (HR: 0.90, 95% CI: 0.89, 0.92). AFP and TFP only had a marginal association with a lower incidence of AF. Both the VAT and ASAT showed a U-shaped relationship with incident AF. Conclusions: Fat mass, mainly leg fat mass, was associated with a lower risk of AF. ASAT did not exert protective effects.

Clinical usefulness of newly developed prognostic predictive score for atezolizumab plus bevacizumab for hepatocellular carcinoma.

AIMS: The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment. METHODS: A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results. RESULTS: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS. CONCLUSION: The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy.

Do the blood anti-Müllerian hormone concentrations in young females correlate with the ovarian follicular population later in life in water buffalo?

In this longitudinal study, the anti-Müllerian hormone (AMH) levels in blood were determined in 32 Murrah buffalo females at 8, 10, 12, 16 and 19 months of age when females were synchronized and the antral follicular population (AFP) was estimated. Correlations of AFP to the AMH level at 19 months of age and retrospectively to younger ages were investigated. Then females were split into high and low AFP, and their AMH levels were compared for all ages and tested as predictors of AFP categories. The highest AMH level (p < .05) was detected at 8 months, reducing but not differing (p > .05) at 10, 12 and 16 months then reducing again (p < .05) at 19 months of age. The mean AFP was 17.6 ± 6.3 follicles, and it was positively correlated with AMH in all ages tested. High AFP females had approximately two times more antral follicles than low AFP (p < .05) and their AMH levels were higher (p < .01) than in low AFP ones in all ages. Only at 8 months, AMH levels can be used to precociously detect high AFP heifers (a cut-off point of 464.7 pg/mL; p < .05), while low AFP heifers could be detected by AMH measurements at 8, 10, 12 and 16 months of age (p < .05). We conclude that AMH of buffalo calves correlates with AFP of heifers later in life and depending on the age, its levels could be used to identify future females with low or high AFP.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

BACKGROUND: Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. AIM: To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. METHODS: Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. RESULTS: When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). CONCLUSION: Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

Alpha-fetoprotein: Past, present, and future.

Alpha-fetoprotein (AFP) is a glycoprotein that plays an important role in immune regulation with critical involvement in early human development and maintaining the immune balance during pregnancy. Postfetal development, the regulatory mechanisms controlling AFP undergo a shift and AFP gene transcription is suppressed. Instead, these enhancers refocus their activity to maintain albumin gene transcription throughout adulthood. During the postnatal period, AFP expression can increase in the setting of hepatocyte injury, regeneration, and malignant transformation. It is the first oncoprotein discovered and is routinely used as part of a screening strategy for HCC. AFP has been shown to be a powerful prognostic biomarker, and multiple HCC prognosis models confirmed the independent prognostic utility of AFP. AFP is also a useful predictive biomarker for monitoring the treatment response of HCC. In addition to its role as a biomarker, AFP plays important roles in immune modulation to promote tumorigenesis and thus has been investigated as a therapeutic target in HCC. In this review article, we aim to provide an overview of AFP, encompassing the discovery, biological role, and utility as an HCC biomarker in combination with other biomarkers and how it impacts clinical practice and future direction.

Specific features of epitope-MIPs and whole-protein MIPs as illustrated for AFP and RBD of SARS-CoV-2.

Molecularly imprinted polymer (MIP) nanofilms for alpha-fetoprotein (AFP) and the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 using either a peptide (epitope-MIP) or the whole protein (protein-MIP) as the template were prepared by electropolymerization of scopoletin. Conducting atomic force microscopy revealed after template removal and electrochemical deposition of gold a larger surface density of imprinted cavities for the epitope-imprinted polymers than when using the whole protein as template. However, comparable affinities towards the respective target protein (AFP and RBD) were obtained for both types of MIPs as expressed by the KD values in the lower nanomolar range. On the other hand, while the cross reactivity of both protein-MIPs towards human serum albumin (HSA) amounts to around 50% in the saturation region, the nonspecific binding to the respective epitope-MIPs is as low as that for the non-imprinted polymer (NIP). This effect might be caused by the different sizes of the imprinted cavities. Thus, in addition to the lower costs the reduced nonspecific binding is an advantage of epitope-imprinted polymers for the recognition of proteins.

Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CONCLUSION: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Evaluation of Circular RNA SMARCA5 as a Novel Biomarker for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth most prevalent type of cancer in Egypt and the sixth globally. Most patients with HCC are typically diagnosed during the advanced stages of the disease due to the absence of biomarkers for early detection. Consequently, these patients miss the optimal timeframe for receiving therapy. OBJECTIVE: we aimed to assess the circular RNA SMARCA5 level and SMARCA5 mRNA gene expression as a potential biomarker for early detection of HCC. METHODS: The present study utilized a case-control design comprising 159 participants. Participants were selected from both inpatient and outpatient hepatology and gastroenterology clinics at the National Liver Institute Hospital, Menoufia University. They were evenly distributed among three groups: Group I: 53 control subjects, Group II: 53 HCV cirrhotic patients, and Group III: 53 HCC patients. Tumor staging was done using BCLC staging system. Each patient underwent a thorough clinical examination, radiological examination, complete history taking, and serum Alpha-fetoprotein (AFP) assessment and detection of circular RNASMARCA5 and SMARCA5mRNA gene sutilizing quantitative real-time polymerase chain reaction. RESULTS: Statistically substantial differences were observed in the examined groups in terms of AFP, SMARCA5, and CircSMARCA5 (P-value = 0.001, 0.001 & 0.001). CircSMARCA5 and SMARCA5mRNA were markedly down regulated in the HCC group compared to HCV cirrhotic patients and controls. ROC analysis for early HCC diagnosis demonstrated that the CircSMARCA5 area under the curve (AUC) at cut-off point 4.55 yielded a specificity of 83.8% and sensitivity of 91.7%. The AUC for AFP at a cut-off point of 515ng/ml yielded a specificity of 89.2% and a sensitivity of 91.3%. CONCLUSION: CircSMARCA5 has the potential to be a more sensitive predictor of HCC disease compared to AFP.

Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.