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BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the LAD Score. An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors

Objective To investigate the value of des- γ -carboxy-prothrombin (DCP) in hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for the clinical data of 179 HCC patients who were admitted to The First Hospital of Jilin University from January 2020 to July 2021, and 207 healthy controls were enrolled as normal group. Magnetic particle chemiluminescence immunoassay was used to measure the serological levels of alpha-fetoprotein (AFP) and DCP. The receiver operating characteristic (ROC) curve was plotted for each indicator measured alone or in combination, and the area under the ROC curve (AUC) was calculated to investigate the value of DCP combined with AFP versus AFP alone in the diagnosis of HCC and the diagnostic efficacy of DCP in AFP-negative patients. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the ROC curve was used to evaluate diagnostic efficiency; the Spearman correlation analysis was used to investigate the correlation of tumor markers with the pathological features of HCC. Results The patients with HCC had significantly higher serum levels of AFP and DCP than the normal group (Z= − 9.562 and − 11.678, P<0.05), and combined measurement of DCP and AFP had a better value than AFP measured alone (Z=5.309, P<0.01). DCP had certain capability in the diagnosis of AFP-negative HCC patients, with an AUC of 0.789 (P<0.000 1), a sensitivity of 61.64%, and a specificity of 86.47%. Serum DCP level was positively correlated with tumor size (r=0.546, P<0.001), TNM stage (r=0.306, P< 0.001), and microvascular invasion (r=0.358, P<0.001) and was negatively correlated with the degree of tumor differentiation (r= −0.220, P<0.05). Conclusions The combined measurement of AFP and DCP can improve the detection rate of HCC, and DCP can be used for supplementary screening in AFP-negative HCC patients. The expression level of DCP is correlated with the clinicopathological features of HCC, including tumor size, TNM stage, microvascular invasion, and the degree of tumor differentiation. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most common primary liver malignancy and the sixth most common cancer globally, remains fatal for many patients with inappropriate responses to treatment. Recent advancements in immunotherapy have transformed the treatment landscape for advanced HCC. However, variability in patient responses to immunotherapy highlights the need for biomarkers that can predict treatment outcomes. This manuscript comprehensively reviews the evolving role of biomarkers in immunotherapy efficacy, spanning from blood-derived indicators—alpha-fetoprotein, inflammatory markers, cytokines, circulating tumor cells, and their DNA—to tissue-derived indicators—programmed cell death ligand 1 expression, tumor mutational burden, microsatellite instability, and tumor-infiltrating lymphocytes. The current body of evidence suggests that these biomarkers hold promise for improving patient selection and predicting immunotherapy outcomes. Each biomarker offers unique insights into disease biology and the immune landscape of HCC, potentially enhancing the precision of treatment strategies. However, challenges such as methodological variability, high costs, inconsistent findings, and the need for large-scale validation in well-powered two-arm trial studies persist, making them currently unsuitable for integration into standard care. Addressing these challenges through standardized techniques and implementation of further studies will be critical for the future incorporation of these biomarkers into clinical practice for advanced HCC. [ABSTRACT FROM AUTHOR]

Background & aimsAlpha-fetoprotein (AFP) predicts hepatocellular carcinoma (HCC) recurrence after liver transplant (LT) but remains an imperfect biomarker. The role of DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) in predicting HCC recurrence remains incompletely characterized. AFP-L3 and DCP could identify patients at high risk of post-transplant HCC recurrence and serve as liver transplant exclusion criteria to defer transplant until patients receive additional risk-reducing pre-transplant locoregional therapy.MethodsThis prospective cohort study included consecutive patients with HCC who underwent LT (within or down-staged to Milan criteria) between 2017 and 2022. Pre-transplant AFP, AFP-L3, and DCP measurements were obtained. The primary endpoint was the ability of biomarkers to predict HCC recurrence-free survival.ResultsThis cohort included 285 patients with a median age of 67 (IQR 63-71). At LT, median biomarker values were AFP 5.0 ng/ml (IQR 3.0-12.1), AFP-L3 6.7% (0.5-13.2), and DCP 1.0 ng/ml (0.3-2.8). Most (94.7%) patients received pre-LT locoregional therapy. After a median post-LT follow-up of 3.1 years, HCC recurrence was observed in 18 (6.3%) patients. AFP-L3 and DCP outperformed AFP with C-statistics of 0.81 and 0.86 respectively, compared with 0.74 for AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted 61.1% of HCC recurrences, whereas HCC only recurred in 7 of 265 (2.6%) patients not meeting this threshold. The Kaplan-Meier recurrence-free survival rate at 3 years post-LT was 43.7% for patients with dual-positive biomarkers compared to 97.0% for all others (p

Simple Summary: The mortality of hepatocellular carcinoma (HCC) is rising globally, against the trend of other cancers. People with liver cirrhosis, even after hepatitis C treatment still face a high risk of HCC, requiring ongoing enrolment in HCC surveillance, and new technologies to improve diagnostic sensitivity are being explored. However, their impact on HCC survival remains uncertain relative to improving adherence to existing surveillance methods. This study uses mathematical modeling to assess how different strategies can reduce deaths from liver cancer in people with cirrhosis after being cured of hepatitis C. We compared the impact of improved adherence to ultrasound screening with increased HCC imaging sensitivity on HCC survival. Notably, we found that even modest enhancements in surveillance adherence (5–10 percentage point increases) exhibited significant survival benefits for people with hepatitis C-related cirrhosis, outperforming improvements in diagnostic sensitivity. Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. Methods: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. Conclusions: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy. [ABSTRACT FROM AUTHOR]

Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is an attractive alternative approach to immunotherapy. However, its efficacy remains insufficiently evaluated in preclinical studies. Here, we investigated HCC-associated self/tumor antigen, α-fetoprotein-based (AFP-based) vaccine immunization for treating AFP (+) HCC mouse models. We found that AFP immunization effectively induced AFP-specific CD8+ T cells in vivo. However, these CD8+ T cells expressed exhaustion markers, including PD1, LAG3, and Tim3. Furthermore, the AFP vaccine effectively prevented c-MYC/Mcl1 HCC initiation when administered before tumor formation, while it was ineffective against full-blown c-MYC/Mcl1 tumors. Similarly, anti-PD1 and anti-PD-L1 monotherapy showed no efficacy in this murine HCC model. In striking contrast, AFP immunization combined with anti-PD-L1 treatment triggered significant inhibition of HCC progression in most liver tumor nodules, while in combination with anti-PD1, it induced slower tumor progression. Mechanistically, we demonstrated that HCC-intrinsic PD-L1 expression was the primary target of anti-PD-L1 in this combination therapy. Notably, the combination therapy had a similar therapeutic effect in the cMet/β-catenin mouse HCC model. These findings suggest that combining the AFP vaccine and immune checkpoint inhibitors may be effective for AFP (+) HCC treatment.

α-Fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell (DC) differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human DC functional suppression, here, we used two recently described single-cell profiling methods, scMEP (single-cell metabolic profiling) and SCENITH (single-cell energetic metabolism by profiling translation inhibition). Glycolytic capacity and glucose dependence of DCs were significantly increased by tumor-derived, but not normal cord blood-derived, AFP, leading to increased glucose uptake and lactate secretion. Key molecules in the electron transport chain in particular were regulated by tumor-derived AFP. These metabolic changes occurred at mRNA and protein levels, with negative impact on DC stimulatory capacity. Tumor-derived AFP bound significantly more polyunsaturated fatty acids (PUFA) than cord blood-derived AFP. PUFAs bound to AFP increased metabolic skewing and promoted DC functional suppression. PUFAs inhibited DC differentiation in vitro, and ω-6 PUFAs conferred potent immunoregulation when bound to tumor-derived AFP. Together, these findings provide mechanistic insights into how AFP antagonizes the innate immune response to limit antitumor immunity.Significanceα-Fetoprotein (AFP) is a secreted tumor protein and biomarker with impact on immunity. Fatty acid-bound AFP promotes immune suppression by skewing human dendritic cell metabolism toward glycolysis and reduced immune stimulation.

BackgroundPatients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC).AimsThe aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound.MethodsWe conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1 cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively.ResultsOf 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7 cm (interquartile range: 0.5-0.8 cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10 ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08).ConclusionsRecall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.

Background Hepatocellular carcinoma (HCC) is the main pathological type of primary liver cancer (PLC) and is closely associated with Hepatitis B virus (HBV) infection. HCC in its early stages often presents no significant symptoms and is usually discovered at an advanced stage with liver, portal vein, or other site metastases, leading to a poor prognosis. Regular screening and early diagnosis in high-risk populations in the early stages of the disease are of great significance for clinical treatment and prognosis. Objective To explore the application value of oligosaccharides and alpha-fetoprotein (AFP) in the risk population and patients of HBV-related HCC, providing a reference for clinical diagnosis. Methods The study included 165 chronic HBV infection patients treated at the First Affiliated Hospital of Soochow University from January to November 2022, comprising 123 non-HCC and 42 HCC patients. Patient data (age, gender, cirrhosis status), laboratory indices[total bilirubin (TB), albumin (ALB), platelet count (PLT), AFP]were collected through electronic medical records, and a liver cancer risk prediction model score for chronic liver disease patients (aMAP score) was calculated, along with oligosaccharide marker test results (G-Test). HCC patients were classified as the HCC group (42 cases), and non-HCC patients were divided based on aMAP scores into low-risk (60 points, 39 cases) groups. Receiver operating characteristic (ROC) curves were plotted to analyze the efficacy of AFP, G-Test, and their combined diagnosis of HCC, calculating the area under the ROC curve (AUC), and the DeLong test was used to compare the differences between combined and single indicator AUCs. Kappa consistency tests were used to analyze the consistency of AFP and G-Test with clinical diagnostic results. Results In patients with HCC, levels of AFP and G-Test were higher compared to those in the low-risk, medium-risk, and high-risk groups (P

Background: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. Methods: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. Results: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. Conclusions: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier. [ABSTRACT FROM AUTHOR]

Aims: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct‐acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction‐associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. Methods: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α‐fetoprotein (AFP), Fibrosis‐4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. Results: A total of 86 patients (6.7%) developed HCC during the follow‐up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04–1.11, P = 0.0008), Fibrosis‐4 index (HR 1.17, CI 1.08–1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40–6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis‐4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. Conclusion: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of serum alpha-fetoprotein (AFP) in diagnosing subcentimeter hepatocellular carcinoma (HCC) on gadoxetic acid–enhanced MRI (EOB-MRI). Methods: This study retrospectively enrolled treatment-naïve patients with chronic hepatitis B who had a solitary subcentimeter observation on EOB-MRI from January 2017 to March 2023. Final diagnosis was confirmed by pathology for HCC and pathology or follow-up for benign controls. The AFP cutoff value for HCC was determined using Youden's index. Diagnostic criteria were developed according to significant findings in logistic regression analyses based on AFP and imaging features. The diagnostic performance of possible criteria was compared to the diagnostic hallmarks of HCC (arterial-phase hyperintensity and portal-phase hypointensity). Results: A total of 305 patients (mean age, 51.5 ± 10.7 years; 153 men) were divided into derivation and temporal validation cohorts. Four findings, namely AFP >13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity, were predictors of HCC. A new criterion (at least three of the four findings) showed higher sensitivity than the diagnostic hallmarks (derivation cohort, 71.6% vs. 52.3%, p < 0.001; validation cohort, 75.0% vs. 47.5%, p = 0.003) without decreasing specificity (derivation cohort, 92.5% vs. 92.5%, p > 0.999; validation cohort, 92.0% vs. 92.0%, p > 0.999). Another criterion (all four findings) achieved a slightly higher specificity than the diagnostic hallmark (derivation cohort, 99.1% vs. 92.5%, p = 0.023; validation cohort, 100.0% vs. 92.0%, p = 0.134). Subgroup analysis for hepatobiliary hypointense observations yielded similar results. Conclusion: Including AFP in the diagnostic algorithm may improve the diagnostic performance for subcentimeter HCC. Clinical relevance statement: Combining imaging features on gadoxetic acid–enhanced MRI with alpha-fetoprotein may enhance the diagnostic performance for subcentimeter HCC in treatment-naïve patients with chronic hepatitis B. Key Points: • The traditional diagnostic hallmark of HCC (arterial-phase hyperintensity and portal-phase hypointensity) shows modest diagnostic performance for subcentimeter HCC on EOB-MRI. • Serum alpha-fetoprotein > 13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity were independent predictors for subcentimeter HCC. • A criterion of at least three of the four above findings achieved a higher sensitivity without decreasing specificity. [ABSTRACT FROM AUTHOR]

PurposeAtezolizumab + bevacizumab is the new standard of care for systemic treatment-naïve, unresectable hepatocellular carcinoma (HCC). This exploratory study investigated on-treatment alpha-fetoprotein (AFP) response as a potential surrogate biomarker of prognosis for the combination therapy.Experimental designData from Group A of the phase Ib GO30140 study were used to identify the optimal time for AFP measurement and AFP cutoffs to differentiate patients by their best confirmed response per independent review facility-assessed RECIST (IRF-RECIST) version 1.1: responders from nonresponders and patients with disease control from primary progressors. We applied these cutoffs to independent data from the atezolizumab + bevacizumab arm of the phase III IMbrave150 trial to distinguish patients based on (i) overall survival (OS) and progression-free survival (PFS) per IRF-RECIST 1.1 and (ii) best confirmed response per IRF-RECIST 1.1.ResultsWe derived AFP cutoffs of ≥75% decrease and ≤10% increase from baseline at 6 weeks to identify responders and those who had disease control, respectively. These cutoffs had high sensitivity and specificity in GO30140. In IMbrave150 patients, sensitivity was 0.59 and specificity was 0.86 for the ≥75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the ≤10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR < 0.5; P < 0.01).ConclusionsAFP response at 6 weeks after initiating treatment is a potential surrogate biomarker of prognosis for patients with HCC receiving atezolizumab + bevacizumab. See related commentary by Cappuyns and Llovet, p. 3405.

The limited performance of guideline-recommended abdominal ultrasound and serum alpha-fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi-analyte blood test combining cell-free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC = 0.851; p < 0.0001) and GALAD (AUROC = 0.899; p < 0.0001). Using a prespecified diagnostic algorithm, the HelioLiver Test showed sensitivities of 85% (95% confidence interval [CI], 78%-90%) for HCC of any stage and 76% (95% CI, 60%-87%) for early stage (American Joint Committee on Cancer [AJCC] I and II) HCC. In contrast, AFP (≥20 ng/mL) alone and the GALAD score (≥-0.63) showed lower sensitivities of 62% (95% CI, 54%-70%) and 75% (95% CI, 67%-82%) for HCC overall, and 57% (95% CI, 40%-71%) and 65% (95% CI, 49%-79%) for early stage (AJCC I and II) HCC, respectively. The specificities of the HelioLiver Test (91%; 95% CI, 85%-95%), AFP (97%; 95% CI, 92%-99%), and the GALAD score (94%; 95% CI, 88%-97%) were similar for control subjects. The HelioLiver Test showed superior performance for HCC detection compared to with both AFP and the GALAD score and warrants further evaluation in HCC surveillance settings.

α-Fetoprotein (AFP) is a fetal glycoprotein produced by most human hepatocellular carcinoma tumors. Research has focused on its immunosuppressive properties in pregnancy, autoimmunity, and cancer, and human AFP directly limits the viability and functionality of human natural killer (NK) cells, monocytes, and dendritic cells (DCs). AFP-altered DCs can promote the differentiation of naïve T cells into regulatory T cells. These properties may work to shield tumors from the immune system. Recent efforts to define the molecular characteristics of AFP identified key structural immunoregulatory domains and bioactive roles of AFP-bound ligands in immunomodulation. We propose that a key mechanism of AFP immunomodulation skews DC function through cellular metabolism. Delineating differences between fetal 'normal' AFP (nAFP) and tumor-derived AFP (tAFP) has uncovered a novel role for tAFP in altering metabolism via lipid-binding partners.

Under current United Network for Organ Sharing (UNOS) policy, patients with hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels ≥1000 ng/mL are required to show a reduction in AFP level to

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patients HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patients HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients estimated HCC risk, instead of our current one-size-fits all strategy.

Objective To investigate the diagnostic efficacy and optimal cut-off values of alpha-fetoprotein (AFP) and alphafetoprotein variant L3(AFP-L3) in hepatitis B virus (HBV)-related early-stage hepatocellular carcinoma (HCC). Methods A total of 1 080 patients with HBV-related HCC (HBV-HCC) who were diagnosed for the first time and not yet treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2019 to July 2022 were enrolled as HCC group in the study, among whom there were 620 patients with CNLC Ⅰa-Ⅱa HCC, and in addition, 346 patients with HBV-related chronic hepatitis B (CHB group) and 293 patients with HBV-related liver cirrhosis (LC group) were enrolled as controls. The diagnostic efficacy of AFP and AFP-L3% in screening for HBV-related early-stage HCC was analyzed, including sensitivity, specificity, and the area under the ROC curve (AUC). The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups；the Kruskal-Wallis H test was used for comparison between multiple groups, and the Bonferroni method was used for further comparison between two groups. Results The HCC group had significantly higher levels of AFP and AFP-L3% than the CHB group and the LC group (H=542.479 and 418.974, both P<0.001). In early-stage HCC, AFP and AFP-L3% had an optimal cut-off value of 8.7 ng/mL and 5%, respectively, and AFP alone had the largest AUC of 0.816, with a sensitivity of 66.9% and a specificity of 85.1%. There was no significant difference in AUC between AFP-L3%+AFP and AFP alone (Z=0.609, P=0.543), but both AFP-L3%+AFP and AFP alone had a significantly larger AUC than AFP-L3% alone (AFP vs AFP-L3%：Z=8.173, P<0.001；AFP+AFP-L3% vs AFP-L3%：Z=8.802, P<0.001). Conclusion AFP has a good value and is superior to AFP-L3% in the diagnosis of HBV-related early-stage HCC, and the screening cut-off value of AFP should be lowered in order to improve the detection rate of early-stage HCC. [ABSTRACT FROM AUTHOR]

Patients with hepatocellular carcinoma at high risk of recurrence after hepatic resection or local ablation often undergo adjuvant immunotherapy with immune checkpoint inhibitors for 1 year in randomized controlled trials, but the appropriateness of this duration is controversial, especially given the risk of adverse events. Here we report the case of a 52-year-old Chinese man with initially unresectable multinodular recurrent hepatocellular carcinoma who underwent two cycles of transarterial chemoembolization, followed by hepatic resection and 24 months of adjuvant therapy with the PD-1 inhibitor tislelizumab. The patient achieved a recurrence-free survival time of 24 months, but he experienced elevated alpha fetoprotein, Grade 2 hypothyroidism and pruritus while on adjuvant therapy. This case highlights the need to optimize the duration of adjuvant immunotherapy after curative treatment for hepatocellular carcinoma in order to minimize risk of not only recurrence but also adverse events. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PIGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. METHODS: Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). RESULTS: A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). CONCLUSIONS: Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications. [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.

BackgroundPreclinical data suggest that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β signaling interact to stimulate angiogenesis and suppress antitumor immune responses. Thus, combined inhibition of both pathways may offer greater antitumor activity compared with VEGF-targeted antiangiogenic monotherapy against hepatocellular carcinoma (HCC).MethodsThis is a multicenter, open-label, phase 1b study of galunisertib, an inhibitor of TGF-β receptor 1, and ramucirumab, an anti-VEGF receptor 2 antibody, in patients with advanced HCC aiming to define the maximum tolerated dose (MTD). Secondary objectives included safety, pharmacokinetics (PK), antitumor efficacy, and plasma alpha-fetoprotein and TGF-β kinetics. Dose escalation employed a 3 + 3 design. Patients received galunisertib at 80 mg (cohort 1) or 150 mg (cohort 2) orally twice a day on days 1-14 of a 28-day cycle combined with ramucirumab 8 mg/kg intravenously every 2 weeks.ResultsEight patients were enrolled: three in cohort 1 and five in cohort 2 (two patients were unevaluable due to rapid disease progression and replaced). No dose-limiting toxicities were observed. Treatment-related adverse events (AEs) of any grade in ≥2 patients included nausea (25%) and vomiting (25%). There was one Grade 3 treatment-related AE, a cerebrovascular accident possibly related to ramucirumab. Galunisertib exposure was dose-proportional and not affected by ramucirumab. The RECIST version 1.1 objective response rate and disease control rate were 0% and 12.5%, respectively.ConclusionCombination therapy was safe and tolerable and displayed favorable PK. The MTD was established at galunisertib at 150 mg orally twice a day and ramucirumab 8 mg/kg intravenously every 2 weeks. The results do not support the preclinical hypothesis that blocking TGFβ signaling enhances efficacy of VEGF-targeted therapy; thus further clinical development was halted for the combination of galunisertib and ramucirumab.

Background & aimsIt has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of wait-list dropout would have done poorly after liver transplantation (LT) because of tumour aggressiveness. To test this hypothesis, we analysed risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score, and applied this score in short (SWRs) and mid-wait regions (MWRs) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome.MethodsUsing the United Network for Organ Sharing database, including all patients with T2 HCC receiving priority listing from 2010 to 2014, a dropout risk score was created from a developmental cohort of 2,092 patients in LWRs, and tested in a validation cohort of 1,735 patients in SWRs and 2,894 patients in MWRs.ResultsOn multivariable analysis, 1 tumour (3.1-5 cm) or 2-3 tumours, alpha-fetoprotein (AFP) >20 ng/ml, and increasing Child-Pugh and model for end-stage liver disease-sodium scores significantly predicted wait-list dropout. A dropout risk score using these 4 variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score ≤7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% vs. 71.8% for those with a score ≤30 (p = 0.004). There were no significant differences in post-LT survival below this threshold.ConclusionsThis study provided evidence that patients with HCC with the highest dropout risk have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of ≤30, priority status for organ allocation could be stratified based on the predicted risks of wait-list dropout without significant differences in post-LT survival.Lay summaryPrioritising patients with hepatocellular carcinoma for liver transplant based on risk of wait-list dropout has been considered but may lead to inferior post-transplant survival. In this study of nearly 7,000 patients, we created a threshold dropout risk score based on tumour and liver-related factors beyond which patients with hepatocellular carcinoma will likely have poor post-liver transplant outcomes (60% at 5 years). For patients below this risk score threshold, priority status could be stratified based on the predicted risk of wait-list dropout without compromising post-transplant survival.

PurposeThe phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes.Patients and methodsSerum AFP was measured every 8 weeks by blinded, centralized testing. Outcomes were analyzed by baseline AFP bifurcated at 400 ng/mL and by on-treatment AFP response (≥20% decrease from baseline at Week 8). The optimal cutoff for change in AFP at Week 8 was evaluated using maximally selected rank statistics.ResultsMedian OS for cabozantinib versus placebo was 13.9 versus 10.3 months [HR, 0.81; 95% confidence interval (CI), 0.62-1.04] for patients with baseline AFP

BackgroundTransforming growth factor beta (TGF-β) signalling is involved in the development of hepatocellular carcinoma (HCC). We followed changes in biomarkers during treatment of patients with HCC with the TGF-βRI/ALK5 inhibitor galunisertib.MethodsThis phase 2 study (NCT01246986) enrolled second-line patients with advanced HCC into one of two cohorts of baseline serum alpha-fetoprotein (AFP): Part A (AFP ≥1.5x ULN) or Part B (AFP 20% from baseline) versus non-responders, median OS was 21.5 months versus 6.8 months (p = 0.0015). In TGF-β1 responders (51% of all patients) versus non-responders, median OS was 11.2 months versus 5.3 months (p = 0.0036).ConclusionsConsistent with previous findings, both baseline levels and changes from baseline of circulating AFP and TGF-β1 function as prognostic indicators of survival. Future trials are needed to confirm and extend these results.

Objective(s): Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability.Materials and Methods: Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer. Results: HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all Ps

Objective: Unusual clinical course Background: Sarcomatoid hepatocellular carcinoma is a rare, primary malignant liver cancer. Its pathogenesis is unknown, but it often occurs in patients who have undergone repeated antitumor therapies for hepatocellular carcinoma. Sarcomatoid hepatocellular carcinoma is more likely to recur and has a worse prognosis than that of hepatocellular carcinoma. As no specific features have been identified in the symptoms, serological findings, or imaging findings, it is difficult to accurately diagnose the disease before surgical resection or autopsy. Case Report: An 83-year-old woman was diagnosed with hepatocellular carcinoma 20 years ago. Radiofrequency ablation was initially performed. Thereafter, invasive, non-surgical treatments were repeated. The most recent treatment was 4 years ago, during which computed tomography suggested recurrent hepatocellular carcinoma. However, upon needle biopsy, histological examination revealed spindle-shaped tumor cells and actively mitotic cells. Immunohistochemical analysis showed negative results for Arginase-1, HepPar1, and Glypican3 and positive results for AE1/AE3, CK7, and vimentin. Therefore, sarcomatoid hepatocellular carcinoma was diagnosed, which was treated with radiofrequency ablation but progressed rapidly thereafter. Considering the rapid disease progression, the patient was treated conservatively. However, the patient's general condition gradually deteriorated, resulting in death. Conclusions: Compared with hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma is more prone to recurrence and has a poorer prognosis. Therefore, aggressive surgical resection seems to be the most appropriate treatment for sarcomatoid hepatocellular carcinoma at present. Additional hepatic resection or follow-up imaging in a short period should be considered at the time of diagnosis of sarcomatoid hepatocellular carcinoma by biopsy, considering the risk of seeding or recurrence. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of alpha-fetoprotein (AFP) response in evaluating the clinical efficacy and safety of sorafenib combined with camrelizumab in the treatment of advanced hepatocellular carcinoma (HCC). Methods Clinical data were collected from 48 patients with advanced HCC who were treated with sorafenib combined with camrelizumab in The First Affiliated Hospital of Xinjiang Medical University from September 2020 to February 2022, and according to the level of AFP response after treatment, they were divided into response group with 32 patients (AFP after 6-8 months of treatment was reduced by more than 20% compared with baseline AFP) and non-response group with 16 patients (AFP after 6-8 months of treatment was reduced by less than 20% compared with baseline AFP). The Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Survival curves were plotted, and univariate and multivariate Cox regression analyses were used to investigate the independent risk factors for overall survival (OS). Progression free survival (PFS) time, OS time, and treatment outcome were compared between the two groups. Results No patient achieved clinical remission in either group. Compared with the non-response group, the response group had significantly higher objective response rate (21.88% vs 0, χ²=2.530, P=0.112) and disease control rate (84.38% vs 43.75%, χ²=6.668, P=0.010). Compared with the non-response group, the response group had longer PFS time (9.9 months vs 6.8 months) and OS time (13.8 months vs 11.1 months). Early non-response of AFP (hazard ratio [HR]=2.624, 95% confidence interval [CI]: 1.097-6.277, P=0.030) and extrahepatic metastasis (HR=0.392, 95%CI: 0.157-0.978, P=0.045) were independently associated with a shorter PFS time. No adverse event leading to drug withdrawal was observed in the study. Conclusion Early AFP response has a high clinical value in predicting the efficacy of sorafenib combined with camrelizumab in the treatment of advanced HCC and the prognosis of such patients. [ABSTRACT FROM AUTHOR]

Objective To establish a scoring system based on the preoperative serum levels of alpha-fetoprotein（AFP） and alkaline phosphatase（ALP), and to investigate its value in predicting the prognosis of patients with resectable hepatocellular carcinoma（HCC）. Methods A retrospective analysis was performed for 154 HCC patients who underwent hepatectomy as the initial treatment in Tianjin First Central Hospital from January 2016 to August 2019. The receiver operating characteristic（ROC） curve was used to determine the optimal cut-off values of serum AFP and ALP; the Kaplan-Meier curve and the log-rank test were used for survival analysis to evaluate the relationship between the AFP-ALP score and disease-free survival（DFS）; univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors for HCC patients. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results The ROC curve analysis showed that serum AFP had an optimal cut-off value of 250.0 ng/mL and an area under the ROC curve（AUC） of 0.674（95% confidence interval [CI]: 0.580-0.767） in predicting DFS, while serum ALP had an optimal cut-off value of 95.5 U/L and an AUC of 0.745（95% CI: 0.652-0.838）. The survival analysis showed that high preoperative serum levels of AFP（≥250.0 ng/mL） and ALP（≥95.5 U/L） were significantly associated with the poor prognosis of HCC patients（P<0.001）. Based on the AFP-ALP score, all HCC patients were further divided into 0-point group（AFP<250.0 ng/mL and ALP<95.5 U/L), 1-point group（AFP≥250.0 ng/mL, ALP<95.5 U/L; or AFP<250.0 ng/mL, ALP ≥95.5 U/L), and 2-point group（AFP≥250.0 ng/mL and ALP≥95.5 U/L）. The survival curves showed that the 0-, 1-, and 2-point groups had a median DFS of 60.0（56.7-67.3） months, 20.0（1.4-36.6） months, and 13.0（7.9-18.0） months, respectively, and there were significant survival differences between the three groups（P<0.05）. Serum AFP-ALP score（1 point vs 0 point: hazard ratio [HR]=4.060, 95% confidence interval [CI]: 2.050-8.039, P<0.001; 2 points vs 0 point: HR=4.583, 95%CI: 2.385-8.805, P<0.001） was an independent prognostic factor for HCC patients. Conclusion The scoring system based on the serum levels of AFP and ALP can effectively identify HCC patients with poor prognosis, and therefore, it might be used as a simple and reliable tool for prognostic assessment in the clinical treatment of HCC. [ABSTRACT FROM AUTHOR]

IntroductionInhibition of tumor growth factor-β (TGF-β) receptor type I potentiated the activity of sorafenib in preclinical models of hepatocellular carcinoma (HCC). Galunisertib is a small-molecule selective inhibitor of TGF-β1 receptor type I, which demonstrated activity in a phase 2 trial as second-line HCC treatment.MethodsThe combination of galunisertib and sorafenib (400 mg BID) was tested in patients with advanced HCC and Child-Pugh A liver function without prior systemic therapy. Galunisertib dose was administered 80 or 150 mg b.i.d. orally for 14 days every 28 days in safety lead-in cohorts; in the expansion cohort, all patients received galunisertib 150 mg b.i.d. Objectives included time-to-tumor progression, changes in circulating alpha fetoprotein and TGF-β1, safety, overall survival (OS), response rate, and pharmacokinetics (PK).ResultsPatients (n = 47) were enrolled from 5 non-Asian countries; 3 and 44 patients received the 80 mg and 150 mg b.i.d. doses of galunisertib, respectively. The pharmacokinetics and safety profiles were consistent with monotherapy of each drug. For the 150 mg b.i.d. galunisertib cohort, the median time-to-tumor progression was 4.1 months; the median OS was 18.8 months. A partial response was seen in 2 patients, stable disease in 21, and progressive disease in 13. TGF-β1 responders (decrease of >20% from baseline) vs nonresponders had longer OS (22.8 vs 12.0 months, P = 0.038).DiscussionThe combination of galunisertib and sorafenib showed acceptable safety and a prolonged OS outcome.

High alpha-fetoprotein (AFP) > 1,000 ng/mL is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). A new national policy has been implemented for AFP > 1,000 ng/mL requiring a decrease to < 500 ng/mL before LT, but there is a paucity of data on the optimal AFP threshold before LT. We aimed to evaluate the effects of a reduction in AFP from > 1,000 ng/mL to different AFP thresholds before LT on survival and HCC recurrence after LT using the United Network for Organ Sharing database. We identified 407 patients who underwent transplant between January 2005 and September 2015 and who had AFP > 1,000 ng/mL at least once before LT. The last AFP measurement before LT was > 1,000 ng/mL in 72.0%, decreased from > 1,000 to 101-499 ng/mL in 9.6%, and decreased to ≤ 100 ng/mL in 14.3%. Local-regional therapy was not performed in 45.4% of patients with AFP > 1,000 ng/mL at LT versus 12.8% of those with AFP of 101-499 ng/mL and 10.3% of those with AFP ≤ 100 ng/mL at LT (P < 0.001). Kaplan-Meier 5-year post-LT survival for those with AFP > 1,000 ng/mL at LT was 48.8% versus 67.0% for those with a decrease in AFP to 101-499 ng/mL (P < 0.001) and 88.4% for those with AFP ≤ 100 ng/mL at LT (P < 0.001). HCC recurrence probability at 5 years was 35.0% for patients with AFP > 1,000 ng/mL versus 13.3% for patients with AFP of 101-499 ng/mL and 7.2% for patients with AFP ≤ 100 ng/mL at LT (P < 0.001). In multivariable analysis, a decrease in the AFP to 101-499 ng/mL was associated with a > 2-fold reduction in posttransplant mortality (P = 0.01) and a nearly 3-fold reduction in HCC recurrence (P = 0.02) compared with AFP > 1,000 ng/mL at LT. Conclusion: Our results demonstrated significantly improved post-LT outcomes when restricting LT to patients with a reduction in AFP from > 1,000 to < 500 ng/mL, validating the recently implemented national policy.

Differentiating tumor versus bland portal vein thrombosis (PVT) is essential in determining liver transplantation (LT) candidacy for patients with hepatocellular carcinoma (HCC). We aimed to evaluate radiographic and clinical features that could noninvasively distinguish tumor PVT from bland PVT in HCC patients. Of 467 patients with HCC listed for LT from 2004 to 2011, 59 (12.6%) had PVT and 12 of 59 (20.3%) were deemed malignant. When comparing tumor versus bland PVT, thrombus enhancement was seen in 100% versus 8.5%; venous expansion was seen in 91.7% versus 10.6%; neovascularity was seen in 58.3% versus 2.1%; and being adjacent to HCC or prior treatment site was seen in 100% versus 21.3% (all P < 0.001). Combining these 4 imaging characteristics with alpha-fetoprotein (AFP) >1000 ng/dL, the presence of ≥3 criteria best characterized tumor PVT with 100% sensitivity, 93.6% specificity, 80% positive predictive value, and 100% negative predictive value. No LT recipients with presumed bland PVT had macrovascular invasion on explant. There were no differences in post-LT survival or HCC recurrence with bland PVT versus no PVT. In conclusion, we proposed noninvasive criteria that could accurately differentiate tumor PVT from bland PVT called A-VENA, which is based on the presence of ≥3 of the following: AFP >1000 ng/dL; venous expansion; thrombus enhancement; neovascularity; and adjacent to HCC. Use of the A-VENA criteria can assist in standardizing the evaluation of PVT in patients with HCC being considered for LT.

Background Alpha-fetoprotein (AFP) is a common diagnostic marker for hepatocellular carcinoma (HCC) , a highly malignant cancer, but its sensitivity is only 41%-65%, and the rate of missed diagnosis is relatively high. Therefore, there is an urgent need to develop new diagnostic markers and methods to improve the detection rate of AFP-negative and other types of HCC. Objective To assess the diagnostic efficacy of muscarinic acetylcholine receptor m3 autoantibody (m3AchR-Ab) in AFP-negative HCC, and to explore the diagnostic value of m3AchR-Ab in HCC. Methods Participants (n=257) were selected from the First Affiliated Hospital of Xinjiang Medical University, including 90 with confirmed diagnosis of HCC, 89 with liver cirrhosis, hepatic hemangioma or other benign liver diseases, and 78 healthy controls. ELISA was the technique used for measuring the serum m3AchR-Ab level in venous blood samples of all cases stored in the serum repository of the hospital from November 2011 to September 2015. Serum m3AchR-Ab levels were compared in the three groups. The associations of serum m3AchR-Ab level with gender, age, size (the maximum diameter) of HCC, number and TNM stage of HCC, prevalence of lymph node metastasis, distant metastasis and HBsAg positivity in HCC patients were analyzed. The efficacy of m3AchR-Ab in the diagnosis of AFP-negative HCC was evaluated by the receiver operating characteristic (ROC) curve. Results HCC patients had higher serum m3AchR-Ab level than benign liver disease patients and healthy controls (P

Researchers in a recent multicenter study developed and validated a novel prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates α-fetoprotein (AFP) at liver transplantation (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet Milan criteria by imaging and underwent LT between 2012 and -2014. On explantation (n = 3276), 13% had microvascular invasion, 30% had no viable tumor, and 15% exceeded Milan criteria. Post-LT survival at 3 years decreased with increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for a score ≥5 (P

BackgroundRising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only 2 data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time.MethodsOur cohort included 336 patients undergoing LT with Model for End Stage Liver Disease exception for HCC within Milan criteria from 2003 to 2013. Most (98%) had pre-LT locoregional therapy. AFP slope was estimated by fitting a regression line to the AFP levels over time.ResultsThe 1- and 5-year post-LT survivals were 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (hazard ratio [HR], 13.1; PMilan criteria (HR, 8.9; P7.5 (HR, 3.0; P=0.03) were significantly associated with HCC recurrence. AFP slope greater than 7.5 was also associated with microvascular invasion (odds ratio, 6.8; P=0.008).ConclusionsAFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT.

PurposeTo conduct a large single-institution comparison of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes in similar groups of patients with hepatocellular carcinoma (HCC).Methods and materialsFrom 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed.ResultsThe TACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease, and baseline liver function. Patients treated with SBRT were older (65 vs 61 years, P=.01), had smaller tumors (2.3 vs 2.9 cm, P

Hepatocellular carcinoma (HCC) ranks as one of the most prevalent malignant tumors globally, being the 5th most common neoplasm and the 3rd leading cause of cancer-related deaths. Despite efforts, current serum biomarkers for HCC surveillance and early diagnosis exhibit low sensitivity and varying specificity, even with different cut-off points and longitudinal assessments. AFP, the most commonly used marker, lacks satisfactory sensitivity and specificity, highlighting an urgent need for more effective markers with higher accuracy for early HCC detection. Exploring novel diagnostic biomarkers holds promise in improving HCC prognosis. There is evidence suggesting that downregulation of MAGE-D1 transcription plays a crucial role in apoptosis and inhibits cancer cell proliferation when expressed ectopically. Moreover, reduced MAGE-D1 expression correlates with improved prognosis in many cancers, underscoring its relevance in cancer development and progression. Therefore, this study aims to evaluate the diagnostic potential of MAGE-D1 in HCC, proposing it as a novel biomarker for early diagnosis and monitoring of tumor progression.

Objectives: We investigated hepatoblastoma with invasion into the vessels of the portal vein and widespread thrombosis of the portal vein, where tumor resection is impossible, that was treated with liver transplant., Materials and Methods: Examination of 5-year-old boy (15 kg) diagnosed with hepatoblastoma of the liver of fetal epithelial variant without signs of metastasis, showed alpha-fetoprotein level of 22684 IU/mL, which decreased to 16 IU/mL after polychemotherapy. Abdominal ultrasonography showed signs of a space-occupying lesion in the right liver lobe, cavernous transformation of the portal vein, hepatosplenomegaly, and diffuse focal changes in the liver. Abdominal computed tomography showed signs of liver space-occupying lesions and invasion into the inferior vena cava and cavernous transformation of the portal vein, hepatosplenomegaly, and dilatation of intra- and extrahepatic bile ducts. The child received transplant of 2 and 3 liver segments from a living related donor. Extensive thrombosis of the portal vein was detected in the recipient, and thrombectomy was performed. To perform a portal anastomosis, a venous graft from the external jugular vein on the left, 3 cm long, was taken from the recipient. Because a portal anastomosis directly with the native portal vein of the recipient was not possible because of multiple vascular transformation, anastomosis was performed between the portal vein of the donor liver and the superior mesenteric vein of the recipient and graft from the external jugular vein., Results: In the early postoperative period, against the background of satisfactory liver graft function, decreased liver transaminases, bilirubin, and alpha-fetoprotein were noted. Doppler sonography showed satisfactory blood flow., Conclusions: Despite pronounced vascular transformation of the portal vein with partial thrombosis of the portal vein in the recipient, the use of a native vascular graft from the external jugular vein of the recipient himself to form a portoportal anastomosis was an optimal solution.