Hepatocellular Carcinoma Score Research Articles

Utility and predictive value of the CRAFITY score in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus tyrosine kinase inhibitors and PD-1 inhibitor

BackgroundThe prognostic significance of the CRAFITY score (CRP and AFP in ImmunoTherapY) has been demonstrated in hepatocellular carcinoma (HCC) patients receiving immunotherapy. The purpose of this study was to investigate the utility and the predictive value of CRAFITY score in HCC after transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) and immunotherapy.Materials and methodsData from patients with advanced HCC treated with TACE plus TKIs and PD-1 inhibitor from January 2019 to June 2022 were collected and analyzed retrospectively. Patients with AFP ≥ 100 ng/mL and those with CRP ≥ 1 mg/dL were assigned a CRAFITY score of 1 point. Patients were divided into three groups according to their CRAFITY score (CRAFITY-low, 0 points; CRAFITY-intermediate, 1 point; and CRAFITY-high, 2 points). The differences in overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were compared among the three groups. Tumor response was evaluated at 3, 6 and 12 months after the first combination treatment. Risk factors for OS and PFS were assessed.ResultsA total of 70 patients were included. The patients were assigned CRAFITY scores of 0 points (CRAFITY-low, n = 25 [35.71%]), 1 point (CRAFITY-intermediate, n = 29 [41.42%]), and 2 points (CRAFITY-high, n = 16 [22.81%]). Multivariate analysis showed that lower CRAFITY score was an independent factor for the improved OS (P =.045) and PFS (P <.001). TACE session was also associated with the OS (P =.048) in the multivariate analysis. The CRAFITY-low cohort achieved a higher objective response rate (ORR) at the 3-month evaluation of tumor response. However, there was no significant difference in ORR and disease control rate (DCR) observed at the 6-month follow-up. DCR showed a statistically significant difference among three groups during the 12-month follow-up period. The percentage of patients with protein urea was highest in the CRAFITY-high group. No significance differences were observed in grade ≥ 3 AEs in three groups.ConclusionThe CRAFITY score is simple and could be useful for predicting treatment outcomes, tumor response and AEs of the HCC patients receiving TACE plus TKIs and PD-1 inhibitor therapy.

Cell-free DNA testing for early hepatocellular carcinoma surveillance

Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. A total of 4367LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P<0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma

This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.

A Liver Stiffness–Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma

Background & AimsThe existing hepatocellular carcinoma (HCC) risk scores have modest accuracy and most are specific to chronic hepatitis B infection. In this study, we developed and validated a liver stiffness-based machine learning algorithm (ML) for prediction and risk stratification of HCC in various chronic liver diseases (CLDs). MethodsMLs were trained for prediction of HCC in 5155 adult patients with various CLDs in Korea and further tested in two prospective cohorts from Hong Kong (HK, N=2732) and Europe (N=2384). Model performance was assessed according to Harrell’s C-index and time-dependent receiver operating characteristic (ROC) curve. ResultsWe developed the SMART-HCC score, a liver stiffness-based ML HCC risk score, with liver stiffness measurement ranked as the most important among 9 clinical features. The Harrell’s C-index of the SMART-HCC score in HK and Europe validation cohorts were 0.89 (95% confidence interval [CI] 0.85-0.92) and 0.91 (95%CI 0.87-0.95), respectively. The area under ROC curves of the SMART-HCC score for HCC in 5 years were ≥0.89 in both validation cohorts. The performance of SMART-HCC score was significantly better than existing HCC risk scores including aMAP score, Toronto HCC risk index, and seven hepatitis B related risk scores. Using dual cut-offs of 0.043 and 0.080, the annual HCC incidence was 0.09%-0.11% for low-risk group, and 2.54%-4.64% for high-risk group in the HK and Europe validation cohorts. ConclusionThe SMART-HCC score is a useful machine learning-based tool for clinicians to stratify HCC risk in patients with CLDs.

Prognosis Prediction of CRAFITY Score in HCC Undergoing TACE Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapy.

The CRAFITY (C-reactive protein and alpha-fetoprotein in immunotherapy) score has demonstrated prognostic significance in hepatocellular carcinoma (HCC) patients undergoing immunotherapy. The study aimed to validate accuracy of CRAFITY score on predicting prognosis for patients with HCC treated with transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapy. Eighty-five HCC patients who underwent TACE in combination with molecular targeted therapy (MTT) and PD-(L)1 Inhibitors were consecutively enrolled from November 2019 to November 2022. Patients were divided into CRAFITY 0 score (n=32), CRAFITY 1 score (n=31), and CRAFITY 2 score (n=22), respectively. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes included tumor response rate and treatment-related adverse events (TRAEs). Factors affecting survival were identified via Cox regression analysis. The median overall survival (OS) for HCC patients with CRAFITY scores of 0, 1, and 2 was 33.4 months (95% confidence interval [CI]: 27.1-39.7), 34.5 months (95% CI: 23.1-45.9), and 24.2 months (95% CI: 13.9-39.3), respectively, there were statistical differences among the three groups (p<0.05). The progression-free survival (PFS) was 14.1 months (95% CI: 10.0-18.2), 14.1 months (95% CI: 9.0-19.2), and 9.3 months (95% CI: 7.2-11.4) for patients with CRAFITY scores of 1, 2, and 3, respectively, with a significant difference between the three groups (p<0.05). In patients with CRAFITY scores of 1, 2, and 3, the disease control rates (DCR) were 94%, 84%, and 73%, respectively (p < 0.05), while the overall response rates (ORR) were 78.1%, 67.7%, and 59.1%, respectively (p = 0.318). A higher CRAFITY score showed a correlation with an increased frequency of fatigue and grade 3 fever (p<0.05). Moreover, CRAFITY 2 score was an independent risk factor for both OS (HR = 2.610(1.281-4.564), p = 0.014) and PFS (HR = 2.419(1.281-4.564), p = 0.006). The CRAFITY score may provide an efficient predictive capacity for prognosis in HCC patients undergoing TACE combined with PD-(L)1 inhibitors and molecular targeted therapy.

A novel immunogenic cell death-related genes signature for predicting prognosis, immune landscape and immunotherapy effect in hepatocellular carcinoma.

Immunogenic cell death (ICD) has emerged as a promising strategy to activate the adaptive immune response, modulate the tumor microenvironment (TME) and enhance the efficacy of immune therapy. However, the relationship between ICD and TME reprogramming in hepatocellular carcinoma (HCC) remains poorly understood. Transcriptional profiles and clinical spectrum of 486 HCC patients were obtained from TCGA and GEO databases. We utilized consensus clustering analysis to construct two distinct molecular subtypes and established an ICD-based scoring system (named ICD score) via WGCNA and LASSO Cox regression to predict the prognosis of the HCC cohort. Then we employed CIBERSORT and ESTIMATE methods to analyze the immune landscape of ICD score in HCC. Subsequently, the immunophenoscore (IPS) and tumor immune dysfunction and rejection (TIDE) analyses were performed to determine whether the ICD score could influence the immune therapeutic effect. Based on the ICD scoring system, a novel nomogram was generated to provide a numerical probability of HCC patients' overall survival (OS). We identified two independent ICD clusters (cluster A/B), and cluster B possessed a worse prognosis and higher immune cell infiltration. Using ICD scoring system, the HCC patients were divided into high- and low-ICD-score groups. Through integrative analyses, the high-ICD cohort owned advanced TNM stage, high pathologic grade and increased suppressive immune cell enrichment. We developed a nomogram containing the ICD score, demonstrating a high predictive accuracy with a C-index of 0.703. We further discovered that PSMD2 and PSMD14 could serve as ICD-associated prognostic biomarkers and therapeutic targets in HCC. The ICD score exhibits a high degree of reliability for predicting prognosis and may provide valuable guidance for the selection of immunotherapy for HCC patients. This novel scoring system enables the estimation of clinical immunotherapy response for HCC patients, offering new opportunities for personalized immunotherapy.

Current Status and Future Direction of Albumin-Bilirubin in Hepatocellular Carcinoma: A Bibliometric Analysis

Introduction: Hepatocellular carcinoma (HCC) is a common malignant tumor, so we need a convenient and objective way to diagnose and treat HCC. We discuss the current situation, progress, hotspots, and existing problems of Albumin-Bilirubin (ALBI) in HCC, which can provide new ideas for the prevention, diagnosis, and treatment of HCC. Methods: We adopt Excel 2019 software and visual analysis tools based on Web of Science database search. This manuscript uses VOSviewer, Co-Occurrence13.3 (COOC13.3) software to conduct overall trend analysis, synonym merging, frequency of countries, journals, institutions, funds, dissimilarity matrices, co-occurrence matrices, bimodal matrices, coupling matrices, cluster analysis of topic evolution time zone graphs. Results: A total of 610 papers were included, and the number of papers output showed an overall upward trend. ALBI has been valued by the industry in HCC and plays an important role in diagnosing and treating HCC, even better than the classic Child-Pugh (C-P) grade. At the same time, hot spots in the treatment of HCC and other applications of ALBI were discovered. Conclusion: ALBI score is a convenient and objective liver function evaluation index, which plays an important role in the prediction of patient survival rate and prognosis. Promoting the ALBI score in HCC can help doctors judge the patient’s condition and improve the diagnosis and precise treatment effect.

A novel prognostic model based on immunogenic cell death-related genes for improved risk stratification in hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) is a prevalent primary malignant tumor with increasing incidence and mortality rates in recent years. The treatment options for advanced HCC are very limited. Immunogenic cell death (ICD) plays an important role in cancer, in particular immunotherapy. However, the specific ICD genes and their prognostic values in HCC remain to be investigated. The TCGA-LIHC datasets were obtained from TCGA database, LIRI-JP datasets were obtained from ICGC database, and immunogenic cell death (ICD) genes datasets were obtained from previous literature. WGCNA analysis identifies ICD-related genes. Functional analysis was used to investigate the biological characteristics of ICD-related genes. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to select prognostic ICD-related genes and construct a prognostic risk score. Prognostic independence of ICD risk scores was determined by univariate and multivariate Cox regression analyses. A nomogram was then constructed and the diagnostic value was assessed using decision curve analysis. Immune infiltration analysis and drug sensitivity analysis were used to investigate immune cell enrichment and drug response in HCC patients classified as low or high risk based on their risk score. Most of the ICD genes were differentially expressed in normal and HCC patients, and some ICD genes were differentially expressed in different clinical groups. A total of 185 ICD-related genes were identified by WGCNA. Prognostic ICD-related genes were selected using a univariate Cox analysis. A model comprising nine prognosis ICD-related gene biomarkers was developed. Patients was divided into high-risk and low-risk groups, and patients in high-risk groups had poorer outcomes. Meanwhile, the reliability of the model was verified by external independent data. The Independent prognostic value of the risk score in HCC was investigated by univariate and multivariate Cox analyses. Diagnostic nomogram was constructed to predict prognosis. Through immune infiltration analysis, we found that some innate and adaptive immune cells were significantly different between low- and high-risk groups. We developed and validated a novel prognostic predictive classification system for HCC based on nine ICD-related genes. In addition, immune-related predictions and model could help predict the outcomes of HCC and could provide a reference for clinical practice.

Donafenib combined with anti-PD-1 antibody and transarterial chemoembolization (TACE) as first-line (1L) treatment for unresectable/advanced hepatocellular carcinoma (HCC).

e16107 Background: Targeted drugs, immune checkpoint inhibitors and TACE are important non-surgical approaches to treat HCC. A triple combination of the three is under investigation. This prospective study was conducted to assess the efficacy and safety of donafenib combined with anti-PD-1 antibody and TACE as first-line treatment for unresectable or advanced HCC. Methods: Patients (pts) who had histologically or clinically confirmed HCC and with no prior systemic therapy, at least one measurable lesion per mRECIST, Child-Pugh score ≤7, and ECOG PS score 0-1 were enrolled and received donafenib 100 mg twice daily, anti-PD-1 antibody Q3W and on-demand conventional TACE. CT/MRI scans were performed every six weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival and safety. Results: A total of 30 pts were enrolled between Dec 2021 and Nov 2022. All pts had HBV-related HCC and baseline ECOG PS score of 0. Baseline characteristics are shown in the Table. As of 6 Feb 2023, eleven pts had discontinued the triple therapy. The median follow up time was 3.6 months (range, 1.8-13.4). The median number of on-study TACE sessions was 2 (range, 1-4). Among 29 efficacy evaluable pts, five pts had disease progression and no death occurred. The median PFS was not reached (95%CI, 2.4 months -NE). The 6-month PFS rate was 69.4% (95%CI, 34.5%-84.0%). Five pts had a complete response and 13 had a partial response (responders). ORR and DCR were 62.1% (95%CI, 42.3%-79.3%) and 86.2% (95%CI, 68.3%-96.1%) per mRECIST. The median time to response was 1.3 months (95%CI, 1.1-1.6). The median duration of response was not reached (95%CI, 3.4 weeks-NE). Four pts (1 with BCLC B, 3 with BCLC C) underwent successful surgical resection after a median treatment duration of 2.9 months (range, 1.8-3.3) and no recurrence was noted with a median of 5.9 months (range, 2.8-10.2) follow-up after hepatectomy. In the safety population (n = 30), any grade and grade 3 treatment-related adverse events (TRAEs) occurred in 15 (50.0%) and 7 (23.3%) pts with no grade 4 TRAEs or toxic death. Rash was the most common grade 3 TRAE (incidence: 13.3%) and led to treatment discontinuation in one pt. Conclusions: The triple combination of donafenib plus anti-PD-1 antibody and TACE showed promising efficacy and was well tolerated in pts with unresectable or advanced HCC. Clinical trial information: NCT05262959 . [Table: see text]

Prognostic significance of the CRAFITY score in hepatocellular carcinoma treated with immunotherapy: a systematic review and meta-analysis

BackgroundThis meta-analysis aimed to assess the performance of the CRAFITY (CRP and AFP in immunotherapy) score as a prognostic factor in hepatocellular carcinoma (HCC) treated with immunotherapy.MethodsThe PubMed, Cochrane Library, and Web of Science databases were searched for published studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) outcomes were pooled using fixed- and random-effects models. Odds ratios (ORs) with 95% CI were used to measure the association of individual CRAFITY scores with the disease control rate (DCR).ResultsFour eligible studies comprising 786 patients were included. The results indicate that a lower CRAFITY score is a significant predictor of better OS (HR = 0.22, 95% CI: 0.10–0.50) and PFS (HR = 0.36, 95% CI: 0.23–0.55) outcomes. In addition, the DCR was significantly higher in patients with lower CRAFITY scores (OR = 3.16, 95% CI: 2.00–4.99). A significant positive association between low CRAFITY scores and favorable prognoses was also observed in Barcelona Clinic Liver Cancer stage B/C/D patients.ConclusionIn this study, a low CRAFITY score was associated with better overall outcomes in HCC patients treated with immunotherapy. However, this finding requires further investigation.

The hemoglobin, albumin, lymphocyte, and platelet score is a prognostic factor for Child-PughA patients undergoing curative hepatic resection for single and small hepatocellular carcinoma.

The hemoglobin, albumin, lymphocyte, and platelet (HALP) score reflects the immune system and the nutritional status of patients, and prognosis in various cancers. However, the HALP score in hepatocellular carcinoma has not been reported. Data were analyzed retrospectively from Child-PughA patients undergoing hepatic resection for single hepatocellular carcinoma ≤5cm. For cross-validation, patients were divided into the training (332 patients) and validation cohort (210 patients). In the training cohort, we divided patients into two groups by appropriate cut-off value of the HALP score, and univariable and multivariable analyses were conducted for disease-free and overall survival (OS) between two groups. In the validation cohort, we examined OS by Kaplan-Meier analysis in the same cut-off value of the HALP score in the training cohort. The HALP-low group was significantly older (p=0.0003), had fewer hepatitisB surface antigen-positive patients (p=0.0369), higher prothrombin time (p=0.0141), lower fibrosis-4 index (p=0.0206), bigger maximum tumor size (p=0.0196), and less histological liver fibrosis (p=0.0077). Multivariate analysis showed that the independent prognostic factors for disease-free survival were fibrosis-4 index ≥2.67 (p=0.0008), simple nodular type with extranodular growth or confluent multinodular type (p=0.0221), and intrahepatic metastasis (p=0.0233), and that for OS were fibrosis-4 index ≥2.67 (p=0.0020), HALP ≤45.6 (p=0.0228), and poor differentiation (p=0.0305). In the validation cohort, Kaplan-Meier analysis revealed the trend toward significantly impaired OS (p=0.0220) in the HALP-low group. We showed that a low HALP score is the independent prognostic factor for Child-PughA patients undergoing curative hepatic resection for single and small hepatocellular carcinoma.

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning.

Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear. Methods: We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored. Results: ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration. Conclusion: In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.

Outcomes for Salvage Abdominal Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma after Liver Transplantation

<h3>Purpose/Objective(s)</h3> While orthotopic liver transplantation (OLT) is considered curative for most hepatocellular carcinoma (HCC) patients, recurrence can occur in 10-20% of these patients. Data has shown stereotactic body radiation therapy (SBRT) to be safe and effective as treatment for primary HCC, however few studies have investigated the safety and efficacy of SBRT as treatment for HCC after OLT. The aim of this study is to evaluate the safety and efficacy of intra-abdominal salvage SBRT for HCC in patients who previously underwent OLT. <h3>Materials/Methods</h3> A retrospective chart review of a single, large institution was conducted to identify patients who received intra-abdominal SBRT as treatment for recurrent HCC after OLT from 1/1/2013 to 12/1/2021. Clinical safety was measured by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0 for grading adverse events, Child-Turcott-Pugh (CTP) score, and Albumin-Bilirubin (ALBI) grade for HCC. Dosimetric analysis was performed. Efficacy was measured by local control (LC) and objective response using modified Response Evaluation Criteria in Solid Tumors (mRECIST). The Kaplan-Meier method was used to evaluate overall survival (OS) and progression free survival (PFS). <h3>Results</h3> 18 lesions, treated among 15 patients were identified that received intra-abdominal SBRT for HCC recurrence after OLT. Nine patients were male, median age was 62 (interquartile range 52 to 80). The American Joint Committee on Cancer stage at diagnosis was most often T1N0M0 (n=8, 53%) or T2N0M0 (n=5, 33%). The most common etiology for HCC diagnosis was hepatitis C virus (n=9, 56%). Median CTP and ALBI scores at baseline were 5 (range 5 to 11) and -3.02 (range -3.36 to -1.35), respectively. Median change in CTP score from baseline to CTP at 3, 6, and 12 months was 0.00, 1.00, and 1.00. Median change in ALBI score from baseline to at 3, 6, and 12 months was 0.14, 0.40, and 0.42. The median treatment dose was 4750 cGy (interquartile range 500 cGy), all patients received 5 fractions. There was no grade 3 or above CTCAE toxicities. During 6 (33%) SBRT treatments, patient experienced grade 1 or 2 CTCAE toxicity with nausea, emesis, or fatigue. Local control was achieved in 94% of lesions (n=17). Local treatment response was: 11 (61.2%) complete response, 5 (27.8%) partial response, 1 (5.5%) stable disease, and 1 (5.5%) progressive disease. After median follow up of 19.2 months, 8 patients (53%) were deceased and 7 (47%) had no evidence of disease progression. OS was 100% at 6 months and 60.8% at 12 months. PFS was 92.9% at 6 months and 60.9% at 12 months. No dosimetric factor was found to predict for increased toxicity. <h3>Conclusion</h3> For patients with HCC after OLT, SBRT appears to be a safe and effective treatment modality, as no patients experienced significant toxicities and the majority had complete treatment response.

Comparison of international guidelines for diagnosis of hepatocellular carcinoma and implications for transplant allocation in liver transplantation candidates with gadoxetic acid enhanced liver MRI versus contrast enhanced CT: a prospective study with liver explant histopathological correlation

ObjectivesTo compare the diagnostic performance of international hepatocellular carcinoma (HCC) guidelines with gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed tomography (CECT) and their impact on liver transplant (LT) allocation in cirrhotic patients with explant histopathology correlation.MethodsIn this prospective single-centre ethics-approved study, 101 cirrhotic patients were consecutively enrolled with informed consent from the pre-LT clinic. They underwent CECT and EOB-MRI alternately at three monthly intervals until LT or removal from LT list. Two abdominal radiologists, blinded to explant histopathology, independently recorded liver lesions visible on CECT and EOB-MRI. Imaging-based HCC scores were assigned to non-treated liver lesions utilizing Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian-Pacific Association for the Study of the Liver (APASL) and Korean Liver Cancer Association-National Cancer Center (KLCA) guidelines. Liver explant histopathology was the reference standard. Simulated LT eligibility was assessed as per Milan criteria (MC) in reference to explant histopathology.ResultsOne hundred and three non-treated HCC and 12 non-HCC malignancy were identified at explant histopathology in 34 patients (29 men, 5 women, age 55–73 years). Higher HCC sensitivities of statistical significance were observed with EOB-MRI for LI-RADS 4 + 5, APASL and KLCA compared to LI-RADS 5 and EASL with greatest sensitivity obtained for LIRADS 4 + 5 lesions. HCC sensitivities by all guidelines with both EOB-MRI and CECT were significantly lower if all histopathology-detected HCCs were included in the analysis, compared to imaging-visible lesions only. A significantly greater variation in HCC sensitivity was noted across the guidelines with EOB-MRI compared to CECT. No significant differences in simulated LT eligibility based on MC were observed across the HCC scoring guidelines with EOB-MRI or CECT.ConclusionHCC sensitivities are variable depending on scoring guideline, lesion size and imaging modality utilised. Prior studies that included only lesions visible on pre-operative imaging overestimate the diagnostic performance of HCC scoring guidelines. Per-lesion differences in HCC diagnosis across these guidelines did not impact patient-level LT eligibility based on MC.

Correlation of Abdominal CT scan Score and Alpha-fetoprotein Levels in Hepatocellular Carcinoma

Objective: To assess the correlation between the Alpha-fetoprotein (AFP) level and characteristics of liver lesions listed in the abdominal computed tomography (CT) scan scores in hepatocellular carcinoma.Methods: This was a retrospective analytic observational study with a cross-sectional design conducted at Sanglah Hospital in January 2017–January 2021. Subjects were patients diagnosed with hepatocellular carcinoma based on clinical and laboratory features. Samples were taken by consecutive sampling. The results of the abdominal CT scan were read by two radiologists with a predetermined abdominal CT scan scoring system. The AFP level data were taken at a maximum of 5 days before an abdominal CT scan was performed.Results: A total of 64 subjects were included in this study. The mean serum AFP level was 1,000 IU/mL (range 0.54–61830 IU/mL). The mean abdominal CT scan score by examiner one was 10.093±5.59, while the examiner two provided a score of 10.281±5.45. The difference in mean CT scan scores between the two examiners was very low and insignificant (mean difference score -0.188; 95% CI -1.894–1.519). The rho Spearman value was 0.918 (p&lt;0.001) between serum AFP levels and abdominal CT scan scores. In the partial correlation, the value of r=0.678 (p&lt;0.001) was obtained after controlling for body mass index (BMI), age, and sex variables.Conclusions: There is a strong positive correlation between serum AFP levels and abdominal CT scan scores in hepatocellular carcinoma patients. Further research is needed with a prospective design to reduce research bias.

CDK2AP1 influences immune infiltrates and serves as a prognostic indicator for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a tumor with high malignancy and poor 5-years survival rate. Excellent tumor markers are very important for early clinical diagnosis and prognosis evaluation. Previous studies have shown that CDK2AP1 (Cyclin-dependent kinase 2-associated protein 1) is involved in cell-cycle and epigenetic regulation. In the present study, we assess CDK2AP1 expression, prognostic value, immunomodulatory and possible influencing pathways in HCC. Method: The Cancer Genome Atlas (TCGA) database was used to analyse gene expression, clinicopathology and prognosis. The protein level of CDK2AP1 in HCC tissues was detected in the Human Protein Atlas (HPA) database. The immune score in HCC to CDKAP1 expression were analyzed using ESTIMATE. Furthermore, we use Tumor IMmune Estimation Resource (TIMER) database to study CDK2AP1 expression and Immune Infiltration Levels in HCC. Co-expressed genes of CDK2AP1 were predicted and elaborated by LinkedOmics. Results: In normal liver tissues, the expression of CDK2AP1 was significantly lower than tumor tissues, and was correlated with the level of clinical stage and histologic grade in HCC patients. Patients with high expression of CDK2AP1 have a poor prognosis than patients with low CDK2AP1 expression. CDK2AP1 expression level exhibits significantly positive correlations with the number of infiltrating B cells, CD4+ T cells, CD8+ T cells, Macrophages, Neutrophils, and DCs in HCC tissues. KEGG enrichment analysis showed that the related pathways affected by CDK2AP1 mainly include: Fc gamma R-mediated phagocytosis, Th1 and Th2 cell differentiation, Cell cycle, etc. Both in vitro and in vivo experiments confirmed that CDK2AP1 promotes the proliferation and metastasis in hepatocellular carcinoma. Our results highlight the role of CDK2AP1 as an important prognostic indicator and immunotherapy target for HCC patients. Conclusion: We found CDK2AP1 as a new prognostic biomarker for HCC, which could help explain changes in the biological processes and immune environment lead to liver cancer development. Therefore, CDK2AP1 is a potential new target for HCC therapy.

Comprehensive analysis to identify the neurotransmitter receptor-related genes as prognostic and therapeutic biomarkers in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with high morbidity and mortality, which accounts for the fourth most common cause of cancer-related deaths. Reports suggest that the neurotransmitter receptor-related genes (NRGs) may influence the tumor microenvironment and the prognosis of patients with HCC. Methods: The clinical information and RNA-seq data of patients with HCC were acquired from the ICGC-LIRI-JP dataset and the TCGA-LIHC dataset. Effects of 115 NRGs on the prognosis of HCC patients were analyzed in the ICGC-LIRI-JP dataset. The least absolute shrinkage and selection operator (LASSO) regression model was utilized to generate a risk score formula based on the critical NRGs. Next, the risk score effectiveness was validated both in the TCGA-LIHC dataset and in our clinical HCC samples. Based on the risk scores, patients with HCC were divided into two groups. Moreover, differentially expressed genes (DEGs) were screened. The gene ontology (GO) was used to analyze the functional enrichments of DEGs and to identify potential signaling pathways. To test the diagnostic effectiveness of our model, the receiver operator characteristic curve (ROC) analysis and nomogram were used. Finally, potential targeted drug prediction was performed based on DEGs of nine clinical HCC samples. Results: Nine NRGs were correlated significantly with the prognosis of patients with HCC, and eight NRGs were successfully included in the LASSO regression model. The Kaplan-Meier analysis of overall survival (OS) suggested that patients in the high-risk score group had worse prognosis; on the other hand, ROC analysis revealed a high prognostic value of the risk score in HCC. Several critical signaling pathways, such as lipid metabolism, organic acid metabolism, cell migration, cell adhesion, and immune response, were enriched both in public datasets and clinical samples. Nomogram results also suggested that the risk scores correlated well with the patients’ prognosis. Potential targeted drugs prediction revealed that tubulin inhibitors might be the promising drugs for patients with HCC who have high risk scores based on the NRGs. Conclusion: We established a prognostic model based on critical NRGs. NRGs show a promising prognostic prediction value in HCC and are potential therapeutic targets for the disease treatment.

Prognostic impact of C-reactive protein and alpha-fetoprotein in immunotherapy score in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: a multicenter retrospective study.

This study aimed to investigate the utility of C-reactive protein (CRP) and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score in hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/Bev). This retrospective cohort study included a total of 297 patients receiving Atez/Bev from September 2020 to November 2021 at 21 different institutions and hospital groups in Japan. Patients with AFP ≥ 100ng/mL and those with CRP ≥ 1mg/dL were assigned a CRAFITY score of 1 point. The patients were assigned CRAFITY scores of 0 points (n = 147 [49.5%]), 1 point (n = 111 [37.4%]), and 2 points (n = 39 [13.1%]). AFP ≥ 100ng/mL and CRP ≥ 1.0mg/dL were significantly associated with progression-free survival (PFS) and overall survival (OS). The median PFS in the CRAFITY score 0, 1, and 2 groups was 11.8months (95% confidence interval [CI] 6.4-not applicable [NA]), 6.5months (95% CI 4.6-8.0), and 3.2months (95% CI 1.9-5.0), respectively (p < 0.001). The median OS in patients with CRAFITY score 0, 1 and 2 was not reached, 14.3months (95% CI 10.5-NA), and 11.6months (95% CI 4.9-NA), respectively. The percentage of patients with grade ≥ 3 liver injury, any grade of decreased appetite, any grade of proteinuria, any grade of fever, and any grade of fatigue was lowest in patients with a CRAFITY score of 0, followed by patients with CRAFITY scores of 1 and 2. The CRAFITY score is simple and could be useful for predicting therapeutic outcomes and treatment-related adverse events.

Validation and prognostic value of EZ-ALBI score in patients with intermediate-stage hepatocellular carcinoma treated with trans-arterial chemoembolization

BackgroundHeterogeneity of liver function and tumor burden in intermediate-stage hepatocellular carcinoma (HCC) results in different outcomes after transarterial chemoembolization (TACE). Easy albumin-bilirubin (EZ-ALBI), a simplified albumin-bilirubin (ALBI) score, has recently been proposed as a new prognostic score for HCC. This study aimed to validate the EZ-ALBI score and evaluate the impact of dynamic changes in patients with intermediate-stage HCC undergoing TACE.MethodsAll patients with HCC treated with TACE at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2015 and December 2019 were prospectively enrolled. Intermediate-stage HCC was defined as Barcelona Clinic Liver Cancer (BCLC) stage B or unresectable single HCC with size > 5 cm in BCLC stage A. EZ-ALBI and ALBI scores were calculated and stratified into three different grades. Overall survival (OS) and prognostic factors were assessed using the Kaplan–Meier curve and Cox proportional hazard model. Decision analysis curves were used to evaluate the clinical utility of the predictive scores.ResultsAmong 672 patients with HCC treated with TACE, 166 patients with intermediate-stage HCC who met the eligibility criteria were enrolled. The median OS of all patients in the cohort was 21 months. A good correlation between the EZ-ALBI and ALBI scores was observed (correlation coefficient 1.000, p < 0.001). The baseline EZ-ALBI grades 1, 2, and 3 were 24.5%, 70%, and 5.5%, respectively. EZ-ALBI grade can stratify patients with significantly different prognoses (p = 0.002). Baseline EZ-ALBI grade 2, 3, and serum alpha-fetoprotein > 20 ng/ml were significantly associated with OS [hazard ratio (HR) 2.20 (95% confidence interval [CI] 1.24–3.88, p = 0.007), 3.26 (95% CI 1.24–8.57, p = 0.016), and 1.77 (95% CI 1.10–2.84, p = 0.018), respectively]. Following TACE, 42 (29.6%) patients had a worsening EZ-ALBI grade. However, the EZ-ALBI grade migration was not significantly correlated with OS. EZ-ALBI and ALBI score provided improved discriminatory ability (Harrell’s concordance index 0.599 and 0.602, respectively) and better net benefit compared with Child-Turcotte-Pugh and Model for End-stage Liver Disease scores.ConclusionsThe baseline EZ-ALBI score demonstrated good predictive performance for survival and a strong correlation with conventional ALBI scores. Both the EZ-ALBI and ALBI scores outperformed other prognostic models in patients with intermediate-stage HCC receiving TACE. However, the dynamic change in the EZ-ALBI grade after TACE was not associated with postprocedural survival.

Black race is independently associated with underutilization of transplantation for clinical T1 hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. Operative management of early disease includes ablation, resection, and transplantation. We compared the operative management of early-stage HCC in patients stratified by race. We identified patients with cT1 HCC and Charlson-Deyo score 0-1 in the National Cancer Database (2004-2016). We compared operative/non-operative management by race, adjusting for clinicodemographic variables. We performed marginal standardization of logistic regression to ascertain adjusted probabilities of resection or transplantation in patients under 70 years of age with insurance. A total of 25,029 patients were included (White=20,410; Black=4619). After adjusting for clinico demographic variables, Black race was associated with a lower likelihood of undergoing operative intervention (OR 0.89,p=0.009). Black patients were more likely to undergo resection (OR 1.23,p<0.001) and less likely to undergo transplantation (OR 0.60,p<0.001). Marginal standardization models demonstrated Black race was associated with increased probability of resection in patients >50yrs, with private insurance/Medicare, and lower probability of transplantation regardless of age or insurance payor. Black race is associated with lower rates of hepatic transplantation and higher rates of hepatic resection for early HCC regardless of age or insurance payor. The etiology of these disparities is multifactorial and correcting the root causes represents a critical area for improvement.