Alpha-fetoprotein Score Research Articles

Prognostic significance of C-reactive protein in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ+BEV) for unresectable hepatocellular carcinoma (HCC). A total of 213 patients who received ATZ+BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score. Compared with patients with baseline CRP <1mg/dL, those with baseline CRP ≥1mg/dL (n=45) had a significantly higher baseline albumin-bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313-5.107; log-rank test, p<0.001). Multivariate analysis identified CRP ≥1mg/dL, AFP ≥100ng/mL, and modified albumin-bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ+BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively. CRP was a significant biomarker in patients treated with ATZ+BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ+BEV therapy.

AFP score and metroticket 2.0 perform similarly and could be used in a “within-ALL” clinical decision tool

Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p= 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ("within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC.

The prognostic potential of fragmented CK18 serum levels in HCC patients reflecting disease progression and overall hepatocyte damage.

BackgroundFragmented cytokeratin 18 (fCK18) is released from damaged hepatocytes undergoing apoptosis and is recognized as a liver condition biomarker. We have developed a highly sensitive serum fCK18 CLEIA and reported that serum levels of this caspase-derived protein were significantly associated with hepatocyte ballooning, thus assisting in the accurate diagnosis of nonalcoholic steatohepatitis (NASH). We aim to investigate serum fCK18 levels in a variety of chronic liver diseases and to explore its potential as a prognostic marker of survival in hepatocellular carcinoma (HCC) patients.MethodsSerum fCK18 levels were measured using a highly sensitive CLEIA in 497 chronic liver disease patients (297 outpatients and 200 hospitalized with HCC).ResultsIn 497 chronic liver disease patients, serum fCK18 levels were significantly correlated with overall liver condition, including ALT, FIB-4 index and albumin-bilirubin (ALBI) score and were significantly increased in patients with HCC. In 200 HCC patients, serum fCK18 levels were significantly correlated with alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), and were significantly associated with HCC stage, whereas FIB-4 index and ALBI score were not changed based on HCC stage. The Survival group had significantly lower levels of serum fCK18, AFP, DCP, FIB-4 index and ALBI score. A ROC analysis yield area under the curve (AUC) value of 0.728 for serum fCK18 is a significantly high value when compared to AUC measurements for other factors. Notably, AUROC values for serum fCK18 levels were constant in the short- and long-term by time-dependent ROC analysis for the prediction of HCC patient survival. HCC patients with serum fCK18 measured at < 1.15 ng/mL, AFP < 7.7 ng/mL, DCP < 133 mAU/mL, ALBI score < -2.97 or FIB-4 index < 6.4 had significantly longer rates of survival when compared to patients with values exceeding these thresholds. Serum fCK18 (HR, 3.5; P < 0.0001), DCP (HR, 3.2; P < 0.0001) and Barcelona Clinic Liver Cancer (BCLC) (HR, 2.4; P = 0.001) values were independent predictors of patient survival. [Conclusion] Serum fCK18 levels reflect overall liver function, the level of liver fibrosis and the progression of HCC, and are a potential predictor of survival in HCC patients.

Progression of AFP SCORE is a Preoperative Predictive Factor of Microvascular Invasion in Selected Patients Meeting Liver Transplantation Criteria for Hepatocellular Carcinoma.

Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study's aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35-49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2-11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI.

The Toronto Postliver Transplantation Hepatocellular Carcinoma Recurrence Calculator: A Machine Learning Approach.

Liver transplantation (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate posttransplantation HCC recurrence prediction calculator. Patients with HCC listed for LT from 2000 to 2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and posttransplantation outcomes. We compared the CoxNet (regularized Cox regression), survival random forest, survival support vector machine, and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it with other currently available recurrence risk algorithms on a held-out test set (AFP, Model of Recurrence After Liver Transplant [MORAL], and Hazard Associated with liver Transplantation for Hepatocellular Carcinoma [HALT-HCC score]). The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% confidence interval [CI], 0.64-0.84). In comparison, the recalibrated risk algorithms' concordance scores were as follows: AFP score 0.64 (outperformed by the CoxNet model, 1-sided 95% CI, >0.01; P=0.04) and MORAL score 0.64 (outperformed by the CoxNet model 1-sided 95% CI, >0.02; P=0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI, 0.63-0.81) and was not significantly outperformed (1-sided 95% CI, ≥0.05; P=0.29). Developing a comprehensive posttransplantation HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting.

Validation of an alpha-fetoprotein model to predict recurrence after liver resection for hepatocellular carcinoma.

To validate a previously reported alpha-fetoprotein (AFP) model (including three variables: preoperative image-diagnosed tumor number and size and AFP level) for the prediction of recurrence in hepatocellular carcinoma (HCC) patients who have undergone liver resection (LR). This retrospective study enrolled patients who underwent curative LR for newly diagnosed HCC in our institution between 2011 and 2018. The probabilities of overall survival (OS) and recurrence were compared according to the aforementioned AFP model. A total of 838 patients were included. AFP score ≥ 3 versus ≤ 2 independently predicted recurrence and OS. However, net reclassification improvements (NRI) indicated that the AFP model was not superior to the Barcelona Clinic Liver Cancer (BCLC) system for predicting 1-year recurrence (p = 0.746). Relatedly, we developed a modified AFP model based on our cohort. The modified AFP score ≥ 3 versus ≤ 2 independently predicted recurrence and OS. However, NRI again indicated that the modified AFP model was not superior to the BCLC system for predicting 1-year recurrence (p = 0.69). Patients with a modified AFP score ≤ 2 had a risk of recurrence similar to that of patients with a modified AFP score ≥ 3 in BCLC stage 0-A (p = 0.57). However, patients with a modified AFP score ≤ 2 had a lower risk of recurrence than patients with a modified AFP score ≥ 3 in BCLC stage B-C (p = 0.02). The original AFP model was not feasible in our cohort. However, the modified AFP model may be useful for predicting recurrence in BCLC B-C patients who underwent LR in our cohort.

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein improves diagnostic accuracy for hepatocellular carcinoma.

BACKGROUNDDiagnostic accuracy of various tumor markers and their combinations for hepatocellular carcinoma (HCC) was not fully investigated.AIMTo evaluate the diagnostic accuracy of alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) and their combination for HCC diagnosis.METHODSPatients with newly detected liver mass or elevated serum AFP levels were considered eligible. Serum AFP level, AFP-L3 fraction, and PIVKA-II level were measured at the first visit.RESULTSIn total, 622 patients were included; 355 patients (57.1%) had chronic liver disease, and 208 (33.4%) had liver cirrhosis. HCC was diagnosed in 160 patients (25.7%). The area under the receiver operating characteristics curves (AUROCs) of the serum AFP, AFP-L3 fraction, AFP-L3, and PIVKA-II levels for the diagnosis of HCC were 0.775, 0.792, 0.814, and 0.834, respectively. A novel diagnostic model was developed by classifying patients in a 1:1 ratio into training and validation sets. Using the binary regression analysis of the training cohort, the AFP, AFP-L3 fraction, and PIVKA-II (ALPs) score was calculated as follows: ALPs score = 3.8 × [serum AFP level (ng/mL) × AFP-L3 fraction (%) × 0.01] + 0.2 × PIVKA-II level (mAU/mL). The AUROC of the ALPs score for diagnosis of HCC was 0.878, significantly higher than that of serum AFP level (P < 0.001), AFP-L3 fraction (P < 0.001), PIVKA-II level (P = 0.036), and AFP-L3 level (P = 0.006). The optimal ALPs score cut-off was 5.3 (sensitivity, 85.0%, specificity 80.1%). The validation cohort showed similar results.CONCLUSIONThe ALPs score calculated using serum AFP level, AFP-L3 fraction, and PIVKA-II level showed improved accuracy in HCC diagnosis.

Evaluation of the Alpha-Fetoprotein Model for Predicting Recurrence and Survival in Patients With Hepatitis B Virus (HBV)-Related Cirrhosis Who Received Liver Transplantation for Hepatocellular Carcinoma.

Introduction: The alpha-fetoprotein (AFP) model is superior to the Milan criteria in predicting the recurrence of hepatocellular carcinoma (HCC) after liver transplantation in European and Latin American populations. The purpose of this study was to determine the predictive value of the AFP model in Chinese hepatitis B virus (HBV)–related cirrhosis HCC patients.Methods: A total of 189 patients with HBV-related cirrhotic HCC were included. The recurrence rate and survival rate were estimated, and predictability was assessed by the Net Reclassification Improvement (NRI) method.Results: Of the 189 patients, patients with an AFP score >2 had a higher recurrence rate at 5 years (48.94 vs. 13.53%, p < 0.05) and lower survival rate (43.96 vs. 68.97%, p < 0.05). Considering patients within the Milan criteria, a higher 5-year recurrence rate and lower survival rate were observed in patients with an AFP model score >2 points compared to patients with a score of ≤ 2 points (recurrence rate: 58.75 vs. 12.98%, p < 0.05; survival rate: 28.57 vs. 67.41%, p = 0.047). NRI analysis showed that the AFP model exhibited superior predictability as compared to the Milan criteria.Conclusions: The AFP model may be used as a selection tool for Chinese HBV patients who require liver transplantation due to HCC.

Effect of sofosbuvir plus daclatasvir on virological response and liver function tests as a line of treatment for HCV related cirrhosis (a prospective cohort study)

BackgroundPatients with chronic HCV infection are the most in need for antiviral treatment. However, patients with cirrhosis exhibit difficulty with direct antiviral agents (DAA) treatment. We intended to evaluate the virological response of DAA in HCV-related cirrhosis treatment as well as its effect on liver function tests and other laboratory tests. Our study was a prospective cohort study of 240 patients with HCV-related liver cirrhosis. Those patients were consecutively selected from Gastroenterology and Hepatology out-patient clinic at Aswan University Hospital. They were subjected to the DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg).ResultsThe study showed a rapid decrease in HCV viral load; HCV RNA was undetectable in 65% of patients on 4th week of treatment and in 88.3% of patients on 8th week of treatment. It was undetectable in 100% of patients on 12th week of treatment and remained unchanged until therapy was completed (24 weeks). The SVR (sustained virological response) was 96.3%. Other laboratory tests demonstrated that serum level of alanine aminotransferase (ALT) decreased rapidly to normal limits on 4th week of treatment and remained within normal range until 12th week post-treatment. Significant improvements in serum albumin, total bilirubin, INR, and alpha-fetoprotein (AFP) levels were observed during and after treatment. Child-Pugh score showed a significant improvement post-treatment. We also observed a significant improvement in platelet count during and after treatment.ConclusionThe DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg) for treatment of HCV-related liver cirrhosis can achieve satisfactory virological response (SVR more than 96%). It can lead to improvement of serum ALT, serum albumin, total bilirubin, INR, AFP, and Child-Pugh score and also increase in platelet count after treatment.

Socioeconomic Deprivation Does Not Impact Liver Transplantation Outcome for HCC: A Survival Analysis From a National Database.

To investigate the value of European deprivation index (EDI) and hepatocellular carcinoma (HCC) characteristics and their relationships with outcome after liver transplantation (LT). Patients undergoing LT for HCC were included from a national database (from "Agence de la Biomédecine" between 2006 and 2016. Characteristics of the patients were blindly extracted from the database. Thus, EDI was calculated in 5 quintiles and prognosis factors of survival were determined according to a Cox model. Among the 3865 included patients, 33.9% were in the fifth quintile (quintile 1, N = 562 [14.5%]; quintile 2, N = 647 [16.7%]; quintile 3, N = 654 [16.9%]; quintile 4, N = 688 [17.8%]). Patients in each quintile were comparable regarding HCC history, especially median size of HCC, number of nodules of HCC and alpha-fetoprotein score. In the univariate analysis of the crude survival, having >2 nodules of HCC before LT and time on waiting list were associated with a higher risk of death (P < 0.0001 and P = 0.03, respectively). EDI, size of HCC, model for end-stage liver disease score, Child-Pugh score were not statistically significant in the crude and net survival. In both survival, time on waiting list and number of HCC ≥2 were independent factor of mortality after LT for HCC (P = 0.009 and 0.001, respectively, and P = 0.03 and 0.02, respectively). EDI does not impact overall survival after LT for HCC. Number of HCC and time on waiting list are independent prognostic factors of survival after LT for HCC.

A scoring model combining serum alpha-fetoprotein and tumor size and number predicts prognosis in hepatitis B virus-related hepatocellular carcinoma patients after curative hepatectomy.

BackgroundMore in-depth models, such as biomarker and anatomical information, are needed to predict individualized prognoses of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative liver resection. alpha-fetoprotein (AFP) has conflicting value in predicting prognosis. We aimed to investigate the significance of an AFP score model as a potential predictor of prognosis after radical resection in patients with HBV-related HCC.MethodsThis study retrospectively analyzed 397 patients with HBV-related HCC who underwent hepatic resection between 2001 and 2013. Serum AFP level, tumor size, and tumor number were calculated by adding individual points for the AFP score model. Patient and tumor characteristics were tested for prognostic significance using ANOVA and chi-squared test, respectively. The receiver operating characteristic (ROC) curve was used to identify the AFP score model with or without other risk factors to discriminate patients. Kaplan-Meier and Cox’s analyses were performed to pinpoint risk factors for overall survival (OS) and disease-free survival (DFS) in the patients.ResultsThe cutoff value for the AFP score model was set at 2 using the ROC curve, with good specificity and sensitivity for OS and DFS. According to the AFP score model, 185 patients were in the AFP score >2 group, and 212 were in the AFP score ≤2 group. The median OS in the AFP score ≤2 and AFP score >2 groups were 173.4±1.00 vs. 50.30±8.67 m, respectively (P=0.000). The median DFS in the AFP score ≤2 and AFP score >2 groups were 17.20±3.66 vs. 73.7±10.39 m (P=0.000), respectively. Analyses from Cox’s multivariate proportional hazard model indicated that AFP score (HR =0.563, 95% CI: 0.398–0.798, P=0.001), MVI (HR =0.653, 95% CI: 0.441–0.967, P=0.033), and cirrhosis (HR =0.358, 95% CI: 0.185–0.696, P=0.002) were risk factors for OS. The multivariate Cox model identified MVI (HR =1.589, 95% CI: 1.496–2.854, P=0.003) and AFP score (HR =0.876, 95% CI: 0.404–0.925, P=0.040) as risk factors of DFS. According to the stratification by the AFP score with MVI, the mean OS in the AFP score >2 group combined with the MVI group was significantly shorter, compared with that in the AFP score >2 group without the MVI group (65.58±9.18 vs. 94.21±8.25 m, P=0.024). The mean OS in the AFP score >2 group combined with the cirrhosis group is significantly shorter than that in the AFP score ≤2 group without the cirrhosis group (64.08±7.38 vs. 145.31±8.38 m, P=0.000).ConclusionsThe AFP score model categorizes HCC patients with relatively good liver function after radical resection with low- and high-risk prognosis.

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method. Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients. The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV.

THU-039 - Prognosis Value of Skeletal Muscle Index and Alpha Fetoprotein Score in Patients Treated by Trans-Arterial Chemoembolization

THU-039 - Prognosis Value of Skeletal Muscle Index and Alpha Fetoprotein Score in Patients Treated by Trans-Arterial Chemoembolization

The role of chemokine CC ligand 20 in patients with liver cirrhosis and hepatocellular carcinoma

To evaluate the role of chemokine CC ligand 20 (CCL20) as a biomarker for hepatocellular carcinoma (HCC). Ninety patients in four groups were enrolled in this prospective cross-sectional study: 30 with HCC (group I), 30 with liver cirrhosis (group II), 15 with hepatitis C virus infection (group III), and 15 healthy blood donors as controls. Alpha fetoprotein (AFP), CCL20 and vascular endothelial growth factor (VEGF) were measured in all groups. Serum levels of CCL20 were significantly different among the study groups (F=230.979, p<0.001). The highest level was found in HCC patients (57.305 ± 6.386 pg/mL) followed by patients with cirrhosis (45.999 ± 5.165 pg/mL) compared with 22.781 ± 5.986 pg/mL and 18.585 ± 3.554 pg/mL in asymptomatic patients with HCV infection and controls, respectively. In HCC patients, CCL20 significantly correlated with VEGF (r=0.559, p=0.001), AFP (r=0.814, p<0.001), Child score (r=0.748, p<0.001), and tumor size (r=0.825, p<0.001). The cutoff value of CCL20 for the detection of HCC in HCV-infected patients was 54 pg/mL with 93.1% accuracy, 89.6% negative predictive value, 92.6% positive predictive value, 83.3% sensitivity, and 93.3% specificity. In patients with cirrhosis, CCL20 significantly correlated with VEGF (r=0.455, p=0.011), AFP (r=0.975, p<0.001), and Child score (r=0.977, p<0.001). CCL20 may be used for the detection of HCC in HCV-infected patients with comparable specificity and higher sensitivity than AFP.