AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND & AIMS: Alpha-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. METHODS: This 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. RESULTS: This 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 <0.001). CONCLUSIONS: Dual-positivity for AFP-L3 ≥15% and DCP ≥7.5 strongly predicted post-LT HCC recurrence. This model could refine LT selection criteria and identify high-risk patients who require additional locoregional therapy prior to LT. IMPACT AND IMPLICATIONS: Alpha-fetoprotein (AFP) is used to predict hepatocellular carcinoma (HCC) recurrence after liver transplant, but it remains an imperfect biomarker. In this prospective study, the biomarkers DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) strongly predicted early HCC recurrence and outperformed AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted the majority of recurrences and could be used to further refine liver transplant eligibility criteria.

Chinese expert consensus statement on the clinical application of AFP/AFP-L3%/DCP using GALAD and GALAD-like algorithm in HCC.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most prevalent world-wide malignancies. Half of the newly developed HCC occurs in China. Optimizing the strategies for high-risk surveillance and early diagnosis are pivotal for improving 5-year survival. Constructing the scientific non-invasive detection technologies feasible for medical and healthcare institutions is among the key routes for elevating the efficacies of HCC identification and follow-up. RESULTS: Based on the Chinese and international guidelines, expert consensus statements, literatures and evidence-based clinical practice experiences, this consensus statement puts forward the clinical implications, application subjects, detection techniques and results interpretations of the triple-biomarker (AFP, AFP-L3%, DCP) based GALAD, GALAD like models for liver cancer. CONCLUSIONS: The compile of this consensus statement aims to address and push the reasonable application of the triple-biomarker (AFP, AFP-L3%, DCP) detections thus to maximize the clinical benefits and help improving the high risk surveillance, early diagnosis and prognosis of HCC.

Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) predicts complete responses of transarterial chemoembolization for hepatocellular carcinoma.

BACKGROUND/PURPOSE: Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is a diagnostic marker for hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the standard management for intermediate stage HCC but lacks effective response predictors. We investigated the utility of PIVKA-II as a predictor of TACE response. METHODS: This prospective study included consecutive patients with HCC undergoing TACE in Taiwan. Serum PIVKA-II levels were measured before and serially after TACE. Multivariable analyses were conducted to evaluate predictors of mortality, complete responses (CR) to TACE and unTACEable progression. RESULTS: We included 46 patients with HCC (median age: 64 years, men:72%), and Barcelona Clinic Liver Cancer (BCLC) stages A (17%), B (65%), or C (17%). Before TACE, the median PIVKA-II level was 189 mAU/mL. After a median follow-up of 16 months, 27 (59%) patients died. PIVKA-II was positively correlated with tumor burden. Patients with infiltrative HCC or HCC exceeding the up-to-7 criteria had significantly higher baseline PIVKA-II levels than those without. Multivariable analysis indicated the infiltrative HCC independently predicted mortality. In patients BCLC A and B (n = 38), low baseline PIVKA-II (<26 mAU/mL) predicted CR to TACE, whereas high PIVKA-II predicted unTACEable tumor progression. Observations from a validation cohort corroborated the initial result that low PIVKA-II predicts CR. Moreover, serial PIVKA-II levels post TACE were significantly lower in patients with a CR to TACE compared with those without. CONCLUSION: Low baseline PIVKA-II level helps to predict a CR of TACE in patients with HCC.

Validation of a novel model for the early detection of hepatocellular carcinoma.

BACKGROUND: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. METHODS: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. RESULTS: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95% CI 0.93-0.98), with a sensitivity of 93% and a specificity of 84% in the development cohort, and an AUC of 0.87 (95% CI 0.85-0.90), sensitivity of 74%, and specificity of 85% in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95% CI 0.81-0.88), sensitivity was 70%, and specificity was 86%. CONCLUSIONS: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.

Highly sensitive alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxyprothrombin for hepatocellular carcinoma detection.

AIM: Hepatocellular carcinoma (HCC) develops with high incidence in patients with chronic liver disease (CLD), and particularly in those with cirrhosis. Currently, diagnosis and surveillance are mainly based on imaging methods. The aim of this study was to evaluate the diagnostic accuracy of highly sensitive measurement of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxyprothrombin (DCP) alone and in combination, for HCC detection. In addition, a recently proposed statistical model, including these three biomarkers plus sex and age, the GALAD model, was applied. METHODS: In a total of 98 patients (44 CLD patients without HCC [23 men, 21 women; mean age, 53.2 ± 13.4 years] and 54 patients with HCC [45 men, nine women; 69.5 ± 9.8 years]), AFP, AFP-L3 and DCP levels were determined using a highly sensitive assay on an µTASWako i30 immuno-analyzer. Areas under the curve (AUC), sensitivity and specificity were calculated and compared to assess diagnostic performance of the HCC biomarkers and of the GALAD model. RESULTS: AFP, AFP-L3 and DCP serum levels were significantly elevated in HCC compared with CLD patients (P < 0.0001). AUC values were 0.891, 0.867 and 0.870, respectively. The combination of the three biomarkers resulted in an AUC of 0.947, whereas the GALAD model showed an AUC of 0.976 with a difference between AUC values of 0.029 (P = 0.028). CONCLUSION: The combination of AFP, AFP-L3 and DCP is superior to a single biomarker in HCC detection. Furthermore, GALAD model performance is significantly higher than simple combination of these three biomarkers.

Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma.

Tumor markers [alpha-fetoprotein (AFP) or des-gamma-carboxyprothrombin (DCP)] and neutrophil/lymphocyte ratio (NLR) reportedly correlate with long-term outcomes for hepatocellular carcinoma (HCC). However, no standardized method has been established for evaluating the pretransplant data. One hundred and twenty-four patients who underwent living donor liver transplantation (LDLT) were retrospectively reviewed. The best predictive parameters for tumor recurrence were maximum values for AFP or DCP and 90-day mean values for NLR, respectively, and multivariate analysis confirmed these values were correlated with tumor recurrence. However, receiver operating characteristic analysis revealed that discriminative powers were sufficient only in maximum AFP [area under the curve (AUC) 0.88, P < 0.001] and maximum DCP (AUC 0.76, P < 0.001), while mean NLR was less predictive (AUC 0.62, P = 0.20). When incorporating AFP and DCP to the Tokyo criteria (≤5 tumors with each tumor ≤ 5 cm), the presence of at least two of the following factors: (i) beyond the Tokyo criteria, (ii) AFP>250 ng/ml, and (iii) DCP > 450 mAu/ml (>450 ng/ml), was correlated with a worse 5-year disease-free survival rate (20.0% vs. 96.8%, P < 0.001) and 5-year overall survival rate (20.0% vs. 84.0%, P < 0.001). The prognosis of patients undergoing LDLT for HCC strongly relies on maximum AFP or DCP values before transplantation, while the prognostic impact of NLR is limited.

Development and Validation of a Prognostic Nomogram for Patients with AFP and DCP Double-Negative Hepatocellular Carcinoma After Local Ablation.

Purpose: Although alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) have a certain predictive ability for the prognosis of hepatocellular carcinoma (HCC), there are still some cases of aggressive recurrence among patients with AFP and DCP double-negative HCC (DNHC) after local ablation. However, prediction models to forecast the prognosis of DNHC patients are still lacking. Thus, this retrospective study aims to explore the prognostic factors in DNHC patients and develop a nomogram to predict recurrence. Patients and methods: 493 DNHC patients who underwent the local ablation at Beijing You'an Hospital between January 1, 2014, and December 31, 2022, were enrolled. A part that was admitted from January 1, 2014, to December 31, 2018, was designated to the training cohort (n = 307); others from January 1, 2019, to December 31, 2022, were allocated to the validation cohort (n = 186). Lasso regression and Cox regression were employed with the aim of screening risk factors and developing the nomogram. The nomogram outcome was assessed by discrimination, calibration, and decision curve analysis (DCA). Results: Independent prognostic factors selected by Lasso-Cox analysis included age, tumor size, tumor number, and gamma-glutamyl transferase. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training and validation groups (0.738, 0.742, 0.836, and 0.758, 0.821) exhibited the excellent predicted outcome of the nomogram. Calibration plots and DCA plots suggest desirable calibration performance and clinical utility. Patients were stratified into three risk groups by means of the nomogram: low-risk, intermediate-risk, and high-risk, respectively. There exists an obvious distinction in recurrence-free survival (RFS) among three groups (p<0.0001). Conclusion: In conclusion, we established and validated a nomogram for DNHC patients who received local ablation. The nomogram showed excellent predictive power for the recurrence of HCC and could contribute to guiding clinical decisions.

The Characteristics and Prognosis of Alpha-Fetoprotein and Des-Gamma-Carboxy Prothrombin Double-Negative Hepatocellular Carcinoma at Baseline in Higher BCLC Stages.

Alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) are widely used as tumor markers to diagnose hepatocellular carcinoma (HCC). Some advanced HCCs demonstrate neither AFP nor DCP. This study investigated the characteristics and prognosis of AFP (<20 ng/mL) and DCP (<40 mAU/ml) double-negative HCC (DNHC) in higher-stage HCC. Between April 2012 and March 2022, 419 consecutive patients were enrolled with newly diagnosed HCC and 372 patients were selected that were diagnosed by histopathology and/or imaging. AFP-negative, DCP-negative, and double-negative HCC were identified in 262 patients (70.4%), 143 patients (38.2%), and 120 patients (32.3%), respectively. In higher-BCLC stages (BCLC-B, C, and D), 17 patients (14.7%) were DNHC. Although there was no difference in BCLC staging, there were more cases under TNM Stage III in DNHC (71.0% vs. 41.4%, p = 0.026). The median maximum tumor diameter was smaller in DNHC [3.2 (1.8−5.0) vs. 5.5 (3.5−9.0) cm, p = 0.001] and their median survival time was significantly better, even in higher-stage HCC [47.0 (24.0−84.0) vs. 19.0 (14.0−30.0) months, p = 0.027). DNHC in higher-BCLC stage HCC is independent of BCLC staging, characterized by a tumor diameter < 5 cm, and is treatable with a good prognosis.

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Purpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Common Sensitive Diagnostic and Prognostic Markers in Hepatocellular Carcinoma and Their Clinical Significance: A Review.

Liver cancer is one of the most serious cancers that lead to death around the world. In Saudi Arabia, it represents 4.1% of all diagnosed cancers in 2020. The total survival rate for all stages of liver cancer is 15% at five years after diagnosis, and this can be affected by the available therapy. Hepatocellular carcinoma (HCC) is known to be the most prevalent primary malignant tumor of the liver, and several studies have been conducted to improve the management approach in the early and late stages. Biomarkers are a useful tool for early diagnosis, disease progression, prognosis, and targeted therapy for patients with liver cancer. The most important biomarker that has been studied is alpha-fetoprotein (AFP), which is elevated in 70% of patients with liver cancer. Also, des-gamma-carboxyprothrombin (DCP) is a more specific biomarker in HCC compared to AFP as it is elevated in HCC, which can be elevated in several conditions that cause active hepatitis. In addition, squamous cell carcinoma antigen (SCCA) and Golgi protein 73 (GP73) have high sensitivity compared to AFP and DCP but poor specificity. All of these markers are useful in the diagnosis, management, and prognosis prediction of liver cancer, especially the combination of AFP and DCP.

Liver Tumor Markers, HALP Score, and NLR: Simple, Cost-Effective, Easily Accessible Indexes for Predicting Prognosis in ICC Patients after Surgery.

INTRODUCTION: To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619). CONCLUSIONS: Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.

Diagnostic value of alpha-fetoprotein, Lens culinaris agglutinin-reactive alpha-fetoprotein, and des-gamma-carboxyprothrombin in hepatitis B virus-related hepatocellular carcinoma.

OBJECTIVE: This study aimed to explore the use of different combinations of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) for the early diagnosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). METHODS: There were 167 subjects, including 100 with HCC and 67 with LC, who were enrolled into this study. Serum AFP, AFP-L3, and DCP levels were detected by chemiluminescent enzyme immunoassay and analyzed using the receiver operating characteristics (ROC) method. RESULTS: The sensitivity and specificity of AFP and DCP for differentiating between early HCC and HBV-associated LC were 51.5% and 92.5%, and 60.0% and 84.7%, respectively. Comparative analysis of ROC curves showed no significant difference in the area under the curve (AUC) for AFP and DCP. Moreover, the combination of AFP and DCP showed the largest AUC value with a diagnostic sensitivity and specificity of 67% and 83.1%, respectively. CONCLUSION: These results suggest that AFP is the best single biomarker for distinguishing between HBV-associated LC and early HCC induced by HBV. However, the combination of AFP and DCP can enhance the diagnostic value of AFP for differentiating between these diseases.

Evaluation of serum AFP and DCP levels in the diagnosis of early-stage HBV-related HCC under different backgrounds.

OBJECTIVE: This study compared the diagnostic performance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in early-stage hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) under different backgrounds. METHODS: Patients were enrolled and divided in four groups: chronic HBV infection (CHB), liver cirrhosis (LC), early-stage CHB-HCC, and early-stage LC-HCC. Serum AFP and DCP levels were measured. Receiver-operating characteristic (ROC) curve and area under the curve (AUC) analyses were applied to compare the diagnostic performance of DCP and AFP for HCC. RESULTS: In total, 200 patients were enrolled, including 48, 64, 33, and 55 patients with CHB, LC, CHB-HCC, and LC-HCC, respectively. ROC curve analysis revealed that the AUCs of AFP, DCP, and their combination in differentiating early-stage LC-HCC from LC were 0.776, 0.758, and 0.786, respectively. The values of these markers in discriminating early-stage CHB-HCC from CHB were 0.828, 0.731, and 0.862, respectively. CONCLUSIONS: DCP was inferior to AFP in differentiating early-stage CHB-HCC from CHB. However, AFP and DCP displayed similar performance in distinguishing early-stage LC-HCC and LC.

Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models.

AIM: To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma (HCC) patients after liver transplant. METHODS: BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios (HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS: During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42 (1.18-5.00), 1.86 (0.98-3.52), and 2.83 (1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48 (1.15-1.91) and 1.59 (1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45 (1.06-1.98) and 1.38 (1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65, 0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant (S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION: BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter (S-LAD).

Combining des-gamma-carboxyprothrombin and alpha-fetoprotein for hepatocellular carcinoma diagnosing: an update meta-analysis and validation study.

Controversies about the combination of des-gamma-carboxyprothrombin (DCP) and alpha-fetoprotein (AFP) for hepatocellular carcinoma diagnosing still exist. Hence, we performed this updated meta-analysis to estimate the diagnostic value of DCP , AFP and DCP + AFP in HCC. In addition, we conducted a validation study to analyze the performance of the candidate makers. After a systematic literature review, 27 studies from 20 articles were identified from four major databases. The pooled sensitivity and specificity were 69% and 89%, respectively, for DCP; for AFP, they were 65% and 88%, respectively; and they were 82% and 85%, respectively, for DCP + AFP. The values of the area under the curve (AUC) for DCP, AFP, DCP + AFP, respectively, were 0.88, 0.75, and 0.90. The validation study confirmed that the performance of DCP + AFP (sensitivity = 84%, specificity = 86%; AUC = 0.887) was higher than that of DCP (sensitivity = 76%, specificity = 92%; AUC = 0.843) or AFP (sensitivity = 73%, specificity = 92%; AUC = 0.837) alone.