Combined use of AFP,PIVKA-II,and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients

Objective: As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3). Material and methods: This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence. Results: Most patients were men (n?=?431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n?=?467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728–0.801) for AFP; 0.823 (95% CI, 0.791–0.854) for PIVKA-II; and 0.755 (95% CI, 0.718–0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691–0.816) for AFP, 0.701 (95% CI, 0.630–0.771) for PIVKA-II, and 0.670 (95% CI, 0.596–0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851–0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704–0.841) for early HCC diagnosis. Conclusion: Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.     

Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. RESULTS: Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. CONCLUSIONS: Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.     

AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC

Background

Alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxy prothrombin (DCP), and Golgi protein-73 (GP73) have been used or proposed as tumor markers for hepatocellular carcinoma (HCC).

Methods

They were measured in 96 patients undergoing hepatectomy for HCC to investigate their treatment response and association with variables linked with tumor invasiveness and/or prognosis. Values at 1 month post-surgery in the 77 patients without recurrence within 6 postoperative months were adopted as those after surgery.

Results

GP73 levels did not change after hepatectomy, but levels of other markers decreased and areas under receiver operating characteristic curves (95% CI) were: 0.64 (0.56–0.72), 0.63 (0.55–0.71), 0.79 (0.73–0.86), and 0.63 (0.55–0.71) for AFP, AFP-L3, DCP, and combination of AFP and AFP-L3, respectively. Cutoff points giving specificities of 96.1% (sensitivities at these points) were: 124 ng/mL (28.1%), 10% (21.9%), and 60 mAU/mL (52.1%), for AFP, AFP-L3, and DCP, respectively. The combination of AFP and AFP-L3 provided a sensitivity of 26.0% at a specificity of 96.1%. The increased DCP value was, or tended to be, associated with a larger tumor, vascular invasion, intrahepatic metastases, and a lower grade of tumor cell differentiation. Although similar associations were found between AFP and vascular invasion as well as a lower grade of tumor cell differentiation, no such relationship was found with AFP-L3.

Conclusions

DCP is a more effective tumor marker than AFP and AFP-L3. AFP-L3 showed comparable accuracy to AFP but no benefit was found in their combination. GP73 did not play a significant role in this context. Indices of tumor invasiveness were most closely associated with DCP.     

Clinical Evaluation of Lens Culinaris Agglutinin-Reactive α-Fetoprotein and Des-γ-Carboxy Prothrombin in Histologically Proven Hepatocellular Carcinoma in the United States

There is no established clinical role for the lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) and des-γ-carboxy prothrombin (DCP) in the management of the U.S. hepatocellular carcinoma (HCC) patient population. In order to clarify the clinical usefulness and characteristics of AFP-L3% and DCP, a prospective study was performed on United States patients having histologically proven hepatocellular carcinoma. Ninety-nine histologically proven HCC patients, who were diagnosed with unresectable cancer between July 1999 and March 2001 at the Liver Cancer Center of the University of Pittsburgh Medical Center, were included for analysis. The sensitivity of AFP-L3%, DCP, and AFP was 61.6%, 72.7%, and 67.7%, respectively. The highest sensitivity, 85.9%, was obtained in the combination of three markers. Statistically significant differences were observed for portal vein invasion in AFP-L3% and AFP levels (P=0.0059 and P=0.0360, respectively). DCP was significantly associated with metastasis (P=0.0368). There were significant associations between AFP-L3% and AFP results and patient survival (P=0.0150 and P=0.0020, respectively). AFP-L3%, platelet count,and albumin showed a significant difference with respect to outcomes on Cox’s proportional hazard model (P=0.0059, P=0.0073, and P=0.0265, respectively). The combination of AFP-L3%, DCP, and AFP was determined to be superior for detection of HCC compared with each marker alone or to other combinations. AFP-L3% was significantly related to portal vein invasion and patient outcomes and appears to be a useful prognostic marker for HCC.     

经导管肝动脉化疗栓塞术治疗肝细胞癌疗效及复发预测

目的 探讨肝细胞癌(HCC)患者经导管肝动脉化疗栓塞术(TACE)前、术后脱γ-羧基凝血酶原(DCP)、甲胎蛋白异质体(AFP-L3)、甲胎蛋白(AFP)的变化及其与预后关系.方法 纳入96例接受TACE作为初始治疗的HCC患者,分别于术前,术后4～5周及术后6～12个月检测血清DCP、AFP-L3、AFP等水平.根据...     

Serum des-gamma-carboxy prothrombin levels determined by a new generation of sensitive immunoassays in patients with small-sized hepatocellular carcinoma

OBJECTIVE: Des-gamma-carboxy prothrombin (DCP), also called protein induced by vitamin K absence or antagonist II (PIVKA-II), is a tumor marker complementary to AFP for the diagnosis of hepatocellular carcinoma (HCC). Currently available immunoassays for DCP are not sensitive enough to detect HCC at an early stage. Recently, two new immunoassays with enhanced sensitivity were developed. The aim of this study was to assess the diagnostic values of the new methods in patients with small-sized HCC. METHODS: Coded serum samples obtained from 36 patients with small-sized and single-nodular HCC (< or = 3 cm in diameter) and 49 patients with posthepatitic cirrhosis not carrying HCC were analyzed. DCP levels were determined in three different ways: 1) conventional EIA; 2) a new immunoassay using the electrochemiluminescence (ECLIA) detection system; and 3) a new immunoradiometric assay (IRMA). Lectin-reactive profiles of AFP (AFP-L3) were also determined. RESULTS: In 36 patients with small-sized HCC, the rates of abnormal values obtained by the conventional, ECLIA, and IRMA methods were 2.7%, 27.8%, and 16.7%, respectively. An ROC analysis of the two new methods (ECLIA vs IRMA) revealed a better performance by the ECLIA method (p < 0.05). The true positive rate of AFP-L3 was 22.2%, whereas a combination assay of ECLIA for DCP and AFP-L3 resulted in a 41.7% sensitivity with a specificity of 90%. CONCLUSIONS: Compared with the conventional method, the sensitivity in detecting small-sized HCC was increased in the two new DCP immunoassays (ECLIA and IRMA). The overall performance as evaluated by an ROC analysis was significantly better in ECLIA than in IRMA.     

Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus

Background  

Increases in tumor markers are sometimes seen in patients with chronic liver disease without hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between the levels of three tumor markers [alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3%), and des-γ-carboxy prothrombin (DCP)] and hepatic carcinogenesis to identify hepatitis C virus (HCV) carriers at high risk for cancer development.     

Tumor markers after radiofrequency ablation therapy for hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to evaluate the clinical value of measurement of the AFP-L3 fraction before and after radiofrequency ablation (RFA) therapy for HCC, compared with the measurement of total AFP and des-gamma-carboxy prothrombin (DCP). METHODOLOGY: One hundred and twenty-four patients with HCCs were evaluated for their complete response with a 5-mm-thick safety margin around the tumor. Three tumor markers (AFP, DCP, AFP-L3) were measured after RFA therapy, and their clinical significance was studied. RESULTS: Multivariate analysis revealed that of the three tumor makers only AFP-L3 showed significant differences in the survival and disease-free rates. CONCLUSIONS: AFP-L3 is the most reliable tumor marker for estimating overall survival and disease-free survival in patients with HCC effectively treated by RFA in contrast to AFP and DCP.     

Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers

Three tumor markers for hepatocellular carcinoma (HCC) are available in daily practice in Japan: alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). To elucidate the predictability of these tumor markers on HCC recurrence after curative ablation, we enrolled 416 consecutive patients with na?ve HCC who had been treated by percutaneous ablation at our department from July 1997 to December 2002. Tumor marker levels were determined immediately before and 2 months after the treatment. Complete ablation was defined on CT findings as nonenhancement in the entire lesion with a safety margin. Tumor recurrence was also defined as newly developed lesions on CT that showed hyperattenuation in the arterial phase with washout in the late phase. We assessed the predictability of recurrence via tumor markers in multivariate analysis, using proportional hazard regression after adjusting for other significant factors in univariate analysis. Until the end of follow-up, tumor recurrence was identified in 277 patients. Univariate analysis revealed the following factors to be significant for recurrence: platelet count; size and number of tumors; AFP, AFP-L3, and DCP preablation; and AFP and AFP-L3 postablation. Multivariate analysis indicated that AFP >100 ng/mL and AFP-L3 >15%, both pre- and postablation, were significant predictors. The positivity of AFP and AFP-L3 preablation that turned negative postablation was not significant. In conclusion, tumor markers pre- and post-ablation were significant predictors for HCC recurrence and can complement imaging modalities in the evaluation of treatment efficacy.     

Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size

OBJECTIVES: Serum levels of des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are known to be useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to examine the diagnostic efficacy of DCP and AFP in differentiating HCC from chronic liver diseases. METHODS: We examined 1,377 HCC patients and 355 patients with chronic hepatitis or cirrhosis (non-HCC) who visited our institute and affiliated hospitals between June 1997 and September 2003. RESULTS: The median values of DCP and AFP were 60 mAU/mL and 34 ng/mL in HCC patients, respectively, and 18 mAU/mL and 3 ng/mL in non-HCC patients, respectively. The areas under the receiver operating characteristic (ROC) curves of DCP and AFP were 0.812 and 0.887, respectively (p < 0.0001). The area under the DCP ROC curve was significantly smaller than that of AFP in tumors less than 3 cm in diameter (p < 0.0001). However, the ROC area of DCP was significantly larger than that of AFP in tumors greater than 5 cm in diameter (p < 0.0001). CONCLUSIONS: The utility of DCP for the diagnosis of HCC was lower than that of AFP for small tumors, but higher than that of AFP for large tumors.     

Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients

Mortality due to hepatocellular carcinoma (HCC) has not improved over the last 20 years. This is in part due to the poor performance of available tumor markers leading to delays in diagnosis. Des-gamma carboxy-prothrombin (DCP) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with alpha-fetoprotein (AFP). We conducted a cross-sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center. Four groups were studied: G1, normal healthy subjects; G2, patients with noncirrhotic chronic hepatitis; G3, patients with compensated cirrhosis; and G4, patients with histologically proven HCC. A total of 207 subjects were enrolled. Both DCP and AFP levels increased progressively from G1 to G4, but DCP values had less overlap among the groups than AFP. ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity (89%; 95% CI, 77%-95%) and specificity (95%; 95% CI, 82%-96%) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis. The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL, the area under the ROC curves being 0.928 versus 0.810, respectively (P =.002). In conclusion, DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease. Prospective studies to evaluate the role of DCP in early HCC are underway.     

Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des‐γ‐carboxyprothrombin (DCP), α‐fetoprotein (AFP) and AFP‐L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden. Methods: Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I–III on liver biopsy) and 49 with cirrhosis. Results: Levels of DCP, AFP and AFP L‐3 were significantly higher in patients with HCC than in those without HCC (P ≤ 0.0001). Receiver–operating curves (ROC) indicated that the cut‐off value with the best sensitivity and specificity for each test was ≥84 mAU/mL for DCP, ≥25 ng/mL for AFP and ≥10% for AFP‐L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP‐L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut‐off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis. Conclusion: DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection.     

Alpha-fetoprotein,protein induced by vitamin K absence or antagonist-II,lens culinaris agglutinin-reactive fraction of alpha-fetoprotein alone and in combination for early detection of hepatocellular carcinoma from nonalcoholic fatty liver disease: A multicenter analysis

BackgroundCurrent surveillance strategies for hepatocellular carcinoma (HCC) among patients with nonalcoholic fatty liver disease (NAFLD) are insufficient. This study aimed to investigate the diagnostic performance of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and their combinations in HCC underlying NAFLD patients.MethodsSerologic AFP, AFP-L3, and PIVKA-II levels in NAFLD patients with and without HCC were measured. By receiver operating characteristic (ROC) analyses, the area under the curve (AUC), sensitivity, and specificity were obtained to evaluate the diagnostic accuracy of each biomarker and their combinations.ResultsThis study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD controls. The elevation of these three biomarkers was observed in patients with NAFLD-HCC compared to those in NAFLD controls (all P < 0.001). When they were analyzed individually, PIVKA-II showed the best performance in diagnosing any-stage HCC with an AUC of 0.869, followed by AFP (0.763; vs. PIVKA-II, P < 0.001) and AFP-L3 (0.689; vs. PIVKA-II, P < 0.001). When they were analyzed in combination, AFP + PIVKA-II yielded the highest AUC (0.906), followed by AFP + PIVKA-II + AFP-L3 (0.904; vs. AFP + PIVKA-II, P = 0.086), PIVKA-II + AFP-L3 (0.881; vs. AFP + PIVKA-II, P < 0.001), and AFP + AFP-L3 (0.759; vs. AFP + PIVKA-II, P < 0.001). Similar findings were obtained in the subgroup with early-stage NAFLD-HCC, as well as the non-cirrhotic subgroup.ConclusionsThese data validated the better diagnostic ability of PIVKA-II than AFP or AFP-L3 alone for diagnosing any-stage HCC among patients with NAFLD, and the combination of AFP + PIVKA-II significantly improved the diagnostic accuracy of NAFLD-HCC.     

Clinicopathologic features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein-L3 and seronegative for des-gamma-carboxy prothrombin in comparison with those seropositive for des-gamma-carboxy prothrombin alone

BACKGROUND: There has been no study of the clinicopathologic features of patients with hepatocellular carcinoma (HCC) who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) alone, or seropositive for AFP-L3 and seronegative for des-gamma-carboxy prothrombin (DCP) in comparison with those who are seropositive for DCP alone. Thus, the present comparative study was performed. METHODS: The clinicopathologic features of HCC patients with either one or two tumors who underwent a hepatectomy (n = 88) were compared among the following five groups according to the seropositivity of AFP, AFP-L3 and DCP: (i) group A, seropositive for AFP above 100 ng/mL, AFP-L3 above 15% and DCP above 100 mAU/mL; (ii) group B, seropositive for AFP-L3 and seronegative for DCP below 40 mAU/mL; (iii) group C, seronegative for AFP below 20 ng/mL, AFP-L3 below 15% and seropositive for DCP; (iv) group D, seropositive for AFP and seronegative for AFP-L3 and DCP; and (v) group E, seronegative for AFP, AFP-L3 and DCP. RESULTS: Group B patients showed a higher incidence of infiltrative-type HCC with an irregular margin (P < 0.05) and a higher frequency of poorly differentiated HCC (P < 0.01) compared with group C patients. Group A patients had larger tumors and more massive-type tumors than group B patients. Our HCC cases showed that advanced clinicopathologic features were demonstrated in the order of group B, group C and group D. Group A and B patients and group D and E patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP-L3 and seronegative for DCP demonstrated clinicopathologic features of more advanced HCC compared with those who were seropositive for DCP alone.     

Usefulness of serum des-γ-carboxy prothrombin in detection of hepatocellular carcinoma

AIM: To evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity, and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77%, and 86.4% re 68.5%, 59%, and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P= 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.     

Diagnostic accuracy of des‐gamma‐carboxy prothrombin for hepatocellular carcinoma in a French cohort using the Lumipulse® G600 analyzer

The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des‐gamma‐carboxy prothrombin (DCP), in comparison with alpha‐fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty‐two patients with virus‐related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof‐of‐concept study. DCP was measured on new Lumipulse^® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow‐up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut‐off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut‐off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI_>0 for the association of “AFP+DCP” were 101%, P<.0001, and 23%, P=.03, compared to “AFP” or “DCP” alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC.     

Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC

BACKGROUND/AIMS: We evaluated the prognostic value of the pretreatment elevation of tumor markers for hepatocellular carcinoma (HCC) in patients who underwent curative treatment. METHODS: We studied 801 patients who had been diagnosed as initial HCC and fulfilled the following criteria: maximum tumor size, < or = 3 cm; number of tumors, < or = 3; remnant liver function, Child-Pugh class A or B; treated by hepatectomy or locoregional thermal ablation (LTA); and alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma carboxy prothrombin (DCP) were measured at diagnosis. We analyzed the effects of elevated tumor markers on patient survival in these 2 distinct groups with different types of treatment, i.e. hepatectomy and LTA. RESULTS: By multivariate analysis in 345 patients who underwent hepatectomy, no tumor marker significantly affected decreased survival rate. In the 456 patients who underwent LTA, the elevation of AFP-L3 (p=0.0171) and DCP (p=0.0004) significantly affected decreased survival rate; DCP elevation had the strongest effect on patient survival. CONCLUSIONS: The prognostic value of pretreatment tumor marker elevation was different in patients who underwent the curative treatment according to the type of treatment. Pretreatment elevation of AFP-L3 and DCP had prognostic values only in patients treated with LTA.     

Usefulness of serum des-γ-carboxy prothrombin in detection of hepatocellular carcinoma

AIM: Des-gamma-carboxy prothrombin (DCP) has been reported to be more sensitive and specific in diagnosing hepatocellular carcinoma (HCC) when compared with alpha-fetoprotein (AFP). However, its ability to identify small HCC still remains unclear. Thus, we conducted a cross-sectional case control study to evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77% and 86.4% vs 68.5%, 59% and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.     

Usefulness of serum des-γ-carboxy prothrombin in detection of hepatocellular carcinoma

AIM: To evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC.METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with noncirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL,respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay.RESULTS: The accuracy, sensitivity, and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77%,and 86.4% vs 68.5%, 59%, and 77.3%, respectively).The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CT, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81],P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%,and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm.CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.     

Staging hepatocellular carcinoma by a novel scoring system (BALAD score) based on serum markers.

BACKGROUND & AIMS: Previously proposed staging systems for hepatocellular carcinoma (HCC) involve clinical, imaging, or pathologic factors in the evaluation. We established and validated a novel staging system for HCC that is based on simply serum markers. METHODS: The new scoring system is based on 5 serum markers: bilirubin, albumin, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) and thus is termed the BALAD score. The system was validated in 2600 HCC patients from 5 institutions. The power of our system to predict patient survival and its discriminative ability were compared with those of previously reported staging systems. RESULTS: The best tumor marker cutoff values were 400 ng/dL for AFP, 15% for AFP-L3, and 100 milli-arbitrary unit/mL for DCP. The patients were classified into 6 categories on the basis of 5 laboratory values. The categories reflected patient survival well. The discriminative ability was comparable to that of previously reported staging systems. CONCLUSIONS: The new staging system for HCC combining serum albumin, serum bilirubin, and 3 tumor markers predicts patient outcomes with excellent discriminative ability. The system is easy to use and objective. In addition, stage can be evaluated with the use of only 1 serum sample. It also allows global comparison of patients with HCC or comparison of patients from different time periods with the same standard.