Culinaris Agglutinin-reactive Fraction Of Α-fetoprotein Research Articles

Preoperative prediction of microvascular invasion classification in hepatocellular carcinoma based on clinical features and MRI parameters.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a critical pathological factor and the degree of MVI influences treatment decisions and patient prognosis. The present study aimed to predict the MVI classification based on preoperative MRI features and clinical parameters. The present retrospective cohort study included 150 patients (training cohort, n=108; validation cohort, n=42) with pathologically confirmed HCC. Clinical and imaging characteristics data were collected from Shengli Oilfield Central Hospital (Dongying, China). Univariate and multivariate logistic regression analyses were conducted to assess the association of clinical variables and MRI parameters with MVI (grade M1 and M2) and the M2 classification. Nomograms were developed based on the predictive factors of MVI and the M2 classification. The discrimination capability, calibration and clinical usefulness of the nomograms were evaluated. Multivariate analysis revealed an association between the Lens culinaris agglutinin-reactive fraction of α-fetoprotein, protein induced by vitamin K absence-II and tumor margin and MVI-positive status, while peritumoral enhancement and tumor size were demonstrated to be marginal predictors, but were also included in the nomogram. However, among MVI-positive patients, only peritumoral hypointensity and tumor size were demonstrated to be risk factors for the M2 classification. The nomograms, incorporating these variables, exhibited a strong ability to discriminate between MVI-positive and MVI-negative patients with HCC in both the training and validation cohort [area under the curve (AUC), 0.877 and 0.914, respectively] and good performance in predicting the M2 classification in the training and validation cohorts (AUC, 0.720 and 0.782, respectively). Nomograms incorporating clinical parameters and preoperative MRI features demonstrated promising potential as straightforward and effective tools for predicting MVI and the M2 classification in patients with HCC. Such predictive tools could aid in the judicious selection of optimal clinical treatments.

Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients.

BACKGROUNDEarly diagnosis of hepatocellular carcinoma (HCC) is necessary to improve the prognosis of patients. However, the currently available tumor biomarkers are insufficient for the early detection of HCC. Acylcarnitine is essential in fatty acid metabolic pathways. A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis (SH) patients. In contrast, another study reported that the level of acetylcarnitine (AC2) - one of the acylcarnitine species - in non-SH patients with HCC was decreased vs that reported in those without HCC.AIMTo investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODSThirty-three non-SH patients (14 with HCC and 19 without HCC) were enrolled in this study. Blood samples were obtained from patients at the time of admission. The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry. The levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) were determined by enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTSThe level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC (P < 0.05). In contrast, the level of lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP) - AFP-L3% - was significantly higher in non-SH patients with HCC vs those without HCC (P < 0.05). However, the levels of total carnitine, free carnitine, AFP, des-γ-carboxy prothrombin, VEGF, and VEGFR-2 were not different between patients with and without HCC. The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC. The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2 (P < 0.05).CONCLUSIONThe metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC. Further studies are warranted to investigate these differences.

Clinical Significance of Preoperative Hepatocellular Carcinoma With High Lens culinaris Agglutinin-reactive Fraction of Alpha-Fetoprotein, But Low Alpha-Fetoprotein.

The aim of this study was to verify the significance of high Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) in patients with hepatocellular carcinoma (HCC) with low AFP. There were 283 patients with low AFP who underwent initial hepatic resection with or without radiofrequency ablation for HCC. Patients were divided into two groups based on AFP-L3 values: >10%: high AFP-L3 (n=24); and ≤10%: low AFP-L3 (n=259). Overall survival (OS) and 2-year recurrence rates were compared, and independent prognostic factors were identified. The OS and 2-year recurrence rates of the high AFP-L3 group were significantly worse than those of the low AFP-L3 group. The independent prognostic factors for poor OS were des-gamma-carboxy prothrombin (DCP) of >40 mAU/ml, microvascular invasion, and invasive growth, and those for 2-year recurrence were 99mTc-galactosyl human serum albumin uptake ratio of <0.90, DCP of >40 mAU/ml, multiple tumors, microvascular invasion, and poor differentiation. DCP levels increased with AFP-L3, and cases with high DCP and AFP-L3 had worse prognoses and higher 2-year recurrence rates compared to those with elevation of only one of these. Patients with high AFP-L3 but low AFP have poor prognosis and high 2-year recurrence rates. DCP strongly reflects HCC malignancy in patients with low AFP.

Is disease progression a contraindication for the strategy of portal vein embolization followed by hepatectomy for hepatocellular carcinoma?

Portal vein embolization has been used worldwide to induce hypertrophy of the future liver remnant and to reduce the risk of hepatic insufficiency and death after major hepatectomy. However, whether disease progression after portal vein embolization can affect long-term oncologic outcomes in patients with hepatocellular carcinoma is uncertain. From a total of 107 patients who underwent portal vein embolization and subsequent hepatectomy between 2000 and 2016, 57 patients with hepatocellular carcinoma were enrolled. We evaluated their long-term oncologic outcomes and investigated whether the disease progression between portal vein embolization and subsequent hepatectomy affected survival. The 5-year overall survival and disease-free survival after hepatectomy were 74.5% and 31.7%, respectively. Multivariate analyses revealed that tumor number before hepatectomy ≥3 (hazard ratio 3.59, P = .019), des-γ-carboxy prothrombin >200 mAU/mL (hazard ratio 3.36, P = .045), and red blood cell transfusion (hazard ratio 11.03, P = .0008) were independent prognostic factors for overall survival. Male sex (hazard ratio 3.74, P = .029), bilobar tumor distribution (hazard ratio 3.65, P = .004), and red blood cell transfusion (hazard ratio 6.22, P = .0026) were independent prognostic factors for disease-free survival. Disease progressions after portal vein embolization, including increases in tumor size, tumor number, α-fetoprotein, lens culinaris agglutinin-reactive fraction of α-fetoprotein, and des-γ-carboxy prothrombin, were observed in 22.8%, 14.0%, 29.8%, 19.3%, and 47.4% of patients, respectively. Only an increase of tumor number significantly decreased the disease-free survival rate after hepatectomy in a univariate analysis, and none of the variables affected overall survival. Disease progression after portal vein embolization did not affect long-term survival in patients with hepatocellular carcinoma if the planned subsequent hepatectomy could be completed.

Clinical Assay for AFP-L3 by Using Multiple Reaction Monitoring-Mass Spectrometry for Diagnosing Hepatocellular Carcinoma.

Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) is a serum biomarker for hepatocellular carcinoma (HCC). AFP-L3 is typically measured by liquid-phase binding assay (LiBA). However, LiBA does not always reflect AFP-L3 concentrations because of its low analytical sensitivity. Thus, we aimed to develop an analytically sensitive multiple reaction monitoring-mass spectrometry (MRM-MS) assay to quantify AFP-L3 in serum. The assay entailed the addition of a stable isotope-labeled internal standard protein analog, the enrichment of AFP using a monoclonal antibody, the fractionation of AFP-L3 using L. culinaris agglutinin lectin, deglycosylation, trypsin digestion, online desalting, and MRM-MS analysis. The performance of the MRM-MS assay was compared with that of LiBA in 400 human serum samples (100 chronic hepatitis, 100 liver cirrhosis, and 200 HCC). Integrated multinational guidelines were followed to validate the assay for clinical implementation. The lower limit of quantification of the MRM-MS assay (0.051 ng/mL) for AFP-L3 was less than that of LiBA (0.300 ng/mL). Thus, AFP-L3, which was not observed by LiBA in HCC samples (n = 39), was detected by the MRM-MS assay, improving the clinical value of AFP-L3 as a biomarker by switching to a more analytical sensitive platform. The method was validated, meeting all the criteria in integrated multinational guidelines. Because of the lower incidence of false-negative findings, the MRM-MS assay is more suitable than LiBA for early detection of HCC.

Activated p53 with Histone Deacetylase Inhibitor Enhances L-Fucose-Mediated Drug Delivery through Induction of Fucosyltransferase 8 Expression in Hepatocellular Carcinoma Cells.

BackgroundThe prognosis of advanced hepatocellular carcinoma (HCC) is dismal, underscoring the need for novel effective treatments. The α1,6-fucosyltransferase (fucosyltransferase 8, FUT8) has been reported to accelerate malignant potential in HCC. Our study aimed to investigate the regulation of FUT8 expression by p53 and develop a novel therapeutic strategy for targeting HCC cells using L-fucose-mediated drug delivery.MethodsBinding sites for p53 were searched for within the FUT8 promoter region. FUT8 expression was assessed by immunoblotting. Chromatin immunoprecipitation (ChIP) assays were performed to analyze p53 binding to the FUT8 promoter. The delivery of Cy5.5-encapsulated L-fucose-liposomes (Fuc-Lip-Cy5.5) to a Lens Culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3)-expressing HCC cells was analyzed by flow cytometry. The induction of FUT8 by histone deacetylase inhibitor (HDACi) -inducing acetylated -p53 was evaluated by immunoblotting. Flow cytometric analysis was performed to assess whether the activation of p53 by HDACi affected the uptake of Fuc-Lip-Cy5.5 by HCC cells. The cytotoxicity of an L-fucose-bound liposome carrying sorafenib (Fuc-Lip-sorafenib) with HDACi was assessed in vivo and in vitro.ResultsThe knock down of p53 with siRNA led to decreased FUT8 expression. ChIP assays revealed p53 binds to the FUT8 promoter region. Flow cytometric analyses demonstrated the specific uptake of Fuc-Lip-Cy5.5 into AFP-L3-expressing HCC cells in a p53- and FUT8-dependent manner. HDACi upregulated the uptake of Fuc-Lip-Cy5.5 by HCC cells by increasing FUT8 via acetylated -p53. The addition of a HDACi increased apoptosis induced by Fuc-Lip-sorafenib in HCC cells.ConclusionsOur findings reveal that FUT8 is a p53 target gene and suggest that p53 activated by HDACi induces Fuc-Lip-sorafenib uptake by HCC cells, highlighting this pathway as a promising therapeutic intervention for HCC.

P0351 : Highly sensitive α-fetoprotein, Lens culinaris agglutinin-reactive fraction of α-fetoprotein and des-γ-carboxy prothrombin for hepatocellular carcinoma detection in an Italian cohort

P0351 : Highly sensitive α-fetoprotein, Lens culinaris agglutinin-reactive fraction of α-fetoprotein and des-γ-carboxy prothrombin for hepatocellular carcinoma detection in an Italian cohort

Prognostic Role of Pre-Treatment Serum AFP-L3% in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

BackgroundSerum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.MethodsEligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.Results Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).ConclusionThe current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration.

Serological and histological indices of hepatocellular carcinoma and tumor volume doubling time

Hepatocellular carcinoma (HCC) frequently develops in cirrhotic liver and is one of the most common malignancies worldwide. The tumor volume doubling time (TVDT) reflects the natural tumor growth rate and is an indicator of the biological malignant potential of a tumor. The present study aimed to elucidate the association between the serological and histological indices of HCC and TVDT. TVDT was analyzed for 53 HCCs by measuring the enlargement of the tumor diameter on dynamic computed tomography. Differences in TVDT were compared among histological grades of HCC differentiation. The α-fetoprotein (AFP) doubling time (T2AFP) for 44 HCCs with AFP levels >200 ng/ml was calculated and the differences in T2AFP were compared according to the histological grade of HCC differentiation and positivity for Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3). Among these 44 HCCs, the correlation between T2AFP and TVDT was analyzed for the 27 tumors for which TVDT could be calculated. The mean ± standard deviation (SD) TVDT in Edmondson grade 1 (Ed1), Ed2 and Ed3 HCC was 138.3±110.3, 94.9±91.5 and 32.2±20.8 days, respectively (P<0.05). The mean ± SD T2AFP in Ed2 and Ed3 HCC was 121.0±167.5 and 37.3±24.6 days, respectively (P<0.01). TVDT and T2AFP decreased with histological dedifferentiation of HCC. The mean ± SD T2AFP in the AFP-L3-positive and -negative groups was 63.2±101.2 and 191.9±209.9 days, respectively, with a statistically significant difference between the groups (P<0.01). A significant correlation was observed between T2AFP and TVDT (correlation coefficient, 0.70; P<0.01). A significant correlation was also observed among TVDT, serological indices and histological grades of HCC differentiation. A short T2AFP and/or AFP-L3-positivity were shown to reflect a poorly differentiated HCC histopathology and a higher malignant potential.

Transcatheter Arterial Chemotherapy Using Miriplatin-Lipiodol Suspension with or without Embolization for Unresectable Hepatocellular Carcinoma

The purpose of this retrospective study was to compare the anti-tumor and adverse effects of transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy using miriplatin-lipiodol suspension in patients with unresectable hepatocellular carcinoma. From 2007 to 2010, 162 consecutive patients with unresectable hepatocellular carcinoma were treated using miriplatin. Of these, 122 patients were treated by transcatheter arterial chemoembolization and 40 were treated by transcatheter arterial infusion chemotherapy. There were no significant differences in baseline characteristics between the two groups, except for prothrombin activity. Assessments were performed 1-3 months after treatment. Objective responses were achieved in 13 patients undergoing transcatheter arterial infusion chemotherapy and 70 patients undergoing transcatheter arterial chemoembolization (33 versus 57%, P = 0.003). By multivariate logistic regression analysis, objective response was significantly associated with (i) a Lens culinaris agglutinin-reactive fraction of α-fetoprotein ≤10% (P = 0.004; risk ratio = 3.09; 95% confidence interval = 1.42-6.70), (ii) no previous transcatheter arterial chemoembolization (P = 0.007; risk ratio = 4.41; 95% confidence interval = 1.49-13.07) and (iii) transcatheter arterial chemoembolization using gelatin sponge 1 mm particles (P = 0.021; risk ratio = 2.97; 95% confidence interval = 1.17-7.49). Fever, anorexia and elevated serum transaminase levels were observed in most patients after miriplatin administration; there were no significant differences in the number of adverse effects between the two groups. These results suggest that the addition of embolizing agents to a treatment regimen using miriplatin-lipiodol suspension can be safely used for patients with unresectable hepatocellular carcinoma. Objective response was achieved in a significantly higher number of transcatheter arterial chemoembolization patients than transcatheter arterial infusion chemotherapy patients.

P05 Combination of serum biomarkers for the diagnosis of hepatocellular carcinoma

IntroductionThe most commonly used serum biomarker for the diagnosis of hepatocellular carcinoma (HCC) is α fetoprotein (AFP). However, AFP is also modestly raised in patients with chronic liver disease, particularly...

Novel Lens culinaris agglutinin-reactive fraction of α-fetoprotein: a biomarker of hepatocellular carcinoma recurrence in patients with low α-fetoprotein concentrations

Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) is a specific marker used to detect hepatocellular carcinoma (HCC). However, its clinical utility is not sufficient in patients with low total AFP concentrations because of limitations in instrument sensitivity. Recent advances have led to the introduction of a highly sensitive AFP-L3% assay (sensitive AFP-L3%), provided by a novel on-chip, liquid-phase binding assay. This cross-sectional study was conducted to evaluate the clinical significance of the sensitive AFP-L3% in determining HCC recurrence in patients with low total AFP concentrations. A total of 370 consecutive patients with HCC were screened within 1-3 months of locoregional treatment, and 215 of the 370 patients showed serum AFP <20 ng/ml. Total AFP, sensitive AFP-L3%, and des-gamma-carboxy prothrombin (DCP) were measured in those 215 patients and HCC recurrence was evaluated by radiological findings. Optimal cutoff values of the markers for detecting HCC recurrence were obtained on the basis of receiver operating characteristic (ROC) curve. The area under the ROC curve of the total AFP, sensitive AFP-L3%, and DCP in HCC patients with serum AFP <20 ng/ml were 0.638, 0.724, and 0.779, respectively. The diagnostic accuracies of the total AFP, sensitive AFP-L3%, and DCP were 60.9% (cutoff value 5 ng/ml), 67.7% (cutoff value 7%), and 64.6% (cutoff value 40 ng/ml), respectively. The new sensitive AFP-L3% assay provides great utility in determining HCC recurrence in patients with low AFP concentrations. Further studies focusing on the combinatorial use of the markers (total AFP, sensitive AFP-L3%, and DCP) are required.

Lens culinaris agglutinin‐reactive fraction of AFP is a useful prognostic biomarker for survival after repeat hepatic resection for HCC

Repeat hepatic resection for recurrent hepatocellular carcinoma (HCC) is effective in improving long-term outcome in selected patients. In the present study, we attempted to identify the prognostic factors influencing overall and recurrence-free survival after the second hepatic resection. From 1 September 1997 to 30 September 2009, 329 consecutive patients with HCC underwent surgical exploration at Yamanashi University Hospital, Japan. Of these, 35 patients underwent curative, second hepatic resection. The survival results in the 35 patients were analyzed retrospectively, and prognostic factors were determined. The univariate analysis revealed that Child-Pugh B, a Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) value more than 15%, and multiple tumors, were associated with significantly worse overall survival (P=0.010, P=0.0003, and P=0.037, respectively) and only AFP-L3 >15% was associated with significantly worse recurrence-free survival after the second hepatic resection (P=0.008). By multivariate analysis, only AFP-L3 >15% was an independent predictor of adverse overall survival. The 1-, 3-, and 5-year survival rates after the second hepatic resection of 27 HCC patients with low AFP-L3 (≤15%) were 100%, 100%, and 91.7%, respectively, whereas the corresponding survival rates of eight HCC patients with high AFP-L3 (>15%) were 100%, 47.6%, and 23.8%, respectively. The preoperative AFP-L3 level was a useful prognostic biomarker for survival after repeat hepatic resection.

Gene Expression Signature of the Gross Morphology in Hepatocellular Carcinoma

To evaluate the gene expression signature of hepatocellular carcinoma (HCC) in relation to the gross morphology. Eggel's nodular type of HCC is morphologically subclassified into the single nodular (SN) type, the single nodular type with extranodular growth (SNEG), and the confluent multinodular (CM) type, but their biomolecular differences remain unclear. The clinicopathological characteristics and genome-wide gene expressions were analyzed in 275 patients with nodular-type HCC (124 SN-type, 91 SNEG-type, and 60 CM-type) who received curative hepatectomy. Significantly poor prognosis was recognized in CM types in overall survival (P = 0.0020) and recurrence-free survival (P = 0.0066). Analysis of the genome-wide expression patterns revealed significant difference of CM-type HCC from either SN- or SNEG-type HCC. In particular, a stem cell marker EpCAM was dominantly expressed in CM-type HCC. Immunohistochemical studies confirmed the specific expression of EpCAM in HCC cancer cells of CM type. In multivariate analysis, the gross morphology of CM type was significantly associated with EpCAM expression (P = 0.0092), α-fetoprotein (P = 0.0424), "lens culinaris agglutinin-reactive fraction of α-fetoprotein" level (P = 0.0288), and the portal vein invasion (P = 0.0150). Furthermore, EpCAM was predictive for poor prognosis in overall and recurrence-free survivals of patients with CM-type HCC (P = 0.0082 and P = 0.0043, respectively). Our studies suggest that the distinct signature of gene expression is closely related to morphological progression in HCC. Especially, EpCAM might play a critical role in the aggressiveness of CM-type HCC.

Clinical and molecular insights into the hepatocellular carcinoma tumour marker des‐γ‐carboxyprothrombin

Des-γ-carboxyprothrombin (DCP) is known as a tumour marker for hepatocellular carcinoma (HCC). Various tumour markers have been developed for serological diagnosis of cancers, including HCC, in order to increase the survival rate of cancer patients. The currently recommended combined testing of DCP and α-fetoprotein (AFP) or Lens culinaris agglutinin-reactive fraction of α-fetoprotein has been established to diagnose HCC. This combined testing using several tumour markers helps to increase the sensitivity of diagnosis of HCC, thus significantly increasing the clinical usefulness of DCP. The excessive production of DCP may be related to worse tumour behaviour, such as the presence of vascular invasion and intrahepatic metastasis of HCC cells. A high level of DCP was suggested to be useful as one of the factors in new recipient selection criteria of liver transplantation. The clinical use of DCP, therefore, might play a vital role in predicting tumour behaviour in patients with HCC. That said, the basic mechanism of DCP production has not been fully clarified. Various factors such as vitamin K(2) and γ-glutamyl carboxylase may contribute to the production of DCP and have a complex relationship. Moreover, recent studies have revealed that DCP functions as a growth factor and might play significant roles in cancer progression. Thus, DCP represents a potential target of drug discovery to establish new chemotherapeutic strategy for HCC. However, various issues have to be resolved to construct a novel therapy for HCC-targeting DCP. Innovation is required to make further progress in examining DCP.

Utility of Lens culinaris Agglutinin-Reactive Fraction of α-Fetoprotein and Des-Gamma-Carboxy Prothrombin, Alone or in Combination, as Biomarkers for Hepatocellular Carcinoma

Des-gamma-carboxy prothrombin (DCP) and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) are surveillance markers used to detect hepatocellular carcinoma (HCC) in Japan. This study evaluated their utility, alone or in combination, in a North American population. Patients with hepatitis C virus-related cirrhosis were followed up prospectively for 2 years. Of 372 patients, HCC developed in 34 of 298 who were free of HCC at entry. The overall sensitivity, specificity, and positive and negative predictive values for only AFP (>20 ng/mL) were 61%, 71%, 34%, and 88%, respectively; for only AFP-L3% (>10) were 37%, 92%, 52%, and 85%, respectively; and for only DCP (>7.5 ng/mL) were 39%, 90%, 48%, and 86%, respectively. Values increased when AFP values were combined with AFP-L3% and DCP to 77%, 59%, 32%, and 91%, respectively. Among patients with increases in AFP levels to 20 to 200 ng/mL, AFP-L3% and DCP were highly specific markers (86.6% and 90.2%, respectively). Of 29 HCC patients with AFP levels less than 20 ng/mL, 13 had increased levels of AFP-L3% or DCP. Increased alanine aminotransferase levels were associated with increased total AFP but not AFP-L3% or DCP levels. Both AFP-L3%- and DCP-positive patients showed significant differences in lower cumulative HCC-free rates compared with the overall group (P < .0001 and P = .0005, respectively). AFP-L3% and DCP levels have higher correlation values with an absence of HCC, as well as a higher specificity and negative predictive value, than total AFP. Although this combination of markers only marginally improves surveillance for early HCC, it could identify individuals with negative imaging results who would benefit from follow-up evaluation.

Usefulness of measurement of lens culinaris agglutinin-reactive fraction of α-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma

OBJECTIVE: Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) is a recently described marker of hepatocellular carcinoma (HCC), and its usefulness has been demonstrated in many studies. We evaluated the usefulness of serial measurement of AFP-L3% as a marker of prognosis and recurrence after treatment of small HCC. METHODS: AFP-L3% was measured before and after initial treatment in 60 patients with small HCC (maximum diameter ≤2 cm). AFP-L3% was taken as the ratio of AFP-L3 to total AFP and multiplied by 100%, and levels ≥10% were considered positive. Outcomes and recurrence were compared between patients AFP-L3%–negative after initial treatment (Group A, n = 43) and patients who were AFP-L3%–positive after initial treatment (Group B, n = 17). RESULTS: Before treatment, AFP-L3% was positive in 14 (23.3%) of the 60 patients. The cumulative survival rate of Group A was significantly longer ( p = 0.0091) than that of Group B. The recurrence rate was significantly higher in Group B ( p = 0.0104) than in Group A. When recurrence was limited to intrahepatic metastasis, the recurrence rate was significantly higher in Group B ( p = 0.0064). However, the recurrence rate of multicentric occurrence did not differ significantly between Groups A and B. CONCLUSIONS: Measurement of AFP-L3% after treatment may be useful for understanding prognosis and recurrence of HCC.

Usefulness of measurement of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma.

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3%) is a recently described marker of hepatocellular carcinoma (HCC), and its usefulness has been demonstrated in many studies. We evaluated the usefulness of serial measurement of AFP-L3% as a marker of prognosis and recurrence after treatment of small HCC. AFP-L3% was measured before and after initial treatment in 60 patients with small HCC (maximum diameter < or = 2 cm). AFP-L3% was taken as the ratio of AFP-L3 to total AFP and multiplied by 100%, and levels > or = 10% were considered positive. Outcomes and recurrence were compared between patients AFP-L3%-negative after initial treatment (Group A, n = 43) and patients who were AFP-L3%-positive after initial treatment (Group B, n = 17). Before treatment, AFP-L3% was positive in 14 (23.3%) of the 60 patients. The cumulative survival rate of Group A was significantly longer (p = 0.0091) than that of Group B. The recurrence rate was significantly higher in Group B (p = 0.0104) than in Group A. When recurrence was limited to intrahepatic metastasis, the recurrence rate was significantly higher in Group B (p = 0.0064). However, the recurrence rate of multicentric occurrence did not differ significantly between Groups A and B. Measurement of AFP-L3% after treatment may be useful for understanding prognosis and recurrence of HCC.