Des-gamma-carboxy Prothrombin Levels Research Articles

Association of Serum Levels and Immunohistochemical Labelling of Des-Gamma-Carboxy-Prothrombin in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular cancer (HCC) is one of the main reasons for liver transplantation (LT). Biomarkers, such as alpha-foetoprotein (AFP) and Des-gamma-carboxy-prothrombin (DCP), can be helpful in defining the recurrence risk post LT. This study aims to evaluate the association between the intensity of DCP immunohistochemical labelling and serum DCP levels in patients undergoing LT for HCC. We carried out a prospective monocentric study including patients who all underwent LT for cirrhosis between 2016 and 2018 and all fell under the Milan criteria. The accepted diagnostic criteria for HCC were contrast-enhanced imaging and histology. Thirty-nine patients were followed for a median of 21 months, with HCC lesions categorized into negative, focally positive, and diffusely positive groups based on DCP immunohistochemistry. The serum DCP levels were significantly higher in the positive groups (258 mAU/mL for the focally and 257 mAU/mL for the diffusely positive) than in the negative group (48 mAU/mL) (p = 0.005) at diagnosis and at the time of liver transplantation (220 mAU/mL for the diffuse positive group). Microvascular invasion (58.8% vs. 19.0% for the diffusely positive and negative groups, respectively, p < 0.001) and lesion size (20 mm in the diffusely labelled group versus 12 mm in the other groups, p = 0.002) were significantly correlated with DCP labelling. Late recurrence occurred only in the positive groups; in the negative group, it occurred within the first 3 months after transplantation. DCP labelling in liver lesions correlates with serum levels and a more aggressive tumour profile. Further investigation is needed to determine if highly DCP-labelled tumours allow for the better selection of high-risk patients before LT.

Des-gamma-carboxy prothrombin and alpha-fetoprotein levels as biomarkers for hepatocellular carcinoma and their correlation with radiological characteristics.

Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients. To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin (DCP) alone and in combination with AFP. In this study, 202 patients with radiologically proven HCC were enrolled, and their DCP and AFP levels were evaluated for their diagnostic performance. The mean age of the enrolled patients was 58.5 years; 72.0% were male. DCP was elevated in 86.6% (n = 175) of all patients, 100.0% (n = 74) of patients with portal vein thrombus, and 87.4% (n = 111) of patients with multicentric HCC. AFP was elevated in 64.3% (n = 130) of all the patients, 74% (n = 55) of the patients with portal vein thrombus, and 71.6% (n = 91) of the patients with multicentric HCC (P = 0.030, 0.001, and 0.015, respectively). In tumors less than 2 cm in size (n = 46), DCP was increased in 32 (69.5%) patients, and AFP was increased in 25 (54.3%) patients (P = 0.801). There was good pairing between DCP and AFP for HCCs of 2 cm size or larger (P < 0.001); however, the pairing among tumors < 2 cm size was not significant (P = 0.210). In 69 of the patients (34.1%), only one of the tumor markers was positive; DCP was elevated alone in 57/202 (28.2%) of all patients, and AFP alone was elevated in 12/202 (5.9%) of the patients. The areas under receiver operating characteristic curves (AUROC) for tumors > 2 cm was 0.74 for DCP and 0.59 for AFP; combining both markers resulted in an AUROC of 0.73. For tumors < 2 cm, the AUROC was 0.25 for DCP and 0.40 for AFP. DCP, as an individual marker, had a better diagnostic performance in many cases of HCC. Hence, DCP may replace AFP as the primary HCC biomarker.

The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma

PurposeThe GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC.MethodsA total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria.ResultsThe GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001).In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP.ConclusionThe GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

Correlation Between Serum ESPL1 and Hepatitis B Virus-related Hepatocellular Carcinoma Histological Grade: A Chinese Single-center Case-control Study.

Serum markers to determine the histological grade of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still limited. This study aimed to investigate if serum extra spindle pole bodies-like 1 (ESPL1) protein could reflect the histological grade of HBV-related HCC. A total of 154 patients with HBV-related HCC were enrolled in the experimental group and 41 non-HBV-related patients in the control. Enzyme-linked immunosorbent assay was used to detect serum ESPL1 levels. The differences in serological ESPL1, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) were compared between the two groups. HCC tumor diameter was measured, and pathological examination was performed to compare the relationship between ESPL1, AFP, and DCP and tumor size and histological grade. Serum AFP and DCP levels showed no significant difference between experimental group and control group, and increased when the tumor diameter increased but were not related to HCC histological grade. Serological ESPL1 levels were higher in the experimental group than those in the control group, and positively correlated with the histological grade. In the experimental group, tumor size and histological grade were almost independent (Kappa=0.000); patients with medium size tumors had the highest serum ESPL1 levels and the highest proportion of poorly differentiated carcinomas, whereas 75.6% of patients with small size tumors had moderately differentiated carcinomas and only 20% well differentiated carcinomas. Serum ESPL1 can reflect the malignant degree of HBV-related HCC and is helpful in identifying small size HCC tumors.

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.

Elevated Alfa-Fetoprotein Levels and Des-Gamma-Carboxy Prothrombin Levels Predict Poor Outcomes after Liver Transplantation for Hepatocellular Carcinoma Beyond the New Japan Criteria

Background: The Japan criteria (JC: the Milan criteria + 5-5-500 rule) was established to select optimal patients with hepatocellular carcinoma for liver transplantation. We aimed to evaluate factors associated with poor prognoses after liver transplantation according to JC and sought whether further extension was worthwhile. Methods: We retrospectively analyzed 86 patients who underwent liver transplantation for hepatocellular carcinoma at our institution. Results: Overall, 69 patients (80.2%) were within and 17 patients (19.8%) were beyond JC. The 5-year cancer specific survival (CSS) of the Within JC group (92.2%) was significantly better than that of the Beyond JC group (39.2%, P<0.001). Univariate analysis revealed that alfa-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were predictive of CSS. According to the receiver operating characteristic curves, the cutoff levels of AFP and DCP was 756 ng/ml and 1976 mAU/ml, respectively. The patients were restratified into 2 groups: a low-risk group (AFP <756 ng/ml and DCP <1976) and high-risk group (either one or both levels of AFP and DCP higher than the cutoff). The 5-year CSS of the low-risk group was significantly better than the patient in high-risk group ((67.5% vs. 0%, p < 0.001). Conclusion: Among HCC patients beyond JC, liver transplantation may yield acceptable oncological outcomes when both AFP and DCP levels are low, suggesting favorable tumor biology.

EVALUATION OF DES-GAMMA CARBOXY PROTHROMBIN AS A BIOMARKER FOR EARLY DETECTION OF HEPATOCELLULAR CARCINOMA ON TOP OF CHRONIC ACTIVE HEPATITIS POST VIRUS C INFECTION

Background: Experience with Des-gamma Carboxy Prothrombin (DCP) is limited. Most studies on HCC biomarkers have focused on the accuracy of markers for diagnosis. Objective: To assess serum level of Des-gamma carboxy prothrombin as a biomarker for early detection of hepatocellular carcinoma post chronic active hepatitis on top of hepatitis C virus infection (HCV). Patients and Methods: This study was conducted on 60 individuals diagnosed as chronic HCV patients, and 30 healthy individuals were selected as a control group. Fifteen patients were suffering from chronic active hepatitis without complications, Fifteen patients were suffering from chronic active hepatitis with complications, Fifteen patients were of early cases of HCC on top of HCV, and Fifteen were patients of late cases of HCC on top of HCV. Des-gamma Carboxy Prothrombin were measured by ELISA. Results: There was significant increase in Des-gamma Carboxy Prothrombin (DCP) in group (II) and group (III) when compared to control group (I). However, Patients in group (III) showed higher levels of DCP when compared to group (II). Conclusion: DCP was promising in overcome AFP insufficiency in identity AFP negative HCC as DCP has a superior performance than AFP in identification of HCC from HCV-related in surveillance studies.

Characteristics of TP53 and CTNNB1 mutation according to the serum tumor markers in hepatocellular carcinoma

Serum alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the United States and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (↑All), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP patients (n = 7 [53.8%]) and RR patients (n = 10 [38.5%]), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients. TP53 sequence variants were associated with ↑AFP (n = 8 [30.8%]) and ↑DCP (n = 4 [30.8%]). The Wnt signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF and VEGF signaling are activated in high AFP&L3, while dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these finding using the remainder of the TCGA-LIHC cohort and showed similar results to the test cohort. Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile.

Identification of the Response-Related Biomarker of Bimonthly Hepatic Arterial Infusion Chemotherapy.

Despite the availability of molecularly targeted agents for advanced hepatocellular carcinoma (aHCC), these are limited to compensated cirrhotic patients, and concerns about decreased hepatic functional reserve (HFR) and unknown adverse events, which may affect long-term survival, remain unaddressed. In this study, we enrolled 96 aHCC patients treated with bimonthly hepatic arterial infusion chemotherapy (B-HAIC) with cisplatin or sorafenib monotherapy (oral sorafenib 400 mg twice daily) not only to demonstrate its efficacy and significance but also to indicate preferable candidates by setting a response-related biomarker. Differences in treatment had no significant effect on overall survival (OS). The response rate in patients treated with B-HAIC was relatively higher than those treated with sorafenib. HFR was well maintained over the treatment course with B-HAIC, while it was significantly impaired with sorafenib. By employing multivariate analysis, we found negative trends between progression-free survival (PFS) periods and serum levels of alpha fetoprotein as well as des-gamma-carboxy prothrombin (DCP). In addition, a logistic regression analysis of the relationship between serum DCP levels and PFS periods over 420 days (14 months) showed that the PFS periods of patients with higher DCP was significantly shorter than those of patients with lower DCP (p = 0.02). Subsequently, the present study demonstrated the efficacy and safety of B-HAIC and identified a predictor of unpreferable patients. Based on these results, B-HAIC might be an alternative treatment after the implementation of new molecularly targeted therapies.

Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is typically accompanied by abundant arterial blood flow. Although angiogenic growth factors such as Angiopoietin 2 (Ang2) play a central role in tumor angiogenesis in HCC, the role of serum Ang2 as a biomarker in HCC remains unclear. In this study, we aimed to investigate the potential of Ang2 as a diagnostic and prognostic biomarker in HCC using a sandwich enzyme-linked immunosorbent assay (ELISA). The median Ang2 levels in controls (n=20), chronic liver disease patients (n=98), and HCC patients (n=275) were 1.58, 2.33, and 3.53 ng/mL, respectively. The optimal cut-off value of Ang2 was determined as 3.5 ng/mL by receiver operating curve analysis. The sensitivity, specificity, and accuracy of Ang2 for HCC detection were 50.9, 83.7, and 59.5%, respectively. Spearman's rank correlation coefficient analysis demonstrated only a weak correlation between Ang2 serum levels and alpha-fetoprotein (AFP) or des-gamma-carboxy prothrombin (DCP) serum levels. The diagnostic value of Ang2 was comparable to those of other existing markers. In addition, 24 out of 73 patients with normal AFP and DCP levels (32.9%) demonstrated abnormally high Ang2 levels (≥3.5 ng/mL). Although no significant difference in overall survival was found between Ang2high and Ang2low patients with curative ablation therapy, recurrence-free survival (RFS) in Ang2high patients was observed to be significantly shorter than those in Ang2low patients. Multivariate analysis demonstrated that high serum Ang2 levels (≥3.5 ng/mL) and the presence of multiple tumors were poor prognostic factors. In conclusion, our findings indicate that serum Ang2 is a potential novel biomarker for both diagnosis and prognosis in HCC.

The Combined Diagnostic Accuracy of Serum Alpha Fetoprotein and Des-Gamma Carboxyprothrombin in Hepatocellular Carcinoma among Chronic Liver Disease Patients in Ilorin

Introduction :Chronic liver disease (CLD) is a disease of public health importance. CLD is defined as a clinical syndrome of liver disease lasting for at least six months with histology showing varying degree of hepatocellular necro-inflammation and fibrosis with or without neoplastic transformation. The disease is a spectrum that manifests initially as chronic hepatitis which may progress to liver cirrhosis and ultimately hepatocellular carcinoma (HCC). The current practice in the field of Gastroenterology has shifted from invasive methods of diagnosing HCC to non-invasive methods using tumor biomarkers. Various biomarkers of HCC have been proposed, but the largest body of evidence exists with alpha-fetoprotein (AFP). Most of the studies on the combined diagnostic accuracy of AFP and des-gamma-carboxyprothrombin (DCP) were done in other populations outside Nigeria. It is necessary to determine the combined diagnostic accuracy of the two tumor markers for early detection of HCC in North-central Nigeria. Materials and Methods: This study was a cross-sectional study and ethical clearance was obtained from the ethical and research committee of UITH, Ilorin. A total of 190 participants consisting of 125 cases and 65 healthy controls that were age and sex-matched were studied. Patients with extra-hepatic malignancies were excluded. The serum levels of AFP and DCP were determined using the enzyme-linked immunoassay (ELISA) technique. A detailed questionnaire was used to document the socio-demographic characteristics, clinical features as well as results of laboratory/radiologic parameters. Percutaneous liver biopsy was carried out on patients that were fit. Test of association between categorical variables was carried out using the Chi-Square Test. The sensitivity, specificity, positive and negative predictive values of the two tumor markers were determined by the area under curve (AUC) at various cut-off levels using the receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p value EiTest MONO P-II kit) were used to assay AFP and DCP respectively. Liver biopsy needle (Menghini needle) was used to carry out liver biopsy. Results: Using a cut-off of 400 ng/ml, the sensitivity of serum AFP for diagnosing HCC was 51.3%. The specificity of AFP at the same cut-off was 87.8%. The positive and negative predictive values were 92.8% and 49.3% respectively. Using a cut-off of 7.5 ng/ml, the sensitivity of serum DCP for diagnosing HCC was 57.1%. The specificity of DCP at the same cut-off was 63.4%. The positive and negative predictive values were 76.2% and 41.9% respectively while the accuracy was 59.2%. The diagnostic accuracy of combined serum AFP and DCP for diagnosis of HCC in University of Ilorin Teaching Hospital, Ilorin was 64.9%. The sensitivity of combined serum AFP and DCP for diagnosing HCC was 55.6%. The specificity of combined serum AFP and DCP was 95.6%. The positive and negative predictive values were 96.2% and 52.3% respectively. Conclusion: Combining these two tumour markers does not significantly improve the diagnostic accuracy of HCC and chronic HBV remains a strong aetiological agent of HCC in UITH, Ilorin.

The Combined Diagnostic Accuracy of Serum Alpha Fetoprotein and Des-Gamma Carboxyprothrombin in Hepatocellular Carcinoma among Chronic Liver Disease Patients in Ilorin

Introduction :Chronic liver disease (CLD) is a disease of public health importance. CLD is defined as a clinical syndrome of liver disease lasting for at least six months with histology showing varying degree of hepatocellular necro-inflammation and fibrosis with or without neoplastic transformation. The disease is a spectrum that manifests initially as chronic hepatitis which may progress to liver cirrhosis and ultimately hepatocellular carcinoma (HCC). The current practice in the field of Gastroenterology has shifted from invasive methods of diagnosing HCC to non-invasive methods using tumor biomarkers. Various biomarkers of HCC have been proposed, but the largest body of evidence exists with alpha-fetoprotein (AFP). Most of the studies on the combined diagnostic accuracy of AFP and des-gamma-carboxyprothrombin (DCP) were done in other populations outside Nigeria. It is necessary to determine the combined diagnostic accuracy of the two tumor markers for early detection of HCC in North-central Nigeria. Materials and Methods: This study was a cross-sectional study and ethical clearance was obtained from the ethical and research committee of UITH, Ilorin. A total of 190 participants consisting of 125 cases and 65 healthy controls that were age and sex-matched were studied. Patients with extra-hepatic malignancies were excluded. The serum levels of AFP and DCP were determined using the enzyme-linked immunoassay (ELISA) technique. A detailed questionnaire was used to document the socio-demographic characteristics, clinical features as well as results of laboratory/radiologic parameters. Percutaneous liver biopsy was carried out on patients that were fit. Test of association between categorical variables was carried out using the Chi-Square Test. The sensitivity, specificity, positive and negative predictive values of the two tumor markers were determined by the area under curve (AUC) at various cut-off levels using the receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p value EiTest MONO P-II kit) were used to assay AFP and DCP respectively. Liver biopsy needle (Menghini needle) was used to carry out liver biopsy. Results: Using a cut-off of 400 ng/ml, the sensitivity of serum AFP for diagnosing HCC was 51.3%. The specificity of AFP at the same cut-off was 87.8%. The positive and negative predictive values were 92.8% and 49.3% respectively. Using a cut-off of 7.5 ng/ml, the sensitivity of serum DCP for diagnosing HCC was 57.1%. The specificity of DCP at the same cut-off was 63.4%. The positive and negative predictive values were 76.2% and 41.9% respectively while the accuracy was 59.2%. The diagnostic accuracy of combined serum AFP and DCP for diagnosis of HCC in University of Ilorin Teaching Hospital, Ilorin was 64.9%. The sensitivity of combined serum AFP and DCP for diagnosing HCC was 55.6%. The specificity of combined serum AFP and DCP was 95.6%. The positive and negative predictive values were 96.2% and 52.3% respectively. Conclusion: Combining these two tumour markers does not significantly improve the diagnostic accuracy of HCC and chronic HBV remains a strong aetiological agent of HCC in UITH, Ilorin.

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

ObjectiveThis 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.MethodsPatients 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.ResultsIn 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.ConclusionsDCP 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.

Switching from Warfarin to rivaroxaban induces sufficiency of vitamin K and reduction of arterial stiffness in patients with atrial fibrillation.

Use of chronic vitamin K antagonist (VKA) induces a long-term deficiency of vitamin K, which may cause arterial stiffness and bone-related disease. Switching from VKA to rivaroxaban could induce rapid sufficiency of vitamin K and improvement of arterial stiffness. The K2 SUMMIT-3 study is a multicenter, open-label, prospective, and randomized design. Patients with atrial fibrillation who have been taking VKA for more than 6months but less than 10years were randomly assigned to two groups; those switching from VKA to rivaroxaban and those continuing with VKA medication. The primary endpoint was the percentage difference of brachial-ankle pulse wave velocity (baPWV) in 3months. A total of 77 patients were randomly assigned to receive rivaroxaban (n = 38) or VKA (n = 39). The average age was 74 ± 9years. The duration for which VKA was prescribed prior to randomization was 90 ± 87months.Abnormally high levels of Des-gamma carboxyprothrombin (PIVKA-II) or uncarboxylated osteocalcin (ucOC) indicating vitamin K insufficiency were observed in 100% or 82% of the patients at baseline but it reduced to 2% (p < 0.0001) or 55% (p = 0.01) at 3months in the rivaroxaban group. To the contrary, theses data had no changes in the VKA group. The percentage difference in baPWV was - 1.4 ± 10.0% vs. 3.5 ± 14.7% in the rivaroxaban and the VKA groups, respectively. (p = 0.02). Switching from VKA to rivaroxaban resulted in rapid sufficiency of vitamin K and reduction of arterial stiffness in 3months.

Des-gamma-carboxy prothrombin affects the survival of HCC patients with marginal liver function and curative treatment: ACRoS1402.

Considering the initial treatment of hepatocellular carcinoma (HCC), the best prognostic index for Child-Pugh classes B and C (CP-BC) patients has not been yet established. This study aimed to elucidate the risk factors for disease-free survival (DFS) and overall survival (OS) in multicenter patients with a poor liver functional reserve after curative treatment. Between April 2000 and April 2014, 212 CP-BC patients who received treatment in five high-volume centers in Japan were included in this study. CP-B and C patients were 206 and 6, respectively. Cox proportional hazard regression analyses for DFS and OS were performed to estimate the risk factors. The mean observation time was 1132days. Mean Child-Pugh score and indocyanine green retention rate at 15min were 7.5 and 31.5%, respectively. Histological chronic hepatitis and liver cirrhosis were observed in 20% and 74% patients, respectively. In the multivariate analysis, the risk factors for DFS were des-gamma-carboxy prothrombin (DCP) [hazard ratio (HR), 1.6; P = 0.012] and treatment without liver transplantation. Moreover, DCP was identified as an independent risk factor for OS (HR, 1.7; P = 0.01). Tumor size, number, tumor thrombus, Milan criteria, liver cirrhosis, and treatment without liver transplantation were not identified as risk factors for OS. The 5-year OS in patients with high serum DCP levels (< 90mAU/mL) was significantly better than that in those with low serum DCP levels (P = 0.003). Serum DCP value before treatment predicted both DFS and OS in CP-BC patients with HCC.

Early Predictors of Objective Response in Patients with Hepatocellular Carcinoma Undergoing Lenvatinib Treatment.

There are limited reports regarding early predictors of objective response (OR) in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. This retrospective study including 70 patients aimed to investigate the efficacy of hepatic biochemical markers. Changes in tumor marker (alpha-fetoprotein (AFP)/des-gamma-carboxy prothrombin (DCP)) levels and albumin–bilirubin (ALBI) score between the baseline value and that estimated one month after treatment were evaluated. We identified several predictors of OR, including changes in tumor marker levels. The OR rate calculated using modified Response Evaluation Criteria in Solid Tumor (mRECIST) was 41.4%. Response was defined as a reduction in AFP and DCP levels of ≥40% from baseline. OR was significantly associated with AFP response, but not with DCP. Predictors of OR were evaluated in two groups (high-AFP group: baseline AFP ≥ 10 ng/mL; low-AFP group: remaining patients). A multivariate analysis identified AFP response (odds ratio, 51.389; p = 0.001) and ALBI score (odds ratio, 6.866; p = 0.039) as independent predictors of OR in the high-AFP and low-AFP groups, respectively. Changes in the ALBI score indicated deterioration in both responders and non-responders, with a significant difference in non-responders (p = 0.003). AFP response, baseline ALBI score, and change in the ALBI score were early predictors of OR in patients with HCC undergoing lenvatinib treatment.

Diagnostic Value of Serum Biomarkers in Combined Hepatocelluar-Cholangiocarcinoma.

To explore the value of des-gamma-carboxyprothrombin (DCP), alpha-fetoprotein (AFP) and carbohydrate antigen-199 (CA-199) for diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CC). Observational correlational study design. The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from June 2016 to June 2019. Patients with cHCC-CC (n = 26) diagnosed by histological examination and immunohistochemical staining were matched as 1:2 to controls (n = 52) based on age (±2 years), gender (male or female), liver texture (cirrhosis or not) and ethnicity. Serum DCP, AFP and CA-199 levels were determined and Youden indices were calculated. Receiver operating characteristic (ROC) curves were generated and areas under the receiver operating characteristic curve (AUC) were calculated. The levels of DCP, AFP and CA-199 were clearly elevated in the cHCC-CC group relative to controls with p-values of <0.001, <0.001 and 0.001, respectively. Youden index values for DCP, AFP, CA-199, and their combination (DCP+AFP+CA-199) were 0.5, 0.423, 0.173 and 0.673, respectively. The AUC curve values for DCP, AFP, CA-199 and their combination (DCP+AFP+CA-199) were 0.759 (95% CI: 0.624 - 0.894), 0.826 (95% CI: 0.720 - 0.933), 0.727 (95% CI: 0.613 - 0.841) and 0.862 (95% CI: 0.755 - 0.968), respectively. DCP, AFP and CA-199 have diagnostic value for cHCC-CC, and the combination of DCP, AFP and CA-199 is useful for assisting diagnosis before histological examination. Clinicians should be alert for cHCC-CC when DCP, AFP, or CA-199 levels are abnormal.

Diagnostic Value of Serum Biomarkers for Patients Undergoing Curative Resection with Non-B, Non-C Hepatocellular Carcinoma.

To determine the diagnostic value of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) for patients with non-B, non-C hepatocellular carcinoma (NBNC HCC). Observational study. The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from June 2016 to June 2019. Patients with NBNC HCC diagnosed by histology were inducted after curative resection. Serum levels of AFP and DCP were determined. Their receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve (AUC) calculated. In subgroup analyses involving patients with hepatitis B core antibody (HBcAb) testing, the AUC of AFP and DCP were also calculated and compared. Serum levels of AFP and DCP were clearly increased in the NBNC HCC group relative to controls (p = 0.000 for both). The AUC for AFP, DCP and their combination (AFP+DCP) were 0.763 (95%CI: 0.712-0.814), 0.853 (95%CI: 0.811-0.894), and 0.867 (95%CI: 0.829-0.906), respectively. For HBcAb-positivity, the AUC of AFP and DCP were 0.7517 (95%CI: 0.6917-0.8116) and 0.8469 (95% CI: 0.7985-0.8963), respectively. For HBcAb-negativity, the AUC of AFP and DCP were 0.8083 (95%CI: 0.6993-0.9174) and 0.8740 (95%CI: 0.7901-0.9580), respectively. A combination of AFP and DCP is useful for assisting the diagnosis of NBNC HCC before surgery. AFP and DCP showed better diagnostic accuracy for HBcAb-negativity compared with HBcAb-positivity in NBNC HCC patients.

Issue Highlights

Issue Highlights

Dynamic Changes in Serum Markers and Their Utility in the Early Diagnosis of All Stages of Hepatitis B-Associated Hepatocellular Carcinoma.

ObjectiveThis study aimed to evaluate the individual and combined diagnostic values of serum alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), glypican-3 (GPC3) and golgi protein 73 (GP73) in diagnosing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).MethodsParticipants from Beijing YouAn Hospital were enrolled and divided into seven groups. Serum was collected and the levels of AFP, GPC3, GP73 and DCP were simultaneously measured with a protein array. Pearson’s χ2 test was applied to compare the clinicopathological characteristics. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance of the four markers.ResultsAs a single biomarker for differentiating HCC from all controls, AFP had a larger area under the curve (AUC) (0.798, 95% CI (0.754–0.838) than the other biomarkers, with a sensitivity of 77.3% and a specificity of 71.1%. Among the other combinations, AFP plus GPC3 and DCP (0.871, 95% CI (0.833–0.903)) was the best at differentiating HCC from all controls. In discriminating very early stage and early stage HCC from all controls, the AUC of GPC3 (0.744, 95% CI (0.690–0.793); sensitivity 62.8%; specificity 83.3%) was better than that of AFP (0.723, 95% CI (0.668–0.774); sensitivity 67.3%; specificity 71.7%). Among all biomarker combinations, the combination of AFP, GPC3 and GP73 had the largest AUC (0.843, 95% CI (0.796–0.883); sensitivity 84.1%; specificity 71.7%). AFP (AUC 0.726, 95% CI (0.662–0.784)) showed the best performance in the very early diagnosis of HBV-related HCC.ConclusionAs a single biomarker, AFP has an advantage in the very early and early diagnosis of HBV-related HCC. The combination of AFP, GPC3 and GP73 is the most suitable marker for the early diagnosis of HBV-related HCC. However, AFP remains the best biomarker for the very early diagnosis of HBV-related HCC, and the adding of one or more markers does not significantly improve the diagnostic accuracy.