Vitamin B12 binding protein as a tumour marker for hepatocellular carcinoma (original) (raw)

Plasma cobalamin level as a considered tumor marker for hepatocellular Carcinoma

Eastern Journal Of Medicine, 2016

Hepatocellular carcinoma (HCC) is one of the most common cancer among men and women. There are many serological tumor markers for the diagnosis of HCC. These are alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin, vitamin B12 binding protein and HCC associated alkaline phosphatase. The aim of this study was to evaluate the possibility of using vitamin B12 as a tumor marker for HCC. This cross sectional study was performed during a 2 year period, and serum samples were obtained from 38 HCC, 57 noncancerous cirrhotic and 82 healthy control groups. Vitamin B12 levels were determined by using an automated chemiluminescence system test kit. All HCC patients also had an underlying cirrhotic pattern. The period of the previous liver disease was 30.7±26.3 month in cirrhotic patients and 15.4±10 month in the HCC group. AFP and vitamin B12 levels in HCC patients were significantly higher (median AFP: 219 ng/ml, median B12:1106 ng/ml) than cirrhosis patients (median AFP:9,7 ng/ml, median B12:445 ng/ml) and control group (median B12:442 ng/ml) (p<0,001). In the HCC group, there was a good positive correlation between level of vitamin B12 and AFP (p:0.002) but this correlation was not appeared in cirrhosis group. We also examined whether the correlation between the tumor size and vitamin B12 levels and AFP levels. There was no correlation between these parameters (p>0.05). Vitamin B12 levels can be useful as tumor marker in addition to other tumor markers and imaging modalities. Additional studies should be performed related to this subject and the other liver masses without malignancies.

Vitamin B12: A Non-invasive Biomarker for Monitoring Hepatocellular Carcinoma Development among Egyptian HCV-Infected Patients

Letters in Applied NanoBioScience

Several studies have revealed an association between the high serum levels of vitamin B12 (vit B12) and the stage of chronic liver diseases. This study analyzes serum vit B12 levels among Egyptian hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) patients. The serum levels of vit B12 were examined in HCV patients without cirrhosis (HCV group, n=30), with cirrhosis (HCV+cirrhosis group, n=24), HCC patients (HCC group, n=30), and healthy individuals (control group, n=16). Serum vit B12 levels increased significantly in HCV+cirrhosis and HCC groups compared with the control group. HCC patients showed a significant increase in vit B12 levels compared with HCV patients with cirrhosis. Moreover, HCV patients without cirrhosis showed no significant increase in vit B12 level than the control group. Also, patients with fibrosis scores (F) from F2 to F4 showed a significant increase in serum vit B12 levels compared with the control group. Regarding correlations with liver functions, ...

Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Diagnostics

Background and Objectives: the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP. Materials and Methods: systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022. ...

Protein Induced by Vitamin K Absence or Antagonist-II Versus Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

Journal of Clinical Medicine Research, 2023

Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC. Methods: A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker. Results: Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70-0.72) and 0.64 (0.63-0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89-0.90) and 0.87 (0.87-0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88-0.90) and 0.78 (0.77-0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100). Conclusion: This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.

Evaluation of Diagnostic Utility of Protein Induced by Vitamin K Absence–II (PIVKA-II) in Hepatocellular Carcinoma

Indian Journal of Medical Biochemistry, 2019

Cancer is one of the leading causes of death in both economically developed and developing countries. Among all the cancers, hepatocellular carcinoma (HCC) was a significant contributor being the fifth most prevalent and third leading global cause of deaths related to cancer. The most common biomarker use in its detection is Alpha-fetoprotein (AFP), but it has low sensitivity and specificity. Many other biomarkers have been evaluated for HCC detection, of which Protein Induced by Vitamin K Absence-II (PIVKA-II) is one, that showed elevated levels in these patients. So, we tried to evaluate the role of PIVKA-II in diagnosing HCC and its usefulness in differentiating HCC and Hepatic Cirrhosis (HC). The study group consisted of 70 patients with liver disease-35 with HCC, 35 with cirrhosis; and 20 healthy study subjects who were age and gender matched. All patients and healthy subjects were evaluated for serum levels of both PIVKA-II and AFP. The median serum concentration of PIVKA-II in HCC, HC patients and healthy subjects were found to be 40.37 (23.3-79.38) ng/mL, 2.33 (1.03-3.72) ng/mL and 2.27 (0.12-12.87) ng/mL, respectively. To assess diagnostic utility, Receiver operating characteristic (ROC) curves plotted for both PIVKA-II and AFP. At a cutoff level of 6.715 ng/mL, PIVKA-II showed 85.71% sensitivity and 95.0% specificity, whereas AFP at a cutoff level of 11.8 ng/mL showed 77.14% sensitivity and 95% specificity. When both combined, their sensitivity increased to 94.29%. Also, there was a positive correlation of PIVKA-II levels with tumor size (p = 0.043), while no such significant association was found with AFP. Therefore, our study concludes that PIVKA-II is more sensitive than AFP in diagnosing HCC and differentiating it from Hepatic Cirrhosis; and when both combined, the sensitivity increased. Also, the positive correlation of Tumour size with PIVKA-II levels indicates that it may be useful in monitoring patients for progression of HCC.

Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

BMC Cancer, 2011

Background Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Methods Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. Results A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II productio...

Evaluation of Alpha-fetoprotein and Prothrombin Induced by Vitamin K Absence for Hepatocellular Carcinoma Diagnosis in Patients Admitted to a Large Transplant Center

Surgery, Gastroenterology and Oncology

Background & aims: Prothrombin induced by vitamin K absence-II (PIVKA II) is a diagnostic marker and a major prognostic factor for hepatocellular carcinoma (HCC) with limited experience in European patients. The aim of this study was to investigate the clinical utility of simultaneous measurement of alphafetoprotein (AFP) and PIVKA II for hepatocellular carcinoma (HCC) diagnosis. Methods: In a Romanian cohort, we performed a case-control study to compare the performances of AFP and PIVKA-II serum levels for HCC diagnosis. To determine the diagnostic value of both biomarkers in distinguishing HCC from liver cirrhosis, receiver operating characteristic (ROC) curves were constructed for each biomarker and their combination. Results: From January 2016 to December 2017, 54 cirrhotic patients and 59 HCC cases were prospectively included. ROC curve analysis showed that 63 mAU/mL and 6 ng/mL were the optimal cutoff values for PIVKA-II and AFP respectively for diagnosis of HCC in our cohort. For HCC diagnosis in patients with AFP levels <20 ng/mL, the combination of AFP and PIVKA II had a specificity of 93.8% vs. 68.8 for AFP (AUC 0.846 vs. 0.732 respectively) (p=0.03). For the diagnosis of early HCC, the combination of AFP and PIVKA-II had a sensitivity of 72.7% and a specificity of 90.9% vs. 69% and 75% for AFP (AUC 0.867 vs. 0.825, respectively). Conclusion: The diagnostic performance of a combination of AFP and PIVKA II is better to that of either marker alone, in the diagnosis of HCC especially in patients with AFP levels <20 ng/mL and in patients with early tumors.

Vitamin B12-binding Protein of Leukocytes as a Possible Major Source of the Third Vitamin B12-binding Protein of Serum

Blood, 1972

Much evidence suggests that granulocytes are a major source of serum vitamin B12-binding protein (BBP). The latter has three components: α-1-globulin BBP (Transcobalamin I, TC I), β-globulin BBP (TC II), and a recently described third BBP. Granulocytic BBP has appeared to be identical to TC I except in electrophoretic mobility. In the present study, the dominant BBP of leukocyte extracts from subjects with and without myeloproliferative disease behaved like the third serum BBP. With a few exceptions, more than half the leukocytic binder eluted with the "β globulins" on rapid DEAE-cellulose chromatography. At pH 8.6, electrophoretic mobility of the leukocytic BBP was always α2 or β. At ph 4.5, normal and chronic myelogenous leukemia leukocytic BBP, unlike TC I and TC II, showed little electrophoretic migration. These findings suggest that leukocytic BBP is probably heterogenous and that its major component resembles the third serum BBP more than it does TC I. The third seru...

Clinical utility of protein induced by vitamin K absence in patients with chronic hepatitis B virus infection

Biomedical reports, 2013

Hepatitis B virus (HBV) is a leading cause of hepatocellular carcinoma (HCC). α-fetoprotein (AFP) is a common tumor marker for the diagnosis of HCC, although not for protein induced by the absence of vitamin K or antagonist-II (PIVKA-II). The present study aimed to evaluate the role of PIVKA-II in the diagnosis of HCC in HBV-infected Vietnamese patients. A total of 166 consecutive HBV-infected Vietnamese patients were enrolled, including 41 HCC, 43 liver cirrhosis (LC), 26 chronic hepatitis (CH) and 56 asymptomatic carriers (ASC). AFP was examined using ELISA, while PIVKA-II was analyzed using Eitest PIVKA-II. The cut-off level of AFP and PIVKA-II was 20 ng/ml and 40 mAU/ml, respectively. Although the markers, AFP (344±356 ng/ml) and PIVKA-II (16,200±25,386 mAU/ml), were the highest in the HCC groups, only PIVKA-II in HCC was significantly higher compared to the other groups (P<0.001). The univariate analysis demonstrated that age over 50, male, genotype C, AFP and PIVKA-II were ...