Vitamin B12: A Non-invasive Biomarker for Monitoring Hepatocellular Carcinoma Development among Egyptian HCV-Infected Patients (original) (raw)
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Vitamin B12 and hepatitis C: molecular biology and human pathology.
Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.
Gut, 2013
In vitro, vitamin B12 acts as a natural inhibitor of hepatitis C virus (HCV) replication. To assess the effect of vitamin B12 on virological response in patients with chronic HCV hepatitis naïve to antiviral therapy. Ninety-four patients with chronic HCV hepatitis were randomly assigned to receive pegylated interferon α plus ribavirin (standard-of-care; SOC) or SOC plus vitamin B12 (SOC+B12). Viral response-namely, undetectable serum HCV-RNA, was evaluated 4 weeks after starting treatment (rapid viral response), 12 weeks after starting treatment (complete early viral response) and 24 or 48 weeks after starting treatment (end-of-treatment viral response) and 24 weeks after completing treatment (sustained viral response (SVR)). Genotyping for the interleukin (IL)-28B polymorphism was performed a posteriori in a subset (42/64) of HCV genotype 1 carriers. Overall, rapid viral response did not differ between the two groups, whereas the rates of complete early viral response (p=0.03), end-of-treatment viral response (p=0.03) and SVR (p=0.001) were significantly higher in SOC+B12 patients than in SOC patients. In SOC+B12 patients, the SVR rate was also significantly higher in carriers of a difficult-to-treat genotype (p=0.002) and in patients with a high baseline viral load (p=0.002). Distribution of genotype IL-28B did not differ between the two groups. At multivariate analysis, only easy-to-treat HCV genotypes (OR=9.00; 95% CI 2.5 to 37.5; p=0.001) and vitamin B12 supplementation (OR=6.9; 95% CI 2.0 to 23.6; p=0.002) were independently associated with SVR. Vitamin B12 supplementation significantly improves SVR rates in HCV-infected patients naïve to antiviral therapy.
Vitamin B12 binding protein as a tumour marker for hepatocellular carcinoma
Gut, 1978
Grossly raised levels of tumour related vitamin B12 binding protein, reflected by rises in serum vitamin B12 and unsaturated vitamin B12 binding capacity (UBBC), were found in three of 44 patients with hepatocellular carcinoma. All three were HBsAg negative and had normal serum alpha fetoprotein levels. The patients did not have underlying cirrhosis and the tumours contained characteristic intracellular inclusions. In the first patient the UBBC level fell during a paitial remission induced by adriamycin therapy and in the second patient UBBC levels rose with progression of her disease. In the third patient serum B12 binding protein levels fell after tumour resection. Assay and subsequent monitoring of serum vitamin B12 and UBCC may prove valuable in the assessment and follow-up of some patients with hepatocellular carcinoma whose alpha fetoprotein levels are normal.
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 ...
World Journal of Hepatology, 2012
AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age-and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at-20 ℃. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and-23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson's correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group Ⅰ) was 15 ± 5.2 ng/mL while in control (group Ⅱ) was 39.7 ± 10.8. For active vitamin D in group Ⅰ as 16.6 ± 4.8 ng/mL while in group Ⅱ was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group Ⅰ and 6.7 ± 2.17 in group Ⅱ. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group Ⅰ and 216.1 ± 5.38 in group Ⅱ. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and-23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group Ⅰa with bright hepatomegaly and included 14 patients. Group Ⅰb with perihepatic fibrosis and included 11 patients. Group Ⅰc with liver cirrhosis and included 11 patients. Group Ⅰd with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and-23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001).
Hepatitis C virus infection and its impact on Liver function in chronic HCV patients
Hepatitis C virus (HCV) is a blood-borne virus whose target organ is the liver. It causes both acute and chronic hepatitis, acute infection becomes chronic in approximately 80% of cases, and patients with chronic hepatitis C areat high risk of life-threatening complications, including cirrhosis in 20% of cases and hepatocellular carcinoma at an incidenceof 4–5% per year in cirrhotic patients. Virological testing has become essential in the management of HCV infection in order to diagnose infection, and most importantly guide treatment decisions and assess the virological response to antiviral therapy. Thus, the aim of presenting work was to investigate the relationship between the viral load and Liver biochemical/function testing according to the results of the laboratory tests.To achieve that aim, 20 chronic hepatitis C patients, enrolled from National Institute of Liver Disease Shebeen EL Koom Menofyia Governorate, Egypt. Blood samples were collected for different analysis including serological test by ELISA and molecular assays by qualitative polymerase chain reaction (PCR), also a routine lab test for measuring liver function test has been done. All patients included in our study were positive for anti-HCV antibody by ELISA test and were positive for the presence of HCV-RNA which detected by PCR. In conclusion, there is no significant variance between liver enzymes function and viral load. Data analysis for detecting HCV was an important factor for understanding the epidemiology and treatment strategies of HCV among Egyptian patients.
Prevalence of Vitamin-D deficiency is related to severity of liver damage in Hepatitis-C patients
Pakistan Journal of Medical Sciences
Objective: Serum Vitamin-D plays pivotal role in inflammatory and infectious diseases; among them liver infections are more distinct. This study was aimed to determine Vitamin-D status in HCV-infected patients and healthy controls in Faisalabad, Pakistan. Methods: We performed randomized cross-sectional study of 74 individuals from 20th August, 2017 to 20th February 2018 at The University of Faisalabad and Dar us Shifa Clinic, Faisalabad. Fifty-one patients were hepatitis C RNA-PCR positive (22 compensated cirrhotic and 29 decompensated cirrhotic patients). In addition, 23 subjects without liver disease were recruited as healthy control. HCV RNA–PCR was performed by ARTUS ® HCV QS-RGQ V1. Vitamin-D levels were measured by chemiluminescence. SPSS version 20 was used for statistical analysis. Results: The mean level of Vitamin-D was significantly lower in HCV patients in compensated and decompensated cirrhotic patients (26.85 ng/mL & 20.65 ng/mL respectively) as compared to healthy co...
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.
PloS one, 2012
In animal models and human cross-sectional studies, vitamin D deficiency has been associated with liver disease progression. Vitamin D supplementation has been suggested as a treatment to prevent disease progression. We sought to evaluate the role of vitamin D levels in predicting chronic liver disease development. We conducted a nested case-control study of vitamin D levels in subjects with (cases) and without (controls) liver histologic progression or clinical decompensation over the course of the HALT-C Trial. Vitamin D levels were measured at 4 points over 45 months. 129 cases and 129 aged-matched controls were included. No difference in baseline vitamin D levels were found between cases and controls. (44.8 ng/mL vs. 44.0 ng/mL, P = 0.74). Vitamin D levels declined in cases and controls over time (P = 0.0005), however, there was no difference in the level of decline (P = 0.37). Among study subjects with diabetes mellitius, baseline vitamin D levels were higher in cases, 49.9 ng/mL, than controls, 36.3 ng/mL. (P = 0.03) In addition, baseline vitamin D levels were higher in black case subjects, 32.7 ng/mL, than in black control subjects, 25.2 ng/mL (P = 0.08) No difference in vitamin D levels was found between patients with and without progression of hepatitis C-associated liver disease over 4 years. Our data do not suggest any role for vitamin D supplementation in patients with advanced chronic hepatitis C and raise the possibility that higher vitamin D levels may be associated with disease progression.