Vitamin D status and viral response to therapy in hepatitis C infected children

AIM: To study the frequency of vitamin D deficiency in patients with hepatitis C virus(HCV) infection and to evaluate the role of vitamin D supplementation in improving antiviral therapy.METHODS: Sixty-six children aged from 7-14 years(mean ± SD, 11.17 ± 2.293) diagnosed with HCV infection were matched to 28 healthy controls. Serum levels of 25(OH) D3, calcium, phosphorus, alkaline phosphatase and plasma level of parathormone were measured. Quantitative PCR for HCV was performed Bone density was determined by dual energy X-ray absorptiometry. All cases received conventional therapy, and only 33 patients received vitamin D supplementation.RESULTS: Children with HCV showed significantly increased levels of HCV RNA(P 0.001), parathormone(P 0.01) and decreased vitamin D levels(P 0.05)(33.3% deficient and 43.3% insufficient) compared with controls. Abnormal bone status(Z score-1.98 ± 0.75) was found in ribs, L-spine, pelvis and total body. Cases treated with vitamin D showed significant higher early(P 0.04) and sustained(P 0.05) virological response. There was a high frequency of vitamin D deficiency among the Egyptian HCV children, with significant decrease in bone density. The vitamin D level should be assessed before the start of antiviral treatment with the correction of any detected deficiency. CONCLUSION: Adding vitamin D to conventional Peg/RBV therapy significantly improved the virological response and helped to prevent the risk of emerging bone fragility.     

Relationship between vitamin D and IL-23,IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

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 ageand 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 subjectswere 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 (groupⅠ) was 15 ± 5.2 ng/mL while in control (group Ⅱ) was 39.7 ± 10.8. For active vitamin D in groupⅠas 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 Ⅰand 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-in-fected 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 he patocellular 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).CONCLUSION:Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.     

Mineralization of ~(14)C-ring Labelled 2,4-D in Egyptian Soils Under Aerobic and Anaerobic Conditions

Obiectives To study the mineralization of 2,4-D in clay and clay loam Egyptian soils under subtropical conditions over a period of 90 d. Methods Using 14C-ring labelled pesticide, laboratory studies under aerobic and anaerobic conditions were conducted. 14C-activity in solutions was directly determined by liquid scintillation counting. Unextractable soil residues were determined by combustion. The nature of methanolic 14C-residues was determined by thin layer and high performance liquid chromatographic analysis. Results Under aerobic conditions 10%-14% of applied dose was mineralized during 90 d irrespective of soil type. The soil extractable pesticide residues decreased with time and the bound residues gradually increased. The highest binding capacity of about 26%-29% was observed in clay soil under aerobic conditions after 90 d. A good balance sheet was obtained and the percentage recovery was generally between 91% and 100%. Conclusion The mineralization of 2,4-D in clay soil was higher than that in c     

槲寄生fraxini-2在晚期肝细胞癌的治疗疗效及安全性:一项Ⅱ期临床实验(英文)

Objective:New systemic therapies are needed to improve the prognosis of patients with advanced-stage hepatocellular carcinoma.The study was conducted to determine the efficacy and safety of viscum fraxini-2 in advanced Hepatocellular carcinoma.Methods:A phase Ⅱ study with a two-stage design that enrolled a total of 120 patients with chemotherapy naive advanced hepatocellular carcinoma.The mistletoe preparation for the study is an aqueous injectable solution that contains one milliliter of viscum fraxini.Two...     

Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children

AIM:To investigate the safety and efficacy of a Hansenula-derived PEGylated(polyethylene glycol)interferon(IFN)-alpha-2a(Reiferon Retard)plus ribavirin customized regimen in treatment-na?ve and previously treated(non-responders and relapsers)Egyptian children with chronic hepatitis C infection.METHODS:Forty-six children with chronic hepatitis C virus(HCV)infection were selected from three tertiary pediatric hepatology centers.Clinical and laboratory evaluations were undertaken.Quantitative polymerase chain reaction(PCR)for HCV-RNA was performed before starting treatment,and again at 4,12,24,48,72wk during treatment and 6 mo after treatment cessation.All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk.Thirty-four patients were treatment-na?ve and 12 had a previous treatment trial.Patients were then divided according to PCR results into two groups.GroupⅠincluded patients who continued treatment on a weekly basis(7-d schedule),while groupⅡincluded patients who continued treatment on a 5-d schedule.Patients from either group who were PCR-negative at week 48,but had at least one PCRpositive test during therapy,were assigned to have an extended treatment course up to 72 wk.The occurrence of adverse effects was assessed during treatment and follow up.The study was registered at www.ClinicalTrials.gov(NCT02027493).RESULTS:Only 11 out of 46(23.9%)patients showed a sustained virological response(SVR),two patients were responders at the end of treatment;however,they were lost to follow up at 6 mo post treatment.Breakthrough was seen in 18(39.1%)patients,one patient(2.17%)showed relapse and 14(30.4%)were non-responders.Male gender,short duration of infection,low viral load,mild activity,and mild fibrosis were the factors related to a better response.On the other hand,patients with high viral load and absence of fibrosis failed to respond to treatment.Before treatment,liver transaminases were elevated.After commencing treatment,they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment,while they increased again significantly in non-responders(P=0.007 and 0.003 at week 24 and 72 respectively).The 5-d schedule did not affect the response rate(1/17 had SVR).Treatment duration(whether 48 wk or extended course to 72 wk)gave similar response rates(9/36 vs 2/8 respectively;P=0.49).Type of previous treatment(short acting IFN vs PEG-IFN)did not affect the response to retreatment.On the other hand,SVR was significantly higher in previous relapsers than in previous non-responders(P=0.039).Only mild reversible adverse effects were observed and children tolerated the treatment well.CONCLUSION:Reiferon Retard plus ribavirin combined therapy was safe.Our customized regimen did not influence SVR rates.Further trials on larger numbers of patients are warranted.