vitamin-b-12 and Hepatitis-C

Neurological complications occur in a large number of patients with chronic hepatitis C virus (HCV) infection and range from peripheral neuropathy to cognitive impairment. We studied the association between neuropathy and HCV-related chronic liver disease.. Fifty patients with HCV-related chronic liver disease were enrolled in this prospective case-control study. Patients were classified into two groups: mild and severe corresponding to a model for end-stage liver disease (MELD) score <14 and a MELD score >14, respectively. Complete neurological examination and nerve conduction studies have been done for all patients. All patients in addition to 25 healthy control subjects were tested for their serum B12 levels.. Twenty-two percent of patients had sensory abnormality, 18 % had motor abnormality, while 10 % had both sensory and motor abnormalities. Autonomic function tests and nerve conduction studies revealed that 23 patients (46 %) had evidence of neuropathy and 10 patients (20 %) had both peripheral and autonomic neuropathy. Neuropathies were not related to the severity of the liver disease. Serum B12 level had a very wide range among patients with no relation between its level and neuropathy. Vitamin B12 level was significantly and directly correlated to MELD score and age.. Peripheral and autonomic neuropathy has high prevalence in patients with HCV-related chronic liver disease. On the other hand, vitamin B12 level is high in those patients and there is no role for vitamin B12 in the liver cirrhosis-related neuropathy.

Topics: Adult; Aged; Autonomic Nervous System; Autonomic Nervous System Diseases; Case-Control Studies; Female; Hepatitis C; Humans; Liver Cirrhosis; Male; Middle Aged; Neural Conduction; Peripheral Nervous System Diseases; Prospective Studies; Severity of Illness Index; Vitamin B 12; Vitamin B Complex; Young Adult

The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism.

Topics: Animals; Antiviral Agents; Biomarkers; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation, Viral; Genes, Reporter; Green Fluorescent Proteins; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Interferon alpha-2; Interferon-alpha; Larva; Liver; Mutant Chimeric Proteins; Recombinant Proteins; Ribavirin; RNA, Messenger; Viral Core Proteins; Vitamin B 12; Zebrafish

A better understanding of the relationship of homocysteine with cardiovascular risk factors is needed. The objectives of this study were to assess the serum level of homocysteine in HIV-infected patients and to analyse the possible association of increased levels of the amino acid with cardiovascular risk factors, demographic and clinical characteristics of participants.. Cross-sectional study carried out as a supplementary task to the usual controls necessary in HIV-infected patients in the outpatient clinic of the Hospital General of Castellon, Spain. For two consecutive visits the demographic, clinical and HIV-related characteristics and blood analyses results were obtained for each participant. Homocysteine serum level was documented and the possible association of the amino acid with all the other study variables was assessed with a multiple linear regression analysis.. A total of 145 patients were included. The mean homocysteine serum level of all participants was 11.9 ± 5.9 µmol/L. A total of 54 patients (37%) presented homocysteine serum levels higher than the upper limit of normal. An association was found between higher homocysteine serum level and the following variables: family history of early coronary disease (P = 0.027), sexual HIV risk behaviour (P = 0.016), hepatitis C virus co-infection (P = 0.002), higher height (P = 0.002), higher diastolic blood pressure (P = 0.049), lower serum level of folic acid (P <0.001), and lower serum level of vitamin B12 (P = <0.001).. In the HIV population, increased homocysteine serum level is associated with sexual risk behaviour and hepatitis C virus coinfection.

Topics: Adult; Cardiovascular Diseases; Coinfection; Cross-Sectional Studies; Female; Folic Acid; Hepacivirus; Hepatitis C; HIV; HIV Infections; Homocysteine; Humans; Male; Risk Factors; Risk-Taking; Sexual Behavior; Vitamin B 12

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.

Topics: Antiviral Agents; Base Sequence; Classical Swine Fever Virus; Dose-Response Relationship, Drug; Encephalomyocarditis virus; Hepacivirus; Hepatitis C; Humans; Liver; Molecular Sequence Data; Protein Binding; Protein Biosynthesis; Regulatory Sequences, Nucleic Acid; Ribosomes; Substrate Specificity; Thermodynamics; Viral Load; Virus Replication; Vitamin B 12

The treatment of two cases of hepatitis C using herbal medicine and nutritional supplements is presented. The selection of medicinals was based upon both biomedical findings and traditional Chinese medical diagnosis. The text describes the course of each patient's illness documented both subjectively and objectively using blood values and traditional Chinese medicine analysis as parameters. Explanation and/or citations are given for each medicinal used. Both patients improved during the course of treatment; subjective signs and symptoms (especially fatigue) as well as liver enzyme levels demonstrated improvement.

Topics: Ascorbic Acid; Diagnosis, Differential; Drugs, Chinese Herbal; Female; Folic Acid; Hepatitis C; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Vitamin B 12