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Hepatitis C Viral Infection (hepatitis + c_viral_infection)
Selected AbstractsExperimental models for hepatitis C viral infection,HEPATOLOGY, Issue 5 2009Andre Boonstra Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The majority of infected individuals develop a persistent infection, which is associated with a high risk of liver cirrhosis and hepatocellular carcinoma. Since its discovery 20 years ago, progress in our understanding of this virus has been suboptimal due to the lack of good model systems. However, in the past decade this has greatly accelerated with the development of various in vitro cell culture systems and in vivo small-animal models. These systems have made a major impact on the field of HCV research, and have provided important breakthroughs in our understanding of HCV infection and replication. Importantly, the in vitro cell culture systems and the small-animal models have allowed preclinical testing of numerous novel antiviral compounds for the treatment of chronic HCV infection. In this article, we give an overview of current models, discuss their limitations, and provide future perspectives for research directed at the prevention and cure of hepatitis C. (HEPATOLOGY 2009.) [source] Increased hepatotoxicity of tumor necrosis factor,related apoptosis-inducing ligand in diseased human liver,HEPATOLOGY, Issue 5 2007Xandra Volkmann Tumor necrosis factor,related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not in most normal cells and has therefore been proposed as a promising antitumor agent. Recent experiments suggested that isolated primary human hepatocytes but not monkey liver cells are susceptible to certain TRAIL agonists, raising concerns about the use of TRAIL in cancer treatment. Whether TRAIL indeed exerts hepatotoxicity in vivo and how this is influenced by chemotherapeutic drugs or liver disease are completely unknown. Employing different forms of recombinant TRAIL, we found that the cytokine can induce proapoptotic caspase activity in isolated human hepatocytes. However in marked contrast, these different TRAIL preparations induced little or no cytotoxicity when incubated with tissue explants of fresh healthy liver, an experimental model that may more faithfully mimic the in vivo situation. In healthy liver, TRAIL induced apoptosis only when combined with histone deacetylase inhibitors. Strikingly, however, TRAIL alone triggered massive apoptosis accompanied by caspase activation in tissue explants from patients with liver steatosis or hepatitis C viral infection. This enhanced sensitivity of diseased liver was associated with an increased expression of TRAIL receptors and up-regulation of proapoptotic Bcl-2 proteins. Conclusion: These results suggest that clinical trials should be performed with great caution when TRAIL is combined with chemotherapy or administered to patients with inflammatory liver diseases. (HEPATOLOGY 2007.) [source] Living related renal transplantation for end-stage renal disease after liver transplantation from a brain-dead donorINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2003TAKASHI KOBAYASHI Because the transplanted liver function had been excellent with the use of tacrolimus and mycophenolate mofetil, the same immunosuppressive agents with prednisolone were employed for the renal transplantation. Both grafts are functioning well without recurrence of hepatitis at 10 months after the renal transplantation. From our experience, renal transplantation should not be contraindicated even if the patient has undergone liver transplantation or has hepatitis C viral infection. [source] Single nucleotide polymorphism of the MxA gene promoter influences the response to interferon monotherapy in patients with hepatitis C viral infectionJOURNAL OF VIRAL HEPATITIS, Issue 3 2004F. Suzuki Summary. The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2,,5, oligoadenylate synthetase, dsRNA-activated protein kinase and MxA protein. Among these, MxA protein is assumed to be the most specific surrogate parameter for IFN action. This study was performed to elucidate whether a single nucleotide polymorphism (SNP) (G/T at nt-88) in the promoter region of the MxA gene influences the response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection. Polymorphisms of the MxA gene in 235 HCV patients were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequency of SNP was compared between sustained-responders (n = 78) and nonresponders (n = 157), as determined by biochemical and virological responses to IFN. Multivariate analysis showed that among all patients, HCV genotype, HCV RNA level and the SNP of the MxA gene were independent and significant determinants of the outcome of IFN therapy [odds ratio 3.8 (95% confidence interval 2.0,7.0), P < 0.0001; 0.27 (0.15,0.50), P < 0.0001; 1.8 (1.0,3.4), P = 0.0464, respectively]. Furthermore, among patients with a low viral load (,2.0 Meq/mL), MxA-T-positive patients were more likely to show a sustained response compared with MxA-T-negative patients [2.87 (1.3,6.3); 62%vs 36%; P = 0.0075]. Our findings suggested that the SNP of the MxA gene is one of the important host factors that independently influences the response to IFN in patients with chronic HCV infection, especially those with a low viral load. [source] Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 9 2006Qi He Abstract: Background/Aims: The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C (CHC). The aim of this study was to explore the relationship of the toll-like receptor (TLR) expression with the outcome of antiviral therapy in hepatitis C viral infection. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC patients before a 48-week treatment with pegylated interferon (PEG IFN) ,-2a and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase chain reaction (RT-PCR) was used to compare the relative abundance of TLR2,9 transcripts. Results: mRNA levels of TLR2, 3 and 6 were significantly higher in CHC subjects compared with normal controls (n=8). When patients were classified into non-responders (n=8) and sustained virological responders (n=7) according to the virological outcome of the treatment, there was a clear difference in baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition, the mRNA expression of IFN-, and nuclear factor of activated T cells (NFAT), which is exclusively expressed in activated T cells, was inversely correlated with that of TLR4, 6 and 9 in non-responders. Conclusions: TLRs mRNA levels are differentially expressed in baseline PBMC of chronic HCV-infected subjects with or without responsiveness to antiviral therapy. [source] Diffusion-weighted MR imaging of the liver of hepatitis C patientsNMR IN BIOMEDICINE, Issue 3 2003Yvan Boulanger Abstract Magnetic resonance diffusion-weighted imaging (DWI) of the liver was investigated to determine whether this method could be used to differentiate between the stages of fibrosis and inflammation for hepatitis C viral infection. DWI data were recorded for 18 hepatitis C patients and 10 control subjects using a modified pulse sequence allowing a 52,ms echo time delay. Acquisitions were performed with breath holding using five different b gradient factor values ranging between 50 and 250,s/mm2 and in the three axes. Apparent diffusion coefficient (ADC) values were measured from a 5.7,cm2 area in the central region of the liver. The inflammation and fibrosis grades were evaluated histologically on a biopsy sample. The mean ADC values were 2.30,±,1.28,×,10,3 and 1.79,±,0.25,× 10,3,mm2/s for hepatitis C patients and control subjects, respectively. Using our technique, no correlation could be found between the ADC values and the inflammation or fibrosis scores, indicating that tissue changes produced by hepatitis C do not appear to be quantifiable by DWI. Copyright © 2003 John Wiley & Sons, Ltd. [source] | ||||||||||