Automated summaries of serious adverse events in the hepatitis C antiviral long-term treatment against cirrhosis trial.

BACKGROUND: Even though adverse event (AE) collection and official accounting are mandatory for clinical trials, there are limited detailed guidelines specifying how to summarize the event for reporting in a timely and expeditious manner. This article details the AE and serious adverse event (SAE) reporting summary developed for a large multi-center National Institutes of Health (NIH)-sponsored clinical trial. PURPOSE: To review and analyze the large volume of AE data reported by 10 sites (806 SAEs and 19,034 AEs from August 2000 to May 2007) the automated SAE summary was developed. It was designed to ensure timeliness and clarity in the complex process of AE review and reporting. METHODS: The AE and SAE case report forms (CRFs) as well as the automated SAE summary were developed within a database management system developed by the Data Coordinating Center (DCC) which allowed for web-based data entry at the DCC and 10 sites and offered immediate overall and site-specific reports accessible by the DCC, site, and NIH project staff. RESULTS: The automated SAE summary pulled data from multiple CRFs to create a succinct and informative summary and allowed for prompt and easy reporting to the regulatory agencies. The summary was adaptable to the needs of reviewers because of the availability of multiple search options.

Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-alpha and plasmacytoid dendritic cell loss in chronic HCV infection.

IFN-alpha production by plasmacytoid dendritic cells (PDCs) is critical in antiviral immunity. In the present study, we evaluated the IFN-alpha-producing capacity of PDCs of patients with chronic hepatitis C virus (HCV) infection in treatment-naive, sustained responder, and nonresponder patients. IFN-alpha production was tested in PBMCs or isolated PDCs after TLR9 stimulation. Treatment-naive patients with chronic HCV infection had reduced frequency of circulating PDCs due to increased apoptosis and showed diminished IFN-alpha production after stimulation with TLR9 ligands. These PDC defects correlated with the presence of HCV and were in contrast with normal PDC functions of sustained responders. HCV core protein, which was detectable in the plasma of infected patients, reduced TLR9-triggered IFN-alpha and increased TNF-alpha and IL-10 production in PBMCs but not in isolated PDCs, suggesting HCV core induced PDC defects. Indeed, addition of rTNF-alpha and IL-10 induced apoptosis and inhibited IFN-alpha production in PDCs. Neutralization of TNF-alpha and/or IL-10 prevented HCV core-induced inhibition of IFN-alpha production. We identified CD14+ monocytes as the source of TNF-alpha and IL-10 in the HCV core-induced inhibition of PDC IFN-alpha production. Anti-TLR2-, not anti-TLR4-, blocking Ab prevented the HCV core-induced inhibition of IFN-alpha production. In conclusion, our results suggest that HCV interferes with antiviral immunity through TLR2-mediated monocyte activation triggered by the HCV core protein to induce cytokines that in turn lead to PDC apoptosis and inhibit IFN-alpha production. These mechanisms are likely to contribute to HCV viral escape from immune responses.

The role of hepatitis C support groups.

Chronic hepatitis C infection has become the most common blood-borne pathogen in the United States, affecting an estimated 4 million Americans. The diagnosis of chronic hepatitis C carries with it threats to quality of life and life expectancy. Furthermore, the label of chronic hepatitis C encumbers the individual with concerns about contagiousness, social isolation, altered role function, stigmatization, loss of control, and the uncertainty and anxiety inherent in any chronic illness. These factors have a significant emotional effect on the affected individual and his or her family. Although biomedical research continues to seek new therapies for hepatitic C virus and methods of prevention and control, our health and social systems also must develop strategies to facilitate adjustment, provide education and caring, and enhance well-being. Abundant research supports the premise that social support facilitates patient well-being and contributes to health and health promotion through interpersonal interactions. Gastroenterology nurses are well positioned to facilitate improved outcomes in patients with chronic hepatitis C virus by initiating interventions designed to enhance existing sources of social support or to promote new ones. Development of psychosocial interventions, such as support groups, aimed at maintaining or fostering social support, may improve health outcomes and promote a higher health-related quality of life for persons living with chronic hepatitis C virus.