Hepatitis C: Natural History, Pathogenesis, Therapy and Prevention

The summary for the Hepatitis C: Natural History, Pathogenesis, Therapy and Prevention grant is detailed below. This summary states who is eligible for the grant, how much grant money will be awarded, current and past deadlines, Catalog of Federal Domestic Assistance (CFDA) numbers, and a sampling of similar government grants. Verify the accuracy of the data FederalGrants.com provides by visiting the webpage noted in the Link to Full Announcement section or by contacting the appropriate person listed as the Grant Announcement Contact. If any section is incomplete, please visit the website for the National Institutes of Health, which is the U.S. government agency offering this grant.

Hepatitis C: Natural History, Pathogenesis, Therapy and Prevention: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Allergy and Infectious Diseases (NIAID), and National Institute on Drug Abuse (NIDA), invite grant applications for both basic and clinical research in the areas of pathogenesis, natural history, therapy and prevention of hepatitis C. According to the National Health and Nutrition Examination Survey (NHANES) of 19881994, 3.9 million Americans were infected with hepatitis C, and of this group, 2.7 million are estimated to have chronic infection. These estimates likely under represent the true prevalence of HCV infection since NHANES was a population-based household survey that excluded several groups with a substantially increased prevalence of infection, such as persons who are incarcerated, homeless, or institutionalized due to disability or mental illness. HCV is the most common blood-borne infection in the United States. HCV transmission occurs primarily through exposure to infected blood. Transmission risk factors include injection drug use, blood transfusion prior to 1992, solid organ transplantation from infected donors, unsafe medical practices, occupational exposure to infected blood, birth to an infected mother, multiple heterosexual partners, and high-risk sexual practices. High HCV seroprevalence rates (from 15 to 50 percent) have been observed in specific subpopulations, such as the homeless, incarcerated persons, veterans being followed at Veterans Affairs Medical Centers, and hemophiliacs, with the highest rates (70 percent to 90 percent) reported in injection drug users. In the general population, persons aged 40 to 59 years have the highest prevalence of HCV infection, and in this age group, the prevalence is highest in African-Americans (6.1 percent). Because of the high rate of persistent infection long-term complications of chronic HCV infection are projected to increase in the next 15 years. Acute hepatitis C leads to chronic infection in approximately 75 percent of cases. Age at the time of infection appears to be an important contributing factor, spontaneous remission occurring more frequently in younger infected individuals. Chronic hepatitis C is often asymptomatic and can be mild; but in 20 percent of patients, the chronic infection leads to progressive liver disease and ultimately cirrhosis and end stage-liver disease. These conditions increase the risk of developing hepatocellular carcinoma (HCC). There is little evidence that the risk of progression of liver disease is affected significantly by virologic factors, including viral levels in the serum, viral genotype, and quasispecies diversity. However, many host factors have been found to increase this risk, including older age, male gender, and an immune suppressed state, such as HIV co-infection. Environmental factors that may complicate or worsen the course of chronic hepatitis C are alcohol, iron overload, obesity, nonalcoholic fatty liver disease, schistosomal co- infection, hepatotoxic medications, and possibly environmental contaminants. The incidence of HCV-related liver cancer is continuing to rise in the United States and worldwide, in part because of the increasing numbers of persons who have been chronically infected for decades, the presence of comorbid factors, and the longer survival of persons with advanced liver disease due to improved management of complications. Although significant advances have been made in the development of treatments for chronic hepatitis C, their efficacy is not universal, and outcome of treatment is considerably affected by viral and host factors. In optimally selected patients, the best current therapies are effective in 40 to 50 percent of cases infected with viral genotype 1 and in 70 to 80 percent of those infected with genotype 2 and 3. Thus, the focus of the RFA is to elucidate the mechanism(s) responsible for the acute and chronic injury caused by hepatitis C, define the factors that determine the course and long-term outcome of chronic infection, including a search for markers of fibrosis progression, and establish the basis for resistance to the current therapeutic regimens followed by focused efforts to improve the response rate with better and less toxic drugs. Since the most effective way to prevent the liver disease caused by hepatitis C is through the development of a preventive vaccine, this RFA also supports the submission of applications that aim at generating a vaccine for hepatitis C.