Clinical and Basic Characterization of a New Hepatitis-Associated Agent

Recently, Liver Research Unit in Chang Gung Medical Center has conducted a pilot study to search for new hepatitis virus. By performing nonspecific PCR followed by elimination of chromosome-derived sequences, foreign DNA fragments were obtained from the serum of a patient with non-A to E hepatitis. One of the sequences, named NV-F, contained a partial open reading frame, which was incomplete at the 5』 and 3』 ends. Using primers engineered against this sequence, the NV-F was detected in 17 of 69 (24.6%) patients with non-A to E hepatitis, including one with fulminant hepatitis. In contrast, it was detected in only 5 of 180 (2.8%) healthy individuals (see preliminary data). We hypothesized that the NV-F sequence was part of the genome of a hepatitis-associated agent, presumably from a new hepatitis virus. In this proposal, we aimed at defining the clinical and basic characteristics of this new hepatitis virus. In the following three years, we will performed the following projects: Year-1. Basic characterization of a new hepatitis-associated agent. We will characterize the NV-F associated agent, including nature of the genome, size, densities in cesium chloride gradient analysis, prevalence of coinfection in hepatitis B or C patients, and serum concentrations. Furthermore, we will develop an antibody against the putative partial reading frame. The antibody will be used to detect NV-F antigen in the liver biopsy tissues. Finally, we will try to clone the whole genome of NV-F. Year-2. Role of a new hepatitis virus in hepatocellular carcinoma. We will investigate the role of NV-F in hepatocellular carcinoma. Serum samples collected from patients with hepatocellular carcinoma will be subjected to NV-F detection. The clinicopathological characteristics as well as the treatment outcome of the hepatoma patients positive for NV-F will be analyzed to understand whether NV-F plays a role in hepatocellular carcinoma. Year-3. Clinical investigation of a new hepatitis virus in patients with chronic hepatitis C. We will study the pathological role of NV-F in patients with chronic hepatitis C. The prevalence of NV-F coinfection in hepatitis C will be determined. The clinicopathological characteristics will be compared between those with and without NV-F coinfection. All patients will subsequently receive standard treatment using Peg-interferon and ribavirin. The sustained response rate between the two groups of patients will be compared. The clearance rate of NV-F will be documented.

Project ID:PC9706-0009
External Project ID:NSC95-2314-B182-016-MY3