History and Background of Hepatitis C Virus

Human hepatitis C virus (HCV) was identified in 1989 using molecular biological techniques.  The explosion of information following the description of the nucleic acid sequences, and genomic complexity, has enhanced our understanding of the epidemiology of majority of HCV serotypes,. The infection process, and patho-biology of this agent is currently being investigated in many laboratories. 

HCV exists as a single stranded, rapidly mutating, heterogeneous group of viruses sharing sequence homology.  HCV is similar to the viruses of human flavivirus group, a member of the animal pestivirus family. The flaviviruses are the causative agents of dangue fever and yellow fever in man, while the pestiviruses cause bovine diarrhea. 

Several genotypes of HCV, their subtypes, roughly correlate with geographic distribution of hepatitis. The significance of this heterogeneity is currently not understood. The natural history of chronic infection with HCV is not known due to the absence of an in-vitro system with self replicating HCV. At CIMM, we have developed a method for the in-vitro isolation and replication of HCV from infected patients. The acquisition of HCV may be due to several sources of exposure such as infected blood and blood products (e.g., platelets, packed cells, plasma, clotting factor), and drug abuse. In addition, it can be acquired sporadically from unknown sources or from the community.  Roughly, half of all patients with HCV have no known source of infection, and the remainder includes intravenous drug abusers (42%), blood transfusion patients (6%), individuals with history of hemodialysis, and health care workers exposed to blood (2%).

Electron micrograph of HCV grown in vitro from a human patient at CIMM

In May 1990, serologic tests for the detection of anti-HCV antibody by EIA were licensed and became commercially available in the United States.  Studies have shown that HCV is the etiologic agent of hepatitis in majority of patients. It is transmitted as a blood born agent causing hepatitis worldwide.  This type of nonA-non-B hepatitis was first identified and characterized in studies of post transfusion hepatitis in early 1970s. Persons at increased risk of acquiring hepatitis C include potential drug users, health-care workers with occupational exposure to blood; hemodialysis patients, and recipient of whole blood, cellular blood components.  Approximately 4 million Americans are considered to be chronically infected by HCV. 

An average of 50% of patients with either post-transfusion or community-acquired hepatitis C followed for at least twelve months develop biochemical evidence of chronic liver disease.  Of patients with transfusion-associated chronic HCV hepatitis who undergo biopsy within 5 years after onset, greater than or equal to 40% have histologic evidence of chronic active hepatitis and 10-20% have evidence of cirrhosis; many of these patients have no clinical manifestations of their disease.  In contrast, biopsy specimens from patients with community-acquired chronic hepatitis, less than 20% have evidence of chronic active hepatitis and 3% have evidence of cirrhosis within 4 years after the onset of disease. 

Human herpes virus type-6 (HHV-6)History and Background

Neuronal cell