There are 71 million patients infected with hepatitis C worldwide. After decades of infection, chronic hepatitis C will further damage the liver and increase its risk of developing liver disease and liver cancer. Today, in the United States, the virus is the leading cause of death from liver disease.
Since the development of combination therapy, hepatitis C has been resistant to antiviral drugs and is highly likely to cause treatment failure. Resistance is particularly important in a group of drug therapies, but its mechanism of action to prevent viral reproduction is poorly understood. Researchers at the University of North Carolina at Chapel Hill have for the first time discovered how antiviral drugs known as NS5A inhibitors work with viruses, and their findings have found differences in hepatitis C virus. The results of this study have been published in PLOS Pathogens.
“When hepatitis C virus infects liver cells, it establishes replication complexes (RCs) within the cell,” said Dr. McGivern, associate professor of the UNC Infectious Diseases Division and the lead author of the study. “These can be seen as a factory that specifically replicates the genetic material of the virus. We want to know how long these plants will remain in infected cells after treatment with NS5A inhibitors.”
Before The team has found that NS5A inhibitors block the formation of new RCs, but do not affect existing RCs, but they eventually disappear during treatment. The team tested the half-life of existing RCs using NS5A inhibitors and found that different hepatitis C bacteria had different stopping phases.
“Most patients will get their hepatitis C infection clean after using antiviral therapy,” McGivern. “However, about 5% of patients fail during treatment, usually because of drug resistance. Our findings have been very important for this small group of patients. Is treatment failure due to replication complex conversion? Is it slow? Does some hepatitis C strains require longer treatments to work? Exploring these problems in depth will help to treat more viruses more effectively.” (Qiu Hai 205623)