doi:10.1038/nindia.2012.128 Published online 31 August 2012
Using mathematical models to understand the behavior of the deadly hepatitis C virus, Indian scientists have shown that the microbe's sensitivity towards drugs varies in various phases of the disease1. They say early treatment could actually clear the virus entirely from the system for a sustained period.
"There are multiple phases when the sensitivity of the infection to drug treatment varies. We found that early treatment of the infection is likely to result in sustained virological response," says Raghvendra Singh, an assistant professor in the Department of Chemical Engineering at the Indian Institute of Technology Kanpur.
Singh got interested in the area partially from the concern that many victims may neither know of their infection nor when or how they got the virus, and partially while working with retroviruses as a gene delivery vehicle during his doctorate.
A large number of people around the world are infected with hepatitis C, the virus that primarily affects liver cells or hepatocytes. Majority of the newly infected patients become chronic carriers of the virus. Chronic infection progressively causes liver damage, resulting in cirrhosis and liver failure. Some patients also develop liver cancer due to the harmful proteins produced from the HCV genetic material in the infected cells. After the initial infection, the virus enters the blood stream and reaches the target tissues.
Then, the HCV particles attach themselves to the wall of the hepatocytes through receptors and co-receptors and the virus enters the cell. Inside the cell, it uses the host machinery to produce its proteins and replicate its genetic material, needed for the assembly and release of the new viral particles from the cells.
Significant progress has been made towards understanding the pathogenesis of the disease, structure of the virus, finding drug targets and development of drugs as well as understanding their effects on the disease. Yet, in nearly half of the treated patients, the virus persists or rebounds after the therapy.
Singh and his team's mathematical model also showed that the drug, which blocks new infections of the target cells, is more potent in clearing the infection than the drug, which blocks the production of the virus from the infected cells.
Currently, most patients are treated during the late phase of the infection, partly due to the late detection of the disease. "Our finding, on the other hand, recommends treatment during the acute phase and development of more sensitive screening methods to detect the infection early," he says.
Since vaccines for HCV and HIV are not available yet, drugs are the only hope for millions infected with these viruses. "It is encouraging to see that besides the interferon- and ribavirin, many newer drugs are undergoing clinical trial for HCV and there is a sense of optimism that the cure may be in sight," Singh says.