Published June 24, 2014
A study led by Andrew H. Talal, MD, is the first to trace in real time how the drug telaprevir inhibits viral replication in the liver and clears hepatitis C virus (HCV) from the cells and plasma of infected patients.
“Our findings begin to define for how long patients may need to be treated in order to achieve viral eradication,” says Talal, professor of medicine in the Division of Gastroenterology, Hepatology and Nutrition.
“Until now, there has been no precise definition of the duration of treatment based upon serial measurements of the virus in the liver,” he explains. “This is the first time such measurements have been performed during antiviral therapy.”
The study, conducted at Weill Cornell Medical College in New York City, involved 15 patients with chronic HCV infection who were treated with telaprevir-based triple therapy.
The researchers sampled their livers at various intervals before and after treatment. They measured viral kinetics, resistance patterns, drug concentrations and host transcription profiles.
The triple therapy is an HCV treatment regimen approved by the Food and Drug Administration in 2011.
Findings regarding the rate of decay for viral ribonucleic acid (RNA) — an indicator of how quickly the virus is being eradicated — are of particular interest.
“We found that HCV RNA decay in the liver lagged behind that in the peripheral blood, which has implications for how long the virus may persist in the body and the possible duration of treatment needed,” Talal says.
Researchers also found higher levels of telaprevir in blood than in the liver.
“These findings can affect the duration of therapy,” said Talal, adding that they can also help identify when drug-resistant variants of the virus emerge in the blood and liver.
The findings also may have relevance for the development of other methods of treating HCV, such as vaccines to control the infection, he adds.
Talal and his team used fine-needle aspiration to sample the livers and blood of patients in the study.
Compared to more invasive core needle biopsy used in previous studies, this technique is better tolerated by patients and allows for repeated sampling at more time points.
“Fine-needle aspiration enables us to sample the liver repeatedly during the course of treatment to better understand what’s happening with the virus, how these drugs work and how to tailor therapy to the patient,” says Talal.
The study, Telaprevir-Based Treatment Effects on Hepatitis C Virus in Liver and Blood, has been published in Hepatology. Other UB co-authors are:
Additional co-authors are from Weill Cornell, InnovaTID Pharmaceuticals and Vertex Pharmaceuticals.