BUFFALO, N.Y. – As new treatments for hepatitis C virus
(HCV) are approved, biomedical scientists are exploring their
mechanisms and what they reveal about the virus. An online
publication this month in Hepatology is the first to report
real-time tracking of viral decay in the liver and blood in 15
patients with HCV.
Led by Andrew H. Talal, MD, University at Buffalo professor of
medicine in the Division of Gastroenterology, Hepatology and
Nutrition and corresponding author, the study is the first to trace
in real-time how the drug telaprevir inhibits viral replication in
the liver and how it clears HCV from infected cells and plasma of
The study was sponsored by Vertex Pharmaceuticals, which makes
telaprevir, an HCV protease inhibitor.
“Our findings begin to define for how long patients may
need to be treated in order to achieve viral eradication,”
“There has been no precise definition of the duration of
treatment based upon serial measurements of the virus in the
liver,” said Talal. “This is the first time that serial
measurements in the liver have been performed during antiviral
In previous studies, a more invasive procedure – core
needle biopsy – was used to sample the liver in HCV
infection. In the current study, fine needle aspiration was used;
this method is better tolerated by patients and allows for repeated
sampling at more time points than core needle biopsy.
“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,” Talal explained.
In the study, conducted at Weill Cornell Medical College in New
York City, 15 patients with chronic HCV infection were treated with
telaprevir-based triple therapy (consisting of telaprevir/pegylated
interferon alfa/ribavirin), an HCV treatment regimen that was
approved by the Food and Drug Administration in 2011.
Fine needle aspiration of the liver was performed before
treatment on all 15 patients and at these intervals following
treatment: ten hours, on days 4 and 15, and at week eight. Viral
kinetics, resistance patterns, drug concentrations and host
transcription profiles were measured.
Of particular interest were the study’s findings regarding
the rate of decay for viral ribonucleic acid (RNA), an indicator of
how quickly the virus is being eradicated.
“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,” said Talal.
They also found higher levels of the drug in blood than in the
“These findings can affect the duration of therapy,”
said Talal, adding that they can also help to identify when
drug-resistant variants of the virus emerge in blood and in the
The findings also may have relevance to the development of other
methods of treating HCV, such as vaccines that could be used to
control the infection, he added.
Talal conducts research on HCV in the Clinical and Translational
Research Center in the School of Medicine and Biomedical Sciences
and he sees patients as a physician with UBMD, the physician
practice plan of the UB medical school. Talal has had additional
research projects funded by Vertex Pharmaceuticals.
In addition to Talal, who has an adjunct appointment at Weill
Cornell, co-authors of the paper are: Rositsa B. Dimova, PhD,
research assistant professor in the departments of medicine and
biostatistics at UB; Marija Zeremski, PhD, senior research
associate at Weill Cornell and research assistant professor of
medicine at UB; Christine M. Cervini, RN, staff associate in
medicine and Ira M. Jacobson, MD, chief of the division of
gastroenterology and hepatology, both of Weill Cornell; Eileen Z.
Zhang, Min Jiang, Marina S. Penney, James C. Sullivan, Martyn C.
Botfield, Ananthsrinivas Chakilam and Rishikesh Sawant, all of
Vertex Pharmaceuticals and Ann D. Kwong, of InnovaTID
Pharmaceuticals, formerly of Vertex Pharmaceuticals. Jacobson has
served as a paid consultant to Vertex.