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 infected patients.
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,” explains Talal.
“There has been no precise definition of the duration of treatment based upon serial measurements of the virus in the liver,” says Talal. “This is the first time that serial measurements in the liver have been performed during antiviral therapy.”
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 says.
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: 10 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,” says Talal.
They also found higher levels of the drug in blood than in the liver.
“These findings can affect the duration of therapy,” says Talal, adding that they can also help to identify when drug-resistant variants of the virus emerge in blood and in the liver.
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.
Source: University at Buffalo
Dear Helpdesk: Working in a Toxic Health Care Environment
March 28th 2024Dear Helpdesk is your steadfast companion, offering life coaching and workplace advice from 2 seasoned IPs for some of your most challenging real-life situations. Let us help you navigate the intersection between work and life, guiding you to navigate the dynamic world of infection prevention with confidence and grace. This article is on handling a toxic health care environment.
Product Locator: Spring and Early Mother's Day Gift Guide for Infection Prevention Personnel
March 27th 2024Whether it's a spring holiday, birthdays, or no reason at all, infection prevention personnel love to give and receive gifts that help at the end of a stressful day. Infection Control Today® offers some gift ideas for infection prevention personnel and their families.
Catching Up With Vangie Dennis, AORN 2022-2023 President at AORN 2024
March 26th 2024Infection Control Today (ICT) had the privilege of catching up with Vangie Dennis, MSN, RN, CNOR, CMLSO, at the Association of periOperative Registered Nurses' (AORN’s) International Surgical Conference & Expo 2024. As the former president of AORN and an esteemed figure in perioperative services, Vangie Dennis shared insights into her recent endeavors and the exciting new chapter she's embarked upon.
How To Optimize Your Time Management Strategies for the Busy Infection Preventionist
March 25th 2024Is your calendar resembling a chaotic masterpiece of overlapping tasks? Join the club of infection preventionists striving to balance responsibilities. Dive into proven strategies from a fellow infection preventionist to reclaim control of your time, streamline tasks, and boost productivity effectively. This is an IP Lifeline article.