Hep C is acquired from blood products mostly, and intimate contact not so much, but it causes chronic hepatitis with liver failure in some, and can even cause liver cancer.
It is more treatable now than ever.
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STORY OF THE WEEK
Treatment Strategies for Hepatitis C
Review · April 15, 2014
TAKE-HOME MESSAGE
This review describes the rapid evolution of hepatitis C treatment strategies within the last few years, including the second-generation protease inhibitor simeprevir and the nucleotide polymerase inhibitor sofosbuvir.
In the near future, patients with hepatitis C will be able to choose from a variety of treatment options and potential cures, including those currently approved and other new and promising agents that are now awaiting FDA approval.
1 Expert Comment
Primary Care
Scott Cotler MD
A long-awaited transformation in the treatment of hepatitis C virus (HCV) is underway. Interferon-based regimens were fraught with adverse effects, long duration of therapy, and relatively low sustained virologic response (SVR) rates (where SVR = virologic cure). The first class of direct-acting antiviral agents (DAAs) to be approved were protease inhibitors, which block viral replication by inhibiting the HCV protease responsible for post-translational processing of the viral polypeptide. The addition of protease inhibitors (boceprevir, telaprevir, simeprevir) to pegylated interferon and ribavirin improved SVR rates and reduced treatment duration but added complexity and adverse effects. The next step was the approval of sofosbuvir, a nucleotide analogue that inhibits the HCV RNA-dependent RNA polymerase. Sofosbuvir, in combination with pegylated interferon and ribavirin for HCV genotype 1 improves SVR rates, reduces treatment duration to 12 weeks, and adds few adverse effects (headache and perhaps fatigue in some cases). Even more exciting, the interferon-free regimen of sofosbuvir and ribavirin achieves SVR rates > 90% when given for 12 weeks in patients with genotype 2, and slightly lower SVR rates with 24 weeks of treatment in genotype 3. We are now awaiting approval of all oral regimens for HCV genotype 1, which accounts for about 85% of HCV in the US.
The editorial by Hoofnagle and Sherker1 references three studies of the combination of sofosbuvir and ledipasvir, administered as one pill, once a day, for HCV genotype 1. Ledipasvir inhibits the HCV NS5A protein, which is involved in viral replication and assembly. Sofosbuvir and ledipasvir, given for 8, 12, or 24 weeks, depending on patient characteristics, consistently achieved SVR rates > 90%. These findings represent not merely a transformation, but a revolution, and additional DAA combination therapies with high SVR rates are in development.
Yet barriers to care for HCV remain. Only one-half of the > 3 million persons with HCV in the US have been diagnosed. To address this issue, the CDC and USPSTF recommend age-based screening for all persons born between 1945 and 1965, as well as risk-based screening. Cost is another matter. The retail cost for 12 weeks of sofosbuvir is $84,000 ($1000 per pill), and the price of DAA combination therapy has yet to be determined. Finally, as treating HCV becomes as easy as prescribing a pill for a few weeks, we must remember that HCV is a liver disease as well as an infectious disease. Patients with cirrhosis require specialized care and remain at risk for hepatocellular carcinoma even after achieving SVR (virologic cure).
Reference
Hoofnagle JH, Sherker AH. Therapy for Hepatitis C – The Costs of Success. N. Engl. J. Med. 2014;370(16):1552-1553.
ABSTRACT
Hepatitis C virus (HCV) treatment took a major step forward at the end of 2013 with the approvals of the second-generation protease inhibitor simeprevir (Olysio) and the nucleotide polymerase inhibitor sofosbuvir (Sovaldi). The interferon-free regimen of sofosbuvir and ribavirin is now available for genotype 2 and 3 patients. This regimen for 12 weeks is highly effective for genotype 2, whereas genotype 3 has proven to be more challenging and requires 24 weeks of therapy. Genotype 1 patients have reduced exposure to peginterferon-α with a 12-week regimen with sofosbuvir and a 24-week regimen with simeprevir. Genotype 4, 5, and 6 patients also respond well to the regimen of sofosbuvir, peginterferon-α, and ribavirin. In another landmark event, the initial approval of sofosbuvir included HCV/HIV-1 coinfected patients. Simeprevir and sofosbuvir also provide a window to the future with sustained virologic response (SVR) rates of >90% for genotype 1 when these agents are combined. Interferon-free regimens for genotype 1 patients have anticipated approvals in late 2014 or early 2015. Clinicians and patients will have the opportunity to discuss and select from current treatment options or await upcoming regimens. These potent new agents provide the tools to cure HCV for many patients.
Related Items
Costs of Hepatitis C Therapy Options
The Revolution Is Underway: New Treatment Options in Hepatitis C
The American Journal of Gastroenterology
The Rapid Evolution of Treatment Strategies for Hepatitis C
Am. J. Gastroenterol 2014 Apr 15;[EPub Ahead of Print], AJ Muir
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This abstract is available on the publisher’s site.
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Copyright © 2014 Elsevier Inc. All rights reserved.