Data suggest liver experts should take care when prescribing novel antiviral HCV drugs

Apr 02, 2011

Data presented at the International Liver Congress highlight the fact that new novel antiviral compounds for the treatment of hepatitis C virus (HCV) must be prescribed and monitored by experts and specialists to ensure resistance is minimised.1,2,3,4,5,6

Several studies observed the rapid onset of HCV resistance in patients treated with NS3-protease, NS5b-polymerase and NS5a inhibitors. Although these direct anti-virals are effective in both treatment-naive HCV patients and those who've been previously unresponsive to current treatment options, the development of resistant viral variants may cause problems in the future. In fact, two studies found HCV strains resistant to novel antiviral compounds pre-existed in patients who had never previously been exposed to the new antiviral compounds. In these patients, the variants were selected out by treatment.

Professor Heiner Wedemeyer, EASL's Secretary General, said: "While the regulatory approval of these new treatments is a highly anticipated milestone in HCV therapy, these studies show that care must be taken in the prescription and use of the new compounds. What we want to avoid is a rapid spread of HCV resistance within the patient population, which could drastically lower the effectiveness of the ."

The current standard of care for chronic HCV is the combination of pegylated interferon-alfa and , but only 40-54% of patients infected with HCV genotype 1 achieve a sustained virological response (SVR).7,8 Novel antiviral therapeutics are much sought after to treat patients who don't respond to the current standard of care. As such, a large number of new drugs for HCV are at various stages of preclinical and clinical development.9

However, as each new copy of the HCV genome exhibits on average one nucleotide change per replication cycle, HCV's replication machinery allows the virus to quickly come up with mutations that render it resistant to . This is a major concern for successful anti-HCV therapy.10

NS3 protease inhibitors block the function of the HCV NS3 protease, an enzyme essential for HCV's replication. NS5A replication complex inhibitors block the function of HCV nonstructural protein 5A, a multifunctional protein essential for HCV replication.10

Explore further: Unidentified fever kills 13 in DR Congo in 10 days

More information: References

1. McPhee F et al. Charactarizaion of virologic escape in HCV gentotype 1 null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052. Abstract presented at The International Liver Congress 2011

2. Chevaliez S et a. Molecular characterization of HCV resistance to telaprevir by means of ultra-deep pyrosequencing: pre-existing resistant variants and dynamics of resistant populations. Abstract presented at The International Liver Congress 2011

3. Hebner C et al. Emergence and persistence of ns5b mutations following combination treatment with tegobuvir (gs-9190) plus standard of care--long-term follow-up from the phase iib study gs-us-196-0103. Abstract presented at The International Liver CongressTM 2011

4. Zeuzem S et al. Boceprevir Resistance-Associated Variants (RAVs) are observed more frequently in HCV (gt1)-infected Patients with poor response to peginterferon alfa- 2B/ribavirin. Abstract presented at The International Liver Congress 2011 (1621)

5. Svarovskaia E et al. Abundant minority drug-resistant ns3 mutants detected by deep sequencing in hcv patients as early as 24 hours after initiating antiviral treatment. Abstract presented at the international liver congresstm 2011 (1773)

6. Sullivan J et al. Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials. (1783)

7. Fried M.W et al. "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection." New England Journal of Medicine 347.13 (2002): 975-82

8. Hadziyannis S J et al. "Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C - A randomized study of treatment duration and ribavirin dose." Annals of Internal Medicine 140.5 (2004): 346-55.

9. Shiffman M L. "Treatment of hepatits C in 2011:what can we expect?" Curr.Gastroenterol.Rep. 12 (2010): 70-75

10. Raffaele De Francesco and Giovanni Migliaccio (2005). Challenges and successes in developing new therapies for hepatitis C. Nature, 436, 953-960

Provided by European Association for the Study of the Liver

not rated yet
add to favorites email to friend print save as pdf

Related Stories

New treatment therapy helps inhibit hepatitis C

Jul 31, 2008

Two new studies examine the use of the nucleoside polymerase inhibitor, R1626, to the standard therapy for hepatitis C. The reports appear in the August issue of Hepatology, a journal published by John Wiley & Sons on beh ...

Scientists Model Hepatitis C Virus

May 25, 2007

One of the most common life-threatening viral infections in the United States today is hepatitis C virus (HCV). The standard treatment is successful in only about 50 percent of treated HCV chronic patients, with no effective ...

Early treatment is key to combating hepatitis C virus

Aug 08, 2008

Canadian researchers have shown that patients who receive early treatment for Hepatitis C virus (HCV) within the first months following an infection, develop a rapid poly-functional immune response against HCV similar to ...

Recommended for you

Nigeria confirms two new Ebola cases

6 hours ago

Two new cases of Ebola have emerged in Nigeria and, in an alarming development, they are outside the group of caregivers who treated an airline passenger who arrived with Ebola and died, Health Minister Onyebuchi ...

Senegal closes border as UN warns on Ebola flare-up

10 hours ago

Senegal has become the latest country to seal its border with a west African neighbour to ward off the deadly Ebola virus, as the new UN pointman on the epidemic said preparations must be made for a possible flare-up of the ...

Climate change could see dengue fever come to Europe

11 hours ago

Dengue fever could make headway in popular European holiday destinations if climate change continues on its predicted trajectory, according to research published in open access journal BMC Public Health.

American Ebola doc: 'I am thrilled to be alive'

19 hours ago

Calling it a "miraculous day," an American doctor infected with Ebola left his isolation unit and warmly hugged his doctors and nurses on Thursday, showing the world that he poses no public health threat ...

User comments : 0