Newest developments in antiviral treatment options in hepatitis C virus infection (HCV)

Last Updated on July 9, 2014 by Joseph Gut – thasso

July 09, 2014 – A very exiting review article in the British Medical Journal (BMJ) on July 07, 2014 discusses the newest developments in the treatment options in HCV infection. This is an excerpt from the article, which can be found here.

Hepatitis C virus (HCV) infection is a substantial health problem worldwide. Most patients infected with HCV remain chronically infected, with an increased risk of cirrhosis and hepatocellular carcinoma. Although they are associated with toxicities and low sustained viral response rates, interferon alfa and ribavirin have been the mainstay of treatment until recently. New direct acting antivirals, specifically designed to inhibit three viral proteins (the NS3/4A protease, the NS5A protein, and the NS5B RNA dependent RNA polymerase) are now becoming available. The NS3/4A inhibitor simeprevir and NS5B inhibitor sofosbuvir have recently been licensed and can reduce the length of antiviral treatment, improve response rates, and allow for interferon-free regimens for some HCV genotypes. Several other newer direct acting antivirals (protease inhibitors and NS5B inhibitors) and classes (NS5A inhibitors) of direct acting antivirals are likely to be licensed. Newer protease inhibitors will broaden the range of peginterferon-ribavirin containing regimens available, but most importantly the options available for interferon-free regimens will grow. The combinations of sofosbuvir-ledipasvir (which will be coformulated), sofosbuvir-GS-9669, and the regimens of ABT-450-ritonavir-ombitasvir-dasabuvir, and daclatasvir-asunaprevir-BMS-791325 are expected to be approved in the near future. These interferon-free regimens could enable many patients with HCV (even those with cirrhosis and those who have not responded to previous protease inhibitor based treatment) to be cured with an oral course of antivirals without the use of interferon and its associated side effects. Despite this optimism, challenges remain, particularly in the treatment of patients with HCV GT3, cirrhosis, hepatic decompensation, and liver transplantation.

This recent availability of new direct acting antivirals for the treatment of HCV infection has already completely changed recommendations for treatment, and allows for a shortened and easier to tolerate treatment course for most patients infected with the virus. The optimal treatment regimens remain to be determined. Over the next year or two we expect that even more effective interferon-free regimens, with high cure rates in almost every patient, will become available. These agents are expensive; however the potential for shortened courses of treatment with high cure rates should make them cost effective, and the availability of many newer agents may lead to some price competition.

Guidelines

HCV treatment guidelines are available from both the American Association for the Study of Liver Disease (AASLD; www.aasld.org) and the European Association for the Study of Liver Diseases (EASL, www.easl.eu). At the time of writing, while recommendations on use of the direct acting antivirals telaprevir and boceprevir are provided, neither of these guidelines includes the recently licensed agents simeprevir and sofosbuvir. Owing to the rapidly changing treatment landscape, AASLD and the Infectious Diseases Society of America (www.idsociety.org) have produced a website with newer guidelines for treatment of HCV (www.hcvguidelines.org). It is anticipated that this will be updated regularly as new agents become available.

Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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