Entering a new era in the treatment of hepatitis C

Treatment of hepatitis C virus (HCV) infection was formally initiated in the early Eighties with the experimental administration of interferon to patients with non-A, non-B hepatitis, at a time when a serological diagnosis of the infection was still far from being available. Thirty years later, with the regulatory approvals of the nucleotide polymerase inhibitor sofosbuvir in the U.S. (December 3, 2013), Canada (December 12, 2013) and European Union (January 17, 2014), the most awaited, golden era of interferon-free therapy for chronic hepatitis C, has begun. Such a remarkable shift in the therapeutic paradigm of hepatitis C has recently been consolidated by the publication on the row of a series of multinational studies with all-oral regimens: one combining sofosbuvir with ribavirin or the inhibitors of the NS5A replication complex daclatasvir or ledipasvir or the second wave inhibitors of NS3/4A protease, Simeprevir, and another one based on multiple direct acting antiviral agents (DAAs) including an inhibitor of NS3/4 protease and the NS5A replication complex and a non nucleoside inhibitor of NS5B polymerase of HCV. Remarkably, all regimens combining more than one DAA led to the permanent virological cure of more than 90% of the previously difficult-to-cure patients infected by genotype 1 HCV following a course of 12 weeks of therapy, only. While the success of these regimens was anticipated at the last meeting of the European Association for the Study of the Liver (EASL, London April 2014), in the same meeting this was topped by the reports of equally effective oral regimens administered for 6–8 weeks only. This clearly indicates that interferon-based therapy of hepatitis C with its burden of adverse effects and limited patient access has come to an end and is ready to be replaced by user friendly regimens that grant for universal patients access and cure of hepatitis C. This rapid, and to some extent, dramatic shift in the therapeutic paradigm of hepatitis C comes at the expense of harsh arguments in the field of distributive justice. The therapeutic revolution of HCV will not be taking place at the same pace in every country, even in the industrialized world, being strongly constrained by the burden of costs that has solicited treatment strategies driven by cost effectiveness criteria. This was one of the concerns that led EASL to release updated recommendations for the treatment of hepatitis C even before field practice data with these regimens had become available. Recommendations still also include interferon-based regimens with simeprevir or daclatasvir to treat the prevalent population infected by HCV genotype 1, with the clear objective of counterbalancing the disproportionate costs of the newer all oral combinations of DAA's. Indeed, the economic burden of the new DAAs is not a trivial point, given that 150 million people among the 170 million infected with HCV live outside the target high income market, thereby having in the best case scenario a yet limited access to interferon, only. While the high cost of DAAs and absence of effective screening programs are real hurdles against strategies of global eradication of HCV infection, the breakthrough represented by the arrival of all oral therapeutic regimens has fueled discussions on which strategies should be undertaken to comply with the expectations of patients and their advocacies. Given the current prices of oral regimens, treating all comers with the aim of eradicating HCV stands as the least affordable strategy, even though this approach would have the benefit of a reduction of liver related mortality in the general population. Under the perspective of a life-saving strategy, an alternative choice would simply be to treat selected groups of patients, such as those with severe hepatitis and those who are unfit or contraindicated to receive interferon, an approach considered by many far from being cost effective, yet respectful of widely accepted criteria of prioritization. In the present issue of DLD, the new therapeutic regimens of HCV are critically presented and discussed by worldwide renown opinion leaders, thereby offering the readers a chance of directly evaluating the pros and cons of the above mentioned strategies for HCV therapy.Conflict of interestMassimo Colombo has the following conflicts of interest to declare: grant and research support from BMS, Gilead Science; advisory committees: Merck, Roche, Novartis, Bayer, BMS, Gilead Science, Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, GSK, GenSpera, AbbVie, AlfaWasserman, Jennerex; speaking and teaching: Tibotec, Roche, Novartis, Bayer, BMS, Gilead Science, Vertex, Merck, Janssen, Sanofi. Markus Peck-Radosavljevic has acted as speaker for AbbVie, BMS, Boehringer-Ingelheim, GSK, Gilead, MSD, Novartis; he has been an advisor to AbbVie, BMS, Gilead, MSD, and Roche and has received grants from Gilead, MSD, and Roche.This article is part of a supplement supported by an unrestricted educational grant from Gilead Sciences Europe Ltd. Gilead has had no editorial control or involvement in the content of this article. The views and opinions within this supplement are those of the authors and not necessarily those of Gilead. Treatment of hepatitis C virus (HCV) infection was formally initiated in the early Eighties with the experimental administration of interferon to patients with non-A, non-B hepatitis, at a time when a serological diagnosis of the infection was still far from being available. Thirty years later, with the regulatory approvals of the nucleotide polymerase inhibitor sofosbuvir in the U.S. (December 3, 2013), Canada (December 12, 2013) and European Union (January 17, 2014), the most awaited, golden era of interferon-free therapy for chronic hepatitis C, has begun. Such a remarkable shift in the therapeutic paradigm of hepatitis C has recently been consolidated by the publication on the row of a series of multinational studies with all-oral regimens: one combining sofosbuvir with ribavirin or the inhibitors of the NS5A replication complex daclatasvir or ledipasvir or the second wave inhibitors of NS3/4A protease, Simeprevir, and another one based on multiple direct acting antiviral agents (DAAs) including an inhibitor of NS3/4 protease and the NS5A replication complex and a non nucleoside inhibitor of NS5B polymerase of HCV. Remarkably, all regimens combining more than one DAA led to the permanent virological cure of more than 90% of the previously difficult-to-cure patients infected by genotype 1 HCV following a course of 12 weeks of therapy, only. While the success of these regimens was anticipated at the last meeting of the European Association for the Study of the Liver (EASL, London April 2014), in the same meeting this was topped by the reports of equally effective oral regimens administered for 6–8 weeks only. This clearly indicates that interferon-based therapy of hepatitis C with its burden of adverse effects and limited patient access has come to an end and is ready to be replaced by user friendly regimens that grant for universal patients access and cure of hepatitis C. This rapid, and to some extent, dramatic shift in the therapeutic paradigm of hepatitis C comes at the expense of harsh arguments in the field of distributive justice. The therapeutic revolution of HCV will not be taking place at the same pace in every country, even in the industrialized world, being strongly constrained by the burden of costs that has solicited treatment strategies driven by cost effectiveness criteria. This was one of the concerns that led EASL to release updated recommendations for the treatment of hepatitis C even before field practice data with these regimens had become available. Recommendations still also include interferon-based regimens with simeprevir or daclatasvir to treat the prevalent population infected by HCV genotype 1, with the clear objective of counterbalancing the disproportionate costs of the newer all oral combinations of DAA's. Indeed, the economic burden of the new DAAs is not a trivial point, given that 150 million people among the 170 million infected with HCV live outside the target high income market, thereby having in the best case scenario a yet limited access to interferon, only. While the high cost of DAAs and absence of effective screening programs are real hurdles against strategies of global eradication of HCV infection, the breakthrough represented by the arrival of all oral therapeutic regimens has fueled discussions on which strategies should be undertaken to comply with the expectations of patients and their advocacies. Given the current prices of oral regimens, treating all comers with the aim of eradicating HCV stands as the least affordable strategy, even though this approach would have the benefit of a reduction of liver related mortality in the general population. Under the perspective of a life-saving strategy, an alternative choice would simply be to treat selected groups of patients, such as those with severe hepatitis and those who are unfit or contraindicated to receive interferon, an approach considered by many far from being cost effective, yet respectful of widely accepted criteria of prioritization. In the present issue of DLD, the new therapeutic regimens of HCV are critically presented and discussed by worldwide renown opinion leaders, thereby offering the readers a chance of directly evaluating the pros and cons of the above mentioned strategies for HCV therapy. Conflict of interestMassimo Colombo has the following conflicts of interest to declare: grant and research support from BMS, Gilead Science; advisory committees: Merck, Roche, Novartis, Bayer, BMS, Gilead Science, Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, GSK, GenSpera, AbbVie, AlfaWasserman, Jennerex; speaking and teaching: Tibotec, Roche, Novartis, Bayer, BMS, Gilead Science, Vertex, Merck, Janssen, Sanofi. Markus Peck-Radosavljevic has acted as speaker for AbbVie, BMS, Boehringer-Ingelheim, GSK, Gilead, MSD, Novartis; he has been an advisor to AbbVie, BMS, Gilead, MSD, and Roche and has received grants from Gilead, MSD, and Roche.This article is part of a supplement supported by an unrestricted educational grant from Gilead Sciences Europe Ltd. Gilead has had no editorial control or involvement in the content of this article. The views and opinions within this supplement are those of the authors and not necessarily those of Gilead. Massimo Colombo has the following conflicts of interest to declare: grant and research support from BMS, Gilead Science; advisory committees: Merck, Roche, Novartis, Bayer, BMS, Gilead Science, Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, GSK, GenSpera, AbbVie, AlfaWasserman, Jennerex; speaking and teaching: Tibotec, Roche, Novartis, Bayer, BMS, Gilead Science, Vertex, Merck, Janssen, Sanofi. Markus Peck-Radosavljevic has acted as speaker for AbbVie, BMS, Boehringer-Ingelheim, GSK, Gilead, MSD, Novartis; he has been an advisor to AbbVie, BMS, Gilead, MSD, and Roche and has received grants from Gilead, MSD, and Roche. This article is part of a supplement supported by an unrestricted educational grant from Gilead Sciences Europe Ltd. Gilead has had no editorial control or involvement in the content of this article. The views and opinions within this supplement are those of the authors and not necessarily those of Gilead.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.