HCV New Drugs

Patrick Marcellin
Article first published online: 4 JAN 2011
DOI: 10.1111/j.1478-3231.2010.02412.x
© 2011 John Wiley & Sons A/S

Volume 31, Issue Supplement s1, pages 1–2, January 2011


Viral hepatitis in 2011: a major step forward

This supplement of Liver International provides the state of the art on the management of patients with hepatitis B and hepatitis C in 2011 as presented at the fourth Paris Hepatitis Conference (PHC). Once again, this year, outstanding international experts will be presenting reviews of the most up-to-date information as well as their opinion on its clinical applications.

Knowledge about viral hepatitis has grown exponentially over the past few years with more and more available information on the virology, natural history and treatment of these diseases. The relevance of this information needs to be clarified for clinicians. The aim of this meeting is to facilitate the translation of the most recent scientific knowledge into daily clinical practice, thus improving the management of patients with viral hepatitis.

Since the last meeting, historical milestones have been achieved: in chronic hepatitis B, long-term follow-up of patients receiving the most potent available antivirals has shown high sustained virological response (SVR) rates with undetectable hepatitis B virus DNA using sensitive polymerase chain reaction assays, associated with a persistent biochemical response, increasing rates of HBeAg seroconversion and HBsAg loss in HBeAg-positive patients. Furthermore, no or very little resistance was observed and the SVR has been associated with the regression of liver fibrosis even in patients with advanced fibrosis or cirrhosis.

Long-term follow-up studies of responders who have received pegylated interferon have shown a progressive increase in the rate of HBsAg loss. HBsAg loss is the closest thing to a cure of this disease and is associated with an improved prognosis with a decreased risk of decompensation and hepatocellular carcinoma. The quantification of HBsAg has emerged recently as a potential new tool for predicting post-treatment outcome. Indeed, a significant decline in HBsAg levels is associated with a SVR and the probability of HBsAg loss.

A spectacular step forward was made in chronic hepatitis C with the results of phase 3 studies of triple therapy combining protease inhibitors, telaprevir or boceprevir, with pegylated interferon and ribavirin and resulting in approximately 70% SVR. This advance is as important as that observed more than 10 years ago with dual therapy combining interferon and ribavirin. And triple therapy will undoubtedly become the new standard of care in the next couple of years in patients infected with HCV genotype 1.

These first-generation triple therapies open a new era and promising results have already been reported with new more potent direct antiviral agents (DAAs), protease inhibitors and polymerase inhibitors, with easier administration schedules, less resistance and a better safety profile. Interestingly, the proof of concept of interferon-sparing DAA combinations with or without ribavirin has opened the door to short-duration completely oral treatment for chronic hepatitis C.

At the same time, the non-1 genotypes and other difficult-to-treat populations encountered in routine clinical practice must also be considered. New drugs must be developed to effectively treat non-1 genotypes, which are common in high-prevalence areas such as genotype 4 in Egypt and the Middle East or genotype 3 in India. Rare genotypes such as 5 and 6 are also common in areas such as South Africa or Asia. Furthermore, clinical trials are also needed in special populations such as human immunodeficiency virus-positive patients, transplant patients and patients with compensated or decompensated cirrhosis in whom hepatitis C virus-related disease can be especially severe.

Finally, genetics have now been shown to play a role in predicting response to therapy. In particular, the polymorphism in the IL28 region has a strong predictive value for a sustained response to the current standard of care, with 80% of SVR in patients with the C/C and 25% in patients with the T/T allelle. This discovery helps explain the differences in efficacy among Asians, Caucasians and Africans who have proportionally less of the C/C pattern respectively. This is a first step to individualized therapy. Further studies are needed to identify more accurate genetic markers, to understand the mechanisms involved in non-response and to apply these markers to new therapies. Furthermore, an understanding of the genetic factors involved in the response to therapy will certainly help explain the mechanisms involved in chronic HCV infection and the progression of liver disease.

The aim of this supplement of Liver International as well as of the PHC is to provide clinicians with the state of the art and its clinical applications in this field to optimize the management of patients with hepatitis B and hepatitis C. But our ultimate goal is to provide optimal therapy and the best chance of cure to as many patients as possible, worldwide.

Conflicts of interest
Patrick Marcellin is an investigator, speaker and expert for Roche, Schering Plough, Gilead, BMS, Novarties, Tibotec and Intermune He receives a grant from Roche, Schering Plough and Gilead. He is an investigator and expert for Vertex, MSD, and Biolex; an expert for Pharmasset and Zymogenetics; and an investigator for Boehringer.
He receives no salary, regular renumeration or royalties from any drug company or owns any stock options.

http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02412.x/full