Monday, September 10, 2012

Challenges remain in reaching 100% cure rate in HCV

SAN FRANCISCO — More than 20 years after hepatitis C was first discovered, its incidence has increased significantly, but there have also been significant advances in its treatment, according to a keynote lecture by Charles M. Rice, PhD, at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Charles Rice, PhD
Rice, the Maurice R. and Corinne P. Greenberg Professor in Virology at The Rockefeller University, discussed how far we’ve come in identifying and treating hepatitis C, but also emphasized that challenges remain to reach the 100% cure rate goal.

“The treatment for hepatitis C is going to get more complicated before it gets simple,” Rice said. “The good news is that the field is changing on a daily basis.”

Burden of HCV
Hepatitis C is a global problem, affecting more than 130 million people worldwide. Although its incidence in the United States has declined since 2007, the mortality associated with hepatitis C has surpassed that of HIV and it is expected to continue to rise. In fact, it is not expected to peak until about 2020, Rice said.

According to Rice, one of the reasons that hepatitis C has taken a back seat to other infectious diseases is that it is initially asymptomatic. There is a slow progression to symptomatic disease, so most people do not know that they are infected.

“We are unable to predict which patients are going to go on to develop liver cancer or cirrhosis, or which people are going to live 50+ years and ultimately succumb to another illness,” Rice said. “This is a frustrating aspect of hepatitis C, for both patients and clinicians.”

Since its discovery in 1989, there have been several goals related to hepatitis C. One, cleaning up the blood supply, has been successfully reached in the United States. An ongoing goal is educating high-risk people and another goal, treatment success, is dependent on identifying people who are infected.

“Many people don’t know of their infection until they already have severe liver damage,” Rice said. “Less than 50% of people with hepatitis C know that they have it.”

As for research of hepatitis C, there are challenges. The first is that the virus is difficult to replicate in cell cultures. The ideal model for research is the chimpanzee model, which is the most important model for all hepatitis viruses. The problem is that it is very difficult and expensive to work with.

There is not yet a small animal model that is ideal for researching the virus.

Despite these challenges, the good news is that successful treatment does represent a cure in most cases, Rice said. Sustained virologic response is defined as having undetectable virus at 6 months after treatment. In 95% of the cases that achieve that, the response is durable.

Treatment response
Treatment for hepatitis C has also improved since interferon alfa was approved by the FDA for treatment. The addition of ribavirin to interferon significantly improved the rate sustained virologic response, though alone, ribavirin had no effect. Later, the introduction of pegylated interferon also demonstrated a benefit.

Within the past year, the most significant addition to the treatment armamentarium has been protease inhibitors, boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex).

However, although we are approaching a 75% cure rate with the protease inhibitors, they are associated with adverse effects. Patients who are receiving these therapies, along with pegylated interferon and ribavirin, are often hospitalized, Rice said. The drugs are also expensive.

“We’re at a stage where we have good proof of concept that these antivirals can improve therapy, but we still have a long way to go,” Rice said.

Eventually, the goal is to find treatment regimens that do not include pegylated interferon, and if possible, regimens that include neither pegylated interferon or ribavirin, Rice said. One promising option is the combination of daclatasvir (Bristol-Myers Squibb) and GS-7977 (Gilead), which resulted in a cure rate of 100% just 4 weeks after going off treatment, according to a study presented at the European Association for the Study of Liver Disease this year.

“This is very exciting,” Rice said. “We’ve gone from the mystery virus discovered in the mid-80s, to having diagnostics in place in the early 90s, and now approaching a 75% cure. The question is how do we get to a 100% cure? This is the ultimate goal.”

For more information:
Rice C. Emerging New Issues in the Management of Hepatitis C Infection. Presented at: 52nd ICAAC; Sept. 9-12, 2012; San Francisco.

Disclosure: Dr. Rice reports financial relationships with Apath, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, iTherX, Merck, Novartis and Vertex Pharmaceuticals.

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