Introduction: Evolution of Therapy for Chronic Hepatitis C

Dr. Eugene R. Schiff, M.D.

EUGENE R. SCHIFF, MD: Thank you. On behalf of my friend and colleague, Willis Maddrey and myself, we also would like to welcome you to this evening’s symposium. We think it’s quite exciting. And in essence, you’re going to hear where we are right now with combination therapy. To put that in perspective, let’s see what’s happened over the past year.

What have we learned? We know that interferon in combination with ribavirin therapy increases the likelihood of a sustained viral response in naive patients and in patients who have relapsed following interferon therapy. The sustained response rates to combination therapy in naive patients are over 40 percent. Side effects are real, but they’re not synergistic. And the duration of therapy may be individualized based on pretreatment characteristics, and you’re certainly going to hear about that.

If we look at this cartoon, it sort of puts in perspective what’s gone on since the introduction of interferon in 1986, and we’ll all recall then some frustration because clearly it was an advance, we didn’t have anything else. And we treated for six months. And across the board, we got about 10 percent sustained viral remission. But that was across the board. When we looked at our genotype 1 cases, which make up the majority of the patients we treat…usually 70, 80 percent of our patients. We were talking about two percent sustained viral remission. So it was frustrating, both to patients and to physicians. And we all are aware of that.

Then we improved things. We found out, and we’re up here to about 1996, that if we treated for a longer period of time, we could significantly increase that rate of sustained viral remission. That’s really our target here – to try to get rid of the virus. And it was up to about 20 percent overall, but if we looked at genotype 1, it was less than 10 percent. So again, we had improvement, but 10 percent in genotype 1 wasn’t the greatest.

The big breakthrough…I don’t think there’s any question about it…has been combination therapy, which is no surprise when we look at management of other viral infections, and we can even look at what’s happened with HIV, which seems to be the prototype here where combination therapy has made a major difference. And that’s where we are now. You’re going to hear about that in detail.

What can we expect in the future?
I think we’re going to see some exciting new antivirals, but it’s going to be a while. And we’re not talking next year. We’re talking about different approaches that will include one or more of the following: ribozymes, helicase inhibitors, protease inhibitors, polymerase inhibitors. I think we can anticipate that we’ll have long-acting interferons before that…PEGylated interferons in particular. And when we put that in combination with ribavirin, we can anticipate doing better than we are doing now. But we’re doing pretty good now, considering where we’ve come from.

So if we look ahead in the next decade, we’re going to see an increased number of patients coming to us. As you know, it isn’t because of an increased incidence: the incidence of acute hepatitis C is actually decreasing. But what it is is with these awareness campaigns that are starting, that cohort of some 4 million people, many of whom don’t know they have the disease and are not diagnosed, will be diagnosed. And unfortunately, that cohort is aging, relatively speaking, and with the aging we are seeing progression of disease. So we can anticipate, unfortunately, seeing more patients with cirrhosis and more patients with hepatocellular carcinoma.

I don’t think there’s any question that all the patients who meet treatment criteria…unless there’s a contraindication…should be offered treatment, at least offer it to them. Hopefully we will be treating them. Now, to do an effective job here, we as specialists…and I think most of the audience are specialists…have to be able to interact with our colleagues, both in primary care and other disciplines, so that the net result of a concerted effort is that we can intervene earlier in the natural history of this disease and render more people virus-free and sustain that viral remission.

[Symposium Contents]