David Wohl, M.D., talks with Phyllis Tien, M.D., about the under-diagnosis of hepatitis C among people with HIV in the United States. Dr. Tien is an assistant adjunct professor of medicine at the University of California, San Francisco. She presented a fascinating study at AIDS 2006 looking at factors associated with the occurrence of seronegative chronic hepatitis C in HIV-infected people.

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So now I'm standing before Phyllis Tien from the University of California, San Francisco [UCSF], who is a leader in many fields including hepatitis C [HCV]. She has helped draft important guidelines for hepatitis C management in the co-infected patients.

In the VA [Veterans Administration] system.

Phyllis, one of the most impressive things I have taken home from this conference is that we may be under-diagnosing hepatitis C. I work in prison systems, which are [only] slightly different than the VA [and] where there's a concentration of hepatitis C, and [it] really has me wondering: Are we missing patients [with hepatitis C], with catastrophic results? What do you think we should do as far as screening for hepatitis C in HIV-infected people?

Certainly HCV screenings should be done on everyone with HIV infection, but there is a group of people who may be missed by using the standard HCV antibody test. [This is] the data we found from our FRAM study, combined with three other studies that actually have been published in this area. But the cases were very small, so they were not able to actually provide a definitive answer in terms of the risk factors for this phenomenon called seronegative HCV.

So this would be where antibodies are negative for some reason -- maybe an immunological reason because the person can't make antibodies but yet they have hepatitis C.

Correct.

You could find the virus in their blood.

Right, yes.

So how often does that happen?

What we found when we pooled the four studies is, as you said, there was a prevalence of about 3.2 percent, when you combine all four. And then the factors that were associated with this appeared to be yet elevated ALT levels if you had a history of injection drug use and if you had a CD4 count less than 200. So I think that there should be serious consideration of people who are within -- you know, who have those kind of risk factors for testing of HCV RNA.

What about people who have a low CD4 cell count and injection drug use and normal transaminases? Would that be someone who, if their hepatitis C antibody is negative, you would turn around and get the viral load?

I would totally consider it. That would be a strong consideration, because right now I think if we see someone who has elevated LFTs and then they also have a CD4 less than 200, that's what's driving us to test. But I think with our findings, the ALT with CD4 less than 200 and history of injection drug users, they were -- history of injection drug use [IDU] -- they were all independent predictors of seronegative HCV.

They were each independent predictors, so any one of them with the HCV negative antibody would really maybe lead you to get the viral load test.

Yes. But I think we're talking also about a cost issue, because we're talking about doing HCV RNA levels. So actually when we can find people, for instance, with a CD4 less than 200, ideally we saw an even higher prevalence of seronegative HCV infection.

Right, and that may be more worthwhile.

Yes, and when you take into account the cost factors, I would probably think about someone with a history of IDU, CD4 count less than 200, as a potential for this kind of test.

Let me ask you one last thing and then I'll let you go. I've been thinking a lot about hepatitis C lately. I think a lot of infectious disease doctors are trying to catch up and understand more about how to manage it. Where do you think we're headed? I know there's a lot of talk about the use of protease inhibitors and stuff like that. It seems to me right now that for the foreseeable future, we're wedded to interferon and ribavirin. I guess I also wonder, will we ever not use interferon? Is that something that we're going to be doing -- even if there's a protease inhibitor tomorrow for hepatitis C, won't we likely use it with other drugs and especially immunologically boosting or active drugs? What are your thoughts about where we might be headed?

I've actually seen some data that's been presented on HCV protease inhibitors and it looks incredibly promising. I think that we will see that drug being tested in humans very, very soon. So I think that will be great, and I think one of the other things is, I do think that we probably will have to continue to use it in combination with another drug, probably interferon, from the data that I've heard presented. It showed really great response when we combined it with interferon. I think with HIV, for instance, we're taking that model of combination therapy and ...

And increasing with hepatitis B, although that's still a little bit ...

Yes. We're probably heading down that direction.

OK. Well, that's helpful, because I think that helps confirm some of the things that we're seeing and hearing and it just gives us a better perspective. I think a lot of people think, oh, when protease comes out, we won't need to use interferon, warts and all, and the way that limits our therapy. But it's likely that we will be using some interferon for the foreseeable future.

Yes.