Robert Perrillo is the Associate Director of Hepatology at Baylor University Medical Center at Dallas and Director of the Hepatology Fellowship Program. Dr. Perrillo is internationally recognized for his work on antiviral therapy of chronic hepatitis B and the scientist that AASLD suggested me in order to have a talk about hepatitis B. I met him in San Francisco during the Liver meeting.
This 2011 seems to be the year of hepatitis. There is a lot effort in order to increase awareness about hepatitis C and hepatitis B all over the world. Here, during the Liver meeting i there were two sessions devoted to the global program against hepatitis, one driven by CDC and the other one together with NIAID. But many of the noise rased is realted to HCV. About hepatitis B, where we are?
Well, hepatitis B is a condition that afflicts 400 million people worldwide and I think that the United Stated has been considered traditionally as a low-incidence area, a low-risk geographic region. But now we all of the practicing physicians who see such patients are noticing that we are seeing a lot more patients who are of the immigrant populations to the United States, not just Asian Americans, but also those from the continent of Africa and also those from the Eastern European nations, who have immigrated here and have brought hepatitis B with them. So, the prevalence for hepatitis B in the United States has been traditionally underestimated: it is probably above 2 million people. Now, that pales in comparison to hepatitis C where we think it’s more like 4 million people, but both of these conditions are very significant. Hepatitis B, like hepatitis C, can establish a chronic carrier state and can lead to cirrhosis and liver cancer and actually is a leading cause of death in people that have the affliction of hepatitis B from early in their life, where 15% or more of adult, generally younger males in their middle ages can have a decompensating form of liver disease or liver cancer, so it must be taken seriously. The two major types of therapeutic agents that we have available to treat it are an injectable material called interferon, which is also currently being used as part of a triple therapy regimen for hepatitis C. Interferon has been a license for hepatitis B for approximately 18 years now, and it tends to be not utilized, because of some adverse events. Into the past five years, we had availability of nucleoside analogues or nucleotide analogues: pills that can be taken orally, once a day, and they inhibit and suppress hepatitis B virus. Interferon, unlike the oral drugs, actually augments cell-mediated immunity against hepatitis B and therefore the state of the art is moving towards a direction of looking at combination therapy, where we are using interferon to stimulate immune responses against the virus in conjunction with a potent suppressive agent that can be taken orally. First past studies, five-six years ago, looked at interferon with a less than completely effective nucleotide analogue and so these studies where not definitive by their very nature. We now have oral drugs, such as tenofovir and entecavir, that can be taken with a very slight risk of developing drug resistance, then had stymied us in the past and prevented us looking at monotherapy as a long-term kind of beneficial way of treating the infection. Unfortunately, the problem with the nucleosides still remains: they are only effective as long as you take them. So, there is indefinite treatment needed, sometimes you could conceive of this as being in excess of six or ten years while waiting for the markers to change sufficiently that you would be able to stop therapy, so we don’t really know when we can stop in many patients. The combination of interferon and a nucleoside offers the option to come up with a higherquality response, perhaps getting down to even minute levels of virus remaining in the liver tissue and for all intents and purposes coming as close to a clinical cure of the disease as we come.
This is the reason why we need the new drugs? Yes, we need new drugs all the time.
The biggest gap of what we really need is a drug that like interferon can stimulate the immune response against the virus, get to a greater state of viral elimination and yet not have the unpleasant side effects. So, the magic bullet for the future will be an immunostimulatory compound that doesn’t have a lot of side effects.
Notwithstanding, until we come up with such a drug, the combination of interferon and nucleoside analogue therapy can be an effective tool that we hope will bear fruit.
There are many studies ongoing now to look at this, sometimes these studies use the drugs simultaneously, sometimes there is a leadin with the interferon to induce an immune active state before you add on the viral suppressive agent. In some studies they are looking at people that have been on the oral pills for a while and haven’t come to a complete satisfactory response where you’d feel comfortable stopping: so they had interferon on the trailing edge of that therapy to see if they can come to a higher-quality response where you can lose the hepatitis B surface antigen, which is the outside envelope of the virus, at which point you can be pretty sure you that are going to have a long-term response if you stop the therapy. I think the field is exciting, there aren’t as many new drugs being developed as in hepatitis C, but we are coming to a far better understanding of how to use the existing drugs for hepatitis B.
The issues you have mention explain why adherence is a key issue in the management of a patient with HBV…
Adherence will always be an issue, whether you are taking one pill or four pills a day, because of the human character. Hepatitis B and C are often asymptomatic or minimally symptomatic, so it’s hard to stay with a relatively costly drug therapy for an indefinite period, which is what we often do with hepatitis B, hepatitis C has more time-defined therapy, so we have side effects but we hope to get the patients through before the side effects become limiting. With hepatitis B, with the oral drugs that we have, we don’t have side effects, we do have cost, we do have an asymptomatic condition.
Unfortunately, there is an undeserved stigma from having hepatitis B. Many people who are in the immigrant populations who have it would rather not have it and cause concern for their family members, as well as the cost of care. In fact, the sad truth is that in hepatitis B we estimate that at least 50% of the people in the US are foreign born who have it and these are people that don’t always have the greatest access to care, so as a result we can’t reach the net out there, the health net to treat these people very effectively, there are cultural barriers against seeing doctors for this condition. Diabetes, hypertension and high cholesterol get more attention that hepatitis B which can be life threatening over a long period of time.
Articolo presente in – HAART and correlated pathologies n. 13 –
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