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Hello. I'm Paul Martin, Professor of Medicine, Chief of Hepatology at the University of Miami in Florida. I'm here at AASLD [American Association for the Study of Liver Diseases] 2010 in Boston [Massachusetts], and I'd like to review some of the sessions on hepatitis B for Medscape.

The first study that I wanted to discuss is what I call the inactive carrier state revisited. This is a study by Simons and colleagues from Alaska,[1] in which they studied 97 chronically infected Alaskan natives who had persistently normal alanine aminotransferase (ALT) levels with low-level hepatitis B virus (HBV) DNA levels. These individuals were followed over a period of several years.

In these 97 patients, they identified 3 patterns of activity. Some patients had a steady low-level replicative state. Other patients had fluctuating replication with a change in HBV DNA levels in a magnitude of 2-3 logs. Then, finally, a group of patients were persistently HBV DNA negative.

Very importantly, in each of these 3 groups, the ALT levels stayed normal, and these individuals would be normally characterized as in the inactive carrier state, but very importantly, the third group, who had an absence of HBV DNA during the period of follow-up, went on to lose hepatitis B surface antigen in a significant number of instances. Indeed, of the 97 patients in this study, 16 of whom have lost surface antigen, 14 of these came from the group with persistently negative HBV DNA.

The investigators have coined the term "elite control group," and this suggests that even with the apparently inactive carrier state, there are subsets of patients whose prognosis differs. It is crucial to determine for long-term follow-up whether there is a complete absence of HBV DNA, because this seems to predict a high likelihood of ultimate clearance of hepatitis B surface antigen.

The next study that I want to discuss is a study comparing tenofovir vs tenofovir and emtricitabine in adefovir-experienced patients. This was reported by Berg and colleagues.[2] The entry criteria for this particular study were adefovir use in patients who remained persistently HBV DNA negative, in this instance greater than 1000 copies/mL with ALT levels less than 10 times the upper limits of normal. Of importance, 58% of the group as a whole had previous lamivudine exposure.

In this long-term study, by week 156, 85% of the patients enrolled had excellent suppression of HBV DNA, down to less than 400 copies/mL. Very importantly, this included 10 adefovir-resistant patients, and as I mentioned earlier, more than half of the patients also had previous lamivudine exposure. Of importance, in this study, in terms of control of replication, there was no difference between tenofovir and a combination of tenofovir and emtricitabine. This suggests for patients who have had a suboptimal response to adefovir, the use of tenofovir over a protected period of time leads to excellent control of hepatitis B replication, including in this study a small group of patients who were adefovir resistant.

The final study that I want to discuss looks at long-term efficacy of tenofovir in patients who had a high baseline viral load. This was reported by Gordon and colleagues,[3] and the study included both HBeAg+ and HBeAg- patients. In this study, by the end of follow-up, 75% of the patients had achieved an HBV DNA less than 200 copies/mL, and 23% of the HBeAg+ patients had seroconverted, that is, had lost e antigen and had developed an e antibody. Very importantly, in the HBeAg+ patients overall, 15% of these individuals cleared the hepatitis B surface antigen. During this long-term study, no resistance was detected.

The important implications of this study include the fact that there is excellent control of even high-level replication in patients with chronic hepatitis B infection, and, ultimately, many of these individuals will go on to clear hepatitis B surface antigen. Finally, over a 4-year period, no resistance was observed. This confirms earlier studies that suggest there is a very low rate of intrinsic resistance with tenofovir therapy.

Thank you for joining us. This is Paul Martin for Medscape.


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