Interview with Prof. Fusheng Wang in the APASL 2009

Hepatology Digest: We’re here with Professor Fu-Sheng Wang of Beijing at APASL 2009.  Thank you professor, it’s a pleasure to have you join us.  First of all, how about the conference so far, what do you feel has been a hot topic and what are some of the highlights for you especially?

Pro. Wang: I think this 19th APASL conference, is so far so good.  Firstly it is very well organized although there are some things that need to be improved.  In my opinion, the hot fields are the virologic studies, and the immunologic study as well as the diagnosis and treatment for the viral hepatitis and liver cancers.  There are many advances in this field in my mind.

Hepatology Digest: And how about obviously it is not for another year but next year APASL will be held in Beijing.  So what are you looking forward to as far as 2010 APASL and what are some things you hope to see in 2010 APASL?

Pro. Wang: This is a very good question and I’m very interested.  Next year yes the APASL conference will be held in Beijing.  I have talked with Professor Jia (Ji-Dong Jia) and also We need to do a lot of things, not only including the organization of the conference but also we need to think about inviting the prestigious medical speakers for this conference, not only from the United States but also from Europe or from the Asia Pacific region. In China in my opinion, we need to invite some of the hepatologist in China to give out talks in this conference.  I’m looking forward to the coming of the APASL meeting to be held in Beijing, I’m confident that the APASL meeting will be successful.

Hepatology Digest: I’m sure as well.  It’s very exciting, it’s the first time it will be held in Beijing and in mainland china so it’s very exciting.

Pro. Wang: Also we are looking forward to probably more and more Chinese hepatologists will attend or participate in this important conference.

Hepatology Digest: Sure I’m sure it’s much easier because of the travel issues and such and it will really make the local Chinese attendance higher than perhaps when it was held in other locations such as Tokyo or Seoul.

Pro. Wang: Yeah.  I think probably that the estimated participants will be over four thousand.

Hepatology Digest: I’m sure it will be a very successful conference.  So moving on to some things that are more technical in nature, when we talk about innate immunity and adaptive immunity, which one might play a more important role in the elimination of the Hepatitis B virus?

Pro. Wang: Well I think this is a very good question, also a very tough question to answer.  Generally speaking in human body the innate immunity and the adaptive immunity both of them play an equal important role in control of the viral infection as well as the clearance of the virus in vivo.  Generally speaking, the innate immunity just plays a very quick rapid role in control of viral replication. When the virus enters the human body maybe within 20 minutes this innate immune system plays a very important role in controlling the virus.  Combatants of innate immunity include NK cells (natural killer), macrophages, dendritic cells as well as other neutrophils.  For example the dendritic cells, one of them is the   plasmacytoid dendritic cells.  They just release a huge amount of interferon-alpha when the virus enters the human body so in this way innate immunity plays a very crucial roles in control of viral implications.  But on the other hand, we can see the adaptive immunity also plays a very important role in controlling the virus.  For example, the innate immunity cannot completely clarify the virus in vivo, when the adaptive immunity works at the same time or we can say simultaneously, the innate immunity can induce or activate the adaptive immunity and then the viral specific CD8 (cytotoxic) T-cells can be produced and these cells are very unique and very special to control the viral infection also they clean out the virus in hepatocytes or within cells.  Both of them are very important.

Hepatology Digest: How does the research in these two fields contributing to the development clinically influence on which agents are developed?  How is that influencing development?

Pro. Wang: Well so far more attention has been focused on the adaptive immunity.  In particular many studies have focused on the HBV specific CD8 t-cells because these kinds of cells are very important.  They play a very important role in clarifying the in vivo virus by two mechanisms.  One mechanism is non-cytotoxic effect.  We just call this ‘HBV specific’.  CD8 t-cells can release the endogenous interferon-alpha, TGF-beta (TGF-β) and then TNF-alpha and interferon-gamma (IFN-γ).  The endogenous interferon-gamma can clarify the infected virus within hepatocytes but on the other hand the HBV specific CD8 t-cells can damage the hepatocytes.  The t-cells have been infected by the HBV so this can lead to the damage of the hepatocytes and then induce the elevation of ALT levels in serum.

Hepatology Digest: Some new immune agents have been added to the therapy regime of some viral diseases and treatment too such as peptide vaccines ect.  What are their applications in treatment of chronic hepatitis B?

Pro. Wang: Well so far there are many clinical trials.  We just call it immune therapy or regulatory immune therapy for patients with chronic hepatitis B.  This includes HBV antigen positive dendritic cells or we just call it HBV DNA vaccine or we call it the cytokine-induced killer cells, CIK cells.  This kind of immunocells right now has been used in clinical trials for immune therapy in patients with chronic Hepatitis B.  So far all the clinical trials just in on going studies, the efficacy of these kinds of immune therapies needs to be carefully evaluated in the future.

Hepatology Digest:  And you mentioned ongoing clinical trials, how about you personally, what are some of the things the research that you are really focusing on and some of the latest studies that you are working on?

Pro. Wang: Well I’m very interested in these fields.  So far I am involved in two projects are underway by my team in my clinic department for treatment of the patient with chronic Hepatitis B.  One is the HBV surface core antigen-pulsed dendritic cells.  We have finished the pre-clinical studies and hopefully we just got formal approval for this kind of therapy in clinic.  Just in earlier this year.  Right now, another project we just called CIK therapy we also call autologous cytokine induced killer cell therapy for patient with chronic hepatitis B.  And then we have finished the initial clinical trials.  Our data has been published in the Clinical Immunology just in recent issues and also other paper was published in Liver International.  I think in the February issue of Liver International.

Hepatology Digest: Studies have shown that the expression of Hepatitis B surface antigens and Hepatitis B e-antigen contribute to the immune tolerance of the Hepatitis B virus.  So can you talk about the mechanisms of this?

Pro. Wang: This is also a good question.  Before that I would like to give some comments from our studies of CIK clinical trials.  In our studies clinical trials for CIK therapy for  a patient with chronic Hepatitis B we did find that this kind of therapy we called autologous   CIK therapy could control their HBV replication in vivo.  50% of the patients are definite responders.  This means there is a full viral suppression in the responders.  Anyway in the other remaining 50% of the participants we just call partial or non-responders because the viral suppression is not fully occurred or exist.  Well for your question regarding the HBV antigens’ contribution to the immune tolerance in vivo, so far much attention in all over the board has been paid in this field.  As we know the higher viral load also contributes or leads to the immune tolerance in vivo.  But so far, according to the advances in research we found that antigens also play a very important role.  In this way we just divided this into two aspects.  One aspect we call, called of them the virologic factors that lead to immune tolerance in vivo.  One aspect is the viral load.  This has been discussed before and demonstrated in previous studies but for e-antigen and in the surface antigen the hepatologist considers that they are very important in inducing the immune tolerance because this kind of antigen can induce the impairment of dendritic cells and also can induce the generation of regulatory t-cells.  Regulatory t-cells are a kind of suppressive immunocyte in the human body.  The regulatory t-cells can inhibit the HBV specific CD8 t-cell function.  Also can suppress the immune response against HBV so in this way we can see the surface antigen and the e-antigen both of them efficiently contributed to the occurrence of immunotolerance status in a patient with chronic Hepatitis B.

Hepatology Digest: Once again, Professor Wang, thank you again for joining us today.  It was great to hear about your latest research and we will hopefully see you in Beijing in 2010.  Thank you very much.

Professor Wang: Thank you very much, it’s my great pleasure to be here.