ADD-ON OF PEG-INTERFERON to tenofovir-entecavir

[stef2011]

ADD-ON OF PEG-INTERFERON TO A STABLE NUCLEOS(T)IDE REGIMEN LEADS TO LOSS OF HBS-AG IN PATIENTS WITH CHRONIC HEPATITIS B
J.M. Kittner1*, M.F. Sprinzl2, A. Grambihler1, A. Weinmann1, P.R. Galle1, M. Schuchmann1
11st Medical Dept., University Hospital Mainz, Mainz, 2Institute for Virology, Technical University of Munich, Munich, Germany. ****@****


Objective: Suppression of HBV viral load by nucleos(t)ide therapy effectively reduces disease progression but requires long-term medication. Preferably, self-contained immunological control represented by HBs-Ag seroconversion should be achieved. It is of interest to know whether the addition of peg-interferon to a stable nucleos(t)ide therapy will reduce quantitative HBs-Ag which may be followed by HBs-Ag seroconversion.
Methods: We observed HBs-Ag levels of 12 patients who received additional peg-interferon-alfa2a as an individualized therapy. 9 patients were male, mean age was 44 (range 25-60) years. 3 patients were HBe-antigen positive. Current treatment comprised lamivudine (1pt.), lamivudine plus adefovir (2pts.), entecavir (7pts.), or entecavir plus tenofovir (2pts.). Mean baseline HBs-Ag accounted for 4,695 (range 16-15,120) IU/ml. HBV viral load was below limit of detection ( 6 months.
Results: During add-on therapy, in 2 patients a continuous decline of quantitative HBsAg by -2,6log10 and -3,66 log10 was observed at week 32 and 36, respectively. The decline became detectable from week 8 and 16 on, resp. The first patient was HBe-Ag negative, genotype D, with cirrhosis grade Child-Pugh A, had a low initial HBsAg level of 16 U/l which dropped to 0.04 U/l. HBV-DNA had previously been non-detectable during therapy with entecavir for 27 months.
The second patient was HBe-positive, genotype A, F3 fibrosis (Desmet), and HBV-DNA had been non-detectable for 10 months with entecavir plus tenofovir. Despite a non-response to peg-interferon monotherapy in the past, she now experienced an HBe-antigen seroconversion at week 24. HBs-Ag dropped to 0.54 U/l, and anti-HBs became detectable in week 32.
In the remaining 10 patients quantitative HBsAg declined only by -0.01 to -0.25 log10 (mean 0.09 log10) after 8-24 (mean 16.4) weeks of combination therapy, and therefore interferon was stopped.
No unexpected side effects were observed in combination therapy.
Conclusion: HBs-Ag loss during oral antiviral therapy is rare, even more in HBe-negative patients. Here, we show that the add-on of peg-interferon induced HBsAg loss in 2 of 12 patients (one HBe-Ag negative) and even led to HBs-Ag seroconversion in one patient. This concept merits to be proven in a larger trial.

[stef2011]

this study also shows how hbvdna undetactable means nothing in term of infection evelution, it can only be used as a tool for response to nucs and absense of liver damage when fully und

as a tool to monitor infection...totally useless, hbsag is much better

[stef2011]

i have read another study that found how hbv suppresses natural interferon production or interferon and that the best scheme is:

making hbv und to avoid it can interfere with interferon so that there is always interferon response.probably hbvdna undetactable doens t tell anything maybe a lowering of cccdna or other is needed.anyway once hbvdna is very totaly und for many many months try addon of interferon

alinia (nitazoxanide) is an interferon pathway helper, this might be the solution to interferon non responders once hbvdna und for years on nuc

if once type of interferon doesn t work it is better to try other type because it is possible that hbv cannot block them all, infergene is another type of interferon or interferon lambda or interferon 2b instead of 2a...