Entecavir lowers viral load, but not HBsAg levels

[stef2011]

Entecavir lowers viral load, but not HBsAg levels: Chinese researchers followed 222 patients who were treated with entecavir (Baraclude) for up to five years and found that while the antiviral was very effective in lowering viral load, there was a disappointingly slow decline in HBsAg over the course of treatment.

Clearing HBsAg is an important treatment goal and it greatly reduces the risk of liver damage from the infection.

The researchers, reporting in the December issue of the Journal of Gastroenterology and Hepatology, found that viral load rapidly declined in all patients with entecavir treatment, with 97.1% achieving undetectable viral load after five years. Only two patients (representing 1.2% of those studied) developed resistance to entecavir.

However, "In contrast to the profound HBV DNA suppression, long-term entecavir treatment only achieved a slow decline in serum HBsAg," they wrote. "...Additional therapeutic agents are needed to increase the chance of HBsAg clearance in chronic hepatitis B."

Source: www.ncbi.nlm.nih.gov/pubmed/24325451

[HK_1966]

Stef has been recommending antiviral for 3y, followed by interferon.

Say if a person achieves DNA und 6 months after starting on antivirals, should he still continue for another 2-3years before trying interferon?

Thanks

[StephenCastlecrag]

It is generally suggested by some scientists that long term suppression of hbvdna allows the exhausted T cells response to recover. So far this idea has not been clinically proven. It would be interesting to know why. That is why the other paper about different immune response due to different selection pressure of the particular antiviral is intriguing. Why should there be an immune response?

Amateurs like us do seem to have wilder imagination. LOL.

[StephenCastlecrag]

I agree with your explanation which applies to all potent antivirals that suppress hbvdna. As the authors pointed out in the article, Entecavir is indeed very  potent in suppressing hbvdna, but not HBsAg.  So my point is, Chinese patients are almost all infected at birth, so the slow decline in HBsAg is not due to Entecavir, but due to the type of patients.
There is also another thing that worries me- the quality of Entecavir produced in China. I often read about Entecavir failure after three to four years of good response.

[Mrt79]

The rate of surface antigen decline depends on  individual immune system response to the infected cell clearance as a result of low or no viral replication due to antiviral medication.

[stef2011]

they slow reinfection rate a great deal, so less new cccdna and only cccdna dilution by cell replication or the little refinection left.
then according to the immune response of every single patient there is a difference clearance of infected cells which may reflect a fast hbsag decline or a slow hbsag decline

[StephenCastlecrag]

I fail to see how any antivirals, either Entecavir or Tenofovir, can reduce HBsAg. After all, they only affect the reverse transcription step of hbv replication, and not the transcription and translation of the surface antigens.
However, I do see different qHBsAg and HbeAg seroconversion patterns for different antivirals, there must be other factors involved.

[stef2011]

i do stress entecavir weakness because i experienced that myself:
hbsag increased from about 4000iu/ml to 7300iu/ml

it took about 8months to reach hbvdna undetectable and only add on of alinia (nitazoxanide) made it in 3 months because low hbvdna persisted for a long time, when stopping alinia hbvdna returned detectable so doctors finally moved to entecavir plus tenofovir (stopping alinia) and there has been slow hbsag decline finally.today i stopped entecavir and fully undetectable by tenofovir antiviral monotherapy

i also dont feel the fear of resistance mutations anymore, which is 1.2 to 2% for entecavir in clinical practice