Kinetics and prediction of HBsAg loss during therapy with analogues in patients affected by chronic hepatitis B HBeAg negative and genotype D
Lucio Boglione†,*, Antonio D'Avolio†, Giuseppe Cariti, Gabriella Gregori, Elisa Burdino, Lorena Baietto, Jessica Cusato, Valeria Ghisetti, Francesco G. De Rosa, Giovanni Di Perri
Background & Aims
In patients affected by chronic hepatitis because of HBV infection, long-term suppressive therapy with nucleos(t)ides analogues in the HBeAg− patients has shown low effects on HBsAg titre (qHBsAg) decrease, and HBsAg loss is difficult to achieve. Thus, in this type of patients the main goals of antiviral therapy is the suppression of HBV-DNA and ALT normalization.
We retrospectively evaluated different qHBsAg kinetics in 134 treatment-naïve patients having the same characteristics: HBeAg-, infection sustained by HBV genotype D and persistently undetectable HBV-DNA. Patients were treated with NAs therapy (lamivudine, adefovir, telbivudine, entecavir and tenofovir) for at least 2 years. qHBsAg was performed every 6 months.
Our results showed a significantly greater qHBsAg decline after 2 years in patients treated with tenofovir (0.45 logIU/ml) than in patients treated with telbivudine (0.12 logIU/ml; P < 0.001). The calculated expected time to HBsAg loss was shorter in the tenofovir group than in the telbivudine group (nearly 17 vs 63 years, P < 0.001).
HBeAg negative patients infected by HBV genotype D should be treated with more potent NAs such as entecavir or tenofovir to obtain a significant qHBsAg decrease, but the achievement of HBsAg loss seems to require almost two decades of therapy.
hbsag decline on hbv antivirals, lamivudine, adefovir and telbivudine all useless to clear hbsag except etv and tdf but tdf is much more potent.this data is also at 2 years so we may see an increase of decline by years.another point is we dont point to hbsag clearance but to hbsag 1000-1500iu/ml when pegintf add on will finish the job clearing hbsag in few years on most patients.i do hope we will get data on this soon
as you can see from this chart tdf hbsag decline was about 0.24 to 0.6 log while etv was only 0.2-0.38log , tenofovir is definitely the best hbv antiviral with no comparison to other antivirals as hbsag decline
prediction time to hbsag loss on hbv antivirals, tenofovir 17years we might be lowered to half and maybe even less by pegintf add on, we also assume the decline will keep the same kinetics as seen in 2 years which may be wrong, the decline might go faster
entecavir is 25.4years which is considerably too long, all the others need no consideration at all
all this data was on homogeneous patients, all genotype D and all hbeag negative with same charateristics, previous studies were not homogeneous at all so data was invalid as regards drawing conclusions on hbsag decline
another point it just came to my mind it is sides effect on mitocondria, the most dangerous side effect of these antivirals.
we have experience of about 12-13 years on lamivudine, the first hbv antiviral approved and we have not seen reports of severe sides or mitocondria sides, so we may think a 17 years time can be tollerable but what about 25-30years or lifetime of the other antivirals...
Great article Stef. I have been on tdf for 2 years and 2 months now. The last hbsag test I had was last year. Just had another hbsag test done 2 days ago to track decline progress. Results out next week. Will post results once I have them to support this.
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