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hbsag clearance after stopping adv with charts

http://www.sciencedirect.com/science/article/pii/S0016508512008050
22 Responses
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charts hbsag, ast-alt,hbvdna

http://ars.els-cdn.com/content/image/1-s2.0-S0016508512008050-gre1.jpg
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patients With Chronic Hepatitis B Who Stop Long-term Treatment With Adefovir
Stephanos J. Hadziyannis⁎, ‡, , , Vassilios Sevastianos⁎, Irene Rapti⁎, Dimitrios Vassilopoulos§, Emilia Hadziyannis§
⁎ Department of Medicine and Hepatology, Henry Dunant Hospital, National and Kapodistrian University of Athens, Athens, Greece
§ 2nd Academic Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
‡ Molecular Biology Laboratory of the Liver Unit at the Evgenidion Hospital, National and Kapodistrian University of Athens, Athens, Greece
Received 24 January 2012. Accepted 24 May 2012. Available online 31 May 2012.
http://dx.doi.org/10.1053/j.gastro.2012.05.039, How to Cite or Link Using DOI
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Background & Aims
Little is known about the biochemical and virological effects of stopping long-term nucleos(t)ide analogue therapy for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB).

Methods
We performed a cohort observational study, following 33 HBeAg-negative patients with CHB, undetectable serum HBV DNA, and normal levels of aminotransferases after long-term (4 or 5 years) treatment with adefovir dipivoxil (ADV). All patients were followed for 5.5 years; follow-up visits included measurements of serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and HBV DNA monthly for the first 6 months and every 3–6 months thereafter. Various factors were measured at baseline, the end of treatment (EOT), and following treatment to identify those associated with clearance of HBsAg.

Results
During the first few months of the postdiscontinuation period, all patients experienced virological and 25 (76%) had biochemical relapse. During the follow-up period, 18 patients (55%) who had discontinued antiviral therapy achieved sustained response (HBV DNA level <2000 IU/L, persistently normal level of ALT). Among these, 13 (72%) cleared HBsAg. Fifteen patients (45%) with virological and/or biochemical relapse were re-treated with oral antiviral agents (11 during the first 18 months and 4 after the third year), without evidence of liver decompensation; only 1 lost HBsAg (6%). Higher pretreatment and EOT levels of ALT, no previous treatment with interferon, and lower level of HBsAg at the EOT were significantly associated with HBsAg clearance based on multivariate analysis.

Conclusions
In HBeAg-negative patients with CHB, it is safe and effective to discontinue ADV therapy after 4 or 5 years; 55% of patients have sustained responses, and 39% of patients lose HBsAg.
Avatar universal
clearance is not influenced by hbvdna levels after stopping adv, actually this test is totally useless to predict clearance or responce, values are high in both relapsers and those clearing

ast-alt are the most important, those with normal alt dont clear hbsag

hbsag less than 1000iu/ml and in particular less than 100iu/ml is the most important values to predict clearance

i wonder relapsers may clear by intf instead of restarting adv
Avatar universal

also to note those with high hbsag 10.000iu/ml clear if there are alt flares, it takes 24-66months for these but they clear too

another interesting thing is alt flares are not that high, most below 80
Avatar universal

another interesting thing, relapsers had low hbvdna, normal ast-alt and did not clear hbsag while clearers had abnormal alt but not too high and high hbvdna

i think adefovir and tenofovir probably even better rescue immune cells, these cells need high hbvdna to mount an immune response shown by abnormal alt mostly 40-80 and declining hbsag.
if ast alt stay normal and hbvdn low or und there is no immune response, this is probably what makes antivirals failure to clear hbv.

another strategy, which actually was mentioned in pisa, is long term nucs then intf add on to nucs and then on and off nucs during intf according to alt-hbsag response
Avatar universal
Your charts refer to whom?

It seems that after achieving undetectable viral load for several years using NA, patients can stop. Three outcomes are possible:
1. Patients clear HbsAg
2. Patients retain low viral load and normal ALT
3. Patients need re-treatment with NA.

It seems all patients after stopping NA, have virological breakthrough  (increase in viral load) and 76% have biochemical relapse (increase in ALT). So the trick is: how do doctors and patients decide who should be re-treated or who should wait, and when? After all roughly 50% do not require re-treatment.

And as you suggested, will treatment with Interferon improves the rate of HbsAg clearance? again the question is: who and when?

Low HbsAg level at end of treatment seems to be a good marker - we will need some numbers.
Avatar universal
Hi Stef, I see eag+ may have a hbsag rise at 12th wks and then decline.. am i right mate?
Avatar universal

its all in the charts, they compare relapsers vs clearers and all those with alt increase have declining hbsag.

who should be re-treated or who should wait, and when?

those with normal alt, no hbsag decline and high hbvdna need retreat.download the charts and enlarge, the big difference between the two groups is normal alt in relapsers and increased alt in clearers, alt/hbsag is what to look for
Avatar universal

even those with very high hbsag 10.000iu/ml EOT and high hbvdna cleared although in 66 months, i guess intf will just speed up process
Avatar universal

sorry i dont have checked hbeag+ charts but for hbeag neg it works like that

studyforhope said the hbsag rise is probably purged from infected cells
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Avatar universal
I saw the charts, but need explanations. Does each curve represent one patient? who are the responders (to what)?
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