39% hbsag clearance after 4-5years and adefovir stop

[stef2011]

Author: [email protected]
Date: 2012-06-21 00:51 +200
To: hbv_research
Subject: Sustained Responses and Loss of HBsAg in HBeAg-Negative Patients - Who Stop Long-Term Treatment with Adefovir
Gastroenterology. 2012 May 31. [Epub ahead of print]
Sustained Responses and Loss of HBsAg in HBeAg-Negative Patients with Chronic Hepatitis B Who Stop Long-Term Treatment with Adefovir.
Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E.
Sourcehttp://www.ncbi.nlm.nih.gov/pubmed/22659218
Department of Medicine and Hepatology, Henry Dunant 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.

Abstract
BACKGROUND& AIMS: Little is known about the biochemical and virologic effects of stopping long-term treatment 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 dipivoxyl (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 post-discontinuation period, all patients experienced virologic and 25 (76%) had biochemical relapse. During follow-up period, 18 patients (55%) who had discontinued antiviral therapy achieved sustained response (SR, HBV DNA<2000 IU/L, persistently normal level of ALT). Among these 13 (72%) cleared HBsAg. Fifteen patients (45%) with virologic and/or biochemical relapse were retreated 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 SRs and 39% of the patients lose HBsAg.

[stef2011]

hbsag less than 500iu/ml with genotype D (with no hbsag mutants) is correlated with very low cccdna and immune control, hbvdna doesn t need to be und but below 2000iu/ml.
this immune control usually keeps lowering hbsag year by year with no drugs but there is no 100% guarantee because hbv can also mutate and escape immune control but i guess this is rare at low hbsag/hbvdna

[Bob0620]

If HBSag below 500iu/ml and undetected HBV DNA, can our body control it to the same level without medication forever ?

[stef2011]

thats an old useless view, some patients were thought to have immune control and no liver damage when hbeag neg with low hbvdna and low alt

todays end point of very updated liver specialists is hbsag clearance or its lowering below 500iu/ml which can be really safe off drugs

[grmr]

yet.. why is eag seroconversion considered as one of the end point of TDF+IFN therapy if once you become eag -ve the immune system will be more hurtful to the liver???

[stef2011]

hbeag negative have an higher immune response, much higher, so they have more liver damage
the problem of this higher immune response failing to clear hbv is due to hbv mutations and maybe leel of t regs too.
in this scenario hbeag neg are the best candidtes

hbeag pos have very weak immune response but have higher response to drugs because hbv has not mutated yet to escape immune response.so hbeag pos have less liver damage

[StephenCastlecrag]

NCT01320943

Withdrawal of antiviral therapy can result in hepatic or alanine aminotransferase (ALT) flares as Hepatitis B Virus (HBV) replication resumes; however, in some patients, a flare exacerbates chronic hepatitis temporarily but can also result in viral clearance. Hepatic flares are common after stopping anti-HBV therapy.

Only patients who already are on treatment with tenofovir disoproxil fumarate (TDF) for at least 4 years and who achieved and maintained virologic suppression (< 400 copies/mL) for 3.5 or more years will be included in this study. One treatment arm will stop the TDF therapy while the other treatment arm will continue the TDF therapy.

Patients who stop TDF (Arm A) will be monitored very closely with special focus on biochemical flares (especially ALT increases) and virological relapses (Hepatitis B viral load increases). If any subject in the stop therapy arm exceeds one or more predefined limits for such flares or relapses, TDF will be reinstituted.

The study will assess Hepatitis B surface antigen (HBsAg) loss (i.e. specific Hepatitis B virus components are no longer detectable) and seroconversion (occurrence of Hepatitis B surface antibody, a specific antibody which usually occurs after HBsAg loss) rates during study duration. The percentage of patients who need to restart TDF therapy in the stop arm will also be evaluated.

[4est]

I can't remember if Gilead use Adefovir or they use also some other NUC's

[StephenCastlecrag]

Gilead is conducting a clinical trial to test this strategy, as I mentioned elsewhere.

[ronny12]

Believed that hbeag negative was associated with a poorer prognosis but from the abstract i see it is a different story and yes what if tnf was used that 39 could became 50 or something more i guess. Thanks for the article Stef.

[stef2011]

guess tenofovir is even better, this is probably due to the t-regs decrease which is caused by adv and tdf (no reports from etv), very good try for those with no cirrhosis