Entecavir and interferon-α sequential therapy

[StephenCastlecrag]

http://www.springerlink.com/content/38762457x0341165/?MUD=MP
Entecavir and interferon-α sequential therapy in Japanese patients with hepatitis B e antigen-positive chronic hepatitis B

Masaru Enomoto, Shuhei Nishiguchi, Akihiro Tamori, Sawako Kobayashi and Hiroki Sakaguchi, et al.

Journal of Gastroenterology, Online First™, 1 August 2012

  
Abstract
Background  
The outcomes of sequential therapy with lamivudine followed by interferon have been unsatisfactory in Japanese patients with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B. However, the efficacy of sequential therapy with entecavir and interferon remains unclear.
Methods  
Twenty-four HBeAg-positive patients (23 men and 1 woman; mean age 39 ± 7 years) received entecavir 0.5 mg alone for 36–52 weeks, followed by entecavir plus interferon-α for 4 weeks, and lastly by interferon-α alone for 20 weeks. Twenty-three patients had genotype C infection, and one had genotype A infection.
Results  
No entecavir-resistant mutant variants emerged in any patient. Hepatitis flare occurred in three patients during interferon-α treatment after the withdrawal of entecavir, but none had hepatic decompensation. Serum hepatitis B surface antigen levels did not change during or after therapy. Serum hepatitis B core-related antigen levels were significantly decreased at the start (P < 0.0001) and at the end of interferon-α treatment (P < 0.0001), but returned to baseline levels after treatment. Twenty-four weeks after the completion of the sequential therapy, a sustained biochemical, virological, and serological response was achieved in 5 (21 %) patients. The proportion of patients in whom HBeAg was lost during entecavir treatment was significantly higher among those with a sustained response than among those with no response (P = 0.015).
Conclusions  
The rate of response to sequential therapy with entecavir and interferon-α in Japanese patients with HBeAg-positive chronic hepatitis B was not higher than the rate in previous studies of lamivudine followed by interfero

[calmama]

Agreed.  We need more studies of this type of treatment.  But I do wish they follow up on the patients to see if there is any long term side effect (eg. autoimmune disorders) AFTER the treatment.  Some autoimmune disorders stemming from longer period of interferon treatment may be long term and people need to know about it when they weigh the risk and benefit of this treatment.

[StephenCastlecrag]

With no new HBV drugs in sight, increasingly we have to reply on treatment strategies based on existing drugs: NUC + Interferon. Only with more studies like the one above, can we hope to identify the optimal treatment methods. It may be that we have to have longer period of undetectable viral load (to restore T cell immune functions?) and longer period of Interferon treatment (how long, 48, 96 weeks?); we need better statistics. Also there are the questions of HbeAg status, baseline serum HBsAg level, genotype, IL28 polymorphism etc.

[stef2011]

sorry i m in the intf fever day....

you can t get anything from intf use for only 24 weeks, the max effect of intf on immune system is at 48weeks

genot D are the least responsive to intf over all, geno c might be similar to d

[stef2011]

i think such short studies are useless, you can get anything from intf use for 24 weeks, genot D are the less responsive to intf over all, geno c might be similar to C, a and b are the most responsive

[calmama]

The Milan study was largely on genotype D patients.  This one was on genotype C patients (except one lonely geno A person).  There might be difference there.

[calmama]

Yes, I also noticed the older mean age for this e-positive group.  I remember reading a study about later e-seroconversion (after 40 yrs of age) being a relatively common event for genotype C patients.  So I wasn't really surprised.

[stef2011]

2 notes:
on combos intf+nucs there was hbsag increase the first 4-6months and hbsag decrease was only after 6 months of combo (various nucs used).the milan study

you need about 3 years with etv and tdf to rescue immune system to have an intf response and 4-7 years with adv, lam

so my question is, we already knew of no hbsag effect from other studies in such a little time, what s the use of this study?if just ended in such a short time it is:
money wasted
or one of the studies trying to say intf+nucs have no effect

[StephenCastlecrag]

Good observation. I don't have acess to the whole paper, so cannot confirm.. Interferon is less effective for genotype C, I am also surprised by the relatively older age of the HbeAg positive patients.

[calmama]

"Serum hepatitis B surface antigen levels did not change during or after therapy."

Was that the reason they did only 24 wks of interferon instead of 48 (or even 96)?