Reduction of HBsAg & cccDNA by NUCs

[StephenCastlecrag]

Clin Gastroenterol Hepatol. 2013 Jan 31. pii: S1542-3565(13)00169-9. doi: 10.1016/j.cgh.2013.01.026. [Epub ahead of print]
Reduction of Hepatitis B Surface Antigen and Covalently Closed Circular DNA by Nucleos(t)ide Analogues of Different Potency.
Wong DK, Seto WK, Fung J, Ip P, Huang FY, Lai CL, Yuen MF.

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China; State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
Abstract
BACKGROUND & AIMS:

Few studies have investigated the effects of different nucleos(t)ide analogues against hepatitis B virus (HBV) on level of covalently closed circular (ccc)DNA and hepatitis B surface antigen (HBsAg) in patients. We measured the magnitude of reduction of cccDNA and HBsAg by nucleos(t)ide analogue therapy and assessed the correlation between their reductions.
METHODS:

We recruited 124 patients who were treated with one of the 5 nucleos(t)ide analogues (lamivudine, adefovir, entecavir, telbivudine, or clevudine). All patients had undergone liver biopsy when treatment began (baseline) and 1 year later. cccDNA and HBsAg were measured by real-time PCR and the Elecsys II HBsAg Assay, respectively.
RESULTS:

After 1 year of treatment, HBV in 7 patients had become resistant to the nucleos(t)ide analogue. The remaining 117 patients had an average reduction of approximately 0.2 log10 IU/mL in HBsAg, 5 log10 IU/mL in serum level of HBV DNA, 2 log10 copies/cell in intrahepatic total HBV DNA, and 1 log10 copies/cell in cccDNA. Although 88/117 patients (75%) had undetectable serum levels of HBV DNA (<12 IU/mL), all had detectable levels of HBsAg, and only 5 (4%) had undetectable levels of cccDNA. Upon treatment with nucleos(t)ide analogues, patients with greater reductions in levels of cccDNA had greater reductions in HBsAg, but these reductions did not reach statistical significant correlations .
CONCLUSIONS:

Although nucleos(t)ide analogues potently reduced serum levels of HBV DNA, the reduction of HBsAg and cccDNA was small. In short-term therapy, the magnitude of HBsAg reduction does not correlate with that of cccDNA reduction.

[imran4535]

Hopefully with Myrcludex-B or the discovery of the HBV receptor will lead to therapy that will block or slow down the reinfection cycle.

[StephenCastlecrag]

From a piece of the liver through biopsy. They must have developed assays that would allow them to measure intrahepative (inside the liver) HbsAg, hbvdna and cccDNA from the liver tissue.

[OrientS]

What are the tests/diagnosis that indicate presence of cccDNA?

[stef2011]

i missed the time was so little, 1 year study is absolutely useless for nucs we need a study on 5 years minimum

i think reinfection is the point myrcludex will show if persistance is due to reinfection

[StephenCastlecrag]

The full paper may discuss the differences amongst the antivirals. I am surprised that there are drops in HBsAg and cccDNA, however small. Also remember that this is only a one year study. It will be nice to monitor patients over a longer period of time and offer an explanation for the decrease in cccDNA - is it due to reduction in the refurbishing of the cccDNA pool by re-infection and by recycling, followed by a reduction in the cccDNA pool through loss during cell division? Or is it due loss of infected cells by the actions of temporarily rekindled CD8+ T cells?

[stef2011]

these studies are still missing the most potent antiviral tenofovir or the combo tenofovir plus entecavir or tenofovir plus telbivudine, although there is probably little difference we do need to know the effect on cccdna of the most potent combos
i hope sooner or later we will have these resports and also the reports of cccdna on intfplus tdf

[StephenCastlecrag]

You will have to read the full paper which requires a fee or membership.

[calebz]

Is there any detailed info about the 7 with resistance ? How does it divide upon particular drugs?