peg add on leads to hbsag loss on patients fully suppressed by longterm nucs

[stef2011]

http://www.sciencedirect.com/science/article/pii/S1386653213004113

Abstract
Background and objective
The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment.

Study design
We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years.

Results
HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up.

Conclusions
In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12–18 months of follow up. HBs seroconversion was observed in two patients.

[stef2011]

this reflects the other study with more patients, it was french twoo.some cleared at 48weeks, the others had decline to very low levels and 1 did not respond

a strange point is those on mono nuc cleared while those on combo did not.since patients are really a few this might be coincidence

those clearing were:
3 on mono adv
1 on mono etv
1 on mono lam

genotype looks like having no influence, we had A,B,D,F and those not clearing had A and D

it would be very interesting to see if vitamin d could change all this by boosting peg response

[stef2011]

10 patients
3  got hbsag decline
1  got no response
before IFN add on: 1309iu/ml (1243–1722)
Baseline               1233iu/ml (  974–1754)
Week 24                 481iu/ml (    20–  984)
Week 48                 363iu/ml (    40–1380)
Week 96                 170iu/ml (  115–1110)
6 months post-IFN   173iu/ml (  100–1010)
12 months post-IFN 147iu/ml (   70–1000)

they all got benefit (except the one stopping at 24weeks for non response which keeps the values around 1000iu/ml, but even this patient got continuous slow decline after the 24weeks on peg)

[stef2011]

interesting points of the study:

10 patients
6   got hbsag negative
before IFN add on: 170iu/ml (from 50–6240iu/ml)
Baseline               179iu/ml (from 50–7900iu/ml)
Week 24                37iu/ml (from 15–  240iu/ml)
Week 48                  0iu/ml (0–121)
Week 96                  0iu/ml  (0–20)
6 months post-IFN    0iu/ml  (0–0)
12 months post-IFN  0iu/ml  (0–0)

[studyforhope]

The paper shows the quant hbsag curves for all patients. Of the six responders four were between ten and about two hundred IU of hbsag as baseline, one was 1500 and one was 6000. All four non responders had values over 1000 IU. Only two patients seroconverted.
Re the NAs used only one was on Tdf plus lam, none on Tdf only.

In summary this approach works far better when the spontaneous reduction in cccDNA is already present and a substantial immune response preexists.

The same trend can be seen in other papers that test the na plus peg ifn combo therapy.

[StephenCastlecrag]

The results are slightly more encouraging. Obviously we would like to know the baseline qHBSAg before Intf add-on and their decline during treatment. I wonder whether the length of INTF treatment is influenced by the rate of decline of qHBSAg and how, and whether a stopping rule can be inferred, 96 weeks is awfully long to be on INTF. Finally, I would also like to know the genotype of the patients. A lot of these results do not apply to patients infected at birth as in Asians of genotype. B and C.

[stef2011]

extremely rare since hbsag decrease by pegintf eliminiates almost all cccdna

studies on peg add on never reporeted a relapse

[andrey19]

By the way how often does relapse happen after hbsag loss?

[stef2011]

i posted this study, among the many we are seeing lately about the add on, to see if any member is able to find the hbsag levels of the 3 patients not clearing hbsag

i think it is very important to see if those not clearing were able to get very low levels of hbsag, this would be a good success too.