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LP29
A RANDOMISED PROSPECTIVE OPEN-LABEL TRIAL COMPARING PEGINTERFERON + ADEFOVIR AND PEGINTERFERON +
TENOFOVIR VERSUS NO TREATMENT IN HBeAg NEGATIVE CHRONIC HEPATITIS B PATIENTS WITH LOW VIRAL LOAD:
ANALYSIS OF WEEK 48 RESULTS
A. de Niet1,L. Jansen1, F. Stelma1, S.B. Willemse1
, S.D. Kuiken2,S. Weijer3, K.M. van Nieuwkerk4
, H.L. Zaaijer5,6, R. Molenkamp5,R.B. Takkenberg1
,M.Koot7, J. Verheij8, U. Beuers1, H.W. Reesink1.
1Gastroenterology and Hepatology, Academic Medical Centre,
2Gastroenterology and Hepatology, Sint Lucas Andreas Hospital,Amsterdam,
3Internal Medicine, Medical Centre Zuiderzee, Lelystad,
4Gastroenterology and Hepatology, VU Medical Centre,
5Medical
Microbiology, Academic Medical Centre,
6Blood-borne Infections,
7Virus Diagnostic Services, Sanquin,
8Pathology, Academic Medical
Centre, Amsterdam, Netherlands
E-mail: [email protected]
Introduction:
Chronic hepatitis B (CHB) patients with a low
viral load (LVL) are currently not eligible for antiviral treatment.
However, they comprise the largest group of hepatitis B virus-
infected patients and are still at risk to develop cirrhosis or
hepatocellular carcinoma. Here we present the week 48 results
of a randomized trial comparing combination treatment of
peginterferon alfa-2a (Peg-IFN) and a nucleotide analogue versus
no treatment for CHB patients with LVL.
Material and Methods:
134 CHB patients (HBeAg-negative,
HBV-DNA<20,000IU/mL) were randomized 1:1:1 to receive Peg-IFN+adefovir (arm I; n=46), Peg-IFN+tenofovir (arm II; n=45)
or no treatment (arm III; n=43) for 48 weeks (ITT population)
Randomization was stratified by HBV genotype A (22%), non-A (B7%, C 4%, D 26%, E/F/G 20%), or indeterminate (21%). The median
age was 43 years, 57% were male. Twelve patients discontinued the
study before week 48 (5 in arm I, 6 in arm II, 1 in arm III). HBsAgloss (AxSYM<0.05IU/mL) and quantitative HBsAg level (Architect)
was determined at regular intervals, and were compared using
Fisher’s, Mann–Whitney U or Wilcoxon test.
Results:
At week 48, 4 patients receiving combination therapy
had achieved HBsAg loss, compared to none of the untreated
patients (ITT 4.4% vs 0.0%, p=0.31). Patients with HBsAg loss were
treated in arm I (n=1) and arm II (n=3), and had HBV genotype
A (n=1), B (n=1), or indeterminate (n=2). Baseline HBsAg levels
were comparable between study arms (median 3.34 log IU/mL). In
a per-protocol analysis, HBsAg level had declined significantly in
all arms at week 48; −0.33 (p<0.001), −0.22 (p<0.001), and −0.07
(p=0.02) median log reduction for arms I, II, and III, respectively.
No difference in HBsAg decline was observed between treatment
arms. However, HBsAg declined more in treatment arms I (p<0.001) and II (p=0.002) compared to the control arm III. A strong HBsAg decline of
> 1.0log IU/mL was observed in 17 treated patients (21%), but in none of the untreated patients (p
<0.001). No unexpected
adverse events were observed in the treatment arms.
Conclusions:
In CHB patients with a low viral load, 48 weeks
of combination treatment with Peg-IFN and adefovir or tenofovir resulted in 4.4% HBsAg loss, compared to 0.0% in the untreated
control group. The significant decline in HBsAg at week 48 may
indicate a further increase in the rate of HBsAg loss during treatment-free follow-up. Week 72 results are expected in April 2015.
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