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TO STUDY THE EFFICACY OF PEG-IFN ALPHA IN HBEAG
NEGATIVE CHRONIC HEPATITIS B PATIENTS AFTER STOPPING
NUCLEOTIDE ANALOGUE THERAPYCLINICAL TRAILS.GOV
IDENTIFIER NO: NCT03123653
Karan Kumar1, Shiv Kumar Sarin2, Manoj K Sharma3, Ankur
Jindal4, Manjul Mishra Jr.5, Harsh Vardhan Tevethia3, Apurva
Pande3 and Guresh Kumar Sr.6, (1)Institute of Liver and
Biliary Sciences,New Delhi, India, (2)Institute of Liver and
Biliary Sciences, (3)Institute of Liver and Biliary Sciences,
New Delhi, India, (4)Hepatology, Institute of Liver and Biliary
Sciences, New Delhi,India, (5)Ilbs, (6)Clinical Research,
Institute of Liver and Biliary Sciences
Background: As per APASL guidelines, amongst HBeAg
negative chronic hepatitis B (CHB) patients, nucleot(s)
ide analogues (NAs) can be stopped after ≥2 years with
undetectable HBV DNA on three occasions 6 months apart.
Clinical relapse may occur in 30-50% of these depending
on the race and geography. Whether Peg-IFN therapy can
improve outcomes and viral clearance in post-NA stoppage
has not been adequately studied. We assessed the incidence
and predictors of relapse in HBeAg negative CHB after
stopping NAs and assessed the efficacy and safety of peg-
IFNα-2b (PEG-IFN) therapy Methods: HBeAg negative CHB
patients on long-term NAs (tenofovir or entecavir) and fulfilling
stopping rules for NAs were enrolled, and patients with >F2
fibrosis on biopsy or LSM>8 were excluded. NAs were stopped
and patients were followed for a median of 96 weeks Patients
with clinical relapse (DNA >2000 IU/mL, ALT >80 IU/mL)
were started on Peg-IFN (1 5mcg/kg) therapy for 48 weeks
Results: NA therapy was stopped in 118 HBeAg negative
CHB patients (87 1% male) with mean age of 41 46±12 01
years , mean LSM-5 78±1 14 and having baseline mean
HBsAg levels of 1 55x10^4 ± 1 27x10^3 Forty four (37 3%)
patients developed clinical relapse, all within 6 months of
stopping NAs On multivariate analysis, predictors of relapse
included prior treatment with Peg-IFN [ OR (95% CI) :0.22
(0.05-0.93).], time taken to achieve undetectable HBV DNA
[OR (95%CI): 1.6 (1.35-1.89)] and duration of consolidation
therapy with NAs [OR (95%CI): 0.78 (0.63-0.97)]. ROC
analysis revealed optimum duration of consolidation therapy
as >5.5 years. Relapse occured in 12(20.3%) patients having
consolidation therapy >5.5 years compared to 32 (54.05%)
with < 5 5 years (p-0 03) Six months after the end of 48 week
peg-IFN therapy, of 44 patients, HBV DNA < 2000 IU/mL, >2
Log10 decline in HBsAg, HBsAg <1000 IU/mL, HBsAg <100
IU/mL and HBsAg loss was seen in 44 (100%), 23(52 27%),
19(43 18%), 7(15 4%) and 4 (9 09%) patients respectively
Amongst 74 patients who did not develop clinical relapse
after stopping NAs, > 2 Log10 decline in HBsAg levels, HBsAg
<1000 IU/mL, HBsAg <100 IU/mL and HBsAg loss was
seen in 2 (2 6%),5(6 75%), 1(1 35%) and 0(0%) patients
respectively, after a median follow-up of 22 months after
stopping NAs (Table1) All 44 patients were able to complete
their interferon therapy Adverse events seen with Peg-IFN
therapy were fatigue and malaise(79 54%), anemia (25%),
thrombocytopenia(50%) and leucopenia(34%) Conclusion:
Clinical relapse rate after stopping NAs was seen in 37 3%
Indian eAg-veCHB patients Shorter consolidation period was
a significant predictor of clinical relapse. Peg-IFN therapy
for 48 weeks resulted in >2 Log10 decline in HBsAg levels in
52 7% and HBsAg loss in 9 1%, and thus can be used as
finite duration therapeutic option.作者: StephenW 时间: 2019-10-29 17:54
