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END OF TREATMENT HBsAg, HBCRAG AND HBV RNA LEVELS
PREDICT RISK OF OFF-TREATMENT ALT FLARES IN PATIENTS
WITH CHRONIC HEPATITIS B.
Sylvia Brakenhoff1, Robert J. De Knegt2, Margo Van
Campenhout1, Annemiek A. Van Der Eijk3, Willem Pieter
Brouwer4, Florian Van Bömmel5, Andre Boonstra4, Bettina
E. Hansen6,7, Thomas Berg5, Harry L.A. Janssen8, Robert
A. De Man1 and Milan J. Sonneveld1, (1)Department of
Gastroenterology and Hepatology, Erasmus MC, University
Medical Center, (2)Department of Gastroenterology and
Hepatology, Erasmus University Medical Center Rotterdam,
(3)Department of Viroscience, Erasmus MC, University
Medical Center, (4)Department of Gastroenterology and
Hepatology, Erasmus University Medical Center, (5)Division
of Hepatology, Department of Medicine II, Leipzig University,
Medical Center, Leipzig, Germany, (6)Toronto Center for Liver
Disease, UHN & Ihpme University of Toronto, (7)Institute
of Health Policy, Management and Evaluation, University
of Toronto, (8)Toronto Centre for Liver Disease, University
Health Network
Background: Since ALT flares after therapy withdrawal are
associated with adverse outcomes, risk stratification is of
major clinical importance We aimed to study whether serum
levels of novel biomarkers at end of treatment (EOT) are
associated with occurrence of off-treatment flares. Methods:
We studied chronic hepatitis B patients who participated in
three global randomized trials of peginterferon-based therapy
(99-01 [PEG-IFN alone vs PEG-IFN + lamivudine], PARC
[PEG-IFN alone vs PEG-IFN with ribavirin] and ARES [ETV
with PEG-IFN add-on]) HBV RNA, HBsAg and hepatitis
B core related antigen (HBcrAg) were quantified at EOT.
Associations between biomarker levels and ALT flares were
assessed using continuous data and after categorization
(<3/>3 log for HBsAg, undetectable/detectable for HBV RNA,
and for HBcrAg <3/>3 log for HBeAg-negative and <6/>6 log
for HBeAg-positive patients) SCALE-B score (comprising
HBsAg, HBcrAg, age and ALT) was also calculated and
patients were categorized using previously reported cut-offs
(<260 , 260-320, >320). ALT flares were defined as an ALT
≥5x ULN during the first 6 months after therapy cessation.
Analyses were performed in the overall cohort, and in the
subgroup of patients with an EOT response (defined as
HBeAg negativity with HBV DNA <200 IU/mL) Results:
A total of 344 patients with EOT data were enrolled; 230
HBeAg-positive and 114 HBeAg-negative Patients were
predominantly Caucasian (77 0%) and had genotype A/B/C/D
in 23 3/7 3/13 4/52 3% An EOT response was observed in
120 patients (34 9%) During follow-up, 122 patients (35 5%)
experienced an ALT flare. Higher HBsAg (OR 1.586, 95% CI
1 231-2 043, p<0 001), HBV RNA (OR 1 695, 95% CI: 1 371-
2 094, p<0 001) and HBcrAg (OR 1 518 95% CI: 1 324-1 740,
p<0 001) levels at EOT were associated with higher risks of
ALT flares (figure 1). Combinations of biomarkers, e.g. HBV
RNA with HBsAg or the SCALE-B score, further improved risk
stratification: for example, among 69 patients with both high
HBV RNA and HBsAg levels, 36 (52.2%) experienced a flare,
compared to 0/42 patients (0 0%) with low HBV RNA and
HBsAg levels (p<0.001, figure 1). Findings were consistent
across pre-treatment HBeAg-positive and -negative patients
and in the patients with an EOT response Conclusion:
Higher EOT serum HBsAg, HBcrAg and HBV RNA levels
are associated with a higher risk of ALT flares after therapy
withdrawal. These findings can be used to guide decisionmaking
regarding therapy discontinuation and intensity of
off-treatment follow-up Figure 1. Rates of off-treatment
flares (ALT ≥5x ULN) in the overall cohort, according to
HBsAg, HBcrAg and HBV RNA levels at end of treatment. 作者: StephenW 时间: 2020-10-20 13:01