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P0610
DYNAMIC PREDICTION OF INACTIVE CHRONIC HEPATITIS B
USING REPEATED HBsAg AND HBVDNA LEVEL MEASUREMENTS
THROUGH LONG-TERM FOLLOW-UP
W.P. Brouwer1, H.L.-Y. Chan2, M.R. Brunetto3, M. Martinot-
Peignoux4, P. Arends1, M. Cornberg5, B. Cherubini3, A.J. Thompson6,
Y.-F. Liaw7, P. Marcellin4, H.L. Janssen8, B.E. Hansen1.
1Gastroenterology & Hepatology, Erasmus MC Rotterdam, Rotterdam,
Netherlands; 2Medicine & Therapeutics, Chinese University of Hong
Kong, Hong Kong, Hong Kong, China; 3Hepatology unit, University of
Pisa, Pisa, Italy; 4Gastroenterology & Hepatology, Centre de Recherche
Biom´edicale Bichat-Beaujon, Clichy, France; 5Gastroenterology,
Hepatology and Endocrinology, Hannover Medical School, Hannover,
Germany; 6Gastroenterology & Hepatology, Victorian Infectious
Diseases Reference Laboratory, Melbourne, Australia; 7Liver Research
Unit, Chang Gung Memorial Hospital, Chang Gung University College
of Medicine, Taipei, Taiwan; 8UHN Liver Clinic, Toronto Western and
General Hospital, University Health Network Toronto, Toronto, Canada
E-mail: [email protected]
Background and Aims: A single-point hepatitis B surface antigen
(HBsAg) level below 1,000 IU/mL combined with low HBVDNA
has been shown to identify inactive carriers (IC) after 1 year of
follow-up. Our aim was to evaluate the performance of repeated
HBsAg measurements through long-term follow-up.
Methods: In this retrospective cohort study conducted at 8 tertiary
care centres 293 treatment-naïve non-cirrhotic HBeAg-negative
patients with a normal ALT and HBVDNA <20,000 IU/mL were
included. HBsAg, HBVDNA and ALT levels were measured at each
visit during a median follow-up of 8 years (range 4–9). Patients
were defined IC in case of HBVDNA <2,000 IU/mL and persistent
normal ALT during a complete follow-up year. A fluctuation
>2,000 IU/ml and/or abnormal ALT was defined as HBV activity.
Dynamic regression analysis was used to study changes in HBsAg
levels and HBV phase.
Results: Of 293 patients, 224 (76%) were IC at inclusion. Mean
age was 43±13 years and HBV genotype A/B/C/D was present
in 39/42/33/104 patients. Patients with activity in one year and
a persistently normal ALT and HBVDNA <2,000 IU/mL during the
subsequent year had a 40% chance to have activity again in the year thereafter. By dynamic analysis, the probability to remain IC in the next year given HBsAg levels of <100, 100–1,000 or >1,000 IU/mL was 96%, 86% and 81% (p < 0.001). IC during 2 consecutive years was predictive of IC in the next year, still 10% of patients with HBsAg >100 IU/mL showed disease progression (figure). A single-point HBsAg <100 IU/mL with HBVDNA <2,000 IU/mL could predict IC throughout long-term follow-up with a specificity of 97% and a positive predictive value (PPV) of 95%, while a HBsAg <1,000 IU/mL combined with HBVDNA <2,000 IU/mL had a specificity of 88% and a PPV of 90% for the total cohort. The combined rule of HBVDNA with HBsAg <1,000 IU/mL performed well in HBV genotype D patients (PPV 95%, specificity 92%), still HBsAg levels <100 IU/mL were superior (PPV 99%, specificity 99%).Patients with HBsAg <100 IU/mL also had a high chance of HBsAg loss (HR = 5.1 versus 100–1000 IU/mL, 95% CI:1.9–13.5, p < 0.001).
In those patients with a HBVDNA >2,000–<5,000 IU/mL and a
HBsAg decline of ≥0.5 log IU/mL one year prior, 62% became and
remained IC.
Conclusions: Both HBsAg levels and declines can be used to identifyIC patients. HBsAg levels are predictive of remaining in the IC phase and should be used to define HBV phases.
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