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Quantitative HBsAg is a poor marker of chronic hepatitis B inactive carriage
F. Napoli1; Y. Ngo2; T. Poynard2, 3; V. Thibault1
1. Virology - CERVI, Pitie-Salpetriere Hospital, Paris cedex 13, France.
2. Hepato-Gastroenterology, AP-HP Pitie-Salpetriere Hospital, Paris, France.
3. UMR 8149, CNRS, Paris, France.
Quantitative HBsAg measurement (qHBsAg) has been proposed as an additional predictive marker to accurately classify inactive chronic hepatitis B (CHB) carriers. A retrospective analysis was conducted to analyze the values and evolution of qHBsAg over a 3 year period in CHB according to standard definition of inactive carriage (IC). HBsAg was quantified from serum taken at two time points from 41 patients classified as IC according to the definition of Ngo et al. (2008 Plos One 3(7): e2573) and followed for a mean period of 3.2 years. Patient mean age was 36 yo. (±1.6) and 46% were males. 39% (16) of these patients were defined as IC according to classical criteria: HBeAg negative, HBV-DNA< 2000 IU/mL and persistently normal ALT, with an ALT upper limit set as 26 IU/L. On the first time point, the mean (SE) qHBs value was 7582 IU/mL (±2378). 13 (32%) patients had qHBsAg below 1000 IU/mL but were equally distributed in IC and non IC. On follow-up, a significant (p=0.026) drop of 19% was noticed with a mean qHBsAg at 5793 IU/mL (±1438) and 2 additional patients (37%) reached a value below 1000 IU/mL. No difference in qHBsAg decrease was seen between patients with an initial value below or above 1000 IU/mL. Moreover, no significant qHBsAg difference was observed between IC (standard criteria) and non-IC patients; qHBsAg values at the first time point were 12523 (±5748) and 4420 (±1083) IU/mL, respectively. The same conclusion was verified at the second time point. Over the three year period, 17% of patients had an increase over 10% of qHBsAg, 20% had a qHBsAg steady level (a fluctuation of less than ±10%) and 63% had a decrease over 10%, with a mean decline of 42% (±5). Evolution of qHBsAg over time was not linked to the IC status. Predictive factors based on qHBsAg for accurate classification of IC were assessed using receiver operator characteristics and the best area under curve was obtained after calculation of qHBsAg drop per year with a value of 0.73 IU/mL (±0.081). However, none of the studied parameters (absolute value, drop, kinetics) reached a strong enough predictive value compatible with clinical use. Although different qHBsAg thresholds have been proposed to classify inactive carriers, a dynamic appraisal on at least 2 time points maybe more relevant. Yet, no clinically appropriate algorithm based solely on qHBsAg could be found to accurately classify IC. Regulation of HBsAg production during CHB is complex and single measurement of qHBsAg seems inadequate as predictive marker for inactive carriage in clinical practice.
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