741 — 2020 AASLD THE DYNAMICS OF HBSAG/ANTI-HBS IMMUNE COMPLEX AND QUANTITATIVE HBSAG (QHBSAG) TITERS DURING NUCLEOS(T)IDE ANALOGUE (NA) THERAPY IN PATIENTS WITH HBEAG(-) CHRONIC HEPATITIS B
Clinical Practice
I02 Diagnostics and Biomarkers
Presented on Monday, May 4, 2020 2:45 PM
Author(s): Pir A. Shah1, Mark C. Anderson2, satinder p. kaur1, Mary Kuhns2, Gavin A. Cloherty2, Daryl Lau1
Background and Aims: The interaction between the humoral immune response and HBV with NA therapy is not well understood. Anti-HBs antibodies are known to exist in chronic hepatitis B (CHB) but are mainly detected as complexed to HBsAg due to the high level of circulating HBsAg. We applied a novel immunoassay to evaluate the relationship of HBsAg/anti-HBs immune complex (IC) and qHBsAg levels in HBeAg(-) CHB patients during continuous NA treatment.
Method: HBeAg (-) CHB patients on NA for at least 18 months with available serial sera from baseline were included in this analysis. The research assay by Abbott Diagnostics utilizes anti-HBs monoclonal antibodies to capture HBsAg that are complexed with specific patient-derived anti-HBs antibodies. The concentration of the immune complex (IC) is reported in Relative Light Units (RLUs). Serial IC and qHBsAg (Abbott Architect assay) titers were measured for each patient from pretreatment to last follow up samples.
Results: 11 HBeAg (-) Asian patients with genotype B and C CHB were included. Three (27%) achieved qHBsAg <100 U/ml and 8 (73%) had qHBsAg between 309 and 1675 U/ml after 63 and 50 months of therapy respectively (p=0.2). The baseline qHBsAg titer of the 2 groups were similar (760 vs 921 U/ml p=0.34). HBsAg/anti-HBs IC was detectable in all patients between 748 and 5547 RLUs before treatment. The ratio of IC to qHBsAg at baseline was significantly higher among the 3 who achieved qHBsAg <100 U/ml compared to the other 8 patients (14 vs 2.1 p=0.003). [Figure 1, 2] When the HBV DNA was supressed to <20 IU/ml, the mean IC/qHBsAg ratio further increased to 26 for the 3 excellent responders but remained low at 2.3 for the others. At last follow up, patients with qHBsAg <100 U/ml had a strikingly high IC/qHBsAg ratio of 219 [Figure 1]. In contrast, those with HBsAg >100 IU/ml at last follow up had persistently low IC/qHBsAg ratio at 2.0.[Figure 2]
Conclusion: Patients who achieve qHBsAg <100 U/ml are believed to have an increased rate of functional cure with HBsAg loss. With the novel HBsAg/anti-HBs immune complex assay, we demonstrated the presence of anti-HBs in CHB patients. More importantly, there was a significant increase in IC/qHBsAg ratio associated with the treatment-induced reduction of qHBsAg to <100 IU/ml. These observations implicate the important role of humoral immune response in HBsAg clearance. Further studies are necessary to confirm these results and to delineate the exact immune control mechanism.
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Patients with qHBsAg <100 U/ml at last follow up (N=3)
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Patients with qHBsAg >100 U/ml at last follow up (N=8)
Disclosure: P. A. Shah: No Conflicts; M. C. Anderson: Abbott Laboratories: Employment, Stock Shareholder; s. p. kaur: No Conflicts; M. Kuhns: Abbott Labs: Employment, Employment; G. A. Cloherty: Abbott Labs: Employment, Employment; D. Lau: Abbott: Grant/Research Support; Dicerna: Advisory Committees or Review Panels; Gilead: Grant/Research Support; Roche: Grant/Research Support;
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发表于 2020-5-5 18:17