P322 Hepatitis B reactivation under biologic therapy in patients with HBsAg negative phase of chronic HBV infection

Ergenç, I.(1);Kani, H.T.(1);Karabacak, M.(2);Cömert Özer, E.(3);Mehdiyev, S.(1);Jafarov, F.(1);Abacar, K.Y.(2);Kutluğ Ağaçkıran, S.(2);Seven Sevik, G.(2);Alibaz Öner, F.(2);İnanç, N.(2);Atagündüz, M.P.(2);Gençosmanoğlu, D.S.(3);Özen Alahdab, Y.(1);Ergun, T.(3);Direskeneli, R.H.(2);Atuğ, Ö.(1);

(1)Marmara University School of Medicine, Gastroenterology, istanbul, Turkey;(2)Marmara University School of Medicine, Rheumatology, istanbul, Turkey;(3)Marmara University School of Medicine, Dermatology, istanbul, Turkey


Biologic agents are widely used in immune mediated inflammatory diseases (IMID).  The risk and consequences of hepatitis B reactivation in hepatitis B surface antigen (HBsAg) negative phase of hepatitis B virus (HBV) exposed patients is not clear. We aim to investigate the reactivation rate in biologic exposed patients within surface antigen negative phase of HBV infection.


We identified patients followed up at gastroenterology, rheumatology and dermatology out-patient clinics with a diagnosis of IMID from clinical charts. Patients exposed to biologic agents with a negative HBsAg and positive Anti-HBc IgG were included. Primary outcome was HBV reactivation, which was defined as reverse seroconversion of HBsAg.

Figure 1. Patients included the study


We screened 8266 IMID patients and 2484 of them were exposed to biologic agents. A total of 221 patients were included in the study. The mean age was 54.08 ± 11.69 years and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1 – 6). The mean biologic agent exposure time was 55 (range: 2 – 179) months.  One hundred and fifty-two (68.8%) patients were using concomitant immunomodulatory agents and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of HBsAg positivity was observed in the whole cohort. Antiviral prophylaxis for hepatitis B was given to 48 (21.7%) patients with entecavir, tenofovir or lamivudine. HBV-DNA was screened in 56 (25.3%) patients prior to the biologic exposure.  Two patients had HBV-DNA reactivation with a negative HBsAg during exposure to the biologic agent.
Table 1: Clinical characteristics of the patients.

Diagnosis (n)  
Rheumatoid arthritis 55 (24.9%)
Spondylarthritis 76 (34.4%)
Inflammatory Bowel Disease 20 (9.0%)
Psoriasis 57 (25.8%)
Behçet’s disease 7 (3.2%)
Takayasu arteritis 4 (1.8%)
Still disease 1 (0.5%)
Temporal arteritis 1 (0.5%)
Exposed biological agents n (%)  
Infliximab 41 (18.6%)
Adalimumab 67 (30.3%)
Etanercept 38 (17.2%)
Certolizumab 13 (5.9%)
Golimumab 14 (6.3%)
Ustekinumab 17 (7.7%)
Secukinumab 5 (2.3%)
Abatacept 11 (5.0%)
Ixekizumab 1 (0.5%)
Tocilizumab 4 (1.8%)
Tofacitinib 10 (4.5%)
Hepatitis B DNA screening prior to biologic exposure n (%)  
Screened 56 (25.3%)
Not Screened 165 (74.7%)


Though only 21.7% of our patients used prophylaxis, we found only two reactivations (1%) and no HBsAg seroconversion in our cohort. Our results suggest a re-assessment of antiviral prophylaxis for anti-HBc Ag (+) patients exposed to biologic agents. Current guidelines would be updated in the light of future studies.