Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection

Corticosteroids remain the mainstay of treatment for rheumatic diseases but can cause hepatitis B virus (HBV) reactivation in patients with resolved HBV infection. Risk assessment and stratification are needed to guide the management of these patients before corticosteroid therapy.We prospectively enrolled patients with negative hepatitis B surface antigen positive Anti-hepatitis B core status with or without corticosteroid use and determined corticosteroid exposure by calculating cumulative dose and time-weighted average daily dose of prednisone. The primary outcome was the time to a composite of HBV reactivation, hepatitis flare or severe hepatitis.Among 1303 participants, the median of cumulative dose and time-weighted average dose of prednisone used in this cohort was 3000 mg (IQR: 300-6750 mg) and 15 mg/day (IQR: 10-20 mg/day), respectively. In multivariable analyses, cumulative dose showed inverted V-shaped relationship with primary events, which peaked at a cumulative dose of 1506 mg (HR: 3.72; 95% CI, 1.96 to 7.08). Quartiles of time-weighted average dose were independently associated with a monotonic increase in event risk (HR per quartile increase: 2.15; 95% CI, 1.56 to 2.98), reaching an HR of 49.48 (95% CI, 6.24 to 392.48) in the top quartile. The incidence of primary outcome was 16.67 per 100 person-years in the top quartile of time-weighted average dose (Q4>20 mg/day). Other quartiles all had an incidence of primary outcome less than 10 per 100 person-years.Patients with time-weighted average prednisone dose greater than 20 mg/day would be classified as the high risk for HBV reactivation or hepatitis flare. Prophylactic Anti-HBV therapy may be needed for these high-risk patients.ChiCTR1900023955.