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

Abstract

ObjectivesCorticosteroids 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.MethodsWe 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.ResultsAmong 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.ConclusionPatients 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.Trial registration numberChiCTR1900023955.

Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

“… 120 132–136 A study published after the time frame of this SLR, showed that anti-HBcore-positive patients with uveitis, treated with time-weighted (cumulative dose/drug duration (days)) prednisone more than 20 mg/day were at high risk (incidence more than 10/100 persons-years) of HBV reactivation. 137 Treatment with bDMARDs, other than rituximab, was also associated with low risk of HBV reactivation, as shown by several observational studies 98–104 138–146 147 ( table 4 ). A meta-analysis of nine studies with a total of 468 anti-HBcore-positive patients with AIIRD treated with TNF inhibitors (and with only one study (n=19) using prophylaxis), reactivation was observed in 1.8% of patients.…”

“…Evidence for the effect of glucocorticoids remains generally scarce 120 132–136. A study published after the time frame of this SLR, showed that anti-HBcore-positive patients with uveitis, treated with time-weighted (cumulative dose/drug duration (days)) prednisone more than 20 mg/day were at high risk (incidence more than 10/100 persons-years) of HBV reactivation 137. Treatment with bDMARDs, other than rituximab, was also associated with low risk of HBV reactivation, as shown by several observational studies98–104 138–146147 (table 4).…”

Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection

“…It was also found that there was an increasing trend on HBV DNA level during pregnancy, with average value of 0.4-1log 10 IU/ml ( 100 ). Analysis of causes: On the one hand, high levels of adrenocortical hormone during pregnancy may increase HBV replication ( 101 ). The increase of corticosteroid during pregnancy can activate glucocorticoid response elements in HBV gene, further enhance HBV replication and HBV gene expression.…”

COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature

“…In fact, the high genetic barrier nucleo(t)ide analogues entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) suppress HBV replication but fail to eradicate viral cccDNA which, once antiviral treatment is discontinued, works again as a template for a new HBV production. This may also occur in the case of a reduction in the immune response of various origins, including the high dose and/or long-term administration of corticosteroids [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Under these conditions, HBV reactivation may occur both in hepatitis B surface antigen (HBsAg)-positive subjects and in the HBsAg-negative/hepatitis B core antibody (HBc-Ab)-positive; HBV reactivation, however, is less frequent in HBsAg negative individuals [ 10 , 11 , 12 , 13 ].…”

“…COVID-19 guidelines suggest using dexamethasone at the dose of 6 mg daily for at least one week. In clinical practice, since respiratory failure lasts longer than 10 days, the time span in which corticosteroid use is safe is commonly exceeded [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”