Hepatitis B virus reactivation in rheumatoid arthritis

Table 1 Risk of hepatitis B virus reactivation with different immunosuppressants

Medication	Mechanism	Definition of HBV reactivation	Study population	Reactivation rate
Methotrexate	Suppressive HBV specific cytotoxic T cell response and the production of proinflammatory cytokines	HBV DNA > 103 (copies/mL)	HBsAg-positive	Low risk[29,30]
			HBsAg-negative	Low risk[30]
Leflunomide	Inhibition of the growth of activated lymphocytes by inhibition of dihydro-lactate dehydrogenase	10-fold rise in HBV-DNA compared to baseline or a switch from undetectable to detectable	HBsAg-positive	High risk, contraindicated[31]
			HBsAg-negative	No data
Corticosteroids	Immunomodulatory and anti-inflammatory	Switch from undetectable HBV DNA to detectable or a 10-fold increase compared with baseline[34]	HBsAg-positive	High risk (> 10 mg, > 4 wk); medium risk (< 10 mg, > 4 wk); low risk (< 10 mg, < 1 wk)
			HBsAg-negative	1%-1.8%[34,36]
TNF inhibitor	Dampening of the cytokine cascade and suppression of the cytotoxic CD8+ T-cell responses against HBV	An increase of serum HBV DNA levels by greater than 1 logs10 IU/mL or conversion from HBsAg- to HBsAg+	HBsAg-positive	Medium-high risk (9.1%-75%)[23,38]
			HBsAg-negative	Low risk (0-8.3%)[22,39]
Tocilizumab	Blocks IL-6 signaling by inhibiting its receptor	HBV-DNA level higher than 2.0 log copies/mL	HBsAg-positive	No data
			HBsAg-negative	Low risk (8%)[40]
Tofacitinib	Inhibition of JAK signal pathway	An increase in HBV DNA by greater than 1 to 2 logs10 IU/mL or a reappearance of HBsAg	HBsAg-positive	High risk (100%)[41]
			HBsAg-negative	Low risk (0)
Abatacept	Blocks co-stimulation of T lymphocytes	Conversion from HBsAg- to HBsAg+	HBsAg-positive	Medium risk[34]
			HBsAg-negative	Low risk[34]

HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus.