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.

Table 2 Characteristics of different phases of hepatitis B virus infection

				HBsAg	Anti-HBs	HBeAg	Anti-HBe	Anti-HBc	HBV DNA	ALT
HBV seronegative				-	+/-	-	-	-	-	Normal
HBV infection	Phase 1	Chronic HBV infection		+	-	+	-	+	> 20000 IU/mL	Normal
	Phase 2	CHB	HBeAg(+)	+	-	+	-	+	> 20000 IU/mL	> 2 ULN
	Phase 4	CHB	HBeAg(-)	+	-	-	+	+	> 2000 IU/mL	> 2 ULN
	Phase 3	Inactive HBsAg carrier		+	-	-	+/-	+	< 2000 IU/mL	Normal
	Phase 5	Resolved infection		-	+/-	-	+	+	-	Normal

HBsAg: Hepatitis B surface antigen; anti-HBs: Antibody to hepatitis B surface antibody; HBeAg: Hepatitis B e antigen; anti-HBe: Antibody to hepatitis B envelope antigen; anti-HBc: Antibody to hepatitis B core antigen; CHB: Chronic hepatitis B; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; ULN: Upper limit of normal.