Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations

Table 4 Characteristics and outcomes of rheumatic disease patients with resolved hepatitis B virus infection who experienced viral reactivation during treatment with biological disease-modifying antirheumatic drugs

Case	Age/sex	Disease	Anti-HBs/anti-HBe	DMARDs	Duration	HBV-DNA1 (copies/mL)	ALT2 (IU/L)	Antiviral therapy	Outcomes	Ref
1	71/F	RA	Pos./Pos.	IFX, MTX, PSL	16 mo	ND	NR	-	-	[119]
				ADM, MTX, PSL	11 mo	1 × 109	674	Yes	Died5
2	80/F	RA	ND	IFX, MTX, PSL	48 mo	Neg.	NR	-	-	[51]
				ETN, MTX, PSL	4 mo	Neg.	NR	-	-
				ADM, MTX, PSL	15 mo	Pos.3	NR	No	Recovered
3	73/M	AS	Pos./Pos.	ETN, PSL	14 mo	8.8 × 103	65	Yes	Recovered	[118]
4	54/F	RA	Neg./Pos.4	ETN, MTX, PSL	5 mo	1.6 × 106	199	Yes	Recovered	[53]
5	75/ND	RA	ND	ETN, MTX, PSL	ND	2.5 × 102	NR	Yes	Recovered	[49]
6	60/ND	RA	ND	ETN, LEF	ND	1.0 × 102	NR	No	Recovered	[49]
7	49/ND	RA	ND	ETN, BUC, PSL	ND	2.5 × 107	NR	Yes	Recovered	[49]
8	46/ND	RA	ND	ETN, MTX, TAC	ND	5.0 × 103	NR	Yes	Recovered	[49]
9	65/ND	RA	ND	ETN, PSL	ND	1.0 × 105	NR	Yes	Recovered	[49]
10	77/ND	RA	ND	TCZ, MTX	ND	1.0 × 102	NR	No	Recovered	[49]
11	75/M	RA	ND	TCZ, PSL6	2 mo	Pos.3	NR	No	Recovered	[59]
12	55/F	RA	ND	IFX	25 mo	Neg.	NR	-	-	[59]
				ETN	35 mo	Neg.	NR	-	-
				TCZ, MTX PSL6	2 mo	Pos.3	NR	No	Recovered
13	60/F	RA	ND	ETN, MTX, PSL6	65 mo	Pos.3	NR	No	Recovered	[59]
14	64/F	RA	Pos./ND	RTX, MTX	24 mo	> 1.0 × 108	72	Yes	Recovered	[123]
15	71/F	RA	Neg./ND	RTX, PSL	4 wk	Pos.	NR	No	Recovered	[52]
16	64/F	RA	Pos./Neg.	RTX, MTX	2 yr	1.1 × 108	605	Yes	Recovered	[124]
17	78/M	RA	Pos./ND	IFX, MTX, PSL	ND	ND	NR	-	-	[122]
				RTX, PSL	27 mo	107	421	Yes	Recovered
18	68/F	RA	Neg./Pos.	ABT, MTX	10 mo	1.1 × 108	NR	Yes	Recovered	[125]
19	72/F	RA	Pos./Pos.	ADA, PSL	2 yr	Neg.	NR	-	-	[120]
			Pos./Pos.	ABT, LEF, PSL	13 mo	7.0 × 104	2 × ULN	Yes	Recovered

No patients had received preemptive therapy against HBV infection. Underlined entries represent biological agents.

¹HBV-DNA levels were determined at diagnosis of HBV reactivation;

²ALT values were determined at diagnosis of HBV reactivation or were the highest values measured after HBV reactivation;

³HBV-DNA tested positive on real-time PCR, but DNA levels were below 2.1 log copies/mL;

⁴An HBV-DNA level was 3.5 log copies/mL;

⁵The patient died of hepatic failure;

⁶The patient continued biological therapy after HBV reactivation. RA: Rheumatoid arthritis; AS: Ankylosing spondylitis; DMARDs: Disease-modifying antirheumatic drugs; PSL: Prednisolone; MTX: Methotrexate; BUC: Bucillamine; LEF: Leflunomide; TAC: Tacrolimus; RTX: Rituximab; ADM: Adalimumab; IFX: Infliximab; ETN: Etanercept; TCZ: Tocilizumab; ABT: Abatacept; HBV: Hepatitis B virus; anti-HBs: Anti-hepatitis B surface antibody; anti-HBe: Anti-hepatitis B e antibody; ALT: Alanine aminotransferase; Neg.: Negative; Pos.: Positive; ULN: Upper limits of normal; NR: Normal range; ND: Not determined or not described.