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

Table 5 Characteristics and outcomes of rheumatic disease patients with resolved infection who experienced viral reactivation during treatment with non-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	74/F	DM	ND /Pos.	AZA, PSL	12 mo	1.7 × 107	146	Yes	Died7	[75]
2	43/F	RA	ND/Pos.	LEF, SSZ, PSL	1 mo	3.5 × 103	79	Yes	Recovered	[54]
3	73/F	RA	Pos./Pos.3	MTX	10 mo	5.0 × 104	480	Yes	Recovered	[50]
4	72/M	TA	Neg./ND	MTX, PSL	6 mo	> 1.0 × 108	308	Yes	Recovered	[123]
5	57/F	RA	ND4	MTX, PSL	5 mo5	> 1.0 × 109	2012	Yes	Recovered	[121]
6	59/F	RA	ND	MTX, PSL	7 yr	1.6 × 107	378	Yes	Died7	[117]
7	47/F	RA	ND/Pos.	MTX, SSZ, PSL	15 mo	6.5 × 103	31	No	Recovered	[54]
8	75/M	DM	Neg./ND	MTX, AZA, CYA, PSL	15 mo	7.4 × 105	657	Yes	Recovered	[123]
9	67/F	RA, MCD	ND	MTX	37 mo	Neg.	NR	-	-	[51]
				MTX, TAC, PSL6	5 mo	Pos.3	NR	Yes	Recovered
10	74/ND	RA	ND	MTX, PSL	ND	1.0 × 103	NR	Yes	Recovered	[49]
11	77/F	RA, IP	Pos./ND	TAC, PSL6	4 wk	4.2 log	NR	Yes	Recovered	[52]
12	78/F	MPA	Neg./ND	CPA, PSL	8 wk	1.8 log	NR	No	Recovered	[52]
13	58/F	SLE	Neg./ND	CPA, TAC, PSL6	4 wk	7.5 log	NR	Yes	Died7	[52]
14	30/F	SLE	Neg./ND	CPA, PSL6	8 wk	Pos.	Elevated	ND	Died7	[52]
15	59/F	SLE	Pos./ND	CPA, PSL6	4 wk	Pos.	NR	ND	Died7	[52]

No case had received preemptive therapy against HBV infection.

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 level was below 2.1 log copies/mL but HBV-DNA tested positive on real-time PCR;

⁴Anti-HBc was also not searched;

⁵The patient had received PSL and MTX (10 mg/wk) for 15 and 5 years prior to viral reactivation, respectively. Five months previously, the MTX dose had been increased to 12 mg/wk;

⁶The patient received steroid pulse therapy;

⁷The patients died of cerebral infarction (case 1), liver failure (case 6), sepsis (cases 13 and 14), and hemolytic anemia (case 15). DM: Dermatomyositis; RA: Rheumatoid arthritis; MCD: Minimal change disease; IP: Interstitial pneumonia; MPA: Microscopic polyangiitis; SLE: Systemic lupus erythematosus; DMARDs: Disease-modifying antirheumatic drugs; PSL: Prednisolone; MTX: Methotrexate; AZA: Azathioprine; CYA: Cyclosporine A; LEF: Leflunomide; SSZ: Sulfasalazine; TAC: Tacrolimus; CPA: Cyclophosphamide; 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.