Table 5.

Case reports of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing tocilizumab

Ref.	Study design	Patient charachteristics	Therapy	Basal virological Status	Timing of HBV reactivation	Antiviral Therapy	Results	Comments
Nagashima et al[92]	Case Report	60-year-old female RA pt, RA test and ACPA positive with erosive disease, starting TCZ after IFX and methotrexate	TCZ + steroids	HBsAg-10 yr before TCZ start, basal serological screening not performed	6, 5 years after TCZ start	Entecavir Ongoing TCZ	Subclinical, good serological and virological responses	Diagnosis made by detection of persistently high serological markers in an asymptomatic pt without liver function tests’ alterations
Tsuboi et al[93]	Case Report	59-year-old female RA pt initially treated with IFX thus withdrawn for HBV reactivation	IFX and then TCZ (after HBV reactivation)	Serological screening not performed before IFX. At 5th IFX infusion HBsAg+/HBV-DNA+/HBeAg+	32 wk after IFX start	Lamivudine Ongoing TCZ	Good clinical, serological and virological response until 2 years after TCZ start	-
Kishida et al[94]	Case Report	Adult-onset Still’s disease pt affected with CHB	TCZ + ongoing entecavir	HBsAg+	No reactivation observed	-	Good clinical, serological and virological response until end of follow-up	-
Nakamura et al[81]	Retrospective	Among 9 RA pts treated with TCZ (7 with TCZ alone and 2 with TCZ and ABA in sequence), 2 cases of HBV reactivation were detected: (a) 75-year old male pt starting TCZ as a first line therapy	TCZ monotherapy	HBcAb+ Undetectable HBV-DNA	4 mo after TCZ start	-	Subclinical, subserological, good virological response	HBV-DNA fluctuated always < 2, 1 log copies/mL throughout 4 mo until it became persistently undetectable, even after switch to ETN (due to lack of efficacy)
		(b) 55-year-old female pt starting TCZ after IFX and ETN	TCZ + methotrexate	HBcAb+ Undetectable HBV-DNA	2 mo after TCZ start	-	Subclinical, subserological, good virological response	HBV-DNA fluctuated always < 2, 1 log copies/mL throughout 5 mo until it became persistently undetectable, even after switch to ADA (due to lack of efficacy)
Droz et al[38]	Retrospective (subgroup analysis)	1 pt affected with immune-mediated inflammatory disease treated with TCZ	Not specified	Not specified	median of 35 wk after therapy start (global data)	Not specified	No cases of fulminant hepatitis	Early reactivation in HBsAg+/HBV-DNA+ pts (global data)

Pts: Patients; ACPA: Anti-citrullinated peptide antibodies; IFX: Infliximab; CHB: Chronic hepatitis B; ABA: Abatacept; ETN: Etanercept; HBsAg: Hepatitis B surface antigen; TCZ: Tocilizumab; HCV: HCV: Hepatitis B virus.