Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Table 6 Case reports of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing abatacept

Ref.	Study design	Patientscharacteristics	Therapy	Basal virological status	Timing of HBV reactivation	Antiviral therapy	Results	Comments
Kim et al[95]	Retrospective	8 RA pts affected with CHB	ABA + pre-emptive NAs (4 pts: 3 with entecavir and 1 with tenofovir) ABA without antiviral prophylaxis (4 pts)	HBsAg+ Detectable HBV-DNA in 3/8 pts	Not specified	Not specified	Among pts receiving NAs, no cases of HBv reactivation. Among pts without antiviral prophylaxis, all pts experienced HBV reactivation	Among pts receiving NAs, a statistically significant improve in DAS28-ERS was detected; which was not noted in the control group
Germanidis et al[96]	Case Report	72-year-old female RA pt starting ABA after ADA	ABA + leflunomide	Anti-HBc+/HBsAg-/anti-HBs+/anti-HBe+	6 mo after ABA start	ABA and leflunomide withdrawal Consequent anviral treatment with tenofovir (12 about 1 yr later)	Good clinical, serological and virological response to tenofovir	2 mo time lag between ABA withdrawal and liver tests flare, suggesting that HBV reactivation evolved in parallel with T cell immune reconstitution
Fanouriakis et al[97]	Case report	68-year-old female RA pt with erosive disease	ABA + methotrexate	HBsAg-/anti-HBc+ Basal HBV-DNA unknown	10 mo after ABA start	Tenofovir ABA withdrawal	Good clinical, serological and virological response	-
De Nard et al[98]	Case series	9 RA pts treated with ABA	ABA 8/9 pts treated with concomitant methotrexate Lamivudine in 2 pts (1 HBsAg+ and 1 HBsAg-) from baseline, and in 1 pt with comorbid HCV infection after ABA start	8 HBsAg-/anti-HBc+ 1 HBsAg+/HBV-DNA-	1 pt with comorbid HCV infection experienced aminotransferases elevation (< 2 x ULN) 2 mo after ABA start	Lamivudine Ongoing ABA	Subclinical, gradual amelioration of liver function tests, persistently undetectable HBV-DNA	No cases of HBV reactivation among pts receiving pre-emptive NAs
					1 pt with resolved HBV infection not receiving NAs developed HBV-DNA positivation 12 mo after ABA start	Ongoing ABA No prophylaxis	ConsecutiveHBV-DNA fluctuations; no flares in liver function tests even after entecavir initiation at 24 mo while switching to ADA (unpublished data)
Droz et al[38]	Retrospective (subgroup analysis)	1 pt affected with immune-mediated inflammatory disease treated with ABA	Not specified	Not specified	median of 35 wk after therapy start (global data)	Not specified	No cases of fulminant hepatitis (global data)	Early reactivation in HBsAg+/HBV-DNA+ pts (global data)

Pts: Patients; CHB: Chronic hepatitis B; NAs: Nucleot(s)ide analogues; ADA: Adalimumab; HBsAg: Hepatitis B surface antigen; HCV: Hepatitis B virus.