Review
Copyright ©The Author(s) 2015.
World J Hepatol. Mar 27, 2015; 7(3): 344-361
Published online Mar 27, 2015. doi: 10.4254/wjh.v7.i3.344
Table 3 Hepatitis virus B reactivation in rheumatoid arthritis patients receiving tumor necrosis factor-α inhibitors: studies in patients with markers of chronic or remote hepatitis virus B infection
Ref.Study designTarget populationNo. of patientsTreatmentAntiviral ProphylaxisHBsAg+Anti-HBc+ and anti-HBs-Anti-HBc+ and anti-HBs+HBV-DNA+Anti-HBs+/anti-HBc-Reactivation
Carroll et al[69]Case seriesRheumatic pts or pts with IBD with CHB1311 treated with IFX, 2 treated with ETNLamivudine13 pts (100%)----7 cases with IFX, 2 cases with ETN
Charpin et al[70]ProspectiveRA (12)/SpA (9) pts with resolved HBV infection214 treated with IFX, 14 with ETN, 3 with ADA0 pts0 pts0 pts 100% (with 3 pts < 100 UI/mL)0 pts-Mean decrease in anti-HBs titre 8%; no cases of HBV reactivation
Chung et al[71]RetrospectiveRA (41), SpA (60), JIA (2) pts103TNFα inhibitors0 pts8 pts--0 pts-1/8 HBsAg+ (12.5%) after 6 wk of IFX
Caporali et al[72]ProspectiveRA (59), SpA (8) pts with resolved HBV infection6725 treated with IFX, 23 with ETN, 19 with ADA0 pts0 pts46 pts28 pts0 pts-No cases of HBV reactivation
Vassillopoulos et al[73]ProspectiveRA (66), SpA (64), other (1) patients with actual/remote HBV infection or vaccinated for HBV13143 treated with IFX, 64 with ETN, 62 with ADA14 pts (100% of CHB group): 11 with lamivudine, 2 with entecavir, 1 with telbivudine14 pts19 pts0 pts among CHB group19 pts (vaccinated)No cases of HBV reactivation in pts with resolved HBV infection. In vaccinated pts, slight decrease in anti-HBs titres (median 163 > 105 IU/mL,P= 0.01). Among CHB pts, 1 (7%) treated withLamivudine + ETN developed HBV reactivation due to a resistant mutant strain
Mori et al[74]ProspectiveRA pts with actual/remote HBV infection2399 treated with IFX, 18 with ETN, 2 with ADA, 5 with TCZ, 28 with csDMARDs2 (100% of HBsAg+ pts) with entecavir2 pts60 pts0 pts-2 cases of HBV reactivation in anti-HBc+ pts (3.3%), 1 with csDMARDs and 1 with ADA
Tamori et al[75]ProspectiveRA pts with positive anti-HBc5022 treated with IFX, 20 with ETN, 2 with ADAEntecavir5 pts45 pts--2/5 (40%) cases of HBV reactivation among HBsAg+ pts; 1/45 (2%) cases of HBV reactivation among HBcAb+/HBsAg- pts, not under TNFI
Pérez-Alvarez et al[76]Systematic reviewTNFI-treated pts257Anti-TNF (not specified)Not specified89 pts168 pts--HBV reactivation in 35 (39%) pts among HBsAg+ group, fatal in 4 cases. Lower risk if pre-emptive NAs (23%vs62%,P= 0.003). Higher risk with IFXvsETN. Nine cases (5%) of HBV reactivation in HBcAb+/HBsAg- pts, fatal in 1 pt
Lan et al[77]ProspectiveRA anti-HBc+ pts8840 pts treated with ETN, 48 with ADA10 HBsAg+ pts treated with lamivudine18 pts12 pts58 pts0 pts22 pts (vaccinated)Among HBsAg+ pts, no cases of HBV reactivation if pre-emptive NAs; mean decrease in HBV-DNA = 153 IU/mL (P < 0.001); 5/8 cases of reactivation without antivirals. 1 case of HBV reactivation in the HBsAg-/anti-HBs- group
Lee et al[78]Systematic reviewHBsAg+ rheumatic disease-positive pts12214 pts treated with IFX, 56 with ETN and 25 with ADA48 pts (drug not specified)122 pts--Not specified-15 cases (12.3%) of HBV reactivation, including 1 SpA patient treated with pre-emptive lamivudine
Lee et al[79]Systematic ReviewHBsAg-/anti-HBc+ rheumatic disease-positive (RA 327, SpA 121) pts468100 pts treated with IFX, 269 with ETN and 95 with ADANot specified0 ptsNot specifiedNot specifiedNot specified-8 cases (1.7%) of HBV reactivation, 7 with ETN and 1 with ADA; satisfactory clinical outcomes with antiviral therapy
Droz et al[38]RetrospectivePts with immune-mediated inflammatory diseases (RA 14, CTD 7, vasculitis 5, other 9) developing HBV reactivation357 pts treated with TNF-α inhibitors (not specified), 4 with RTX, 1 with ABA, 1 with TCZ, the others with steroids and/or other immunosuppressants5 pts (drug not specified)23 pts12 ptsNot specified-Reactivation occurred a median of 35 wk after therapy start. 88.6% were asymptomatic; 25.7% had severe hepatitis. Management were NAs in 91.4% cases and decrease/withdrawal of immunosuppressants in 45.7%. Pooling these data with literature, earlier reactivation for RTX and HBsAg/HBV-DNA+ pts
Ye et al[80]ProspectiveInflammatory arthritis pts (50 RA, 37 SpA)87TNFα inhibitors: 56 treated with IFX, 31 with ETN)4 pts among CHB group , 9 pts among inactive carriers (not specified)37 (6 HBV-DNA+, 31 HBV-DNA-) pts50 ptsNot specified-2 cases of HBV reactivation among CHB pts not receiving pre-emptive NAs, none in those receiving it. Among inactive HBsAg carriers, 6 cases of reactivation in pts who didn’t receive NAs, none in those who did. No cases in HBsAg- pts
Nakamura et al[81]RetrospectiveRA5748 treated with TNFα inhibitors (including 9 receiving also TCZ); 7 with TCZ alone and 2 with TCZ and ABA0 pts0 pts11 pts38 pts0 pts8 pts (not vaccinated)HBV-DNA detected in 3 pts (5.3%), 2 receiving TCZ and 1 receiving ETN, with serum HBV-DNA < 2,1 log copies/mL, and subsequent undetectable HBV-DNA within months
Pts: Patients; CHB: Chronic hepatitis B; IFX: Infliximab; ETN: Etanercept; IBD: Inflammatory bowel disease; SpA: Spondyloenthesoarthropaties (psoriatic arthritis included); csDMARDs: Conventiona Synthetic disease-modifying antirheumatic drugs; JIA: Juvenile idiopathic arthritis; TCZ: Tocilizumab; NAs: Nuclet(s)ide analogues; CTD: Connettive tissue disease; RTX: Rituximab; ABA: Abatacept. Adapted from Lunel-Fabiani et al[82] Joint Bone Spine 2014.