Table. Case reports of HBV reactivation among rheumatic patients treated with TNF-α inhibitors or rituximab.
| Drug | Indication | Age | Sex | Pre-treatment serology | Duration | Other Drugs | Anti-viral prophylaxis | Outcome |
|---|---|---|---|---|---|---|---|---|
| Infliximab28 | RA | 49 | M | HBSAg+, anti-HBe+, anti-HBc+ | 18 months | MTX 10 mg/wk, prednisone 8 mg | No | Hepatitis (AST 336 and ALT 573, HBV DNA 1492 pg/ml). Treated with lamivudine. |
| Etanercept29 | RA | 62 | F | HBSAg+, anti-HBe+, anti-HBc+ | 2 years | MP 8 mg, MTX 10-15 mg/wk, HCQ 200 mg | No | Hepatitis (AST 112 and ALT 234, HBV DNA 1590 copies/mL). Etanercept later restarted with lamivudine prophylaxis. |
| Etanercept30 | RA | 48 | F | HBsAg+, HBV DNA- | 13 months | MTX, SSZ, HCQ | No | Slight increase in transaminases; HBV DNA 514 copies/ml. |
| Infliximab31 | AS | 43 | M | HBsAg+, HBeAg-, anti-HBe+, anti-HBc+ | 14 weeks (5 mg/kg) | None | No | ALT increased to 49. HBV DNA became positive. Lamivudine started and infliximab successfully continued. |
| Etanercept32 | AS | 73 | M | HBsAg-, anti-HBs+, anti-HBc+, anti-HBe+ | 14 months | Prednisone 5 mg | No | AST rose to 141, ALT to 65. HBV DNA 1507 IU/ml. Treated with lamivudine. Etanercept later restarted successfully with concomitant lamivudine. |
| Infliximab33 | AS | 35 | F | HBsAg+, HBe-, anti-HBe+, HBV DNA- | 3 infusions | MTX 15 mg/week | No | Hepatitis (ALT 10 times normal; HBV DNA positive). Treated with lamivudine and infliximab successfully continued. |
| Infliximab34 | AS | 31 | M | HBsAg+, HBe-, anti-HBe+, HBV DNA - | 3 infusions (5 mg/kg) | -- | No | Hepatitis (AST 457, ALT 1054, HBV DNA 3,130,000 IU/ml). Resolved with entecavir. This patient was the only patient to reactivate out of 8 HBV carriers in a population of 103 patients treated with anti-TNFα therapy. |
| Rituximab21 | RA | 56 | F | HBsAg+, HBe-, anti-HBe+, HBV DNA 9.6 × 102 IU/ml | 2 infusions (1000 mg) | -- | Yes | Hepatitis (AST 110, ALT 150, HBV DNA>1.1 × 108 IU/ml). Tenofivir added to lamivudine; transaminases normalized. |
| Rituximab35 | ANCA-vasculitis | 73 | M | HBsAg-, Anti-HBc+ | 4 infusions (375 mg/m2) | Prednisolone 40 mg | No | HBsAg+, HBV DNA>110 × 106 IU/ml 11 months later. Patient died of renal failure; unclear if HBV reactivation contributed to decline. |
RA=rheumatoid arthritis, AS=Ankylosing spondylitis, ANCA=anti-neutrophil cytoplasmic antibodies, MTX=methotrexate, MP= methylprednisolone, HCQ=hydroxychloroquine, SSZ=sulfasalazine, TNF=tumor necrosis factor.