Background and objective: Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus.
Methods: We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg-/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort.
Results: Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg-/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3-8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg-/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users.
Conclusions: In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg-/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg-/HBcAb+ patients is probably safe.