Commensurate incidence and outcomes of liver enzyme elevation between anti-tumor necrosis factor users with or without prior hepatitis B virus infections
Journal
PLoS ONE
Journal Volume
13
Journal Issue
4
Date Issued
2018
Author(s)
Abstract
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 antirheumatic 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. ? 2018 Chiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
adalimumab; alanine aminotransferase; cyclophosphamide; cyclosporine; etanercept; golimumab; hepatitis B core antibody; hepatitis B surface antigen; hydroxychloroquine; leflunomide; methotrexate; salazosulfapyridine; tumor necrosis factor inhibitor; alanine aminotransferase; antirheumatic agent; hepatitis B antibody; hepatitis B surface antigen; tumor necrosis factor; adult; aged; alanine aminotransferase blood level; ankylosing spondylitis; Article; cholecystitis; chronic liver disease; clinical outcome; cohort analysis; controlled study; disease severity; drug safety; drug use; female; heart failure; hepatitis B; human; hypertransaminasemia; incidence; liver congestion; major clinical study; male; medical history; pancreas cancer; psoriatic arthritis; retrospective study; rheumatoid arthritis; risk assessment; sepsis; tuberculosis; virus reactivation; antagonists and inhibitors; blood; drug effect; enzymology; hepatitis B; immunosuppressive treatment; incidence; liver; middle aged; very elderly; virology; virus activation; young adult; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Humans; Immunosuppression; Incidence; Liver; Male; Middle Aged; Retrospective Studies; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha; Virus Activation; Young Adult
Publisher
Public Library of Science
Type
journal article